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Biomedical subjects

M López

Publications and source records attributed to M López.

At least 19 recordsLinked to original sources

Neuromedin s as novel putative regulator of luteinizing hormone secretion.

Neuromedin S (NMS), a 36 amino acid peptide structurally related to neuromedin U, was recently identified in rat brain as ligand for the G protein-coupled receptor FM4/TGR-1, also termed neuromedin U receptor type-2 (NMU2R). Central expression of NMS appears restricted to the suprachiasmatic nucleus, and NMS has been involved in the regulation of dark-light rhythms and suppression of food intake. Reproduction is known to be tightly regulated by metabolic and photoperiodic cues. Yet the potential contribution of NMS to the control of reproductive axis remains unexplored. We report herein analyses of hypothalamic expression of NMS and NMU2R genes, as well as LH responses to NMS, in different developmental and functional states of the female rat. Expression of NMS and NMU2R genes was detected at the hypothalamus along postnatal development, with significant fluctuations of their relative levels (maximum at prepubertal stage and adulthood). In adult females, hypothalamic expression of NMS (which was confined to suprachiasmatic nucleus) and NMU2R significantly varied during the estrous cycle (maximum at proestrus) and was lowered after ovariectomy and enhanced after progesterone supplementation. Central administration of NMS evoked modest LH secretory responses in pubertal and cyclic females at diestrus, whereas exaggerated LH secretory bursts were elicited by NMS at estrus and after short-term fasting. Conversely, NMS significantly decreased elevated LH concentrations of ovariectomized rats. In summary, we provide herein novel evidence for the ability of NMS to modulate LH secretion in the female rat. Moreover, hypothalamic expression of NMS and NMU2R genes appeared dependent on the functional state of the female reproductive axis. Our data are the first to disclose the potential implication of NMS in the regulation of gonadotropic axis, a function that may contribute to the integration of circadian rhythms, energy balance, and reproduction.

Aging↗

Modelling thermal inactivation of Listeria monocytogenes in sucrose solutions of various water activities.

The heat resistance of Listeria monocytogenes was determined in sucrose solutions with water activity (a(w)) ranging from 0.99 to 0.90. At all temperatures investigated shape of the survival curves depended on the a(w) of the treatment medium. The survival curves for a(w)=0.99 appeared to be linear, for a(w)=0.96 were slightly upwardly concaved and for a(w)=0.93 and 0.90 were markedly concave upward. A mathematical model based on the Weibull distribution provided a good fit for all the survival curves obtained in this investigation. The effect of the temperature and a(w) on the Weibull model parameters was also studied. The shape parameter (p) depended on the a(w) of the treatment medium but in each medium of different a(w) the temperature did not have a significant effect on this parameter. The p parameter followed a linear relationship with a(w). The scale parameter (delta) decreased with the temperature following an exponential relationship and increased by decreasing the a(w) in the range from 0.99 to 0.93. However the delta parameter of survival curves obtained at a(w)=0.90 were lower than those obtained at a(w)=0.93. A mathematical model based on the Weibull parameters was built to describe the joint effect of temperature and a(w) on thermal inactivation of L. monocytogenes. This model provides a more complete information on the influence of the a(w) on the L. monocytogenes than the data initially generated. The model developed indicated that the effect of the a(w) on the thermal resistance of L. monocytogenes varied depending upon the temperature of treatment.

Colony Count, Microbial↗

Analysis of electroencephalograms in Alzheimer's disease patients with multiscale entropy.

The aim of this study was to analyse the electroencephalogram (EEG) background activity of Alzheimer's disease (AD) patients using multiscale entropy (MSE). MSE is a recently developed method that quantifies the regularity of a signal on different time scales. These time scales are inspected by means of several coarse-grained sequences formed from the analysed signals. We recorded the EEGs from 19 scalp electrodes in 11 AD patients and 11 age-matched controls and estimated the MSE profile for each epoch of the EEG recordings. The shape of the MSE profiles reveals the EEG complexity, and it suggests that the EEG contains information in deeper scales than the smallest one. Moreover, the results showed that the EEG background activity is less complex in AD patients than control subjects. We found significant differences between both subject groups at electrodes F3, F7, Fp1, Fp2, T5, T6, P3, P4, O1 and O2 (p-value < 0.01, Student's t-test). These findings indicate that the EEG complexity analysis performed on deeper time scales by MSE may be a useful tool in order to increase our knowledge of AD.

Aged↗

Perinatal overfeeding in rats results in increased levels of plasma leptin but unchanged cerebrospinal leptin in adulthood.

OBJECTIVE: To study the effect of perinatal programming and overfeeding on the hypothalamic control mechanisms of food intake in adult rats. DESIGN: Neonatal programming effects on body weight, food intake, central and peripheral leptin levels, hypothalamic neuropeptides, leptin receptors and central leptin responsiveness in adult rats. MEASUREMENTS: Plasma and cerebrospinal fluid (CSF) leptin levels were analyzed using radioimmunoassay. Neuropeptide mRNA levels were analyzed using in situ hybridization. Leptin receptor mRNA levels were analyzed using reverse transcriptase-polymerase chain reaction. RESULTS: Perinatally overfed rats growing up in small litters (SL) maintain their obese and hyperleptinemic phenotype in adulthood. However, leptin levels in CSF are abnormally low considering the plasmatic hyperleptinemia. In contrast to the already reported changes in perinatally overfed juvenile rats, perinatally overfed adult rats did not show any alteration in the expression of leptin receptor isoforms and evaluated neuropeptides. Moreover, SL adult rats showed a normal sensitivity regarding the inhibitory effect of intracerebroventricular leptin administration on food intake. CONCLUSION: Perinatal overfeeding does not induce alterations in either the anorectic response to central leptin administration or expression of leptin receptors and neuropeptides in adulthood. The leptin resistance to peripheral leptin in SL adult rats may be related to impaired leptin transport across the blood-brain barrier.

Animals↗

Variable very-high-energy gamma-ray emission from the microquasar LS I +61 303.

Microquasars are binary star systems with relativistic radio-emitting jets. They are potential sources of cosmic rays and can be used to elucidate the physics of relativistic jets. We report the detection of variable gamma-ray emission above 100 gigaelectron volts from the microquasar LS I 61 + 303. Six orbital cycles were recorded. Several detections occur at a similar orbital phase, which suggests that the emission is periodic. The strongest gamma-ray emission is not observed when the two stars are closest to one another, implying a strong orbital modulation of the emission or absorption processes.

Journal Article↗

Reference ranges for Doppler parameters of the fetal aortic isthmus during the second half of pregnancy.

OBJECTIVE: To establish reference ranges for blood flow velocity waveforms (FVW) of the fetal aortic isthmus (AoI) during the second and third trimesters of pregnancy. METHODS: This was a prospective cross-sectional observational study involving 458 uncomplicated singleton pregnancies between 19 and 37 weeks of gestation. Fetal AoI Doppler parameters were assessed in either the longitudinal aortic arch view or the three vessels and trachea view. Regression analysis was used to determine gestational-age-specific reference ranges and to construct nomograms for the following Doppler parameters: pulsatility index (PI), resistance index (RI) and peak systolic (PSV), end-diastolic (EDV) and time-averaged maximum (TAMXV) velocities. Intra- and interobserver reproducibility were evaluated by calculating intraclass correlation coefficients (ICCs) and limits of agreement. RESULTS: Reliable FVW in the AoI were obtained in all cases. Acceptable intra- and interobserver reproducibility was obtained. With advancing gestation, there was a significant increase in PSV, TAMXV and PI, whereas RI and EDV remained constant during the second half of pregnancy. No cases of absent or reversed flow during diastole were detected. CONCLUSION: Normal data of the fetal AoI blood FVW throughout the second and third trimesters of pregnancy are provided. The reported Doppler profiles may be of clinical use in the assessment of hemodynamically compromised growth-restricted fetuses.

Adult↗

Prevalence of HLA antibodies and its impact on graft function in a group of kidney transplant recipients: a cross-sectional study.

UNLABELLED: HLA alloantibodies (Abs) are associated with chronic rejection and poorer graft survival. The current study was designed to document the prevalence of HLA Abs in a group of kidney transplant recipients (KTR) and its impact on graft function. PATIENTS AND METHODS: 283 KTR transplanted between January 1990 and December 2003 who had a functional graft were invited to participate. 198 KTR were enrolled. HLA class I and II Abs were measured by Luminex-One Lambda. Graft function was assessed by DeltaCr and GFR calculated by the Levey formula. RESULTS: Median post-kidney transplant (post-KT) follow-up was 51.4 (4.3 to 176.3) months. Forty-four (22.2%) KTR were found to have class I and/or class II Abs. Eleven had both class I and II Abs, ten were positive only for class I, and 23 for class II. Overall, no significant difference was seen in renal function. The DeltaCr for Ab positive and Ab negative were -0.24+/-0.84 and -0.17+/-0.60 mg/dL (P=0.54), respectively. The GFR for Ab positive and Ab negative were 64.4+/-26 and 60.2+/-20 mL/min (P=0.25), respectively. No statistically significant difference was found between HLA Abs and number of HLA mismatches, gender, blood transfusions, pre-KT pregnancies, DGF, history of acute rejection, and chronic allograft nephropathy. Adjusting analysis by transplant year showed no significant difference. CONCLUSION: The prevalence of HLA antibodies was similar to previous reports. In this cross-sectional study, the presence of HLA antibodies was not related to a negative impact on renal function.

Cross-Sectional Studies↗

[Management of congenital tracheomalacia: a single institution experience].

INTRODUCTION: Congenital tracheomalacia (CTM) is a rare disease causing tracheal wall collapse when breathing. Herein, we show our experience in the management of this type of airway anomaly, settling the indications for surgical or endoscopic treatment. PATIENTS AND METHODS: We have performed a retrospective study, from 1991 to 2003, of patients with a bronchoscopic diagnosis of CTM or bronchomalacia (BM). We have analyzed the following facts: sex, age, indication of the initial bronchoscopy, ethiology, clinical group, anatomic type, associated malformations, treatment modality, complications, results, and time of follow-up. RESULTS: 46 patients have been included in this study: 25 boys (54%) and 21 girls (45%). Mean age at diagnosis has been 11 months. The indications for diagnostic bronchoscopy have been: respiratory distress (24%), lung athelectasia (24%), stridor (21%), congenital tracheoesophageal fistula (11%), extubation failure (11%), apneic spells (6%), and recurrent pneumonia (2%). Secondary CTM has been much more frequent (82%) than the primary type (17%). Patients have been classified into 3 groups according to the severity of symptoms: group I--mild symptoms (7 patients); group II---moderate (22); and group III, severe (17). Tracheomalacia was diagnosed in 26 cases (56%), bronchomalacia in 12 (26%) and tracheobronchomalacia in 8 patients (17%). Almost all the patients (95%) have showed other associated malformations. Medical treatment has been instituted in 29 patients (63%), 15 cases (32%) have been managed surgically or endoscopically, and in 2 cases no treatment was tried because of their critical clinical status. In addition, in 17 patients (37%) an antireflux surgical procedure was performed. Satisfactory results have been achieved in 72% of treated patients, fair results were obtained in 4 (9%), and a poor outcome occurred in 2 (4,5%). Another 8 patients have died during follow-up due to unrelated causes. 36 patients (78%) are alive with a mean follow-up period of 5,3 years. CONCLUSIONS: Most patients with CTM can he treated conservatively though spontaneous resolution may he expected after the first year of life. Surgical or endoscopical procedures are indicated in those patients with severe respiratory symptoms.

Bronchoscopy↗

Randomized phase III study of 3-weekly versus weekly docetaxel in pretreated advanced non-small-cell lung cancer: a Spanish Lung Cancer Group trial.

BACKGROUND: Docetaxel is a widely accepted second-line treatment in advanced non-small-cell lung cancer (NSCLC) with a risk of myelotoxicity. This study evaluated the efficacy and toxicity profile of two docetaxel regimens in NSCLC patients who had failed first-line non-docetaxel-based chemotherapy. PATIENTS AND METHODS: A total of 259 patients from 33 Spanish centers were randomized to receive either docetaxel 75 mg/m(2) administered every 3 weeks (3W arm) or docetaxel 36 mg/m(2) given weekly (1W arm) for 6 weeks followed by 2 weeks of rest. The primary end point was 1-year survival; secondary end points were median survival, time to progression, response and toxicity. RESULTS: One-year survival was 27% in the 3W and 22% in the 1W arm. Median time to progression was also similar in the two arms. Median survival was 6.6 months in the 3W arm versus 5.4 months in the 1W arm (P = 0.075). Response rates were 9.3% in the 3W arm and 4.8% in the 1W arm. More patients in the 1W arm experienced mucositis [1W, nine patients (7.2%); 3W, two patients (1.6%); P = 0.032], while febrile neutropenia was significantly higher in the 3W arm [3W, 10 patients (7.8%); 1W, one patient (0.8%); P = 0.010]. CONCLUSIONS: Both weekly and 3-weekly docetaxel were effective and well-tolerated, with different toxicity profiles. In general, there was no indication to recommend the weekly schedule. However, the significant lower rate of febrile neutropenia observed in the weekly schedule makes it a good alternative for patients at risk of severe neutropenia.

Adult↗

Temporary inhibition of neuronal apoptosis in Aujeszky's disease virus-infected swine.

Previous studies have shown that during acute infection of the porcine trigeminal ganglia (TG), Aujeszky's disease virus (ADV)-infected neurons are protected from apoptosis induced by the virus itself and by cells of the immune system. However, TG neurons productively infected by ADV finally die and are phagocytosed by adjacent cells, a fact that leads us to speculate that the inhibition of neuronal apoptosis by ADV may be temporary rather than absolute. To address this issue we used TG and brain stem from pigs during acute infection by ADV. Infected cells were detected by immunohistochemical staining of viral antigens, whereas apoptotic cells were identified with an anti-active caspase-3 antibody, the TUNEL assay and by transmission electron microscopy. The results obtained in this study support the contention that the inhibition of neuronal apoptosis by ADV is temporary, since activation of caspase-3 could be detected in infected neurons at late stages in infection and because foci of advanced neuronophagia contained neurons exhibiting typical ultrastructural features of apoptosis.

Acute Disease↗

Mutant prevention concentration of isoniazid, rifampicin and rifabutin against Mycobacterium tuberculosis.

BACKGROUND: Mutant prevention concentration (MPC) is a new parameter that may be of aid in determining the risk of resistant mutants being selected. METHODS: The MPCs of 224 Mycobacterium tuberculosis clinical isolates were estimated by plating more than 10(10) cells on drug-containing agar and determining the concentration that allowed no colony growth. Antibiotics used were isoniazid, rifampicin and rifabutin. RESULTS: The MPC90 of clinical isolates in our setting is 2.4, 2.2 and 0.4 mg/l for isoniazid, rifampicin and rifabutin, respectively. CONCLUSIONS: Isoniazid and rifampicin are two drugs that present a low risk of selection of resistant mutants when used in monotherapy. However, determination of the MPC of each strain can provide data to minimize this risk and thus enable treatment to be optimized.

Antitubercular Agents↗

Usefulness of various antibiotics against Mycobacterium avium-intracellulare, measured by their mutant prevention concentration.

This study looked the selection of resistant mutants in Mycobacterium avium-intracellulare during antibiotic treatment. The mutant prevention concentration (MPC) of 20 Mycobacterium avium and 12 Mycobacterium intracellulare isolates was determined. Fifty percent of Mycobacterium avium strains had MPC (MPC50) values lower than 16, 64, 40, 55 and 60 mg/L for rifabutin, rifampicin, ciprofloxacin, levofloxacin and moxifloxacin, respectively. In the case of Mycobacterium intracellulare, 50% had MPC (MPC50) values below 60, 30, 35, 16, 2.5 and 14 mg/L for linezolid, rifabutin, levofloxacin, gatifloxacin, moxifloxacin and clarithromycin, respectively. The high capacity for selecting resistant mutants of all the antibiotics studied emphasises the need to restore the immune system if necessary and to administer combined treatments in order to cure patients.

Acetamides↗

Cost of renal transplant maintenance immunosuppression: effect of control of vascular risk factors.

In 3 renal transplant cohorts treated in Spain in 1990, 1994, and 1998 (total number, 3279), we studied the frequency of certain cardiovascular risk factors. Their effect on the cost of drugs was assessed from the data from 1 center; the mean cost of antihypertensive agents per patient-year was 349 euros, and of lipid-lowering drugs was 294 euros. Between 1990 and 1998 the frequency of use of antihypertensive agents at 2 years increased from 70% to 80%, and that of lipid-lowering agents from 12% to 46% (P < .001). Patients received various regimens of immunosuppression at the second year, as follows: (1) steroid-free: cyclosporine, 2.3%; tacrolimus, 9.9%; cyclosporine plus mycophenolate, 16.2%; and tacrolimus plus mycophenolate, 11.8% (P < .001); (2) antihypertensive agents: 74.9% of patients receiving tacrolimus, with or without mycophenolate, versus 80.7% of those receiving cyclosporine (P = .022); (3) lipid-lowering drugs: 28.4% of patients receiving tacrolimus, with or without mycophenolate, versus 51.1% of those receiving cyclosporine (P < .001). The increase in associated drug costs must be added to the recent large increase in the cost for immunosuppressive agents, which rose from 3854 euros per year, in 1990 to 5374 euros per year in 1998. A lower cost of associated drugs tends to lessen the overall cost of therapies with tacrolimus. Because cardiovascular disease is the main cause of death, these findings should be taken into account in the assessment of the long-term cost-benefit ratio.

Antihypertensive Agents↗

Effect of new immunosuppressive regimens on cost of renal transplant maintenance immunosuppression.

Although newer immunosuppressive drugs control acute rejection better and have short-term economic advantages, their long-term cost-effectiveness is unknown. We studied the frequency with which different maintenance immunosuppression regimens were used in 3 renal transplantation cohorts treated in 1990, 1994, and 1998 (total number, 3279). We calculated the mean annual immunosuppressive costs based on the true costs in a medium-sized hospital. Cyclosporine, with or without azathioprine, was used almost exclusively as the initial maintenance immunosuppressive therapy in 1990-1994. In 1998, 65% of patients received mycophenolate mofetil (MMF), and 20% received tacrolimus (Tac). A growing number of patients from 1990-1994 were converted to MMF (12%-17%) and Tac (4%-8%), while treatment of those from the 1998 cohort remained stable. According to year 2000 costs, the mean immunosuppressive cost at 1 year in 1998 (5380 euros) was almost twice that of 1994 (2902 euros) or 1990 (2855 euros). In these 2 groups the mean cost was stable until 1996, then increased faster in the 1994 cohort (24.8%) than in the 1990 cohort (17.3%), although it remained significantly lower than that in 1998. Correction of the evolution of drug prices and the purchasing value of the peseta greatly absorbed these changes. The MMF and Tac regimens showed greater mean graft life, but without reaching statistical significance in a multivariate study. The introduction of new immunosuppressive drugs has had an important economic effect since 1996; its cost-effectiveness is still pending confirmation in Spain.

Azathioprine↗

Effect of losartan and spironolactone on left ventricular mass and heart sympathetic activity in prehypertensive obese subjects: a 16-week randomized trial.

Obesity has been shown to be associated with increased left ventricular mass (LVM) and heart sympathetic activity even in nonhypertensive subjects. These factors are predictors of cardiovascular morbidity and mortality independent of other traditional risk factors. We evaluated the effect of losartan and spironolactone on LVM and heart sympathetic activity in prehypertensive obese subjects. A 16-week blinded randomized trial was performed in middle-aged men selected from a Health Public program. Anthropometric and clinical variables were measured at baseline and after losartan (50 mg/day; n=25) or spironolactone (25 mg/day; n=25) treatment. Heart sympathetic activity was evaluated with 60-min electrocardiograph monitoring, and spectral analysis was carried out. LVM was measured by echocardiography according to Devereux and Reicheck's formula indexed for body height (m2.7) to account for obesity. Anthropometric variables, systolic, and diastolic blood pressure levels decreased in both groups of treatment without statisticall difference between them. Losartan increased heart rate variability (from 70.0 to 82.3 ms; P=0.01), and decreased low frequency-high frequency index (from 6.6 to 4.9; P=0.001), and LVM (from 49.2 to 45.2 g; P=0.004). In the multiple regression analysis for factors associated with reduction in LVM; treatment with losartan, and decrease in SBP were the only factors included in the model (R2=0.60; P=0.003). To conclude losartan, but not spironolactone, decreased LVM and heart sympathetic overactivity in prehypertensive obese subjects after 16 weeks of treatment. Regression on LVM was associated with reduction on SBP levels.

Adult↗

Monte Carlo calculation of radiation dose in CT examinations using phantom and patient tomographic models.

By using a voxel-based Monte Carlo simulation technique, we developed and validated a method to calculate radiation-absorbed dose in the computed tomography (CT) examinations from the images of phantoms and patients. The ionising radiation transport was simulated using the EGS4 code system. The geometry of the X-ray beam (focus-to-axis distance, field of view, collimation, and primary and beam-shaper filtration) and the X-ray spectral distribution (HiSpeed LX/i) were included in the simulation. Each axial CT image was reduced to a 256 x 256 matrix and stacked in a volume. The patient images were segmented before the simulation of radiation transport by using four categories of materials, such as air, lung, muscle and bone. To test the voxel-based method, the values of the radiation dose derived from a simulated CT exposure were calculated and compared with those obtained from the measurements performed within the dosimetry phantoms. To complete the scope of the work, series of CT scans of the trunk of an anthropomorphic phantom and patients were simulated to calculate the average dose in each 1-cm-wide transverse slice (ADS). The comparison between the simulated and measured dose data for the CT indices showed a difference of <5% in all the cases. The estimated mean values of ADS from the chest, abdomen and pelvis of the anthropomorphic phantom were approximately 1.7-2 times the weighted CT dose index (CTDI(w)) value, whereas the mean ADS values for these anatomical areas were 1.3-2 times the CTDI(w) of patients. The voxel-based simulation method provided a technique for estimating the individual patient doses in the CT examinations.

Air↗