[Methodology of the autoevaluation procedure of the ONT quality control programme].
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Biomedical subjects
Publications and source records attributed to M Alonso.
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The biochemical responses to varying levels of localized heat damage to stems and crowns were studied in Pinus pinaster trees in Galicia, Spain. The objective was to ascertain the utility of secondary metabolites (total polyphenols. condensed tannins, astringency, free and esterified phenolic acids) and pigments (chlorophylls and carotenoids) as chemical indicators of localized fire damage. The study involved three levels of girdling by trunk heating (0%, 60%, and 75%), three levels of crown scorching (0%, 50%, and 75%), and all combinations of those trunk and crown treatment levels. Secondary metabolites and pigments were analyzed in needles before, during, and up to 8 months after fire treatments. High levels of polyphenols, condensed tannin, and pigments occurred in situations where the sole treatment was 75% crown scorching. Low levels of hydroxycinnamic acids were the result when the treatment was 75% trunk girdling. These responses occurred in the first two months after fire. Thereafter, normal values were observed. Low values of chlorophyll a/b ratio and high levels of free protocatechuic and esterified syringic acids were found to be long-term indicators of trunk girdling damage combined with crown scorching.
AIMS: To assess the safety of direct coronary stenting, its influence on costs, duration of the procedure, radiation exposure, clinical outcome and angiographic restenosis. METHODS AND RESULTS: We randomized 416 patients (446 lesions) to direct stent implant or stent implant following balloon pre-dilation. Patients >75 years old, heavily calcified lesions, bifurcations, total occlusions, left main lesions and very tortuous vessels were excluded. Direct stenting was successful in 217/224 lesions (96.8%). No single loss or embolization of the stent occurred. All stents in the group with pre-dilation were effectively deployed. The immediate post-procedure angiographic results were similar with both techniques. Fluoroscopy and procedural time were significantly lower in direct stenting (6.4+/-0.3 and 21+/-0.9 min) than in pre-dilated stenting (9.1+/-0.4 and 27.5+/-1.1 min) (P>0.001). Major adverse cardiac events during hospitalization were one in direct and four in pre-dilated stenting (P=0.05) but there were no significant differences at follow-ups at 1, 6 and 12 months between the two groups. Angiographic reevaluation at 6 months was performed in 94% of the cases. Restenosis rate was 16.5% in direct stenting and 14.3% in pre-dilated stenting (P=ns). CONCLUSIONS: Direct stenting is as safe as pre-dilated stenting in selected coronary lesions. Acute angiographic results are similar but procedural costs, duration of the procedure and radiation exposure are lower in direct stenting. Overall success rate, mid-term clinical outcome and restenosis are similar with both techniques.
This paper proposes a method to estimate absorbed doses to organs in explorations using computed tomography. This Monte Carlo-based method is a generalization of a previous method applied to conventional diagnostic radiology and is also applicable to radiotherapy techniques using photons or electrons. This study is applied to the estimation of absorbed doses to different parts of the head in a simple head CT examination. Simulation was performed for different arrangements (monoenergetic beam, spectrum, different number of histories, etc.). Comparison of the results with experimental doses measured in a human phantom by thermoluminescent dosimeters indicates that the method is capable of adequately estimating doses to organs in computed tomography.
The aims of this study were to estimate the prevalence of major maturity-onset diabetes of the young (MODY) subtypes in Spanish MODY families and to analyze genotype-phenotype correlations. Twenty-two unrelated pediatric MODY patients and 97 relatives were screened for mutations in the coding region of the glucokinase (GCK), hepatic nuclear factor- HNF-1alpha and HNF4alpha genes using PCR-single strand conformation polymorphism and/or direct sequencing. In families carrying GCK mutations, the influence of genetic defects on fetal growth was investigated by comparing the birth weights of 32 offspring discordant for the mutations. Mutations in MODY genes were identified in 64% of the families. GCK/MODY2 mutations were the most frequently found, in 41%: seven novel (R369P, S411F, M298K, C252Y, Y108C, A188E, and S383L) and 2 already described mutations. Four pedigrees (18%) harbored mutations in the HNF-1alpha/MODY3 gene, including a previously unreported change (R271G). One family (4%) carried a novel mutation in the HNF-4alpha gene (IVS5-2delA), representing the first report of a MODY1 pedigree in the Spanish population. The age at diagnosis was prepubertal in MODY2 index patients and pubertal in MODY3 patients. Overt diabetes was rare in MODY2 and was invariably present in MODY3 index patients. Chronic complications of diabetes were absent in the MODY2 population and were present in more than 40% of all relatives of MODY3. Birth weight was lower in the presence of a GCK fetal mutation when the mutation was of paternal origin. The MODY1 patient was diagnosed at 15 yr of age. She developed intermittent microalbuminuria despite good metabolic control, and severe late-onset complications were common within her family. Mutations in the GCK/MODY2 gene are the most common cause of MODY in our population as recruited from pediatric and adolescent index patients. The inheritance of GCK defects by the fetus results in a reduction of birth weight. Clinical expression of MODY3 and MODY1 mutations, the second and third groups of defects found, was more severe, including the frequent development of chronic complications.
The aim of the present study was to evaluate the degree of metabolic control obtained with the use of the insulin analogue lispro compared to the previous regimen with classical regular insulin in children and adolescents with Type 1 diabetes mellitus. HbA1c, lipid metabolism, body mass index (BMI), frequency of severe hypoglycaemia, carbohydrate intake, total daily insulin requirements and its distribution during the day were analysed in 44 diabetics patients (57% males and 43% females) throughout a 3-yr period. The mean age of the patients at the beginning of the study was 15.6 +/- 2.7 yr with a mean duration of the disease of 8.01 +/- 3.4 yr. All data were evaluated for the year before the change of treatment, and 1 yr (44 patients), 2 yr (19 patients) and 3 yr (13 patients) after the change. HbA1c levels did not significantly change (6.6 +/- 1.1% with regular insulin, 6.32 +/- 1.05% in the 1st year with lispro, 6.6 +/- 1.1% in the 2nd yr with lispro, 6.33 +/- 0.9% in the 3rd yr with lispro). However, significant differences (p = 0.03) were found after 3 yr of treatment in those patients who changed to insulin lispro therapy due to a bad glycaemic control. The total daily insulin dose (U/kg/d) remained unchanged. The total short-acting/intermediate-acting insulin ratio significantly decreased (45.9 +/- 0.1% regular insulin; 37.2 +/- 0.1% 1st yr lispro (p < 0.001); 33.6 +/- 0.1% 2nd yr lispro (p < 0.05); 35.5 +/- 0.1% 3rd yr lispro (p < 0.05). BMI and lipid profile remained unchanged. The self-reported daily carbohydrate in take significantly decreased due to a reduction of snacks. Total number of episodes of severe hypoglycaemia did not change significantly. In conclusion insulin lispro treatment did not modify the daily insulin dose, but reduced the short-acting/intermediate acting insulin ratio. The metabolic control remained unchanged. The number of patients reporting severe hypoglycaemia was similar despite the treatment schedule. After this 3-yr duration trial all patients decided to continue the treatment with lispro insulin.
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Length alterations in microsatellite repeats, termed microsatellite instability (MSI), are found in 10-15% of sporadic colon, endometrial, and gastric cancers harboring defects in DNA mismatch repair (MMR) genes We used the microsatellite markers Big Adenine Tract (BAT) 26 and BAT-25 from the reference panel of five markers recommended by the National Cancer Institute to evaluate the incidence of MSI in 206 central nervous system tumors. We screened 102 pediatric and 104 adult cases representing 165 astrocytic and 41 nonastrocytic tumors. The overall incidence of MSI was 8% (16 of 206). All 16 tumors with MSI were found in pediatric rather than adult patients. MSI was associated with two distinct subtypes of pediatric tumors occurring in 27% (12 of 45) of WHO grade III and grade IV astrocytomas and 24% (4 of 17) of gangliogliomas We evaluated the difference in clinicopathological and genetic features among 45 high-grade pediatric astrocytomas by MSI status. The median survival for pediatric patients with MSI (n = 12) was 8 months compared with 15 months for those patients without MSI (n = 33; P = 0.18). The frequency of p53 gene mutations was 13% for pediatric patients with MSI (n = 8) compared with 47% for those patients without MSI (n = 19; P = 0.19). These results revealed a trend between MSI status and prog nosis and MSI status and frequency of p53 gene mutations. Our data suggest that pediatric high-grade astrocytomas can be attributed to two different genetic pathways: a MMR-deficient pathway and a MMR proficient pathway.
Raman spectra of the elastinlike polypentapeptide poly(GVGVP) were measured in H(2)O and D(2)O as solutions and, after increasing the temperature, as suspensions and sediments. In addition, spectra of the polypentapeptide in the solutions of increasing concentration and in the solid state were also investigated by gradually evaporating the water. Significant changes in band frequencies, intensities, and shapes were found for selected Raman bands in the measured spectra, particularly for the C-H stretching, the glycine CH(2) wagging, and some amide vibrations. The C-H stretching vibrations are influenced predominantly by the presence of water, the glycine CH(2) wagging vibrations are associated with conformational transitions. Three possible types of poly(GVGVP)s in the presence of water were indicated: polymer chains in a relatively extended state in the solution, a beta-spiral structure in the suspension, and irregularly bent chains in the sediment.
Rats exposed to a novel environment just prior to or 1-2 h, but not 4 or 6 h, before retention testing exhibited an enhanced retrieval of a one-trial inhibitory avoidance training. The bilateral intrahippocampal infusion of PD098059, an inhibitor of mitogen-activated protein kinase (MAPK), the specific upstream activator of p42 and p44 MAPKs, given 10 min before the exposure to the novel environment, blocked the enhancing effect of novelty on memory retrieval. In addition, prenovelty infusion of DL-2-amino-5-phosphonovalerate (APV), an antagonist of glutamate NMDA receptors, produced similar effects. The exposure to the novel environment is associated with an activation of p42 and p44 MAPKs and an increase in the phosphorylation state of the transcription factor cAMP response element binding protein (CREB). No changes were observed in cAMP-dependent protein kinase (PKA) activity or in alpha-CAMKII activation. Taken together, our results indicate that novelty activates hippocampal MAPKs, which are necessary, along with glutamate NMDA receptors, for the enhancing effect of novelty on retrieval.
It has been recently demonstrated that ubiquitin-proteasome-mediated proteolysis is required for long-term synaptic facilitation in Aplysia. Here we show that the hippocampal blockade of this proteolytic pathway is also required for the formation of long-term memory in the rat. Bilateral infusion of lactacystin, a specific proteasome inhibitor, to the CA1 region caused full retrograde amnesia for a one-trial inhibitory avoidance learning when given 1, 4 or 7h, but not 10 h, after training. Proteasome inhibitor I produced similar effects. In addition, inhibitory avoidance training resulted in an increased ubiquitination and 26S proteasome proteolytic activity and a decrease in the levels of IkappaB, a substrate of the ubiquitin-proteasome cascade, in hippocampus 4 h after training. Together, these findings indicate that the ubiquitin-proteasome cascade is crucial for the establishment of LTM in the behaving animal.
We describe the effect of pretreatment with alpha-2-macroglobulin (A2M) on the susceptibility of the human neuroblastoma SKNMC cell line to infection by herpes virus type 1 (HSV-1). ELISA and co-immunoprecipitation experiments confirmed the A2M-HSV-1 interaction in vitro. Indirect immunofluorescence shows that A2M exacerbated the cytopathic effect induced after HSV-1 infection. However, A2M-pretreated SKNMC cells notably produced fewer HSV-1 particles than did the untreated cells, suggesting that A2M could induce a restrictive infection. Furthermore, high levels of HSV-1 and A2M induced the production of nitric oxide (NO) in SKNMC. Preliminary results suggest that A2M might induce apoptosis in HSV-1-infected cells. These findings affirm the conclusion that A2M may interact directly with HSV-1 and modulate the course of the infection in SKNMC human neuroblastoma cells.
We describe a patient with short stature more than that expected for non-treated congenital adrenal hyperplasia due to nonclassic 21-hydroxylase deficiency with deletions in the long arm of the Y chromosome including the CGY gene and the AZF subregions.
OBJECTIVE: Internationally adopted children are at increased risk of infections acquired in their country of origin. Ongoing surveillance of this unique population is needed to detect changing epidemiology and provide appropriate care. METHODS: We performed a retrospective cohort study of 504 children adopted from abroad and evaluated from 1997 to 1998 to determine the prevalence of and factors associated with various infectious diseases. RESULTS: The mean age of the study participants at medical evaluation was 1.6 years; 71% were girls, and they were adopted from 16 countries, including China (48%), Russia (31%), Southeast Asia (8%), Eastern Europe (8%), and Latin America (5%). Overall, 75 (19%) of 404 children tested had tuberculin skin tests >/=10 mm, but all had normal chest radiographs. BCG vaccination (odds ratio [OR]: 7.37; 95% confidence interval [CI]: 3.29, 17.16) and being Russian born (OR: 2.90; 95% CI: 1.68, 5.00) were risk factors for latent tuberculosis infection. Fourteen (2.8%) children had detectable hepatitis B surface antigen, but no child had active hepatitis C, human immunodeficiency virus, or syphilis. Giardia lamblia antigen was detected in 87 (19%) of 461 tested children, and such children were older (mean: 22 months vs 15.5 months) and more likely to have been born in Eastern Europe (OR: 2.82; 95% CI: 1.70, 4.68). CONCLUSIONS: We demonstrated increased rates of latent tuberculosis infection and G lamblia infection than previously reported. Thus, ongoing surveillance of internationally adopted children, international trends in infectious diseases, and appropriate screening will ensure the long-term health of adopted children as well as their families.
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Endothelial dysfunction associated with both menopause and hypertension could be one of the possible explanations for increased cardiovascular morbidity and mortality in hypertensive postmenopausal women. The aim of the present study was to investigate the long-term effect of menopause (bilateral ovariectomy) on endothelial function in isolated aortic rings of spontaneously hypertensive rats (SHR). Aortic rings were suspended in organ chambers filled with physiological salt solution (95% O2, 5% CO2, 37 degrees C), and isometric tension was measured. In studies designed to assess the tone-related release of nitric oxide (NO) from phenylephrine-precontracted aortic rings, we found that vasoconstriction induced by L-NAME was greater in aortic rings from sham-ovariectomized SHR (SHAM SHR) than in those obtained from ovariectomized SHR (OVX SHR). Concentration-related relaxant responses to superoxide dismutase were significantly greater in the SHAM SHR than in the OVX SHR. In contrast, receptor-mediated release of NO was not altered by ovariectomy, as deduced from acetylcholine (ACh) concentration-responses curves. Responses to the exogenous NO donor sodium nitroprusside (SNP) were also identical in both ovariectomized and sham-ovariectomized groups, ruling out differences in smooth muscle reactivity to NO. These results show that NO release is impaired in OVX SHR, an animal model of simultaneous hypertension and menopause.