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Biomedical subjects

A Costa

Publications and source records attributed to A Costa.

At least 109 records · Page 6Linked to original sources
PubMed2000

Immediate loading of implants used for orthodontic anchorage.

The healing around an immediately loaded screw was described and related to the bone type, manner of loading and observation time. In four adult macaca fasicularis monkeys, 16 titanium vanadium screws were inserted into the infrazygomatic crest and two in the symphysis region. Immediately after insertion, screws were loaded with 25- and 50-g Sentalloy springs extending to the canines. Following an observation period of 1, 2, 4 and 6 months, the screws and the surrounding bone were removed. Undecalcified serial sections perpendicular to the long axis were made and the degree of osseointegration studied. Two of the screws were lost immediately after insertion. Of the remaining screws, osseointegration was present around all, but two. The integration was independent of bone type, trabecular or cortical, but increased with time. Based on the results of this study, the use of screws described in the report can be recommended as anchorage units in cases where conventional anchorage is not possible.

Journal Article↗
PubMed2000

The cognate facilitation effect: implications for models of lexical access.

Do nonselected lexical nodes activate their phonological information? Catalan-Spanish bilinguals were asked to name (a) pictures whose names are cognates in the 2 languages (words that are phonologically similar in the 2 languages) and (b) pictures whose names are noncognates in the 2 languages. If nonselected lexical nodes are phonologically encoded, naming latencies should be shorter for cognate words, and because the cognate status of words is only meaningful for bilingual speakers, this difference should disappear when testing monolingual speakers. The results of Experiment 1 fully supported these predictions. In Experiment 2, the difference between cognate and noncognate words was larger when naming in the nondominant language than when naming in the dominant language. The results of the 2 experiments are interpreted as providing support to cascaded activation models of lexical access.

Adolescent↗
PubMed2000

A new PKLR gene mutation in the R-type promoter region affects the gene transcription causing pyruvate kinase deficiency.

Mutations in the PKLR gene responsible for pyruvate kinase (PK)-deficient anaemia are mainly located in the coding regions: 11 are in the splicing sites and, recently, three mutations have been described in the promoter region. We now report a novel point mutation A-->G on nucleotide 72, upstream from the initiation codon of the PKLR gene, in four Portuguese PK-deficient patients. This new regulatory mutation occurs within the most proximal of the four GATA motifs (GATA-A element) in the R-type promoter region. In two patients who were homozygous for this mutation, a semiquantitative reverse transcription polymerase chain reaction (PCR) procedure was used to evaluate the amount of R-PK mRNA transcript in the reticulocytes. The mRNA level was about five times lower than in normal controls, demonstrating that the PKLR gene transcription is severely affected, most probably because the -72A-->G point mutation disables the binding of the erythroid transcription factor GATA-1 to the GATA-A element. Supporting these data, the two patients homozygous for the -72A-->G mutation had severe haemolytic anaemia and were transfusion dependent until splenectomy. Two other patients who were compound heterozygous for this mutation and the previously described missense mutation 1456C-->T had a mild condition.

Anemia, Hemolytic, Congenital Nonspherocytic↗
PubMed2000

Apoptotic cell death does not parallel other indicators of liver damage in chronic hepatitis C patients.

The mechanisms of hepatocyte damage and the events that lead to high rates of chronic liver disease in hepatitis C virus (HCV) infection remain unclear. Recent in vitro studies have suggested that the HCV core protein may disrupt specific signalling pathways of apoptosis. This prompted us to study patients with chronic HCV infection to: determine the extent of apoptosis in the liver; evaluate whether clinical and biochemical data are correlated with histological findings; and to investigate if apoptosis is related to the histological activity of the disease. Twelve patients with chronic hepatitis C were included in the study. Liver histology was scored by using the histological activity index (HAI) of Knodell et al. DNA fragmentation was assessed in liver tissue by the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end-labelling (TUNEL) assay. Routine methods were used to determine serum markers of liver disease. Bile acids were measured in serum and liver by gas chromatography. Patients were placed, according to their HAI score, into group A (3.8 +/- 0.3) or group B (7.8 +/- 0.8) (P < 0.01). Liver enzymes tended to be higher in group B patients than in patients of group A. Levels of toxic bile acids in serum were greater in patients than in controls (P < 0.01). Chenodeoxycholic acid values were slightly higher in serum and liver of patients in group A. Liver biopsies with low HAI scores showed an increased rate of apoptosis (18.0 +/- 4.0 apoptotic cells per field) compared to those with higher HAI scores (6.6 +/- 2.1, P < 0.05) or to controls (3.5 +/- 0.4, P < 0.01). Hence, less severe liver disease, associated with lower histological grades and biochemistries, as well as increased levels of chenodeoxycholic acid, induces an expanded apoptotic response. The lower apoptotic rate in advanced liver disease may be associated with the high incidence of hepatocellular dysplasia/neoplasia.

Adult↗
PubMed2000

Post-partum reclassification of glucose tolerance in women previously diagnosed with gestational diabetes mellitus.

AIMS: To re-evaluate post-partum screening; fasting plasma glucose (FPG) vs. oral glucose tolerance test (OGTT) in Caucasian women with previous gestational diabetes mellitus (GDM). METHODS: Once breast-feeding had finished, an OGTT was performed in 120 women with previous GDM. They were classified according to World Health Organization (WHO) 1985 and American Diabetes Association (ADA) 1997 criteria. The kappa-statistic measure of agreement was used to compared both diagnostic categories. A receiver-operating characteristic (ROC) curve studied the FPG as a test to detect abnormal glucose tolerance. RESULTS: Identical diabetes prevalence (2%) but quite different intermediate categories (12% impaired glucose tolerance vs. 3% impaired fasting glucose) were observed with both criteria. The kappa-statistic (scaled from 0 to 1) was 0.38 (fair agreement), P = 0.000. The ROC curve area of the FPG was 0.65. CONCLUSIONS: FPG is an unsatisfactory method of evaluating the glucose tolerance of Caucasian women with previous GDM. OGTT may be a better test for such a purpose.

Adult↗
PubMed2000

The effect of intranasal cocaine and lidocaine on nitroglycerin-induced attacks in cluster headache.

The administration of nitroderivatives in cluster headache (CH) sufferers is the most reproducible experimental paradigm to induce spontaneous-like pain attacks. Previous uncontrolled studies have reported that the local use of anaesthetic agents in the area of the sphenopalatine fossa is able to extinguish nitroglycerin (NTG)-induced pain in CH. The present study, carried out according to a double-blind placebo-controlled design, included 15 CH patients, six with episodic CH (mean +/- SD age of 36.8+/-5.6 years), and nine with chronic CH (37.8+/-10.4 years). Patients had undergone a standard NTG test (0.9 mg sublingually), during which the intensity of pain was scored using a visuoanalogic scale (VAS, range 0-10). Nine patients (two with the episodic form, seven with the chronic form) experienced a typical, spontaneous-like attack on the usual side, occurring in all cases within 45 min. In these patients, the test was repeated with an interval of 2 days, and once pain intensity reached 5 on the VAS, a 10% solution of cocaine hydrochloride (1 ml, mean amount per application 40-50 mg), or 10% lidocaine (1 ml), or saline was applied using a cotton swab in the area corresponding to the sphenopalatine fossa, under anterior rhinoscopy. This was done in both the symptomatic and the non-symptomatic side, for 5 min. Treatments were always performed randomly, in separate sessions. All patients responded promptly to both anaesthetic agents, with complete cessation of induced pain occurring after 31.3+/-13.1 min for cocaine and 37.0+/-7.8 min for lidocaine (M+/-SD). In the case of saline application, pain severity increased thereafter, and extinction of the provoked attacks occurred with a latency of 59.3+/-12.3 min (P<0.01 and P<0.01 vs. cocaine and lidocaine, respectively, Mann-Whitney U-test). While further suggesting that the sphenopalatine ganglion participates in the mechanisms of pain, these findings indicate that the local administration of the anaesthetic agents cocaine and lidocaine is effective on NTG-induced CH attacks, and may be used in the symptomatic treatment of this disorder.

Administration, Intranasal↗
PubMed2000

Clastogenic factors as biomarkers of oxidative stress in chronic hepatitis C.

BACKGROUND/AIMS: Clastogenic factors (CFs) are composed of lipid peroxidation products, cytokines and other oxidants with chromosome-damaging properties. They are regularly observed after radiation exposure and in chronic inflammatory diseases, where they are supposed to be risk factors for carcinogenesis. It appeared of interest to investigate their presence in the plasma of patients with chronic hepatitis C. METHODS: CFs are detected by chromosomal breakage studies. They were compared to malondialdehyde (MDA), total plasma thiols (t-SH), alanine aminotransferase (ALT), viral load and histological data. RESULTS: CFs were increased in 19 of 20 patients, 16 had increased MDA levels and 15 had decreased t-SH levels. Mean values were significantly different from the 20 controls (p<0.001). After the first 3 months of interferon treatment, all three markers showed significant improvement, but were not completely normalized. There was a positive correlation between CFs and necroinflammatory activity (p<0.03), while MDA was correlated with fibrosis (p<0.03). Viral load was correlated with necrosis and inflammation (p<0.05). CONCLUSION: The presence of CFs in chronic hepatitis C confirms the occurrence of oxidative stress in this disease and could be useful in clinical trials for testing antioxidants. The CF test is a sensitive assay for the detection of oxidative stress and correlates with necroinflammatory activity.

Adult↗
PubMed2000

Genetic and clinical characterisation of maturity-onset diabetes of the young in Spanish families.

OBJECTIVE: To investigate the frequencies of the major maturity-onset diabetes of the young (MODY) subtypes in a panel of Spanish families and to assess phenotypic differences in patients with the different subtypes of MODY. METHODS: Forty-eight subjects from twenty families with clinical diagnosis of MODY were studied. They underwent a standardised clinical examination and a 75-g oral glucose tolerance test (OGTT) was performed. Estimations of insulin sensitivity (%S) and insulin secretion capacity (%B) were calculated by the computer-solved homeostasis model assessment (HOMA). Mutations in the coding regions of hepatocyte nuclear factor (HNF)-4alpha/MODY1, glucokinase (GCK/MODY2) and HNF-1alpha/MODY3 genes were investigated by single strand comformation polymorphism and sequencing analysis. RESULTS: Mutations in the GCK and HNF-1alpha genes were observed in 5 (25%) and 7 (35%) families respectively. Novel mutations included R385X, M238fsdelT, V226fsdelTinsAA and S418-7del11 in the GCK gene, and S121fsdelC, V133M, R159Q and V259D in the HNF-1alpha gene. No MODY1 families were found. Subjects which were neither MODY2 nor MODY3 (MODY-X) had a higher fasting glucose than subjects in the other groups. Insulin secretion capacity was similar in the three groups and the insulin sensitivity was decreased in MODY-X subjects. Glucose levels were significantly higher and insulin levels significantly lower, throughout the OGTT, in MODY3 compared with MODY2 subjects. CONCLUSIONS: Mutations in the GCK/MODY2 and HNF-1alpha/MODY3 genes account for the majority of cases in a panel of Spanish MODY families, with MODY3 being the most frequent subtype. The relative frequencies and the clinical characteristics of these MODY subtypes are in agreement with data previously reported in other European populations. MODY-X patients seem to present a heterogeneous clinical profile.

Adult↗
PubMed2000

Adaptation to time-compressed speech: phonological determinants.

Perceptual adaptation to time-compressed speech was analyzed in two experiments. Previous research has suggested that this adaptation phenomenon is language specific and takes place at the phonological level. Moreover, it has been proposed that adaptation should only be observed for languages that are rhythmically similar. This assumption was explored by studying adaptation to different time-compressed languages in Spanish speakers. In Experiment 1, the performances of Spanish-speaking subjects who adapted to Spanish, Italian, French, English, and Japanese were compared. In Experiment 2, subjects from the same population were tested with Greek sentences compressed to two different rates. The results showed adaptation for Spanish, Italian, and Greek and no adaptation for English and Japanese, with French being an intermediate case. To account for the data, we propose that variables other than just the rhythmic properties of the languages, such as the vowel system and/or the lexical stress pattern, must be considered. The Greek data also support the view that phonological, rather than lexical, information is a determining factor in adaptation to compressed speech.

Adaptation, Psychological↗
PubMed2000

Effect of nitric oxide donors on the central nervous system--nitroglycerin studies in the rat.

The demonstration that nitrovasodilators act as nitric oxide (NO) donors has favored a resurgence of interest in this class of compounds. The demonstration of the different biological effects of NO in various districts, including the central nervous system, suggests a possible role for these substances besides their well-known cardiovascular activity. Among the various nitrovasodilators commercially available, nitroglycerin represents a well known substance to headache experts because of its capability to provoke spontaneous-like migraine attacks in headache-free migrainous subjects. Basic research has recently demonstrated that nitroglycerin activates a variegate set of brain nuclei following systemic administration via the intervention of selected neurotransmitters and neuromediators, with a specific time-pattern in different brain areas. Increasing evidence suggests that nitroglycerin-induced neuronal activation is mediated by multiple mechanisms that include direct neuronal and vascular action of nitroglycerin-derived and endogenously-synthesized NO, as well as indirect effects related to nitroglycerin-induced changes in cardiovascular and trigeminovascular systems. The study of the neurovascular effects of nitroglycerin in the rat provides relevant information for a better understanding of the pathophysiology of migraine attacks and of their triggers.

Animals↗
PubMed2000

Headache in the Diagnosis-Related Groups (DRG) era: management and appropriateness of admission.

Headache is an extremely common disorder which has a marked impact on the utilisation of healthcare resources and constitutes a considerable socio-economic burden. The related costs, both direct and indirect, are especially high in developed countries, since headache predominantly affects an economically-active section of the population. The Diagnosis-Related Groups (DRG) system, a method for reimbursing healthcare structures for patient admissions, was introduced in Italy in 1995. The aim of the system was to control public health expenditure and to promote better distribution of financial resources. Here, we report the results of the application of the DRG system to headache patients admitted to the Department of Neurology of the University of Pavia in 1996 and 1998. The financial analysis revealed high fixed costs (hospital running costs per days of hospitalisation); by contrast, the impact of the variable costs (those relating to the direct management of the individual patient, i.e. examinations, therapeutic interventions etc.) was low. It was found that reducing the number of days of hospitalisation increases the hospital's income and reduces the mean loss incurred in each DRG. It is therefore suggested that a complete approach to the management of headache must include educational programmes for patients and general practitioners, and that access to headache centres and to hospital care should be restricted to cases of acute, severe headache, or recurrent, chronic headache with/without drug abuse or dependence.

Costs and Cost Analysis↗
PubMed1999

The tRNA N2,N2-dimethylguanosine-26 methyltransferase encoded by gene trm1 increases efficiency of suppression of an ochre codon in Schizosaccharomyces pombe.

In the majority of eukaryotic tRNAs, the guanosine at position 26 is modified by a dimethyl group, but so far a function of this modification has not been detected. We isolated the Schizosaccharomyces pombe gene, trm1, encoding the tRNA N2, N2-dimethylguanosine-26 methyltransferase. Strains having the gene deleted completely lack N2,N2-dimethylguanosine. In strains carrying the weak ochre tRNA suppressor sup3-i, deletion of trm1 abolishes suppression indicating that the trm1 deletion acts as an antisuppressor mutation. The result suggests that in vivo N2, N2-dimethylguanosine-26 increases the capacity of the sup3-i serine tRNA to translate the UAA (ochre) codon.

Alleles↗
PubMed1999

Randomized trial of fenretinide to prevent second breast malignancy in women with early breast cancer.

BACKGROUND: Fenretinide, a vitamin A analogue, has been shown to inhibit breast carcinogenesis in preclinical studies. We determined the efficacy of fenretinide in preventing a second breast malignancy in women with breast cancer. METHODS: We randomly assigned 2972 women, aged 30-70 years, with surgically removed stage I breast cancer or ductal carcinoma in situ to receive for 5 years either fenretinide orally (200 mg/day) or no treatment. The primary end point was the incidence of contralateral breast cancer or ipsilateral breast cancer 7 years after randomization. Other end points considered post hoc were the same outcomes stratified by menopausal status, incidence of distant metastases, overall mortality, and tumors in other organs. The hazards of breast cancer occurrence were determined by Cox proportional hazards regression analysis. Statistical tests were two-sided. RESULTS: At a median observation time of 97 months, there were no statistically significant differences in the occurrence of contralateral breast cancer (P =.642) or ipsilateral breast cancer (P =.177) between the two arms. However, an interaction was detected between fenretinide treatment and menopausal status in both outcomes (P for interaction in both outcomes =.045), with a possible beneficial effect in premenopausal women (contralateral breast cancer: adjusted hazard ratio [HR] = 0.66, and 95% confidence interval [CI] = 0.41-1.07; ipsilateral breast cancer: adjusted HR = 0.65, and 95% CI = 0.46-0. 92) and an opposite effect in postmenopausal women (contralateral breast cancer: adjusted HR = 1.32, and 95% CI = 0.82-2.15; ipsilateral breast cancer: adjusted HR = 1.19, and 95% CI = 0.75-1. 89). There were no statistically significant differences between the two arms in tumors in other organs, incidence of distant metastasis, and all-cause mortality. CONCLUSIONS: Fenretinide treatment of women with breast cancer for 5 years appears to have no statistically significant effect on the incidence of second breast malignancies overall, although a possible benefit was detected in premenopausal women. These studies, particularly the post hoc analyses, are considered exploratory and need to be confirmed.

Adult↗
PubMed1999

Detection of a new variant of the mitochondrial glycerol-3-phosphate dehydrogenase gene in Spanish type 2 DM patients.

To evaluate if potential defects in the FAD-binding domain of the mitochondrial glycerol-3-phosphate dehydrogenase (mGPDH) gene could contribute to susceptibility to type 2 diabetes mellitus, we have screened 151 type 2 DM patients for mutations using PCR single-strand conformational polymorphism. Both a single substitution (T to A) at position 18 and a 6-base-pair deletion (TTTTAA) at position 26 of intron 3 have been detected in five type 2 DM patients and in one control subject. The evolution time of diabetes was longer in patients with these mutations than in patients without (24.2 +/- 11.1 vs 12.6 +/- 8.7 years, p < 0.02). These mutations generate a cryptic site that may have functional significance in the correct mechanism of the FAD-binding domain. In the process of PCR amplification of the mGPDH gene we also unexpectedly amplified the mGPDH retropseudogene. Subsequently, we decided to further characterize and completely sequence 2213 bp of this mGPDH retropseudogene. Our results suggest that two previously reported mGPDH pseudogene partial sequences may be identical copies of the mGPDH gene inserted in two different genomic locations and provide information about the alternative 5'- and 3'-untranslated regions. The data obtained are also important in order to avoid artifactual amplification of the mGPDH pseudogene in the process of screening for mGPDH mutations in diabetic patients.

Base Sequence↗
PubMed1999

Expression of chemokine receptors in the rat brain.

Human immunodeficiency virus (HIV-1) infects the brain and causes a progressive encephalopathy in 20 to 30% of infected children and adults called AIDS dementia complex. Evidence from in vitro and in vivo studies suggests a role for the viral envelope glycoprotein gp120, as a mediator of neurotoxicity. However, the site of interaction of gp120 with neurons and astrocytes to mediate neuronal death is still unknown. Recently the chemokine receptors, CCR5 and CXCR4, have been identified as co-receptors together with CD4 for HIV-1 entry into the target cells, suggesting a possible role for these receptors in the pathogenesis of the HIV-1 infection in the brain. Here we report the expression of CCR5 and CXCR4 in many different rat brain areas. We also found both receptors in cultured type I astrocytes demonstrating that glial cells may represent an important target for chemokines in vivo. Indeed, the functional capacity of CXCR4 receptor in astrocytes was demonstrated showing that SDF 1 alpha induced an increase of intracellular calcium concentration.

Animals↗