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Biomedical subjects

S Santos

Publications and source records attributed to S Santos.

At least 19 recordsLinked to original sources

Risk of ischemic stroke and lifetime estrogen exposure.

BACKGROUND: Estrogen loss has been related to higher incidence of stroke in postmenopausal women, but randomized trials have demonstrated an increased risk of stroke in women receiving hormone replacement therapy (HRT). OBJECTIVE: To assess the relationship between exposure to endogenous ovarian hormones and the risk of noncardioembolic ischemic stroke. METHODS: We conducted a multicenter, age-matched, case-control study in postmenopausal women (case: nonembolic ischemic stroke; control: no stroke) comparing duration of ovarian activity or lifetime estrogen exposure, which was defined as age at menarche to age at menopause. Embolic cardiopathy and unreliable gynecologic data were exclusion criteria. Cardiovascular disease risk factors were recorded. The relationships of the principal variables to the risk of stroke were assessed using a conditional logistic regression analysis. RESULTS: There were 430 cases and 905 controls in the study. In the multivariate analysis, hypertension (odds ratio [OR]: 2.73; 95% CI: 2.09 to 3.58; p < 0.0001), diabetes (OR: 3.38; 95% CI: 2.53 to 4.52; p < 0.0001), hyperlipidemia (OR: 1.31; 95% CI: 1.01 to 1.7; p = 0.045), lifespan of ovarian activity <34 years (OR: 1.51; 95% CI: 1.13 to 2.03; p = 0.005), and menarche at <13 years of age (OR 1.49; 95% CI: 1.15 to 1.92; p = 0.002) were independently related to an increased risk of stroke. Obesity (OR: 0.73; 95% CI: 0.56 to 0.95; p = 0.021) was related to a lower risk of stroke. CONCLUSIONS: Longer lifetime exposure to ovarian estrogens may protect against noncardioembolic ischemic stroke. However, a very early age of exposure onset could be disadvantageous.

Age Factors↗

Calcium hydroxide barrier over the apical root-end of a type III dens invaginatus after endodontic and surgical treatment.

AIM: To report the simultaneous endodontic and surgical treatment of a tooth associated with Oehlers type III dens invaginatus and a persistent periapical lesion, which comprised root-end resection, root-end filling and application of a calcium hydroxide barrier placed on the resected dentine surface. SUMMARY: Three root canals were identified in a tooth with a type III dens invaginatus, which presented with a necrotic pulp, wide foraminal opening and extensive periapical lesion, and with a previous history of acute abscess, intracanal exudate and fistula. After root canal preparation followed by intracanal application of calcium hydroxide pastes, the clinical-pathological status persisted. After periapical curettage and root-end resection, the root canals were filled, followed by root-end filling with Sealer 26 mixed with zinc oxide powder to a clay-like consistency. Calcium hydroxide paste was then applied over the exposed dentinal surface forming a covering over the root apex. At the 20-month follow-up examination the patient had no symptoms and no fistula; advanced periapical bone repair was obvious on the radiograph. KEY LEARNING POINTS: Because of the variable morphology and extent of invagination, type III dens invaginatus represents a challenge for conventional treatment, often leading to the need for a surgical approach. Sealer 26 thickened with zinc oxide powder provided satisfactory clinical properties for use as a root-end filling material. Application of a calcium hydroxide barrier over the resected root-end is a potential treatment option to encourage tissue repair.

Adolescent↗

[Pulmonary varix inside a bulla].

Pulmonary varices are uncommon vascular abnormalities that are usually asymptomatic and so they are normally diagnosed by chance from a chest x-ray. They often present as a pulmonary nodule and can be either congenital or acquired. If acquired, they are associated with pulmonary venous hypertension, usually as a result of mitral valve disease. Pulmonary arteriography provides a definitive diagnosis, although the use of new noninvasive imaging techniques is spreading. Treatment is not normally required unless serious complications arise. We present the case of a pulmonary varix located within a pulmonary bulla. This form of presentation has not been previously reported.

Aged↗

Nonsurgical treatment of extensive cyst-like periapical lesion of endodontic origin.

AIM: To report the repair of an extensive periapical lesion of endodontic origin, following nonsurgical treatment. SUMMARY: Clinical and radiographic examination revealed an extensive periapical lesion related to tooth 22, extending from the distal surface of tooth 21 to the mesial surface of 26. The patient reported a previous history of dental trauma involving this quadrant and had been under orthodontic treatment for a year. Intraoral examination revealed an asymptomatic bony hard swelling, mainly confined to the palate. During root canal exploration irregular walls associated with 3 mm of apical calcification were noted. After apical patency was obtained 1 mL of bloody serous exudate was drained. Intracanal aspiration provided a further 2 mL of yellow serous exudate. Following biomechanical preparation, a dressing of calcium hydroxide with anaesthetic solution was applied and replaced four times over a period of 12 months. The clinical-pathological picture demonstrated resolution of the lesion during this period of time. The 14-month clinical and radiographic examinations revealed normal bony contour and a significant resolution of the maxillary radiolucency. KEY LEARNING POINTS: Periapical lesions of endodontic origin may develop asymptomatically and become large. Proper biomechanical preparation followed by calcium hydroxide medication renewed periodically represents a nonsurgical approach to resolve extensive inflammatory periapical lesions.

Adult↗

Yeast diversity in hypersaline habitats.

Thus far it has been considered that hypersaline natural brines which are subjected to extreme solar heating, do not contain non-melanized yeast populations. Nevertheless we have isolated yeasts in eight different salterns worldwide, as well as from the Dead Sea, Enriquillo Lake (Dominican Republic) and the Great Salt Lake (Utah). Among the isolates obtained from hypersaline waters, Pichia guilliermondii, Debaryomyces hansenii, Yarrowia lipolytica and Candida parapsilosis are known contaminants of low water activity food, whereas Rhodosporidium sphaerocarpum, R. babjevae, Rhodotorula laryngis, Trichosporon mucoides, and a new species resembling C. glabrata were not known for their halotolerance and were identified for the first time in hypersaline habitats. Moreover, the ascomycetous yeast Metschnikowia bicuspidata, known to be a parasite of the brine shrimp, was isolated as a free-living form from the Great Salt Lake brine. In water rich in magnesium chloride (bitterns) from the La Trinitat salterns (Spain), two new species provisionally named C. atmosphaerica - like and P. philogaea - like were discovered.

Biodiversity↗

Outcome of children with B cell lymphoma in Venezuela with the LMB-89 protocol.

BACKGROUND: We analyzed the results of the LMB-89 protocol performed in seven centers in Venezuela in 96 children having B-cell non-Hodgkin lymphoma treated from 1995 to 2002. PROCEDURE: Mean age was 7.1 years with 71 (74%) been male. Eighty-two patients (85%) had diffuse small cell lymphoma Burkitt and Burkitt-like, and 14 (15%) had diffuse large B-cell lymphoma. Initial disease sites included the abdomen in 67%, peripheral nodes in 8%, and mediastinal in 4%. Treatment was directed to risk groups as described for LMB-89 protocol. Group A: seven patients (7%), group B: 80 patients (83%), and group C: nine patients (9%). RESULTS: Mean follow-up was 35 +/- 31 months. Complete remission (CR) occurred in 70 patients (73%); four patients (6%) had relapse during the first year and ten patients (10%) had progressive disease. Overall survival (OS) and event free survival (EFS) were 85 and 80% at 1 year, and 82 and 75% at 2 years, respectively. The EFS by therapeutic groups at 3 years was A: 100%; B: 76%, and C: 56%. TOXICITY: neutropenia in 75%, thrombocytopenia in 63%, febrile neutropenia in 39%. Viral infections: hepatitis B in 20%, hepatitis C in 2%, and Herpes zoster in 3%. Tumor lysis syndrome (TLS) occurred in 9% during induction phase with a high mortality of 44% (urate-oxidase was available only at the end of the study). CONCLUSIONS: The high mortality rate during induction phase prohibited a better EFS. Prophylactic use of xantine-oxidase may improve future results. The high incidence of hepatitis B requires a vaccination program.

Antineoplastic Combined Chemotherapy Protocols↗

The usefulness of computerized dynamic posturography for the study of equilibrium in patients with Meniere's disease: correlation with clinical and audiologic data.

The use of computerized dynamic posturogaphy (CDP) in the evaluation of patients with balance alterations not only allows quantification of the subject's capacity to maintain a stable centre of gravity, but also analysis of the degree to which the subject is able to use different types of sensory information. The present study investigated the possible use of CDP for clinical staging of vestibular diseases, specifically Meniere's disease (MD). We applied CDP sensory organization tests to 75 patients with definitive MD (AAO-HNS 1995 criteria). A total of 98 CDP sessions were included in the analysis, which focused on four CDP parameters specifically related to vestibular function (condition-5 score, condition-6 score, overall balance score, and VEST, a measure of the relative importance of vestibular information for maintenance of balance). We found a statistically significant relationship between audiometric hearing threshold and CDP scores, especially in patients with audiometrically advanced disease. In addition, CDP scores showed statistically significant variation with time elapsed since the last typical vertigo attack, suggesting that patients can be usefully grouped into three MD activity-level categories: recent post-attack (less than 1 week since last vertigo attack), late post-attack (1 week - 60 days since last attack), and inactive MD (more than 60 days since last attack). On the basis of these results, we propose expected ranges for each of the four CDP parameters in each of the three MD activity-level categories, allowing staging in terms of balance and posture. This staging system complements existing staging systems (based on audiometric criteria, and on subjective assessment of the severity of vertigo attacks and their implications for quality of life).

Adult↗

Restriction enzyme digestion chromosome banding in Crassostrea and Ostrea species: comparative karyological analysis within Ostreidae.

Reliable banding techniques are a major necessity for genetic research in oysters. In this study, we carried out the cytogenetic characterization of four oyster species (family Ostreidae) using restriction endonuclease treatments. Chromosomes were treated with three different restriction enzymes, stained with Giemsa, and examined for banding patterns. The following species were studied: Crassostrea gigas (2n = 20; total number of bands with ApaI, 74; HaeIII, 61; PstI, 76), Crassostrea angulata (2n = 20; ApaI, 62; HaeIII, 61; PstI, 55) (subfamily Crassostreinae), Ostrea edulis (2n = 20; ApaI, 82; HaeIII, 59; PstI, 66), and Ostrea conchaphila (2n = 20; ApaI, 68; HaeIII, 62; PstI, 69) (subfamily Ostreinae). Treatment of samples with ApaI, HaeIII, and PstI produced specific banding patterns, which demonstrates the potential of these enzymes for chromosome banding in oysters. This is of special interest, since it has been recently shown in mammalian chromosomes that restriction enzyme banding is compatible with fluorescence in situ hybridization. This study therefore provides a fundamental step in genome mapping of oysters, since chromosome banding with restriction enzymes facilitates physical gene mapping in these important aquaculture species. The analysis of the banded karyotypes revealed a greater similarity within the genera of Crassostrea and Ostrea than between them.

Animals↗

Chromosomal localization of the major satellite DNA family (FA-SAT) in the domestic cat.

A major satellite DNA sequence was isolated from the cat genome and its sequencing data revealed homology to the FA-SAT family. In situ hybridization of the cat satellite DNA and telomeric sequences to cat chromosomes, together with staining of constitutive heterochromatin, allowed the physical mapping of the FA-SAT sequences, and also an overall constitutive heterochromatin study in cat chromosomes.

Animals↗

Pulmonary hypertension in chronic obstructive pulmonary disease.

Pulmonary hypertension is a common complication of chronic obstructive pulmonary disease (COPD). Its presence is associated with shorter survival and worse clinical evolution. In COPD, pulmonary hypertension tends to be of moderate severity and progresses slowly. However, transitory increases of pulmonary artery pressure may occur during exacerbations, exercise and sleep. Right ventricular function is only mildly impaired with preservation of the cardiac output. Structural and functional changes of pulmonary circulation are apparent at the initial stages of COPD. Recent investigations have shown endothelial dysfunction and changes in the expression of endothelium-derived mediators that regulate vascular tone and cell growth in the pulmonary arteries of patients with mild disease. Some of these changes are also present in smokers with normal lung function. Accordingly, it has been postulated that the initial event in the natural history of pulmonary hypertension in COPD could be the lesion of pulmonary endothelium by cigarette-smoke products. Long-term oxygen administration is the only treatment that slows down the progression of pulmonary hypertension in chronic obstructive pulmonary disease. Nevertheless, with this treatment pulmonary artery pressure rarely returns to normal values and the structural abnormalities of pulmonary vessels remain unaltered. Vasodilators are not recommended on the basis of their minimal clinical efficacy and because they impair pulmonary gas exchange. Recognition of the role of endothelial dysfunction in the physiopathology of pulmonary hypertension in chronic obstructive pulmonary disease opens new perspectives for the treatment of this complication.

Humans↗

Elongation of the cytoplasmic domain, due to a point deletion at exon 7, results in an HLA-C null allele, Cw*0409 N.

The development of molecular techniques for HLA typing has allowed the identification of genes previously assigned as serologic blank alleles. Lack or poor cell surface expression has been found for molecules coded by HLA-A, -B, -DRB4, -DRB5, and -DPB1 genes. In this report we describe the first HLA-C gene encoding for a null cell surface molecule. HLA-Cw*0409 N shows a point deletion at position 1095 within exon 7. This mutation provokes a codon reading shift, generating a new translation stop codon 97 bp downstream to that described in alleles normally expressed. This new stop codon location implies the presence of 32 extra amino acid residues in the cytoplasmic domain. Transfection experiments suggest that elongation of the cytoplasmic domain in Cw*0409 N would be the cause of cell surface expression failure, although Cw*0409 N heavy chain is able to create stable complexes with beta2-microglobulin. HLA-C fragment length analysis in a small selected group of samples with B44-Cblk haplotypic associations allowed us to identify two additional subjects showing both a serologic silent Cw*04 allele and a point base deletion at the 3' end of the HLA-C gene. This finding indicates that the allele frequency of Cw*0409 N within serologic C blank alleles would be appreciable, although basically restricted to the (A23)-Cw*0409 N-B*4403-DR7-DQ2 haplotype.

Alleles↗

In situ hybridization and chromosome banding in mammalian species.

Chromosome banding is often required in conjunction with fluorescent in situ hybridization of labelled probes for chromosome painting, satellite DNA and low-copy sequences to allow identification of chromosomes and simultaneous probe localization. Here, we present a method that reveals both patterns with only one observation step. The band pattern is produced by restriction-enzyme digestion of chromosomes, followed by fixation with paraformaldehyde in PBS, a short chromosome denaturation step in hybridization solution, and then standard in situ hybridization, washing and detection protocols. Using a range of different mammalian species, chromosome-banding patterns were immediately recognizable, although synchronisation procedures normally required for high- resolution G-banding were not needed. Unlike other methods available, only one round of observation is required using a conventional fluorescence microscope, the method works without modification in many species, and in situ hybridization is not used for chromosome identification (allowing multiple targets and minimizing background). The banding pattern is probably generated by a combination of DNA dissolution and heterochromatin reorganisation after enzyme digestion, followed by paraformaldehyde fixation of the new chromatin structure and incomplete denaturation. The method is of widespread utility in comparative genomics and genome organization programmes.

Animals↗

Characterization of pulmonary vascular remodelling in smokers and patients with mild COPD.

Intimal enlargement of pulmonary arteries is an early change in chronic obstructive pulmonary disease (COPD). The cellular and extracellular components that are involved in this enlargement are unknown. The present study was designed to characterize the structural changes occurring in pulmonary muscular arteries in the initial disease stages. Lung specimens from patients with moderate COPD (n=8; forced expiratory volume in one second (FEV1), 66 +/- 10% predicted) and smokers without airflow obstruction (n=7; FEV1, 86 +/- 6% pred), were investigated by histochemistry to characterize extracellular matrix proteins and by immunohistochemistry to identify intrinsic cells of the vascular wall. In both COPD patients and smokers, the majority of cells present in the enlarged intimas were stained by specific smooth muscle cell (SMC) markers. No staining with endothelial or fibroblast markers was shown. A proportion of SMCs did not stain with desmin, suggesting cellular heterogeneity in this population. Elastin was the most abundant extracellular matrix protein and collagen was seen in a lower proportion. The amount of collagen was related to the intimal thickness (p<0.001). The findings demonstrated smooth muscle cell proliferation, as well as elastin and collagen deposition, in the thickened intimas of pulmonary arteries in moderate chronic obstructive pulmonary disease patients and smokers, suggesting that these abnormalities may originate at an early stage in cigarette smoke-induced respiratory disease.

Aged↗

Response to hypoxia of pulmonary arteries in chronic obstructive pulmonary disease: an in vitro study.

Patients with chronic obstructive pulmonary disease (COPD) show impaired hypoxic pulmonary vasoconstriction that might contribute to abnormal gas exchange and could be related to endothelial dysfunction in pulmonary arteries. The aim of the study was to investigate the response of PA to hypoxic stimulus in vitro in COPD, and the role of endothelium-derived nitric oxide (NO) in this response. The pulmonary arteries of 25 patients who underwent lung resection were studied. Patients were divided into controls, COPD+normoxaemia (COPDN) and COPD+ hypoxaemia (COPDH). Hypoxic vasoconstriction (HV) was evaluated before and after stimulation or inhibition of the endothelial release of NO, and in the presence of exogenous NO. Compared with the other groups, HV was reduced in COPDH. The magnitude of HV correlated with the oxygen tension in arterial blood. The hypoxic stimulus induced greater contraction after stimulating endothelial release of NO, whereas its inhibition practically abolished HV. Exogenous NO completely inhibited HV. Maximal relaxation induced by endothelium-dependent vasodilators correlated with the magnitude of HV. In conclusion, pulmonary arteries of patients with chronic obstructive pulmonary disease and hypoxaemia have an impaired response to hypoxic stimulus, and the endothelial release of nitric oxide modulates hypoxic vasoconstriction. The depressed response of pulmonary arteries to hypoxia may contribute to abnormal gas exchange in chronic obstructive pulmonary disease.

Aged↗

Functional expression of muscle-type nicotinic acetylcholine receptors in rat forebrain neurons in vitro.

Molecular studies aimed at modifying ligand-gated ion channel function in primary neuronal cultures have been hampered by the limited efficacy of gene transfer techniques. Although viruses can effectively deliver genes to neurons, their preparation requires a substantial effort and their usefulness in delivering multiple subunits of a single protein has not been well established. In this study, we have successfully cotransfected mammalian expression plasmids for all subunits of the muscle nicotinic acetylcholine receptor (nAChR), along with a plasmid containing green fluorescent protein (GFP), into rat forebrain neurons using a calcium phosphate method. Immunostaining experiments and cell counting showed that the nAChR were successfully expressed in approximately 1% of the neurons in the culture. The functionality of the expressed receptors was demonstrated electrophysiologically as carbachol-induced currents were present in nearly 90% of the GFP-positive neurons tested. These currents could be completely inhibited by the irreversible antagonist alpha-cobratoxin. Surprisingly, no currents were obtained in any of the GFP-negative cells tested. These results demonstrate that gene delivery of complex, multi-subunit proteins can be successfully performed in cultured neurons, thereby opening new strategies for the pharmacological study of ligand-gated ion channels.

Animals↗

Reduced expression of endothelial nitric oxide synthase in pulmonary arteries of smokers.

Cigarette smoking has been associated with alterations in the structure and endothelial function of pulmonary arteries. Nitric oxide (NO) and endothelin-1 are endothelium-derived mediators with opposite effects on vascular tone and cell growth. To investigate whether cigarette smoking could induce changes in the synthesis of these mediators in pulmonary arteries, we compared the expression of both endothelial NO synthase (eNOS) and endothelin-1 in the lungs of smokers with that in nonsmokers. Lung tissue samples of 23 smokers and nine nonsmokers were studied. Expression of eNOS and endothelin-1 in pulmonary artery endothelium was evaluated by immunohistochemistry. In protein extracts of lung tissue, the content of eNOS protein was assessed by Western blot analysis and that of endothelin-1 by radioimmunoassay. The immunohistochemical expression of eNOS in arterial endothelium and the eNOS protein content in lung tissue were lower in the smokers than in the nonsmokers. No differences were shown in cell expression and protein content of endothelin-1 between both groups. We conclude that cigarette smoking is associated with reduced expression of eNOS in pulmonary arteries. The diminished synthesis of nitric oxide may contribute to the alterations in the structure and endothelial function of pulmonary vessels in cigarette-smoke-induced respiratory disease.

Aged↗