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Biomedical subjects

A Santos

Publications and source records attributed to A Santos.

At least 109 records · Page 6Linked to original sources
PubMed1999

Genetic risk factors in acute coronary disease.

OBJECTIVE: We investigate whether each of the following: HPA-1, Factor V Leiden, prothrombin gene variant and the methylene tetrahydrofolate reductase gene (MTHFR) mutation, are risk factors for acute coronary disease in Portuguese patients. MATERIAL AND METHODS: 100 blood donors and 52 patients with an established diagnosis of myocardial infarction or unstable angina were evaluated for genetic risk factors, by determining HPA-1 genotype, Factor V Leiden, Prothrombin 20210 variant and MTHFR mutation. RESULTS: We found a prevalence of 2.0% for Factor V Leiden, 5.0% for the Prothrombin 20210 variant and 66% for the MTHFR mutation in blood donors. These values are similar to those found in the patients (1.9, 3.8 and 58%, respectively). We found that 28/100 controls had the PI(A2) polymorphism, a frequency statistically different from that in the patients (23/52). This difference was even more pronounced in patients less than 60 years old (27/96 vs. 13/24). CONCLUSION: Factor V Leiden, Prothrombin 20210 variant and MTHFR mutation do not seem to represent risk factors for acute coronary disease. However, the PI(A2) polymorphism could have a role in the pathogenesis of this disease. The presence of multiple genetic factors, more than single ones, could influence the development and outcome of myocardial infarction and unstable angina. Larger studies are needed in order to have a better insight into the pathophysiological mechanisms of this disease, along with its prevention and the development of new treatments.

Activated Protein C Resistance↗
PubMed1999

A comparison of HIV/AIDS knowledge among high school freshmen and senior students.

Statistical data show that heterosexual transmission of AIDS among teenagers is a significant problem. The purpose of this study was to assess and compare the level of knowledge concerning HIV/AIDS among high school freshmen- and senior-level students and to determine the association between certain demographic variables and the students' knowledge level. A convenience sample of 169 freshmen and 274 senior high school students were surveyed at a local area high school (N = 443). A 49-item knowledge questionnaire, used by the high school district HIV/Abstinence program, and a demographic questionnaire developed by the investigators were used to collect the data. The findings revealed that both the freshmen and senior students had several misconceptions about HIV/AIDS, including the modes of transmission, the sure way of preventing the sexual transmission, donating blood, and the usual causes of death for people with AIDS. A comparison of the mean knowledge scores among freshmen and senior students indicated there was no significant difference among the two groups. The mean knowledge score of the seniors was significantly affected by whether they had received HIV/AIDS education. However, this was not the case for the freshmen. African American students, especially the female students, had significantly lower knowledge scores than other ethnic groups.

Adolescent↗
PubMed1999

[The additional efficacy of the nifedipine-diuretic combination depends on the potency of the drug administered first and not the sequence of administration. A double blind study in salt-sensitive black hypertensives].

OBJECTIVE: To evaluate whether the additional antihypertensive efficacy of the nifedipine-thiazide combination depends on the sequence of drug administration and whether the natriuretic effect of thiazide persists when co-administered with nifedipine. METHODS: Double blind, randomised, crossover, placebo-controlled study, in 12 salt-sensitive hypertensive black patients (SSH). Evaluation of the antihypertensive (24 h ambulatory monitoring) and natriuretic effects of placebo (PL), of nifedipine-GITS (NIF, 30 mg/d) and of hydrochlorothiazide (HCTZ, 25 mg/d) given alone and in combination within two separate therapeutic sequences: PL-->NIF-->NIF + HCTZ and PL-->HCTZ-->HCTZ + NIF (1 month for each therapeutic regimen). RESULTS: NIF induced greater (p < 0.04) reduction of 24 h mean arterial pressure (MAP) (-15.9 +/- 1.9 mm Hg, v PL) than HCTZ (-9.0 +/- 1.3 mm Hg). The association of NIF to HCTZ induced a greater (p < 0.05) additional reduction of MAP-24 h (9.7 +/- 2.2 mm Hg) than that produced by the association of HCTZ to NIF (4.1 +/- 1.3 mm Hg). NIF alone and in combination did not modify the diuresis-natriuresis observed with the previous treatment, whereas HCTZ alone and in combination always increased diuresis (by 25%) and natriuresis (by 53%). There was a significant negative correlation (r = -0.71, p < 0.001) between blood pressure (BP) reduction induced by the drug administered first (NIF or HCTZ) and the additional BP reduction obtained by the association of the second drug. CONCLUSIONS: In most of the SSH the NIF-GITS was more potent than HCTZ. NIF did not modify the diuretic-natriuretic effect of PL and of HCTZ. The greater potency of NIF may explain why in most patients the combination HCTZ to NIF induced a lower hypotensive effect than that of the association of NIF to HCTZ. Independently of the sequence of the drug administration, the lower the hypotensive effect of the drug administered first the greater the additional hypotensive effect that was observed by adding the second drug.

Adult↗
PubMed1999

Molecular analysis of resistance to interferon in patients with laryngeal papillomatosis.

Although interferon (IFN)-alpha has been used successfully as an adjuvant therapy in laryngeal papillomatosis, some patients are resistant to this treatment. In order to know which patients will benefit from the therapy, we have tried to find a relationship between the IFN response and the viral and host parameters in the lesion. Detection of viral type and copy numbers by polymerase chain reaction (PCR) showed that all patients infected with human papillomavirus (HPV)-11 were sensitive to the treatment, in contrast to those infected with HPV-6. These differences could be explained in part by the inability of HPV-11 E7 to inhibit the induction of an IFN-responsive element, whereas HPV-6 E7 almost completely inhibited the activity of this promoter in transient transfection experiments. Local immune status in the lesion showed that all HPV-11-infected patients had detectable levels of interleukin (IL)-15 and IFN-gamma mRNA, in contrast to HPV-6-infected patients, in whom mRNA for these cytokines was almost absent. Viral copy numbers and levels of IL-4 mRNA could not be correlated with IFN response. Only one patient resistant to recombinant IFN-alpha2b and negative for HPV DNA presented high titers of neutralizing anti-IFN-alpha2b antibodies. This patient became sensitive when natural IFN-alpha was administered. These results suggest that response to IFN may be a complex phenomenon resulting from the interaction between viral and host elements.

Adult↗
PubMed1998

Control by thyroid hormone of NGFI-A gene expression in lung: regulation of NGFI-A promoter activity.

In previous studies, it was shown that the expression of the transcription factor NGFI-A is under thyroid hormone (T3) control in developing rat brain. Here, the effect of this hormone on the expression of this gene in lung, as well as the effect of T3 and NGFI-A protein on NGFI-A promoter activity, has been investigated. The results show that T3 regulates NGFI-A gene expression at a pretranslational level in neonatal and adult rat lung, but also at a translational and/or posttranslational level in 5-day-old neonates, since the NGFI-A protein content was decreased in hypothyroid animals without changes in mRNA. Transfection experiments showed an induction of NGFI-A promoter activity by thyroid hormone. NGFI-A protein blocked this stimulation, suggesting a negative interaction between NGFI-A protein and thyroid hormone receptor, which could explain the transient induction by T3 of this gene observed in the first 2-4 h.

Age Factors↗
PubMed1998

Automated FISH spot counting in interphase nuclei: statistical validation and data correction.

The evaluation of an automated system for Fluorescence In Situ Hybridization (FISH) spot counting in interphase nuclei is presented in this paper. Different types of experiments have been performed with samples from known populations. In all of them the goal is to detect mosaicism of chromosome X in leukocytes from mixtures in known proportions of healthy male and female blood. First the initial results from the automatic FISH analysis system were obtained and evaluated. Then the analysis was modified to reduce systematic errors, so that the results are closer to what an experienced human operator would have obtained (system calibration step). Finally, an additional control probe of chromosome Y was used to detect and discard cells where incorrect hybridization or other abnormal situations had occurred. In each step the system sensitivity was determined by the use of two statistical validation tests, so that the improvement brought about by the correction methods could be assessed. The results obtained in the study showed that, using both corrections, the system is able to detect 10% monosomies with a significance level alpha = 0.1%.

Algorithms↗
PubMed1998

Preclinical development of camptothecin derivatives and clinical trials in pediatric oncology.

Although the prognosis of childhood cancers has dramatically improved over the last three decades, new active drugs are needed. Camptothecins represent a very attractive new class of anticancer drugs to develop in paediatric oncology. The preclinical and clinical development of two of these DNA-topoisomerase I inhibitors, i.e. topotecan and irinotecan, is ongoing in paediatric malignancies. Here we review the currently available results of this evaluation. Topotecan proved to be active against several paediatric tumour xenografts. In paediatric phase I studies exploring several administration schedules, myelosuppression was dose-limiting. The preliminary results of topotecan evaluation in phase II study showed antitumour activity in neuroblastoma (response rate: 15% at relapse and 37% in newly diagnosed patients with disseminated disease) and in metastatic rhabdomyosarcoma (40% in untreated patients). Topotecan-containing drug combinations are currently investigated. Irinotecan displayed a broad spectrum of activity in paediatric solid tumour xenografts, including rhabdo-myosarcoma, neuroblastoma, peripheral primitive neuroectodermal tumour, medulloblastoma, ependymoma, malignant glioma and juvenile colon cancer. For several of these histology types, tumour-free survivors have been observed among animals bearing an advanced-stage tumour at time of treatment. The clinical evaluation of irinotecan in children is ongoing. Irinotecan undergoes a complex in vivo biotransformation involving several enzyme systems, such as carboxylesterase, UDPGT and cytochrome P450, in children as well as in adults. Preclinical studies of both drugs have shown that their activity was schedule-dependent. The optimal schedule of administration is an issue that needs to be addressed in children. In conclusion, the preliminary results of the paediatric evaluation of camptothecin derivatives show very encouraging results in childhood malignancies. The potential place of camptothecins in the treatment of paediatric malignant tumours is discussed.

Animals↗
PubMed1998

MRI visualization of small structures using improved surface coils.

In this paper we present the spatial resolution enhancement and noise reduction level achieved with an optimized inductively coupled surface coil specifically designed for our experiments. The technique of designing and implementing customized coils for magnetic resonance imaging of very small structures is described. We have designed a low cost prototype of an inductively coupled circular surface coil, tuned for 1H magnetic resonance imaging at 200 MHz. The coil is mounted on a customized teflon support. The inductive coupling used in this coil improves the signal-to-noise ratio by reducing various loss mechanisms (specially the dielectric losses). Test images have been acquired to determine the evolution of induced articular lesions in a rabbit animal model, as well as brain tumors in rats. The images show high spatial resolution, excellent B1 field homogeneity and no "hot spots". Comparing these images with those acquired with conventional coils, one finds better spatial resolution and signal-to-noise ratio, as well as larger field of view with less intense illumination artifact. The methodology can be used in any application that requires high quality imaging of small structures.

Animals↗
PubMed1998

Hepatic histidase gene expression responds to protein rehabilitation in undernourished growing rats.

We studied the effect of nutritional rehabilitation with a 6, 18 or 50% casein diet in undernourished rats on histidase (Hal) expression. Undernutrition was induced by feeding rats a 0.5% casein diet for 5 wk. Over this period, growth, serum total proteins and insulin-like growth factor-I (IGF-I) levels were significantly lower than those of rats that freely consumed an 18% casein diet. During this period, undernutrition also significantly reduced Hal activity and Hal-mRNA concentration. Nutritional rehabilitation for 21 d with a 6% casein diet did not change any of these variables. Nutritional rehabilitation with an 18 or 50% casein diet for 1 d initiated the restoration of Hal activity and mRNA concentration. After 10 d of consuming 18 or 50% casein diets, Hal activity was 5- and 14-fold, and mRNA concentration was 8.5- and 23-fold higher, respectively, than in the protein-undernourished group (PU). During this period, body weight, total serum proteins and IGF-I levels were also significantly (P < 0.05) higher than those of the PU group. At the end of 21 d of rehabilitation with an 18 or 50% casein diet, Hal activity was 14- and 31-fold higher and Hal mRNA concentration was 10- and 24-fold higher, respectively, than in the PU group. In conclusion, our data showed that rehabilitation of undernourished rats with a 6% casein diet was not sufficient to re-establish growth indicators, Hal activity or gene expression, and that nutritional rehabilitation with an 18 or 50% casein diet effectively re-established body weight , biochemical variables and the capacity of histidase gene expression to eliminate the excess of protein.

Analysis of Variance↗
PubMed1998

Ultrasonographic detection of living adult Wuchereria bancrofti using a 3.5-MHz transducer.

Adult Wuchereria bancrofti can be readily detected by ultrasound in the lymphatic vessels of the spermatic cord with a 7.5-MHz transducer, but most ultrasound machines in developing countries are equipped with 3.5-MHz transducers. To assess the potential for ultrasound as a tool for diagnosis and epidemiologic assessment in lymphatic filariasis, we compared the performance of 3.5-MHz and 7.5-MHz transducers in 61 men in Recife, Brazil. All men had three ultrasound examinations using a 3.5 MHz transducer and an examination with a 7.5-MHz probe. Using the 7.5-MHz transducer, adult W. bancrofti were detected in 41 men; 81 adult worm nests were detected. Sixty-four (79%) nests were detected with the 3.5-MHz probe, each on all three examinations. The 3.5-MHz probe correctly identified 35 (85.4%) of 41 men as infected; sensitivity increased with lymphatic vessel diameter. Ultrasonographic examination with a 3.5-MHz transducer is a sensitive method for detection of adult W. bancrofti in men and merits consideration as a tool for rapid epidemiologic assessment.

Adolescent↗
PubMed1998

[Atrial fibrillation surgery using intraoperative radiofrequency].

Radiofrequency ablation is successful in most supraventricular tachyarrhythmias and the first results in percutaneous applications in atrial fibrillation have been published. At present, all the surgical techniques for the treatment of atrial fibrillation use extensive atrial incisions. A case report is presented of a 67 year old woman with chronic atrial fibrillation and rheumatic mitral and tricuspid valve disease. At surgery, pulmonary vein isolation was performed using a continuous linear ablation around the pulmonary veins, instead of using extensive atrial incisions. Concommitantly, a mitral valve replacement and tricuspid valve annuloplasty were performed. Five months after surgery, the patient remains with a stable sinus rhythm surgery and in functional class I (NYHA).

Aged↗
PubMed1997

Potent therapeutic activity of irinotecan (CPT-11) and its schedule dependency in medulloblastoma xenografts in nude mice.

The anti-tumor activity of irinotecan (CPT-11), a DNA-topoisomerase 1 inhibitor, was evaluated in 5 advanced stage subcutaneous medulloblastoma xenografts in nude mice, using different schedules of administration. With a 5-day schedule, the highest i.v. dose tested (40 mg kg-1 day-1) induced complete regressions in all xenografts but 1, and delays in tumor growth always exceeded 30 days. Two xenografts, IGRM11 and IGRM33, were highly sensitive, and animals survived tumor-free beyond 120 days after treatment. CPT-11 clearly retained its anti-tumor activity at a lower dosage (27 mg kg-1 day-1). CPT-11 was significantly more active than cyclophosphamide, thiotepa and etoposide against the 3 xenografts evaluated. To study the schedule dependency of its anti-tumor activity, CPT-11 was given i.v. at the same total doses over the same period (33 days) using either a protracted or a sequential schedule in IGRM34-bearing mice. With a dose of 10 mg kg-1 day-1 given on days 0-4, days 7-11, days 21-25 and days 28-32 (total dose, 200 mg kg-1), 3 of 6 animals were tumor free on day 378. The same total dose given with a sequential schedule, i.e., 20 mg kg-1 day-1 on days 0-4 and days 28-32, failed to induce complete regression. The plasma pharmacokinetics of CPT-11 and SN-38 were studied in IGRM34-bearing animals after a single i.v. dose of 10 and 40 mg kg-1. The plasma clearance rate of CPT-11 was dose dependent. The ratio between the SN-38 and CPT-11 area under the curve in plasma was 0.4-0.65, i.e., significantly higher than that observed in humans at the maximum tolerated dose (0.01-0.05). Conversely, this ratio was 10-fold lower in tumor than in plasma. Clinical development of irinotecan is warranted in pediatric malignancies.

Animals↗
PubMed1997

Applying watershed algorithms to the segmentation of clustered nuclei.

Cluster division is a critical issue in fluorescence microscopy-based analytical cytology when preparation protocols do not provide appropriate separation of objects. Overlooking clustered nuclei and analyzing only isolated nuclei may dramatically increase analysis time or affect the statistical validation of the results. Automatic segmentation of clustered nuclei requires the implementation of specific image segmentation tools. Most algorithms are inspired by one of the two following strategies: 1) cluster division by the detection of internuclei gradients; or 2) division by definition of domains of influence (geometrical approach). Both strategies lead to completely different implementations, and usually algorithms based on a single view strategy fail to correctly segment most clustered nuclei, or perform well just for a specific type of sample. An algorithm based on morphological watersheds has been implemented and tested on the segmentation of microscopic nuclei clusters. This algorithm provides a tool that can be used for the implementation of both gradient- and domain-based algorithms, and, more importantly, for the implementation of mixed (gradient- and shape-based) algorithms. Using this algorithm, almost 90% of the test clusters were correctly segmented in peripheral blood and bone marrow preparations. The algorithm was valid for both types of samples, using the appropriate markers and transformations.

Algorithms↗
PubMed1997

Regulation by thyroid hormone and retinoic acid of the CCAAT/enhancer binding protein alpha and beta genes during liver development.

The effect of thyroid hormone and retinoic acid on the expression of CCAAT/enhancer binding proteins (C/EBPs) alpha and beta was investigated in rat liver during development. Congenital hypothyroidism caused a significant decrease in both C/EBP alpha and C/EBP beta gene expression at early stages of postnatal development. This effect was tissue specific since thyroid hormone had no effect on the level of C/EBP mRNAs in brown fat. Injection of 15-, and 30-day-old hypothyroid animals with thyroid hormone resulted in a slow recovery of the hepatic levels of both C/EBP alpha and beta mRNA levels. Retinoic acid was a very rapid and potent stimulator compared to thyroid hormone in hypothyroid animals. C/EBP alpha and beta protein levels were markedly diminished in hypothyroid neonates and the kinetics of induction of these proteins by thyroid hormone was faster than the one observed for the corresponding transcripts. The discrepancies observed between mRNA and protein levels suggest a translational or post-translational regulation of these genes as the major point of thyroid hormone action on these genes.

Animals↗
PubMed1997

Preservation of the inner retina in retinitis pigmentosa. A morphometric analysis.

OBJECTIVE: To determine the extent of preservation in the inner retina in retinitis pigmentosa (RP). METHODS: We analyzed sectioned maculae of 21 postmortem eyes with RP and 19 age-matched, normal, postmortem eyes. Eyes were divided into 2 groups: severe and moderate RP. Cell nuclei were counted in the outer nuclear, inner nuclear, and ganglion cell layers within thirty 100-microns intervals from the foveola to 1500-microns eccentricity. RESULTS: Statistically significant (P < or = .05) loss of both the outer nuclear and ganglion cell layers was present in the groups with moderate and severe RP when compared with the control groups. However, even in the group with severe RP, 30% of the ganglion cells were histologically intact. Similarly, 78% and 88% of the inner nuclear layer cells were preserved in the groups with severe and moderate RP, respectively. Different inheritance modes showed no statistically significant differences in any of the retinal layers. CONCLUSIONS: Despite a statistically significant (P < or = .05) loss of cells found in all retinal layers, a large percentage of the inner retinal neurons remained histologically intact. Current experimental therapies, such as photoreceptor transplantation and implantation of a visual prosthesis, are based on the premise that some inner retinal neurons are preserved after death of photoreceptors in RP. Our observations support this assumption.

Aged↗
PubMed1997

Simulated surgery on computed tomography and magnetic resonance images: an aid for intraoperative radiotherapy.

Intraoperative radiotherapy (IORT) is a relatively new technique in which irradiation with electrons is performed during an open surgery procedure. This approach poses significant problems in obtaining accurate dosimetry, since neither the pre- nor the postoperative patient images actually matches the irradiation field. Our objective was to implement a software tool able to provide an estimate of the dose distribution, overcoming the problem of the geometrical mismatch between the images and the surgical field during the irradiation. The program was developed in the C programming language, on a noncommercial version of a Philips EasyVision workstation. The application allows to create a new data set by manipulating the preoperative computed tomography and magnetic resonance images in order to simulate the final geometry of the surgical area during the IORT procedure. The exact dose distribution can then be calculated by transferring these new images to a standard radiotherapy planning system. Also an approximate dose distribution can be quickly displayed by superimposing isodose curves obtained from a water phantom. The proposed approach introduces a helpful tool for dosimetry and planning in IORT protocols, improving their accuracy and safety and allowing for more objective quality control and patient follow-up.

Brain Neoplasms↗