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Biomedical subjects

L Lopes

Publications and source records attributed to L Lopes.

At least 19 recordsLinked to original sources

[Other indications for surfactant].

OBJECTIVE: The introduction of surfactant replacement therapy in the management of respiratory distress syndrome in the premature infant was a remarkable advance in neonatal intensive care. In the last few years, recognition of the role played by surfactant inactivation in the pathogenesis of other respiratory diseases of the newborn has justified new therapeutic applications. The aim of this study was to evaluate the efficacy of treatment with natural exogenous surfactant in situations with secondary surfactant deficiency. METHODS: We performed a retrospective analysis of the evolution of 15 newborn infants treated with natural exogenous surfactant. Nine infants had meconium aspiration syndrome, five had congenital pneumonia and one had adult respiratory distress syndrome. Oxygenation indexes before and after surfactant treatment as well as clinical and radiographic evolution were compared. RESULTS: The 12 surviving infants showed improvement in oxygenation and radiographic alterations after surfactant administration. Three patients with meconium aspiration syndrome died. CONCLUSIONS: These results support the therapeutic use of exogenous surfactant in severe respiratory diseases of the newborn causing secondary surfactant deficiency.

Female↗

A practical method to achieve prostate gland immobilization and target verification for daily treatment.

PURPOSE: A practical method to achieve prostate immobilization and daily target localization for external beam radiation treatment is described. METHODS AND MATERIALS: Ten patients who underwent prostate brachytherapy using permanent radioactive source placement were selected for study. To quantify prostate motion both with and without the presence of a specially designed inflatable intrarectal balloon, the computerized tomography-based coordinates of all intraprostatic radioactive sources were compared over 3 consecutive measurements at 1-min intervals. RESULTS: The placement and inflation of the intrarectal balloon were well tolerated by all patients. The mean (range) displacement of the prostate gland when the intrarectal balloon was present vs. absent was 1.3 (0-2.2) mm vs. 1.8 (0-9.1) mm (p = 0.03) at 2 min respectively. The maximum displacement in any direction (anterior-posterior, superior-inferior, or right-left) when the intrarectal balloon was inflated vs. absent was reduced to < or =1 mm from 4 mm. CONCLUSIONS: Both prostate gland immobilization and target verification are possible using a specially designed inflatable intrarectal balloon. Using this device, the posterior margin necessary on the lateral fields to ensure dosimetric coverage of the entire prostate gland could be safely reduced to 5 mm and treatment could be set up and verified using a lateral portal image.

Brachytherapy↗

Retrovirus-mediated transfer and expression of beta-hexosaminidase alpha-chain cDNA in human fibroblasts from G(M2)-gangliosidosis B1 variant.

Mutations in the alpha-chain of lysosomal hexosaminidase (EC 3.2.1.52) underlie two distinct biochemical phenotypes known as variant B and variant B1 of G(M2) gangliosidosis. This paper shows that the transduction of human B1-type fibroblasts (producing catalytically inactive alpha-chains) with a retroviral vector encoding the human hexosaminidase alpha-chain leads to a complete correction of HexA (alpha beta dimer) activity with both synthetic and natural substrates. The alpha-subunit overexpression leads to a partial HexB (beta beta dimer) depletion corresponding to about 10% of control HexB activity. The newly synthesized enzyme is correctly processed and targeted to the lysosomes in transduced cells. The high levels of recombinant enzyme correctly produced the metabolic defect, enabling the cells efficiently to degrade the accumulated storage product present in lysosomes. The transduced fibroblasts are also able to secrete HexA efficiently into the culture medium. Moreover, transfer of the human transgene product to B1-type deficient fibroblasts lead to an increase of activity against 4MUGS, the alpha-chain specific synthetic substrate, up to 30% of the control mean activity level. This level of activity might be sufficient to restore the normal ganglioside G(M2) metabolism in recipient cells. The data obtained demonstrate that B1-type phenotype can be efficiently corrected by retrovirus-mediated gene transfer.

3T3 Cells↗

A defect in bone marrow derived dendritic cell maturation in the nonobesediabetic mouse.

The pathogenesis of diabetes in the nonobese diabetic (NOD) mouse is characterized by a selective destruction of the insulin-producing beta-cells in the islets of Langerhans mediated by autoreactive T cells. The function of T cells is controlled by dendritic cells (DC), which are not only the most potent activators of naïve T cells, but also contribute significantly to the establishment of central and peripheral tolerance. In this study, we demonstrate that the NOD mouse (H2: K(d), Ag(7), E*, D(b)) shows selective phenotypic and functional abnormalities in DC derived from bone marrow progeny cells in response to GM-CSF (DC(NOD)). NOD DC, in contrast to CBA DC, have very low levels of intracellular I-A molecules and cell surface expression of MHC class II, CD80, CD86 and CD40 but normal beta 2-microglobulin expression. Incubation with the strong inflammatory stimulus of LPS and IFN-gamma does not increase class II MHC, CD80 or CD86, but upregulates the level of CD40. The genetic defect observed in the DC(NOD) does not map to the MHC, because the DC from the MHC congenic NOD.H2(h4) mouse (H2: K(k), A(k), E(k), D(k)) shares the cell surface phenotype of the DC(NOD). DC from these NOD.H2(h4) also fail to present HEL or the appropriate HEL-peptide to an antigen-specific T cell hybridoma. However all the DC irrespective of origin were able to produce TNF-alpha, IL-6, low levels of IL-12(p70) and NO in response to LPS plus IFN-gamma. A gene or genes specific to the NOD strain, but outside the MHC region, therefore must regulate the differentiation of DC in response to GM-CSF. This defect may contribute to the complex genetic aetiology of the multifactorial autoimmune phenotype of the NOD strain.

Animals↗

Immunomodulation using bacterial enterotoxins.

Immunologic unresponsiveness (tolerance) is a key feature of the mucosal immune system, and deliberate vaccination by a mucosal route can effectively induce immune suppression. However, some bacterial-derived proteins, e.g. cholera toxin and the heat labile toxin of Escherichia coli, are immunogenic and immunomodulatory at mucosal surfaces and can effectively adjuvant immune responses to codelivered bystander antigens. This review summarizes some of the structural and biological characteristics of these toxins and provides examples of how these properties have been exploited for tolerance induction and mucosal vaccine development.

Adjuvants, Immunologic↗

The photoreceptor cell-specific nuclear receptor gene (PNR) accounts for retinitis pigmentosa in the Crypto-Jews from Portugal (Marranos), survivors from the Spanish Inquisition.

The last Crypto-Jews (Marranos) are the survivors of Spanish Jews who were persecuted in the late fifteenth century, escaped to Portugal and were forced to convert to save their lives. Isolated groups still exist in mountainous areas such as Belmonte in the Beira-Baixa province of Portugal. We report here the genetic study of a highly consanguineous endogamic population of Crypto-Jews of Belmonte affected with autosomal recessive retinitis pigmentosa (RP). A genome-wide search for homozygosity allowed us to localize the disease gene to chromosome 15q22-q24 (Zmax=2.95 at theta=0 at the D15S131 locus). Interestingly, the photoreceptor cell-specific nuclear receptor (PNR) gene, the expression of which is restricted to the outer nuclear layer of retinal photoreceptor cells, was found to map to the YAC contig encompassing the disease locus. A search for mutations allowed us to ascribe the RP of Crypto-Jews of Belmonte to a homozygous missense mutation in the PNR gene. Preliminary haplotype studies support the view that this mutation is relatively ancient but probably occurred after the population settled in Belmonte.

Chromosomes, Human, Pair 15↗

Free radical scavenging activity of Lafoensia pacari.

The methanolic extract of the stem bark of Lafoensia pacari (Lythraceae) showed free radical scavenging activity in the diphenyl picryl hydrazyl radical (DPPH) decoloration assay and inhibited the enzyme xanthine oxidase 'in vitro'. Bioassay-guided isolation led to ellagic acid (EA) as the main active compound of Brazilian and Paraguayan collections of the plant.

Alcohols↗

Tamsulosin palliates radiation-induced urethritis in patients with prostate cancer: results of a pilot study.

PURPOSE: A pilot study was performed to determine the effectiveness of Flomax (tamsulosin HCl) in the management of acute radiation urethritis in prostate cancer patients undergoing conformal external beam radiation therapy (RT). Potential predictors of response to Flomax were evaluated. METHODS AND MATERIALS: From January 1998 to April 1998, 26 consecutive patients who developed symptoms of radiation urethritis while undergoing RT for prostate cancer were treated with Flomax, a superselective alpha1A-adrenergic antagonist. A genitourinary review of systems served as the instrument used to assess baseline urinary function and treatment response. RESULTS: The initial response rate to Flomax was 62% (16/26) at the 0.4 mg level and 60% (6/10) at the 0.8 mg level. Half of the 16 patients who initially responded to 0.4 mg subsequently progressed. Three-fourths of those patients who progressed, however, achieved a durable response with the 0.8 mg dose. Therefore urinary symptoms were ultimately controlled in 77% (20/26) of the patients. After correcting for the testing of multiple hypotheses (n = 5), the presence of benign prostatic hyperplasia (BPH) approached statistical significance for predicting the initial response to the 0.4 mg dose of Flomax (78% vs. 25%, p = 0.03). CONCLUSION: Flomax appears to be effective in relieving the symptoms of radiation urethritis. A Phase II trial is justified and in progress.

Adrenergic alpha-1 Receptor Antagonists↗

[Tomodensitometric image of the lumbar spine. Study of 150 patients hospitalized for discal sciatica].

OBJECTIVES: There would be some discordance between patient expectations and expert recommendations concerning computed tomography (CT) of the spine for discal disorders. We analyzed patient opinion. PATIENTS AND METHODS: At admission, a 25-item questionnaire was given to 150 patients hospitalized in a rheumatology unit for discal sciatica. Patients were asked to express their expectations concerning the CT exploration. RESULTS: Seventy percent of the patients had already undergone CT explorations requested by a general practitioner (55%) or a specialist (45%), 20% had had two CT explorations and 20% magnetic resonance imaging. Seventy-five percent felt they should have had a CT scan earlier, 85% thought a CT should be performed for back pain of less than one month duration and 96% in case of sciatica for 2 months or more. Patients felt their exploration came "late" because the physician was under financial pressure (52%), had incorrectly appreciated the patient's need (28%) or was incompetent in the matter (22%). Nevertheless, 15% of the patients recognized that the CT scan could be useless and 89% knew that all cases of hernia are not operable. Thirty percent recognized that hernias can go undetected on the CT scan and 78% that they may remain asymptomatic. Finally, 56% of the patients thought that the CT scan would not change their treatment and only 23% expected to undergo surgery sooner because of the CT exploration. DISCUSSION: Several factors would explain what patients expect from CT exploration of the spine: patient understanding that causes other than discal hernia can cause back pain (98%) or sciatic (77%); their fear of having another disorder (56% wanted to be reassured, which would explain in part why 27% hoped the CT would improve pain, 50% wanted to "see" their discal hernia, and 30 wanted to eliminate another cause of their pain); patient distrust of clinical diagnosis which they felt was less pertinent than CT (80% of the patients for generalists and 70% for specialists). Patient expectations did not appear to be limited by fear of irradiation (unrecognized by 90% of the patients) nor the cost of the exploration which was overestimated by 70% of them.

Aged↗

Enhanced human cell engraftment in mice deficient in RAG2 and the common cytokine receptor gamma chain.

Xenotransplantation of human cells into immunodeficient mice has been used to develop models of human haemopoiesis and lymphoid cell function. However, the utility of existing mouse strains can be limited by shortened life-spans, spontaneous production of functional lymphocytes with ageing, and residual innate immunity leading to variable levels of engraftment. Mice with a deletion of the common cytokine receptor gamma chain (gamma c) gene have reduced numbers of peripheral T and B lymphocytes, and absent natural killer cell (NK) activity. A genetic cross with a recombinase activating gene 2 (RAG2)-deficient strain produced mice doubly homozygous for the gamma c and RAG2 null alleles (gamma c-/RAG2-). These mice have a stable phenotype characterized by the absence of all T lymphocyte. B lymphocyte and NK cell function. Injection of human B-lymphoblastoid cells resulted in earlier fatal metastatic lymphoproliferative disease than in NOD/LtSz-scid controls. This was particularly evident in animals injected intravenously, possibly because of residual NK activity in NOD/LtSz-scid mice. Levels of engraftment with peripheral-blood-derived human lymphocytes were also increased and associated with higher CD4/CD8 ratios. These findings demonstrate that this new strain of immunodeficient mice has significant advantages over existing strains for engraftment of human cells, and may be useful for study of adoptive immunotherapy and novel therapies for GvHD and HIV infection.

Animals↗

[Blood pressure normal values in children and adolescents according to age and height].

The assessment of blood pressure in children and adolescents is of great importance in order to gain a better understanding of its pattern of evolution. The authors publish the normal values of blood pressure in Portuguese children and adolescents, according to age and sex, as well as the mean values of the 90th percentile, which are very important to separate normal children from those with high blood pressure. In this study the fifth Korotkoof sound is used to define diastolic blood pressure in all ages. New blood pressure tables are also published, for children and adolescents, that now include the height percentile for age and blood pressure. These new charts have been developed to guide practising clinicians in antihypertensive drug therapy, when indicated.

Adolescent↗

[Blood pressure in a population of youngsters and adults observed after 17 years].

Many studies have assessed the blood pressure tracking among children and adolescents, but the results have been controversial. This study assessed the blood pressure tracking in 224 Portuguese school children and young adults following them for 17 years. The correlations obtained for systolic and diastolic blood pressure in both sexes are not very high, although positive and statistically significant. On the other hand, there was a stronger correlation between anthropometric variables and blood pressure and indices of obesity.

Adolescent↗

Effects of a self-etching primer on enamel shear bond strengths and SEM morphology.

PURPOSE: To study a dental adhesive system containing a self-etching primer, by evaluating the enamel shear bond strengths and comparing the SEM interfacial morphology. MATERIALS AND METHODS: 100 flat enamel bonding sites were prepared to 600-grit on proximal surfaces of caries-free human molars. The bonding surfaces were treated with Clearfil Liner Bond 2 as recommended by the manufacturer, or combined with various acidic etchants. A composite rod (Clearfil Photo Anterior) was applied to the bonding area in two increments in a Teflon mold and polymerized for 100 s. After 24 h of water storage, the specimens were thermocycled and the shear bond strengths measured using an Instron testing machine. Forty extra molar crowns were roughened and treated with Clearfil Liner Bond 2 and alternative etchants, as described. A low-viscosity resin was bonded to the occlusal surfaces of these crowns, which were further demineralized and deproteinized. Field-Emission SEM examinations were carried out to evaluate the effects of different treatments on enamel surfaces. RESULTS: The mean shear bond strengths were in the range of 18.1 MPa to 25.9 MPa, without significant differences between pairs of means. The failures were predominantly of the adhesive type. The use of alternative etchants resulted in the deepest etching patterns. The use of Clearfil Liner Bond 2, according to manufacturer's directions, resulted in a poorly-defined etching pattern. Regardless of the alternative etchant used, the use of the self-etching primer did not affect the mean enamel shear bond strength.

Acid Etching, Dental↗