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M T Santos

Publications and source records attributed to M T Santos.

At least 19 recordsLinked to original sources
PubMed2004

Trends in paediatric health economic evaluation: 1980 to 1999.

BACKGROUND: Although standard methods for conducting economic evaluations have evolved, little attention has been paid to their application in paediatrics. The Paediatric Economic Database Evaluation (PEDE) Project was conceived to promote research into paediatric health economic methods. AIM: To examine trends in paediatric economic evaluation between 1980 and 1999. METHODS: A comprehensive literature database created for the PEDE project was the source of the data. Descriptive statistics were used to summarise trends. Publication volume, study outcome category, analytical technique, and journal type were examined over the study period. RESULTS: The literature search resulted in 787 full paediatric economic evaluations. The volume of publications increased from 61 to 440 citations per 5 year period. The most common health outcome category was cases of disease/condition/abnormality. Cost-effectiveness analysis (CEA) was the most common technique used, accounting for a majority of evaluations in all time periods. The proportion of studies using CEA increased by 23 percentage points, while the proportion using cost-benefit analysis decreased from 31% in 1980-84 to 12% in 1995-99. Cost-utility analysis was the least common analytical technique. Publication in journals of paediatrics/perinatal medicine was the most common venue for all intervals and increased as a proportion of the total over time. CONCLUSIONS: The growth in publication of paediatric economic evaluations suggests that increasing attention should be paid to the application of health economic methods to a paediatric population to ensure high quality allocation decisions.

Child↗
PubMed2002

Solanum paniculatum L. (Jurubeba): potent inhibitor of gastric acid secretion in mice.

Solanum paniculatum L. is used commonly in Brazilian folk medicine for the treatment of liver and gastrointestinal disorders. The freeze-dried aqueous extracts (WEs) obtained from distinct parts of the plant (flowers, fruits, leaves, stems and roots) were tested to determine their antiulcer and antisecretory gastric acid activities using mice. The aqueous extracts of roots, stems and flowers inhibited gastric acid secretion in pylorus-ligated mice with ED50 values of 418, 777 and 820 mg/kg body wt. (i.d.), respectively. Extracts of leaves (0.5-2 g/kg body wt., i.d.) did not affect gastric secretion, whereas fruit extracts (0.5-2 g/kg body wt., i.d.) stimulated gastric acid secretion. The stimulatory effect of the fruit extract was inhibited by pretreatment with atropine (5 mg/kg body wt., i.m.) but not with ranitidine (80 mg/kg body wt., i.p.) suggesting that the fruit extract activates the muscarinic pathway of gastric acid secretion. In contrast, administration of the root extract into the duodenal lumen inhibited histamine- and bethanechol-induced gastric secretion in pylorus-ligated mice. In addition, the aqueous extract of roots (ED50 value, 1.2 g/kg body wt., p.o.) protected the animals against production of gastric lesions subsequent to the hypersecretion induced in mice by stress following cold restraint. This effect was not reproduced when the lesions were induced by blockade of prostaglandins synthesis via subcutaneous injection of indomethacin. Thus, antiulcer activity of the plant extracts appears to be related directly to a potent anti-secretory activity. No toxic signs were observed following administration of different extracts up to 2 g/kg body wt., p.o. Collectively, the results validate folk use of Solanum paniculatum L. plant to treat gastric disorders.

Animals↗
PubMed2001

Patterns of haplotype diversity within the serpin gene cluster at 14q32.1: insights into the natural history of the alpha1-antitrypsin polymorphism.

The levels of haplotype diversity associated with different alpha1-antitrypsin (PI) alleles were assessed by the analysis of three microsatellites located within or close to corticosteroid-binding globulin (CBG), alpha1-antitrypsin [PI-(TG)n] and protein C inhibitor [PCI-(TG)n] loci in three populations with different historic backgrounds: Portugal, the Basque Country and São Tomé Príncipe (Gulf of Guinea). Unlike the more distant PCI-(TG)n repeat, allelic variation at PI-(TG)n reflected distinct phases of mutational recovery of microsatellite diversity around different founder alleles and showed a considerable differentiation between alpha1-antitrypsin protein variants. In accordance with population history, the Basque sample presented overall reduced levels of microsatellite variation. The African sample, although presenting the highest PCI-(TG)n diversity, showed a lineage-specific reduction in PI-(TG)n heterozygosity within the oldest M1Ala213 variant that could have been caused by (1) selection at a closely linked locus or (2) biases in the microsatellite mutation process leading to a stable equilibrium distribution. Age estimates of alpha1-antitrypsin variants based on microsatellite variation suggest that the Z deficiency allele appeared 107-135 generations ago and could have been spread in Neolithic times. The S mutation has an older 279- to 470-generation age, indicating that its high frequencies in Iberia did not result from a recent bottleneck and that PI*S could have originated in this region. M2 and M3 types had lower age estimates than would be expected from their wide geographical distributions, suggesting that their dispersion in Europe might have been preceded by important bottlenecks.

Alleles↗
PubMed2001

Naso-ethmoid schwannoma with intracranial extension: case report.

Intranasal schwannomas are rare lesions, specially when they present with an intracranial extension. The fifth case in the medical literature of a naso-ethmoid schwannoma with extension into the anterior cranial fossa is presented. The magnetic resonance findings and the details of the combined intracranial / transfacial operative approach used are described. The possible origin and the clinical characteristics of this rare lesion are reviewed.

Adult↗
PubMed2000

Participation of tyrosine phosphorylation in cytoskeletal reorganization, alpha(IIb)beta(3) integrin receptor activation, and aspirin-insensitive mechanisms of thrombin-stimulated human platelets.

BACKGROUND: Fibrinogen binding to the active conformation of the alpha(IIb)beta(3) integrin receptor (glycoprotein IIb/IIIa) and cytoskeletal reorganization are important events in platelet function. Tyrosine phosphorylation of platelet proteins plays an essential role in platelet signal transduction pathways. We studied the participation of tyrosine kinases on these aspects of platelet reactivity and their importance in cyclooxygenase (COX)-1-independent mechanisms in thrombin-stimulated human platelets. METHODS AND RESULTS: Using washed platelets from normal donors and tyrphostin-A47 and aspirin as tyrosine kinase and COX-1 inhibitors, respectively, we found that tyrphostin-A47 downregulated (1) the thrombin-activated conformational change of alpha(IIb)beta(3), (2) actin polymerization and cytoskeletal reorganization, and (3) the quantity of tyrosine-phospho-rylated proteins associated with the reorganized cytoskeleton. The latter are important components of multimolecular signaling complexes. Concomitantly, platelet aggregation and secretion were significantly reduced. Aspirin did not affect receptor activation or tyrosine phosphorylation but did decrease the initial (30-second) burst of actin polymerization. Importantly, aspirin significantly amplified the inhibitory effect of tyrphostin-A47 on all aspects of platelet reactivity that we evaluated. CONCLUSIONS: Tyrosine protein phosphorylation is a regulatory control system of the inside-out mechanism of alpha(IIb)beta(3) activation and cytoskeletal assembly in thrombin-stimulated human platelets. Inhibition of these aspects of platelet function with tyrphostin-A47 is amplified when platelets are treated with aspirin. Therefore, tyrosine phosphorylation is a major component of early signaling events and of COX-1-independent mechanisms of thrombin-induced platelet reactivity. The study results may indicate a novel target for therapeutic intervention.

Aspirin↗
PubMed1999

Attenuated severity of new acute ischemic events in patients with previous coronary heart disease receiving long-acting nitrates.

BACKGROUND: Platelet aggregation and secondary vasoconstriction are key events in the genesis of acute coronary syndromes. HYPOTHESIS: Since nitrates have vasodilatory and antiaggregant effects, treatment with long-acting nitrates at the time of onset of acute coronary syndromes could be associated with attenuation of their severity. METHODS: A consecutive series of 533 patients with acute coronary syndrome and past history of coronary artery disease admitted to the Cardiology Service of a general hospital was studied. A specific questionnaire assessed the use of nitrates and other relevant drugs, as well as other clinical variables. The diagnosis of unstable angina or acute myocardial infarction (MI) was established according to clinical, electrocardiographic, and enzymatic criteria. RESULTS: In the whole cohort, 169 patients had MI and 364 had unstable angina. Previous use of long-acting nitrates was significantly more common in patients with unstable angina (56%) than in those with MI (37%) (p < 0.0001). Multivariate analysis identified being a nonsmoker [odds ratio: 95%, confidence limits (CL) 0.37, 0.23-0.59], previous unstable angina (CL 0.62, 0.41-0.92), use of aspirin (CL 0.58, 0.41-0.92), and use of long-acting nitrates (CL 0.61, 0.40-0.93) as the independent predictors of the development of unstable angina rather than MI; of these the combination of nitrates and aspirin was the strongest predictor. CONCLUSIONS: Long-acting nitrates as well as aspirin are suggested to have a protective or modifying effect on the development of acute coronary syndromes, favoring unstable angina rather than acute MI.

Adrenergic beta-Antagonists↗
PubMed1999

Validation of the Agency for Health Care Policy and Research (AHCPR) classification for managing unstable angina.

To validate the AHCPR classification for the prognosis of unstable angina, 225 consecutive patients were recruited with a suspected diagnosis of that condition attending a tertiary hospital from November 1994 through April 1995 and followed for one year. One-hundred fifty-six (69.3%) patients were considered at high risk, 37 (16.5%) at intermediate, and 32 (14.2%) at low risk of cardiac complications. All of the patients with major in-hospital cardiac complications (8 patients) had at least one of the features of the high risk group. The high to intermediate-low hazard ratio (HR) for one-year cardiac complications after the onset of unstable angina was 4.03. Predictors of major complications (myocardial infarction or death) after the follow-up were age > 65 (HR, 5.69); diabetes (HR, 4.94); heart failure (HR, 2.65); and prolonged angina (HR, 2.55). AHCPR classification correctly identified patients with risk of severe outcomes at the hospital. Also, the classification predicted outcomes one year after hospitalization, diabetes being an important determinant of adverse cardiac events.

Aged↗
PubMed1998

Erythrocyte promotion of platelet reactivity decreases the effectiveness of aspirin as an antithrombotic therapeutic modality: the effect of low-dose aspirin is less than optimal in patients with vascular disease due to prothrombotic effects of erythrocytes on platelet reactivity.

BACKGROUND: Aspirin (acetylsalicylic acid, ASA) is widely used for secondary prevention of ischemic vascular events, although its protection only occurs in 25% of patients. We previously demonstrated that platelet reactivity is enhanced by a prothrombotic effect of erythrocytes in a thromboxane-independent manner. This diminishes the antithrombotic therapeutic potential of ASA. Recent data from our laboratory indicate that the prothrombotic effect of erythrocytes also contains an ASA-sensitive component. In accordance with this observation, intermittent treatment with high-dose ASA reduced the prothrombotic effects of erythrocytes ex vivo in healthy volunteers. In the present study, the effects of platelet-erythrocyte interactions were evaluated ex vivo in 82 patients with vascular disease: 62 patients with ischemic heart disease treated with 200 mg ASA/d and 20 patients with ischemic stroke treated with 300 mg ASA/d. METHODS AND RESULTS: Platelet activation (release reaction) and platelet recruitment (fluid-phase proaggregatory activity of cell-free releasates from activated platelets) were assessed after collagen stimulation (1 microg/mL) of platelets, platelet-erythrocyte mixtures, or whole blood. Platelet thromboxane A2 synthesis was inhibited by >94% by ASA administration in all patients. Importantly, platelet recruitment followed one of three distinct patterns. In group A (n=32; 39%), platelet recruitment was blocked by ASA both in the presence and absence of erythrocytes. In group B (n=37; 45%), recruitment was abolished when platelets were evaluated alone but continued in the presence of erythrocytes, indicating a suboptimal effect of ASA on erythrocytes of this patient group. In group C (n= 13; 16%), detectable recruitment in stimulated platelets alone persisted and was markedly enhanced by the presence of erythrocytes. CONCLUSIONS: In two thirds of a group of patients with vascular disease, 200 to 300 mg ASA was insufficient to block platelet reactivity in the presence of erythrocytes despite abolishing thromboxane A2 synthesis. Platelet activation in the presence of erythrocytes can induce the release reaction and generate biologically active products that recruit additional platelets into a developing thrombus. Insufficient blockade of this proaggregatory property of erythrocytes can lead to development of additional ischemic complications.

Adult↗
PubMed1998

[Patients with acute coronary syndrome: therapeutic approach (management patterns) and 1-year prognosis in a tertiary general hospital].

BACKGROUND: To assess the determinants of short-term and one-year prognosis of all patients with suspected acute coronary syndrome seen by the cardiologist on duty in the Emergency Service of a tertiary hospital during a six month period. PATIENTS AND METHODS: 153 consecutive patients with a diagnosis of acute myocardial infarction, 225 with a diagnosis of unstable angina and 89 with a diagnosis of atypical chest pain were identified and their in-hospital characteristics and one-year prognosis were prospectively assessed. RESULTS: Age was higher than 65 years in 53% of acute myocardial infarction and in 54% of unstable angina patients. Only 3 patients were lost to follow-up. 35% of acute myocardial infarction patients had died or had reinfarction after one year and 16% of unstable angina patients had died or had suffered acute myocardial infarction. Baseline features, management patterns and prognosis of patients admitted with acute myocardial infarction to the Cardiology Service, to other hospital areas or to other hospitals were markedly different, and admission in areas other than the Cardiology Service was an independent mortality predictor. In unstable angina, complications happened in patients older than 75 years, those with previous revascularization procedures, those undergoing revascularization or those with lesions not deemed revascularizeable. CONCLUSIONS: a) In the study population there was a predominance of elderly patients; the proportion of patients with poor prognosis was considerably high; b) a sizeable proportion of patients with severe complications was scarcely represented in the major clinical trials; c) the possibility arises of a distribution of care resources tending to concentrate the greater therapeutic efforts in the patients with good prognosis.

Acute Disease↗
PubMed1997

Prothrombotic effects of erythrocytes on platelet reactivity. Reduction by aspirin.

BACKGROUND: Aspirin effectively reduces the incidence of secondary vascular occlusive events in only 25% of patients. Low-dose aspirin as currently used blocks platelet production of prothrombotic thromboxane A2 and allows endothelial synthesis of antithrombotic prostacyclin. This regimen minimizes gastrointestinal toxicity. We previously showed that intact erythrocytes markedly enhance platelet reactivity. Therefore we investigated whether supplementation of low-dose aspirin with a single high dose at 2-week intervals could more effectively block erythrocyte promotion of platelet reactivity. METHODS AND RESULTS: Effects of different aspirin regimens on erythrocyte enhancement of platelet reactivity in normal volunteers were measured with the use of an assay that evaluates both platelet activation and recruitment. After 15 days of daily ingestion of 50 mg aspirin, reactivity of platelets alone was inhibited. However, erythrocyte promotion of platelet activation and recruitment was only inhibited by approximately 50% and persisted in the total absence of thromboxane synthesis. In contrast, if 50 mg/d aspirin was preceded by a single loading dose of 500 mg aspirin, the erythrocyte prothrombotic effect was strongly inhibited (approximately 90%) for 2 to 3 weeks. However, over time, erythrocytes "escaped" from this inhibition, and once again became prothrombotic, even on a daily regimen of 50 mg aspirin. CONCLUSIONS: For clinical purposes, we recommend a loading dose of aspirin (500 mg), followed by daily administration of 50 mg. The loading dose should be repeated at 2-week intervals. This regimen blocks recovery of the erythrocyte capacity to promote platelet reactivity and may amplify the therapeutic potential of aspirin in cardiovascular disease.

Adult↗
PubMed1997

Analysis of the allelic diversity of a (CA)n repeat polymorphism among alpha 1-antitrypsin gene products from northern Portugal.

The level of molecular heterogeneity associated with alpha 1-antitrypsin gene products was assessed in the population of northern Portugal using three restriction fragment length polymorphisms (RFLPs) corresponding to specific amino acid substitutions and a highly variable (CA)n repeat polymorphism located at the 5' end of the PI gene. The allelic affinities inferred from the analysis of the DNA polymorphisms essentially agree with the evolutionary pattern proposed for the PI gene products on the basis of their amino acid sequences. PI*Z can be considered the most recent common PI allele and was found to be associated with the same predominant haplotype previously reported in northern European populations, thus confirming the hypothesis that most European Z alleles are derived from a single mutation. However, a rare deficient variant that is the likely result of a recurrent Z mutation on an M2 or M4 background was additionally observed. PIS was also found to be associated with a strongly predominant haplotype and seems to be the second most recent PI common allele, while M2 and M3 show weaker associations, suggesting more ancient origins of their corresponding mutations. M1Ala213 and M1Vat213 display more homogeneous (CA)n allele frequency distributions, M1Ala213 representing the most ancient PI allele as inferred from its highest variance in (CA)n allele length.

Alleles↗
PubMed1997

Modulatory effect of erythrocytes on the platelet reactivity to collagen in IDDM patients.

Platelets participate in the atherothrombotic complications of diabetes. Recent data demonstrate that platelet reactivity can be modulated via cell-cell interactions with erythrocytes and neutrophils. In this study, platelet reactivity was evaluated in 30 IDDM patients. We used an analytical procedure that permits an independent evaluation of platelet activation (granule release, eicosanoid formation) and platelet recruitment (pro-aggregatory activity of cell-free releasates) after platelet stimulation with collagen in the presence or absence of other blood cells. The interaction between platelets and erythrocytes (hematocrit 40%) resulted in a marked enhancement of platelet activation (5HT, betaTG, TXA2 release) and recruitment in both patients and control subjects. The erythrocyte enhancement of platelet TXA2 synthesis and recruitment was significantly higher in the patients, while no differences were detected in platelet granule release. The elevated platelet recruitment in the IDDM patients was found to be due to 1) increased susceptibility of diabetic platelets to the prothrombotic effect of erythrocytes and 2) the greater response of diabetic platelets to their own cell-free releasate. Patients with poor metabolic control (elevated HbA1c) or longer evolution time had an even greater platelet recruitment. The presence of microalbuminuria is not related to the platelet recruitment. Since platelet recruitment is an essential step in thrombus growth, its enhancement may favor thrombotic complications in IDDM.

Adolescent↗
PubMed1996

Human cryptosporidiosis: detection of specific antibodies in the serum by an indirect immunofluorescence.

Cryptosporidium sp., a coccidian parasite usually found in the faeces of cattle, has been recently implicated as an agent of human intestinal disease, mainly in immunocompromised patients. In the study realized, by an indirect immunofluorescence technique, specific immunoglobulins (IgG and IgM) have been demonstrated in human serum against Cryptosporidium oocysts. Purified oocysts were used as antigens in the indirect immunofluorescence assay. After analyzing this test in sera from selected groups of patients, the frequency of both specific IgG and IgM of immunocompetent children who were excreting oocysts in their faeces was 62% and in children with negative excretion of oocytes was 20% and 40%, respectively. In adults infected with the human immunodeficiency virus (HIV) and who were excreting Cryptosporidium in their stools, the frequency was 57% for IgG but only 2% for IgM. Twenty three percent of immunocompromised adults with not determined excretion of oocysts in their stools had anti-Cryptosporidium IgG in their sera. Children infected with human immunodeficiency virus had no IgM and only 14% had IgG detectable in their sera. The indirect immunofluorescence assay, when used with other parasitological techniques appears to be useful for retrospective population studies and for diagnosis of acute infection. The humoral immune response of HIV positive patients to this protozoan agent needs clarification.

Adult↗
PubMed1995

[Review of the practice of care in a health unit: Experience developed in an integration project between school and service].

The paper shows a program concerning the review of the assistance practice in a Health Unit at the target region of the School-Service Integration Project between the College of Nursing at Ribeirão Preto/University of São Paulo and São Paulo city. The majority of the health workers took part in the program which was developed in 8 meetings where they analysed their own working practice and elaborated several proposals aiming at changing it. The greatest merit of this program was to allow the establishment of a collective and participative process of discussion and reflection.

Education, Nursing, Baccalaureate↗
PubMed1994

Distribution of ACP1, AK1 and ALAD polymorphisms in northern Portugal.

Red cell acid phosphatase (ACP1), adenylate kinase 1 (AK1), and aminolevulinate dehydratase (ALAD) polymorphisms were studied in a population sample from Northern Portugal. The gene frequency estimates found were: ACP1*A = 0.2825, ACP1*B = 0.6625, ACP1*C = 0.0547, ACP1*R = 0.0003 (N = 1517); AK1*1 = 0.9778, AK1*2 = 0.0213, AK1*3 = 0.0009 (N = 1081); ALAD*1 = 0.9094, ALAD*2 = 0.0906 (N = 1043).

Acid Phosphatase↗
PubMed1993

Effects of dipyridamole, pentoxifylline or dipyridamole plus pentoxifylline on platelet reactivity in patients with ischemic cerebrovascular insufficiency.

Platelet activation and the subsequent platelet recruitment induced by activated platelets released products constitute the initial events of platelet thrombus formation. We have evaluated the recruiting activity of collagen-stimulated whole blood in patients with ischemic cerebrovascular insufficiency. This was done using an experimental approach that allows independent evaluation of platelet activation and recruitment. The effects of of treating the patients with dipyridamole (DIP) (300 mg/day), pentoxifylline (POX) (1200 mg/day) or a combination of the two drugs at the same doses was also evaluated before and after 7, 15, and 45 days of treatment. DIP decreased the recruiting activity in a time-dependent manner, while POX did not show any effect. However, the combined treatment with DIP+POX was more effective than DIP alone in reducing platelet recruitment, which was abolished after 45 days of treatment. Studies using the drugs in vitro indicated a greater inhibitory activity of the drug association than either drug individually. The effects of the drug association in vitro, even at high concentrations, was lower than those observed ex vivo after 45 days of treatment. This suggests that DIP+POX in vivo may have effects that condition a reduced platelet response.

Aged↗