Safety and Feasibility of a Novel Dosing Regimen of Tirofiban Administered in Patients with Acute Myocardial Infarction with ST Elevation Before Primary Coronary Angioplasty: A Pilot Study

BACKGROUND: Intravenous glycoprotein GP IIb/IIIa receptor antagonists administered to patients with acute coronary syndromes limit platelet-dependent thrombus formation and vasoconstriction and lower the complication rate of PCI. The efficacy of glycoprotein IIb/IIIa inhibitors critically depends on appropriate suppression of platelet aggregation. A growing body of evidence indicates that regimen of tirofiban used in several recent trials may be suboptimal. We investigated if a novel regimen of dosage of tirofiban administered to patients with acute myocardial infarction with ST elevation (STEMI) before primary angioplasty is safe, feasible and whether such treatment improves coronary flow in infarct-related artery. METHODS: It was an open-label, non-randomized, prospective observational study. 253 consecutive patients with STEMI, qualified to PCI were included. 104 of patients (group 1) received heparin plus tirofiban at a novel regimen (10 microg/kg bolus, followed by 0.4 microg/kg/min for 30 min and then 0.1 microg/kg/min for 12-24 hours) and the remaining 149 of the patients (group 2) received a standard dose of heparin prior to PCI. Bleeding complications were recorded. The primary end point of the study was combined TIMI 1 + 2 + 3 grade flow at the time of first contrast medium injection during angiography for primary PCI. RESULTS: Heparin was administered 50.3 +/- 58.1 minutes (group 1) or 62.3 +/- 67.3 minutes (group 2) ( p = 0.205). Tirofiban was administered for an average of 14.5 +/- 14.4 minutes before TIMI assessment (group 1). In patients treated with heparin + tirofiban the rate of combined TIMI 1 + 2 + 3 coronary flow was higher (38.4% vs. 24.8%, p = 0.020) as compared to patients treated with heparin alone. The difference in the rate of TIMI > or = 2 coronary blood flow between the groups 1 and 2 (24.0% vs. 20.1%) has not reached statistical significance ( p = 0.459). At the same time the significant difference in the rate of TIMI 1 coronary blood flow between the groups 1 and 2 was noted (14.4 vs. 4.7%, p = 0.007). In hospital mortality in the groups 1 and 2 was similar (5.3 vs. 4.8%, p = 0.838). Significant difference was noted between the groups 1 and 2 with regard to minor bleeding complications (17.3 vs. 8.7%, p = 0.041). CONCLUSION: In patients undergoing primary angioplasty for acute myocardial infarction the novel regimen of tirofiban is well tolerated and feasible, and is associated with improvement in coronary blood flow in the infarct related artery. Larger studies assessing the effects of tirofiban on clinical outcomes of patients with AMI undergoing primary angioplasty seem worthwhile.     

Effects of old age on vascular complexity and dispersion of the hepatic sinusoidal network

OBJECTIVES: In old age, there are marked changes in both the structure of the liver sinusoidal endothelial cell and liver perfusion. The objective of this study was to determine whether there are also aging changes in the microvascular architecture and vascular dispersion of the liver that might influence liver function. METHODS: Vascular corrosion casts and light micrographs of young (4 months) and old (24 months) rat livers were compared. Fractal and Fourier analyses and micro-computed tomography were used. Vascular dispersion was determined from the dispersion number for sucrose and 100-nm microspheres in impulse response experiments. RESULTS: Age did not affect sinusoidal dimensions, sinusoidal density, or dispersion number. There were changes in the geometry and complexity of the sinusoidal network as determined by fractal dimension and degree of anisotropy. CONCLUSIONS: There are small, age-related changes in the architecture of the liver sinusoidal network, which may influence hepatic function and reflect broader aging changes in the microcirculation. However, sinusoidal dimensions and hepatic vascular dispersion are not markedly influenced by old age.     

Intergenerational breastfeeding practices among parents and children: 1993 Pelotas (Brazil) birth cohort

The objective of this study was to investigate intergenerational breastfeeding practices according to parental sex and age at delivery in the 1993 Pelotas (Brazil) birth cohort study. This is a prospective birth cohort study, and at the 22‐year follow‐up, a substudy with all children of the cohort members who had become parents was conducted (93Cohort‐II). First generation breastfeeding data were collected at 3 months and 4‐year‐old follow‐ups. In the 93Cohort‐II, parents answered a questionnaire about their children's breastfeeding practices. Adjusted Tobit and Poisson regression models with robust variance were applied to estimate the association between predominant parental breastfeeding duration and exclusive breastfeeding duration of the children at 3 and 6 months. Out of 3,810 cohort participants, 955 (25%) had delivered at least one live‐born infant, and 1,222 children were assessed. Fifty‐four percent of parents were ≤19 years old. Direct effects of predominant parental breastfeeding duration on exclusive breastfeeding duration of their children were only observed when data were stratified by parental age: children born to parents aged ≥20 years old and who were predominantly breastfed for at least 3 months presented higher exclusive breastfeeding duration and higher prevalence of being exclusively breastfed for at least 3 months. When analyses were stratified by mothers and fathers, the result remained significant only among mothers. Longer predominant breastfeeding duration in the first generation was associated with longer exclusive breastfeeding duration in the second generation, but only among older mothers. Education and social support surrounding breastfeeding should be intensified among fathers and younger parents to create a positive environment supportive of breastfeeding.     

Bone mineral density and hip structural analysis in type 1 diabetic men

OBJECTIVE: The risk of non-vertebral fractures is increased in men with type 1 diabetes (DM1) but studies have shown only moderately decreased or normal bone mineral density (BMD) in these patients. No previous studies have evaluated hip strength and geometry indices in DM1 patients. This study was therefore designed to characterize associations between BMD, dual X-ray absorptiometry (DXA)-based hip strength indices, metabolic control, and DM1chronic complications. DESIGN AND METHODS: The study was performed on 36 males aged 43.6 +/- 5.1 years with long-lasting DM1 and 36 healthy males matched for age, weight, and height. BMD in lumbar spine, total hip, upper and lower part of the femoral neck, hip axis length, cross-sectional area and moment of inertia (CSMI), and glycated hemoglobin (HbA1c) were measured. RESULTS: DM1 men had decreased spine BMD (P < 0.05) and normal total hip BMD in comparison with controls. Hip geometry and strength indices were comparable in both groups. However, M1 men had decreased CSMI and upper femur BMD but these differences did not reach statistical significance (P = 0.06). BMD changes and hip strength parameters did not correlate with HbA1c. CONCLUSIONS: Middle-aged DM1 men have decreased lumbar spine BMD, normal hip BMD and normal hip strength indices. These changes are not influenced by metabolic control and presence of chronic microvascular complications.     

High cholesterol dietary intake during pregnancy is associated with large for gestational age in a sample of low‐income women of Rio de Janeiro,Brazil

The association between the quality of maternal dietary fat intake during pregnancy and the infant's birthweight (BW) remains controversial. Our goal was to investigate the association between maternal dietary fat intake during pregnancy and the rate of large for gestational age (LGA) newborns. This study employed a cross‐sectional analysis of 297 pairs of mothers/children attending a public maternity at Rio de Janeiro, Brazil. BW for gestational age according to the Intergrowth 21st was defined as follows: adequate for gestational age (AGA ≤ 90th percentile) and LGA (>90th percentile). The statistical analysis was a Poisson regression with robust estimations of the standard errors. Maternal dietary fat intake variables comprised lipids (% total energy); saturated (mg/1000 kcal), monounsaturated (mg/1000 kcal) and polyunsaturated (mg/1000 kcal) fats; and cholesterol (mg/1000 kcal), all of which were obtained with a Food Frequency Questionnaire. The mean BW was 3338 g (SD = 446.9), and the rate of LGA newborns was 13.1%. The mean maternal total energy intake was 2880 kcal (SD = 1074), cholesterol was 154.3 mg/1000 kcal (SD = 68.1) and monounsaturated fat was 6.9 mg/1000 kcal (SD = 2). Mothers of LGA newborns reported higher cholesterol dietary intake (195.8 vs. 148 mg/1000 kcal; P < 0.001), pre‐pregnancy body mass index (25.1 vs. 23.5 kg/m²; P = 0.026) when compared with mothers of AGA newborns. Women with cholesterol intake within the fourth quartile were 2.48 (95% confidence interval: 1.31–4.66) times more likely to have an LGA infant compared with those in the 1–3 quartiles. Dietary intake of cholesterol during pregnancy influences LGA even after adjusting for other confounders.     

Value of the real-time myocardial contrast echocardiography for risk stratification and for the detection of significant coronary stenosis in patients with end-stage renal disease.

Sir, Coronary artery disease (CAD) is common in patients with end-stagerenal disease (ESRD), and is associated with poor clinical outcome.However, routine screening for CAD in asymptomatic ESRD patientsis usually not required, except for renal transplant candidates[1]. Myocardial contrast echocardiography (MCE) is a new bedsidetechnique providing information regarding myocardial tissueperfusion. The assumption that MCE might be useful in patientswith ESRD has not been previously investigated. Moreover, thereare no published data concerning prognostic utility of MCE inpatients with ESRD. The aim of the study was to assess the prognostic significanceof MCE in patients with ESRD, and to     

Esophageal prothesis for neoplastic stenosis. A prognostic study of 77 cases

Esophageal prothesis (EP) is a palliative treatment for inoperable neoplastic stenosis. Ninety-one patients were candidates for EP placement between 1978 and 1983. EP placement was successful in 77 patients. Of these: 85% had primary esophageal cancer; 15% had bronchial or mediastinal carcinoma; 83% had stenosis in the middle third. Dysphagia was the main symptom in 84%, and tracheoesophageal fistulae in 16%. The observed median survival was 3.2 months +/- 1.9 (2 standard deviations [SD]), and the survival rate at 1 year was 7%. With the single-factor analysis method, not one of 12 factors presented any significance (age, sex, general status, anterior treatment, lesion site, endoscopic feature, stenosis diameter, histologic features, metastasis, tracheal involvement, symptoms, and type of prothesis). Two factors had a P value approaching significance: there were slightly longer survival rates in patients with a stenosis diameter less than 7 mm (P less than 0.07), and with stenosis located in the lower third and cardia (P less than 0.07). By multivariate analysis (Cox model), prognostic significance was found in only one factor: the location in the lower third and cardia (P = 0.002, relative risk = 3). The quality of life after EP placement was briefly improved: 80% of 73 evaluable patients had improvement in dysphagia for a mean duration of 3.7 months +/- 2 (2 SD), especially patients with a good general status (0 and 1; P less than 0.01); and 45% of patients had improvement of their general status for a mean duration of 4.1 months +/- 2 (2 SD). Minor complications related to EP placement were observed in 40% of patients (pain, obstruction, and mobilization), and severe complications were observed in 20% (perforation, 11 cases; fistulae, 5 cases, with death in 3 cases; hemorrhages, 4 cases). In conclusion, EP is a good palliative treatment, although complications are frequent, and evaluation of patient comfort is required to compare this procedure with other available techniques.     

Determinants of postpartum weight retention according to skin color among women in Rio de Janeiro, Brazil]

OBJECTIVE: To investigate factors associated with postpartum weight retention according to skin color in the city of Rio de Janeiro, Brazil, as part of the effort to help control overweight and obesity. METHODS: We carried out a cohort study with data collection at four points after delivery: 15 days, 2 months, 6 months, and 9 months. The 450 participants (15 to 45 years of age) were recruited from a maternity center and a city health center in Rio de Janeiro. Postpartum weight retention was defined as the dependent variable. The following covariates were investigated: maternal age, marital status, ability to read a letter, smoking, monthly family income, number of children, age at first delivery, a score for physical activity at work, and a score for physical activity during leisure time. The data were analyzed using multivariate linear mixed-effects models for longitudinal data. RESULTS: The factors that remained associated with postpartum weight retention for white women were time after delivery (beta = -0.0061, P = 0.0002), marital status (married/single beta = -0.9279, P = 0.0457), and age at first delivery (beta = -0.1553, P = 0.0364). The factors for brown women were time after delivery (beta = -0.0062, P < 0.0001), marital status (married/single beta = -0.6000, P = 0.0145), and work physical activity score (beta = -0.1068, P = 0.0003). The factors for black women were smoking (beta = -1.4635, P = 0.0535) and score for physical activity during leisure time (beta = -0.2422, P = 0.0145). CONCLUSIONS: The factors associated with postpartum weight retention were different for the three skin-color categories. Nevertheless, the data do not indicate the need for different interventions for the three skin-color groups. That is particularly true because the physical activity scores were among the variables associated with weight retention, and any initiative to control obesity should take physical activity into consideration. On the other hand, given the socioeconomic differences among the three skin-color categories, new studies should be developed to investigate in more detail the pattern of postpartum weight retention according to skin color.     

Anxiety during pregnancy, prematurity, and low birth weight: a systematic literature review

The purpose of this systematic literature review was to examine publications that had investigated the effect of anxiety on prematurity and/or low birth weight. The PubMed, BVS, CINAHL, and HEALTHSTAR databases, published from 1966 to 2006, were tracked using the following key words: "anxiety", "pregnancy", "low birth weight", and "prematurity". Thirteen studies were found: 11 cohorts, 1 cross-sectional, and 1 case-control. Most studies (7/13) were conducted in the United States. The most reliable results came from four studies, whose strengths were: exclusion of adolescents and/or women older than 34 years, studies that analyzed anxiety during the second and/or third trimester of pregnancy, used validated scales to measure anxiety, kept loss-to-follow-up rates below 30%, and applied adequate control of confounders. Anxiety during pregnancy was associated with prematurity and/or low birth weight in eight studies. Odds ratios and relative risks varied from 1.08 to 2.31. Carefully designed and well-conducted studies are still needed to clarify the relationship between anxiety during pregnancy, prematurity, and low birth weight considering that the accumulated evidence remains controversial.     

Urgent states in hematology: acute promyelocytic leukemia--principles of diagnosis

A review of diagnosis of acute promyelocytic leukemia (APL) is presented. There are still many patients with progressive disease with leukocytosis at presentation. These are at greater risk of early death due to bleeding (often intracranial), or, less frequently, due to thrombotic complications. In Czechia, we have, in some instances, noted an unacceptably long time from the first symptoms to diagnosis and to administration of the highly specific differentiation therapy with tretinoin (ATRA) along with anthracycline chemotherapy. This combination is highly efficient--cures are seen in some 70% of patients. Therefore, we present a diagnostic minimum for each and every internist, and even better for every general practician, to get acquainted with. All cases of pancytopenia and consumption coagulopathy should be suspected of APL and referred to a specialized hematologist without any delay. In the following more detailed review of diagnostic measures, much attention is given to APL morphology, which is the first clue leading to diagnosis. The finding of the typical hypergranular FAB M3 morphology and of cells with bundles of Auer rods ("faggot cells"), along with the HLA-DR, CD33+ immunophenotype, is highly (but not absolutely) specific for APL. In cases of the micro-/hypo-granular variant FAB M3v Form, and whenever APL cannot be ruled out with certainty, a test to prove the presence of the PML/RARalpha fusion gene is indicated, using either RT-PCR or, eventually, immunological demonstration of the specific distribution of the PML protein in the cell nucleus. Given that morphology of APL cases, as defined according to WHO criteria (95% of which carry the PML/RARalpha fusion gene), admits extremely divergent morphological pictures ofthe variant forms, we recommend these investigations to be performed in every case of de novo acute myeloid leukemia. A review of the less frequent morphological, as well as genetic variants is given, and the principles of immunophenotypic, cytogenetic and molecular diagnostics are also reviewed.