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Biomedical subjects

Joseph Massaro

Publications and source records attributed to Joseph Massaro.

12 recordsLinked to original sources
PubMed2006

Autoantibodies to oxidized LDL and cardiovascular risk: the Framingham Offspring Study.

BACKGROUND: The relation between measures of oxidation of lipid particles and cardiovascular disease has not been extensively investigated prospectively on a population basis. METHODS: A community cohort of 1192 men and 1427 women with measures of IgG antibodies to oxidized LDL were followed 8 years for the development of initial coronary heart disease (CHD) and cardiovascular disease (CVD) events. RESULTS: Levels of IgG autoantibodies to a form of oxidized LDL were significantly associated with age in both sexes, positively with fibrinogen in men and negatively with HDL cholesterol in women. In sex-specific models that adjusted for age alone or those that adjusted for age, cholesterol, HDL cholesterol, smoking, and diabetes mellitus, there was no relation between level of antibodies to oxidized LDL and the development of CHD or CVD. CONCLUSION: Autoantibodies to oxidized LDL were strongly related to age and were not related to incident CHD or CVD over 8 years of follow up.

Adult↗
PubMed2005

Relation of the prothrombotic state to increasing age (from the Framingham Offspring Study).

A greater life expectancy has led to an increasing proportion of elderly patients. Increasing age is an important risk factor for cardiovascular disease, but the mechanism of risk is not well understood. Because thrombosis plays a key role in plaque development and the onset of acute coronary syndromes, the age-related increase in cardiovascular risk may be a result of a prothrombotic imbalance. The study aim was to examine the relation between age and thrombotic potential in the Framingham Offspring Cohort. Hemostatic factors previously associated with cardiovascular risk were measured in 3,230 patients (55% women) without evidence of cardiovascular disease who were participating in cycle 5 of the Framingham Offspring Study. The subjects were divided by age into decades. Advancing age was associated with a significant increase in fibrinogen and von Willebrand factor levels and measures of impaired fibrinolytic potential (plasminogen activator inhibitor and tissue plasminogen activator antigens). For men, the mean fibrinogen levels were 21% higher in those > or =70 years versus those aged <40 years (326 vs 268 mg/dl, p <0.001 for linear trend). The mean fibrinogen levels were 15% higher in older than in younger women (330 vs 286 mg/dl, p <0.001). The significant relations persisted after multivariate adjustment. In conclusion, advancing age is associated with elevated levels of hemostatic factors indicative of a prothrombotic state. Because these factors are also associated with endothelial dysfunction, these findings are consistent with an injurious effect of age on the endothelium. Measures to reduce thrombotic potential may be of particular value in the elderly, because they counter the prothrombotic state that develops with aging.

Adult↗
PubMed2005

Design of a registry to characterize "real-world" outcomes of percutaneous coronary revascularization in the drug-eluting stent era.

BACKGROUND: Clinical trials have shown drug-eluting stents (DES) to be superior to bare metal stents (BMS) in preventing in-stent restenosis and target vessel revascularization. Although these results have ushered in a sea change in the practice of myocardial revascularization, important questions remain unanswered concerning rates of ischemic complications when DES are used in a broader population not represented in the clinical trials. STUDY DESIGN: The EVENT registry will include 7500 to 10,000 patients enrolled at approximately 60 sites across the United States. The intent of the registry is to characterize a population of consecutive patients undergoing percutaneous coronary intervention with stent deployment using BMS and DES in terms of processes and outcomes of care. A unique aspect of EVENT is the prospective assessment of rates of periprocedural myocardial infarction among all patients. These data will allow us to compare rates of periprocedural myocardial infarction and other ischemic complications between patients receiving DES and BMS. In addition, the EVENT registry will characterize temporal changes in the patterns of DES use and the relationship between any such changes and both short- and long-term outcomes.

Angioplasty, Balloon, Coronary↗
PubMed2005

Measures of brain morphology and infarction in the framingham heart study: establishing what is normal.

Numerous anatomical and brain imaging studies find substantial differences in brain structure between men and women across the span of human aging. The ability to extend the results of many of these studies to the general population is limited, however, due to the generally small sample size and restrictive health criteria of these studies. Moreover, little attention has been paid to the possible impact of brain infarction on age-related differences in regional brain volumes. Given the current lack of normative data on gender and aging related differences in regional brain morphology, particularly with regard to the impact of brain infarctions, we chose to quantify brain MRIs from more than 2200 male and female participants of the Framingham Heart Study who ranged in age from 34 to 97 years. We believe that MRI analysis of the Framingham Heart Study more closely represents the general population enabling more accurate estimates of regional brain changes that occur as the consequence of normal aging. As predicted, men had significantly larger brain volumes than women, but these differences were generally not significant after correcting for gender related differences in head size. Age explained approximately 50% of total cerebral brain volume differences, but age-related differences were generally small prior to age 50, declining substantially thereafter. Frontal lobe volumes showed the greatest decline with age (approximately 12%), whereas smaller differences were found for the temporal lobes (approximately 9%). Age-related differences in occipital and parietal lobe were modest. Age-related gender differences were generally small, except for the frontal lobe where men had significantly smaller lobar brain volumes throughout the age range studied. The prevalence of MRI infarction was common after age 50, increased linearly with age and was associated with significantly larger white matter hyperintensity (WMH) volumes beyond that associated with age-related differences in these measures. Amongst men, the presence of MRI infarction was associated with significant age-related reductions in total brain volume. Finally, statistically significant associations were found between the volume of MRI infarcts in cubic centimeters and all brain measures with the exception of parietal lobe volume for individuals where the volume of MRI infarctions was measured. These data serve to define age and gender differences in brain morphology for the Framingham Heart Study. To the degree participants of the Framingham Heart Study are representative the general population, these data can serve as norms for comparison with morphological brain changes associated with aging and disease. In this regard, these cross-sectional quantitative estimates suggest that age-related tissue loss differs quantitatively and qualitatively across brain regions with only minor differences between men and women. In addition, MRI evidence of cerebrovascular disease is common to the aging process and associated with smaller regional brain volumes for a given age, particularly for men. We believe quantitative MRI studies of the Framingham community enables exploration of numerous issues ranging from understanding normal neurobiology of brain aging to assessing the impact of various health factors, particularly those related to cerebrovascular disease, that appear important to maintaining brain health for the general population.

Adult↗
PubMed2005

A multicenter, randomized, masked, comparison trial of lucinactant, colfosceril palmitate, and beractant for the prevention of respiratory distress syndrome among very preterm infants.

BACKGROUND AND OBJECTIVE: Evidence suggests that synthetic surfactants consisting solely of phospholipids can be improved through the addition of peptides, such as sinapultide, that mimic the action of human surfactant protein-B (SP-B). A synthetic surfactant containing a mimic of SP-B may also reduce the potential risks associated with the use of animal-derived products. Our objective was to compare the efficacy and safety of a novel synthetic surfactant containing a functional SP-B mimic (lucinactant; Discovery Laboratories, Doylestown, PA) with those of a non-protein-containing synthetic surfactant (colfosceril palmitate; GlaxoSmithKline, Brentford, United Kingdom) and a bovine-derived surfactant (beractant; Abbott Laboratories, Abbott Park, IL) in the prevention of neonatal respiratory distress syndrome (RDS) and RDS-related death. METHODS: We assigned randomly (double-masked) 1294 very preterm infants, weighing 600 to 1250 g and of < or =32 weeks gestational age, to receive colfosceril palmitate (n = 509), lucinactant (n = 527), or beractant (n = 258) within 20 to 30 minutes after birth. Primary outcome measures were the rates of RDS at 24 hours and the rates of death related to RDS during the first 14 days after birth. All-cause mortality rates, bronchopulmonary dysplasia (BPD) rates, and rates of other complications of prematurity were prespecified secondary outcomes. Primary outcomes, air leaks, and causes of death were assigned by an independent, masked, adjudication committee with prespecified definitions. The study was monitored by an independent data safety monitoring board. RESULTS: Lucinactant reduced significantly the incidence of RDS at 24 hours, compared with colfosceril (39.1% vs 47.2%; odds ratio [OR]: 0.68; 95% confidence interval [CI]: 0.52-0.89). There was no significant difference in comparison with beractant (33.3%). However, lucinactant reduced significantly RDS-related mortality rates by 14 days of life, compared with both colfosceril (4.7% vs 9.4%; OR: 0.43; 95% CI: 0.25-0.73) and beractant (10.5%; OR: 0.35; 95% CI: 0.18-0.66). In addition, BPD at 36 weeks postmenstrual age was significantly less common with lucinactant than with colfosceril (40.2% vs 45.0%; OR: 0.75; 95% CI: 0.56-0.99), and the all-cause mortality rate at 36 weeks postmenstrual age was lower with lucinactant than with beractant (21% vs 26%; OR: 0.67; 95% CI: 0.45-1.00). CONCLUSIONS: Lucinactant is a more effective surfactant preparation than colfosceril palmitate for the prevention of RDS. In addition, lucinactant reduces the incidence of BPD, compared with colfosceril palmitate, and decreases RDS-related mortality rates, compared with beractant. Therefore, we conclude that lucinactant, the first of a new class of surfactants containing a functional protein analog of SP-B, is an effective therapeutic option for preterm infants at risk for RDS.

1,2-Dipalmitoylphosphatidylcholine↗
PubMed2005

A multicenter, randomized, controlled trial of lucinactant versus poractant alfa among very premature infants at high risk for respiratory distress syndrome.

BACKGROUND: Available therapeutic surfactants are either animal-derived or non-protein-containing synthetic products. Animal-derived surfactants contain variable amounts of surfactant apoproteins, whereas the older-generation synthetic products contain only phospholipids and lack surfactant proteins (SPs). Both decrease morbidity and mortality rates associated with respiratory distress syndrome (RDS) among preterm infants, compared with placebo. However, excess mortality rates have been observed with non-protein-containing synthetic surfactants, compared with the animal-derived products. Evidence suggests that synthetic surfactants consisting solely of phospholipids can be improved with the addition of peptides that are functional analogs of SPs. Lucinactant is a new synthetic peptide-containing surfactant that contains sinapultide, a novel, 21-amino acid peptide (leucine and lysine repeating units, KL4 peptide) designed to mimic human SP-B. It is completely devoid of animal-derived components. OBJECTIVE: We hypothesized that the outcomes for premature infants treated with lucinactant and poractant alfa would be similar. Therefore, we compared lucinactant (Surfaxin; Discovery Laboratories, Doylestown, PA) with porcine-derived, poractant alfa (Curosurf; Chiesi Farmaceutici, Parma, Italy) in a trial to test for noninferiority. METHODS: A total of 252 infants born between 24 and 28 weeks of completed gestation, with birth weights between 600 and 1250 g, were assigned randomly in a multicenter, multinational, noninferiority, randomized, controlled study to receive either lucinactant (n = 124) or poractant alfa (n = 128) within 30 minutes of life. The primary outcome was the incidence of being alive without bronchopulmonary dysplasia (BPD) through 28 days of age. Key secondary outcomes included death at day 28 and 36 weeks postmenstrual age (PMA), air leaks, neuroimaging abnormalities, and other complications related to either prematurity or RDS. An independent, international, data and safety monitoring committee monitored the trial. RESULTS: The treatment difference between lucinactant and poractant alfa for survival without BPD through 28 days was 4.75% (95% confidence interval [CI]: -7.3% to 16.8%) in favor of lucinactant, with the lower boundary of the 95% CI for the difference, ie, -7.3%, being greater than the prespecified noninferiority margin of -14.5%. At 28 days, 45 of 119 infants given lucinactant were alive without BPD (37.8%; 95% CI: 29.1-46.5%), compared with 41 of 124 given poractant alfa (33.1%; 95% CI: 24.8-41.3%); at 36 weeks PMA, the rates were 64.7% and 66.9%, respectively. The corresponding mortality rate through day 28 for the lucinactant group was lower than that for the poractant alfa group (11.8% [95% CI: 6.0-17.6%] vs 16.1% [95% CI: 9.7-22.6%]), as was the rate at 36 weeks PMA (16% and 18.5%, respectively). There were no differences in major dosing complications. In addition, no significant differences were observed in the incidences of common complications of prematurity, including intraventricular hemorrhage (grades 3 and 4) and cystic periventricular leukomalacia (lucinactant: 14.3%; poractant alfa: 16.9%). CONCLUSIONS: Lucinactant and poractant alfa were similar in terms of efficacy and safety when used for the prevention and treatment of RDS among preterm infants. The ability to enhance the performance of a synthetic surfactant with the addition of a peptide that mimics the action of SP-B, such as sinapultide, brings potential advantages to exogenous surfactant therapy.

Biological Products↗
PubMed2004

Beyond restenosis: five-year clinical outcomes from second-generation coronary stent trials.

BACKGROUND: In the first year after coronary stent implantation, clinical failures are driven mainly by procedural complications and restenosis, but the subsequent relative contributions of restenosis and disease progression to late failures are less clear. METHODS AND RESULTS: We observed 1228 patients for 5 years after the implantation of stents as part of pivotal second-generation coronary stent trials. Clinical events of death, myocardial infarction, repeat revascularization, and repeat hospitalization for acute coronary syndrome or congestive heart failure were attributed to the index stented (target) lesion or other distinct sites (either in the target or other coronary vessels) and further classified as procedural, restenosis, or nonrestenosis. During the first year the hazard rate was 18.3% for target-lesion events and 12.4% for events unrelated to the target lesion. After the first year the average annual hazard rate was 1.7% for target-lesion events and 6.3% for nontarget-lesion events. By the fifth year, restenosis events occurred in 20.3% of patients, whereas 30-day procedural complications or later nonrestenosis events occurred in 37.9%, including 11.4% who also experienced a restenosis event, for a combined cumulative event rate of 46.4%. Diabetes mellitus and multivessel disease were independently associated with increased risk for both restenosis and nonrestenosis events. CONCLUSIONS: In a low-risk clinical trial population, the clinical outcome beyond 1 year after stenting is determined by a high rate of events related to disease progression in segments other than the stented lesion, which itself remains relatively stable.

Aged↗
PubMed2004

Stroke risk profile predicts white matter hyperintensity volume: the Framingham Study.

BACKGROUND AND PURPOSE: Previous studies of cardiovascular risk factors and white matter hyperintensity (WMH) on brain MRI have been limited by the failure to exclude symptomatic cerebrovascular disease and dementia or by the use of semiquantitative rather than quantitative methods to measure WMH volume (WMHV). We examined the relationship between Framingham Stroke Risk Profile (FSRP) and WMHV measured quantitatively in a stroke and dementia-free subset of the Framingham Offspring Cohort. METHODS: Brain MRI was performed in 1814 members of the Framingham Offspring Cohort. Pixel-based quantitative measures of WMHV corrected for head size were obtained using a semiautomated algorithm. WMHV was not normally distributed and therefore was log-transformed (LWMHV). The FSRP and its component risk factors measured a mean of 7.5 years before MRI were related to both continuous measures of LWMHV and to the presence of large volumes of LWMHV (LWMHV-large). All analyses were adjusted for age and sex. RESULTS: FSRP was strongly associated with LWMHV and LWMHV-large. Age, smoking, history of cardiovascular disease, hypertension, and left ventricular hypertrophy by electrocardiogram were all significantly related to LWMHV or LWMHV-large. CONCLUSIONS: FSRP and several cardiovascular risk factors were related to both WMHV measured continuously and to a categorical designation of large volumes of WMH. These findings provide strong evidence of a vascular basis for WMH.

Adult↗
PubMed2004

Association between obesity and a prothrombotic state: the Framingham Offspring Study.

Although obesity is associated with increased cardiovascular risk, the mechanism has not been fully explained. Since thrombosis is a critical component of cardiovascular disease, we examined the relationship between obesity and hemostatic factors. We studied 3230 subjects (55% females, mean age 54 years) without a history of cardiovascular disease in cycle 5 of the Framingham Offspring Study. Obesity was assessed by body mass index and waist-to-hip ratio. Fasting blood samples were obtained for fibrinogen, plasminogen activator inhibitor (PAI-1) antigen, tissue plasminogen activator (tPA) antigen, factor VII antigen, von Willebrand factor (VWF), and plasma viscosity. Body mass index was directly associated with fibrinogen, factor VII, PAI-1 and tPA antigen in both men and women (p>0.001) and with VWF and viscosity in women. Similar associations were present between waist-to-hip ratio and the hemostatic factors. With minor exceptions for VWF and viscosity, all associations persisted after controlling for age, smoking, total and HDL cholesterol, triglycerides, glucose level, blood pressure, and use of antihypertensive medication. The association between increased body mass index and waist-to-hip ratio and prothrombotic factors and impaired fibrinolysis suggests that obesity is a risk factor whose effect is mediated in part by a prothrombotic state.

Adult↗
PubMed2002

The integration of psychiatric rehabilitation services in behavioral health care structures: a state example.

This article describes a model for integrating psychiatric rehabilitation services in a managed behavioral health care structure. Psychiatric rehabilitation and managed care are two distinct developments in the provision of mental health services that have proceeded independently though they can have compatible methods and outcomes. Descriptive detail is provided about a state initiative in Iowa to provide psychiatric rehabilitation services to those with serious mental illness through the state-contracted managed behavioral health care corporation. The article describes factors leading to the program's implementation, service delivery structures, reimbursements, personnel requirements, and performance indicators. Evidence for supporting this innovation is provided through a case-controlled outcomes study of mental health service units used and their costs for participants and matched controls.

Adult↗
PubMed2002

Clinical and microbial evaluation of a histatin-containing mouthrinse in humans with experimental gingivitis: a phase-2 multi-center study.

OBJECTIVE: P-113, a 12 amino acid histatin-based peptide, was evaluated in a mouthrinse formulation for safety and efficacy in a phase 2 multi-center clinical study. METHOD: 294 healthy subjects abstained from oral hygiene procedures and self-administered either 0.01% P-113, 0.03% P-113 or placebo mouthrinse formulations twice daily over a 4-week treatment period. During this time, the safety, anti-gingivitis, and anti-plaque effects of P-113 were evaluated. RESULTS: There was a significant reduction in the change from baseline to Day 22 in bleeding on probing in the 0.01% P-113 treatment group of the intent to treat population (p=0.049). Non-significant trends in the reduction of the other parameters were observed in this population (p> or =0.159). A sub-group of subjects which developed significant levels of disease within the four-week timeframe of the study was identified based on baseline gingival index scores > or =0.75. Significant findings were observed for bleeding on probing, gingival index and plaque index within this population (p<0.05). There were no treatment-related adverse events, and there were no adverse shifts in supragingival microflora during the study. Significant amounts of the peptide were retained in the oral cavity following rinsing. CONCLUSION: These data suggest that P-113 mouthrinse is safe and reduces the development of gingival bleeding, gingivitis and plaque in the human experimental gingivitis model.

Adult↗