Background—Both matrix metalloproteinase-2 (MMP-2) and -9 (MMP-9) have been postulated to play roles in the pathophysiology of giant cell arteritis (GCA) because of their ability to degrade elastin. Understanding the specific mediators of arterial damage in GCA could lead to new therapeutic targets in this disease. Methods and Results—Temporal artery biopsy specimens were obtained from 147 consecutive patients suspected of GCA. Clinical and histopathological data were collected according to protocol. Using immunohistochemistry, we compared the expression of MMP-2 and MMP-9 in the temporal artery biopsies of both GCA cases (n=50) and controls (n=97). MMP-9 was found more frequently in positive than in negative temporal artery biopsies (adjusted odds ratio [OR], 3.20; P=0.01). In contrast, the frequency of MMP-2 was not significantly different between positive and negative biopsies (adjusted OR, 2.18; P=0.22). Both MMP-2 and MMP-9 were found in macrophages and giant cells near the internal elastic lamina and in smooth muscle cells and myofibroblasts of the media and intima. MMP-9 was also found in the vasa vasorum. MMP-9 but not MMP-2 was associated with internal elastic lamina degeneration, intimal hyperplasia, and luminal narrowing, even after adjustment for possible confounding variables. Conclusions—MMP-9 appears more likely than MMP-2 to be involved in the pathophysiology of GCA. MMP-9 not only participates in the degradation of elastic tissue but also is associated with intimal hyperplasia, subsequent luminal narrowing, and neoangiogenesis. The expression of MMP by smooth muscle cells implicates these cells as potential secretory cells in GCA.
BACKGROUND The present analyses investigated possible pathways for earlier reported associations in the National Heart, Lung, and Blood Institute Family Heart Study between hostility and coronary and carotid end points. METHODS The cross-sectional design recruited 535 women and 491 men with average familial risk for coronary heart disease and 1950 women and 1667 men with high familial coronary risk from 3 prospective ongoing studies at 4 sites. Recruitment of high-risk participants was based on family risk score. Average-risk participants came from a randomly selected group. Outcome measures were plasminogen activator inhibitor type 1 (PAI-1), homocysteine, fibrinogen, fasting glucose, blood pressure, high-density lipoprotein cholesterol, triglycerides, low-density lipoprotein cholesterol, and "lipid metabolic disorder" (LMD) (defined as systolic blood pressure >/=140 mm Hg or diastolic blood pressure >/=90 mm Hg); fasting glucose >/=126 mg/dL (>/=7.0 mmol/L) or the use of diabetes medications; body mass index (calculated as weight in kilograms divided by the square of height in meters) >/=30; triglycerides >/=250 mg/dL (>/=2.8 mmol/L), high-density lipoprotein cholesterol <40 mg/dL (<1.0 mmol/L) in men and <50 mg/dL (<1.3 mmol/L) in women; and low-density lipoprotein cholesterol level >/=130 mg/dL (>/=3.4 mmol/L). RESULTS After adjustment for age and risk-related behaviors, hostility was significantly associated with glucose level and LMD in high-risk women, with LMD in average-risk women, with PAI-1 and LMD in high-risk men, and with fibrinogen level in average-risk men. CONCLUSIONS Associations between hostility and physiological risk were only partially accounted for by health behaviors, suggesting that further investigation of mechanistic pathways is warranted.
OBJECTIVES:This study was designed to evaluate the clinical and angiographic outcomes of sirolimus-eluting stent (SES) implantation for ostial left anterior descending (LAD) lesions compared with bare-metal stent (BMS) implantation.BACKGROUND:The effectiveness of SES implantation for ostial LAD lesions is currently unknown.METHODS:Sirolimus-eluting stents were implanted in 68 consecutive patients with ostial LAD stenoses. The control group was composed of 77 patients treated with BMS during the preceding two years. In the SES group, for complete lesion coverage, stent positioning was intentionally extended into the distal left main coronary artery (LMCA) in 23 patients (34%) with intermediate LMCA narrowing.RESULTS:Compared with the BMS group, the SES group had more multivessel involvement, received fewer debulking atherectomies, underwent more direct stenting, had a greater number of stents, and had more segments stented. The procedural success rate was 100% in both groups. The six-month angiographic restenosis rate was significantly lower in the SES group than in the BMS group (5.1% vs. 32.3%, p < 0.001). During the one-year follow-up period, neither death nor myocardial infarction occurred in either group, but target lesion revascularization was less frequent in the SES group than in the BMS group (0% vs. 17%, p < 0.001). In the SES group, there were no restenoses in cases with LMCA coverage, compared with three restenoses (7.9%) in cases with precise stent positioning (p = NS).CONCLUSIONS:Sirolimus-eluting stent implantation in ostial LAD lesions achieved excellent results regarding restenosis and clinical outcomes compared with BMS implantation. This finding may be associated with reduced neointimal hyperplasia and complete lesion coverage.
Background—Surgical myectomy has been the standard treatment for patients with drug-refractory obstructive hypertrophic cardiomyopathy. The clinical and echocardiographic predictors of long-term survival and freedom from cardiovascular morbidity after myectomy have been unclear. Methods and Results—We studied a consecutive cohort of 338 adult patients (age at operation 47±14 [range 18 to 77] years, 60% male) who underwent myectomy at our institution. Preoperative resting left ventricular outflow tract (LVOT) gradient was 66±32 mm Hg (range 5 to 158 mm Hg). Early postoperative mortality was 1.5% (5 deaths): 4 deaths occurred between 1978 and 1992, and 1 death occurred between 1993 and 2002. During long-term follow-up, 83% of patients reported an improvement to functional class I or II. The majority of patients (98%) had no resting LVOT gradient. Long-term survival was excellent, with 98±1% survival at 1 year, 95±1% at 5 years, and 83±3% at 10 years after myectomy. Multivariable Cox regression analysis identified 5 predictors of overall mortality: (1) age ≥50 years at surgery (hazard ratio [HR] 2.8, 95% CI 1.5 to 5.1, P=0.001), (2) female gender (HR 2.5, 95% CI 1.5 to 4.3, P=0.0009), (3) history of preoperative atrial fibrillation (HR 2.2, 95% CI 1.2 to 4.0, P=0.008), (4) concomitant CABG (HR 3.7, 95% CI 1.7 to 8.2, P=0.001), and (5) preoperative left atrial diameter ≥46 mm (HR 2.9, 95% CI 1.6 to 5.4, P=0.0008). Significant predictors of late major cardiovascular events found on multivariable analysis were (1) female gender (HR 3.3, 95% CI 2.0 to 5.4, P<0.0001), (2) history of preoperative atrial fibrillation (HR 1.9, 95% CI 1.1 to 3.3, P=0.02), and (3) preoperative left atrial diameter ≥46 mm (HR 2.5, 95% CI 1.5 to 4.3, P=0.0008). Conclusions—Myectomy provides excellent relief for LVOT obstruction in patients with hypertrophic cardiomyopathy. Preoperative clinical and echocardiographic variables can predict long-term outcome after myectomy.
Context Interventions to promote guideline-recommended care have met with limited success. Quality improvement experts believe that multicomponent interventions are more effective than simpler strategies, but this belief rests on limited evidence. Contribution In this randomized trial of 20 primary care practices, intervention practices received quarterly site visits and 2 network meetings about quality improvement in addition to copies of practice guidelines and quarterly performance reports. Intervention practices had greater improvement in providing guideline-recommended care for cardiovascular disease prevention and treatment than practices that received only the guidelines and performance reports. Cautions The study involved a small number of practices. The Editors Widespread evidence reveals inadequate implementation of evidence-based clinical practice guidelines for prevention and management of cardiovascular disease and stroke in primary care settings (1-3). Primary prevention deficiencies exist in the screening and management of dyslipidemia (4) and hypertension (5). Secondary prevention deficiencies include inadequate treatment of dyslipidemia in patients with coronary heart disease (CHD) (6) and inadequate use of antiplatelet therapy in patients with CHD or cerebrovascular disease (7), inadequate use of -blockers after myocardial infarction (8), inadequate use of angiotensin-converting enzyme inhibitors or angiotensin-receptor blockers in patients with heart failure (9), and inadequate use of oral anticoagulant therapy in patients with atrial fibrillation (10). Finally, patients with diabetes mellitus who are at high risk for cardiovascular disease as well as microvascular disease infrequently receive recommended screening and adequate treatment for elevated glycosylated hemoglobin levels, hypertension, and dyslipidemia (11). Published systematic reviews point to the importance of multifaceted interventions in increasing adherence to practice guidelines and improving disease control (12, 13). Little is known, however, about the relative effectiveness of different implementation strategies. More research is needed to develop and validate effective, theoretically sound, and practical strategies for improving the provision of evidence-based medicine in primary care. Particularly important are studies that address multiple common, chronic conditions, which together reflect a large proportion of the work of primary care providers (14). This study was designed as a pragmatic clinical trial (15), intended to assess whether a multimethod quality improvement intervention was more effective than a less intensive intervention for improving adherence to 21 quality indicators relevant to the primary and secondary prevention of cardiovascular disease and stroke. The multi method quality improvement intervention added practice site visits (for academic detailing and quality improvement facilitation) and network meetings (for sharing best practices) to the approach of guideline dissemination and audit and feedback used in the less intensive intervention. The study was conducted in a practice-based research network (PPRNet) among users of a common electronic medical record (Practice Partner Patient Records, Seattle, Washington), which historically provided audit and feedback to its practice members. Audit and feedback have already been shown to improve the practice of health care professionals, particularly in prescribing and test ordering (16). Additional research is needed to assess the effect of audit and feedback in combination with other interventions. Methods Design The design was a cluster randomized, controlled clinical trial, with the practice as the unit of randomization. Twenty-three office-based primary care practices in 15 states agreed to participate. The institutional review board at the Medical University of South Carolina approved the study. Study Indicators We derived the study indicators (Table 1) from published sources (17-22). Fourteen were process measures, which reflected whether recommended tests were done, appropriate diagnoses made, or appropriate medication prescribed. Seven were outcome measures, which reflected whether patients achieved recommended treatment goals. Some of the measures represented primary prevention, for example, screening for hypertension or dyslipidemia. Others represented secondary prevention, for example, reaching treatment goals for glycosylated hemoglobin levels, low-density lipoprotein (LDL) cholesterol levels, and blood pressure in patients with diabetes. An additional indicator, hormone replacement therapy for postmenopausal women, was included at the beginning of the study but was withdrawn in July 2002 when the results from the Women's Health Initiative trial were published (23). Table 1. Study Indicators We determined practice performance for each study indicator at baseline and quarterly throughout the study. To determine performance, participating practices ran a computer program to extract patient activity during the previous quarter from their electronic medical record. To protect patient confidentiality, the extract program assigned a unique, anonymous numerical identifier to each patient. The extract program obtained demographic information, such as age, race, and sex; diagnoses; medications; laboratory data; and vital signs. Text of progress notes, consultation reports, and discharge summaries were not extracted. The data were copied to a diskette and mailed to PPRNet or sent electronically via a secure server. In the PPRNet offices, the data were bridged to standard data dictionaries and converted to SAS data sets (SAS Institute, Inc., Cary, North Carolina) on standard microcomputers for analyses. Interventions The intervention began on 1 January 2001 and was completed on 1 January 2003. During the first quarter of 2001, the medical director of each practice was sent printed copies of each practice guideline referenced in the study. Beginning in the first quarter of 2001, the medical director was sent quarterly performance reports documenting the practice's adherence to each of the 21 study indicators. Each report contained the practice's current performance, calculated as the percentage of eligible patients who had received the recommended service, the number of patients who were receiving the recommended medication, or the number of patients who had achieved the treatment goal. The report also presented data on the practices' previous performance since the beginning of the study and the performance target, calculated as the 90th percentile at baseline among all practices. In practices with more than 1 clinician, individual provider data were not given because the study emphasized improvement at the practice level. The medical director was encouraged to share the reports with others in the practice in order to stimulate motivation for improvement. The 90th percentile was selected as the performance target because it reflected a bold but achievable goal (at least 2 practices were at this level of performance at baseline). Practices in the control group received no other interventions during the study. An example of 1 page of a practice report is available in the Appendix Figure. Appendix Figure. Sample practice report for blood pressure in coronary heart disease. Practices in the intervention group also participated in practice site visits and network meetings. Six or seven 1- or 2-day site visits were held at each practice approximately every 3 months during 2001 and 2002. The practice site visit was led by 1 of the physician coauthors, assisted during the first few visits in 2001 by a clinical pharmacist with expertise in academic detailing (24), and at later visits by other coauthors with expertise in quality improvement. Initial site visits focused on engaging clinicians and staff members in the project, through a formal presentation by the site visitors and group discussion with all members of the practice team, including providers, nurses, medical assistants, and reception and administrative personnel. Because of vacation or hospital coverage responsibilities, 1 or 2 providers were occasionally absent in the multiprovider practices, and 1 practice involved only a few members of their staff. We placed detailed attention on the scientific justification for the chosen study indicators and on published frameworks for clinician behavior change (25, 26). Baseline practice performance on each study indicator was discussed, and previous evidence of the ability of PPRNet practices to improve care was presented (27). Practices were encouraged to increase the use of quality improvement tools available in the electronic medical record, such as note templates with embedded practice guidelines, query functions, prompts, reminders, and messaging. At each visit, a participatory planning session was held in which practice members identified specific clinical indicators they wished to work on and improvement activities to conduct before the next site visit. Lessons from complexity theory were used in this exercisethe influence of each practice member on the system, the importance of replicating successful approaches and focusing on motivators for patients and staff, and the notion that simple changes are easiest to adopt and can have profound effects. In subsequent site visits, we focused on discussing the practice's success in adopting its planned improvement activities, presenting updated performance data, and planning additional practice-level interventions. The site visitors presented results from recently published studies relevant to the study indicators. Successful and unsuccessful approaches to improvement by other intervention sites were also presented. Two-day network meetings were held in Charleston, South Carolina, in May 2001 and May 2002. The lead clinician from each intervention practice and the research team attended the first meeting. At this me
PurposeTo assess if lipid-lowering interventions (statins, fibrates, resins, n-3 fatty acids, diet) prevent nonfatal and fatal strokes in patients with and without coronary heart disease.MethodsWe systematically searched the literature up to August 2002 to retrieve all randomized controlled trials of lipid-lowering interventions that reported nonfatal and fatal stroke and mortality data. The search yielded 65 trials with 200,607 patients for a meta-analysis to determine whether treatment effects differed between types of lipid-lowering interventions and between patient samples with and without coronary heart disease.ResultsThe risk ratio for nonfatal and fatal stroke for statins as compared with control interventions was 0.82 (95% confidence interval [CI]: 0.76 to 0.90). The corresponding risk ratios for statins as compared with control were 0.75 (95% CI: 0.65 to 0.87) for patients with coronary heart disease and 0.77 (95% CI: 0.62 to 0.95) for those without coronary heart disease. The confidence intervals of risk ratios for nonfatal and fatal stroke associated with fibrates, resins, n-3 fatty acids, and diet all included 1, as did the confidence intervals for these interventions in patients with and without coronary heart disease. Weighted meta-regression analysis suggested a stronger association of stroke reduction with statin treatment than with the extent of cholesterol reduction.ConclusionThis meta-analysis suggests that statins reduce the incidence of stroke in patients with and without coronary heart disease.
Background In recent years, the importance of circulating levels of proinsulin and apolipoproteins as risk factors for myocardial infarction (MI) has been highlighted. The aims of the current study were to investigate whether introduction of these new markers of coronary risk could improve the performance of a risk prediction score and to compare this new score with traditional scoring schemes, such as the Framingham Study and the Prospective Cardiovascular Munster (PROCAM) Study schemes.Methods From 1970 to 1973 all 50-year-old men in Uppsal a, Sweden, were invited to participate in a health survey aimed at identifying risk factors for cardiovascular disease (the Uppsala Longitudinal Study of Adult Men [ULSAM] cohort). The current study investigated metabolic characteristics at baseline and the incidence of fatal and nonfatal MI (n 25 1) during 28.7 years of follow-up in 1108 men who were free of coronary heart disease at baseline.Results The risk prediction score was derived from one half of the population sample from the ULSAM cohort and included systolic blood pressure, smoking, family history of MI, serum proinsulin, and the ratio between apolipoprotein B and apolipoprotein A1 The score was highly predictive for future MI (hazard ratio, 1.77 for a 1 SD increase; 95% Cl, 1.49 to 2.10, P <.0001) in the other half of the population that was not used for generating the score. The ULSAM score performed slightly better than the Framingham and PROCAM scores, (evaluated as areas under the receiver operating curves; Framingham, 61%; PROCAM, 63%; ULSAM, 66%; P =.08).Conclusions A risk prediction score for MI including proinsulin and the ratio between apolipoprotein B and apolipoprotein A1 was developed in middle-aged men. This score was highly predictive for future fatal and nonfatal MI and proved to be at least as good as the Framingham and the PROCAM scores, being based on traditional risk factors.
Background: Abdominal aortic aneurysms (AAAs) are characterized by histologic signs of chronic inflammation, destructive remodeling of extracellular matrix, and depletion of vascular smooth muscle cells. We investigated the process of extracellular matrix remodeling by performing a genetic association study with polymorphisms in the genes for matrix metalloproteinases (MMPs), tissue inhibitors of metalloproteinases (TIMPs), and structural extracellular matrix molecules in AAA. Our hypothesis was that genetic variations in one or more of these genes contribute to greater or lesser activity of these gene products, and thereby contribute to susceptibility for developing AAAs.Methods: DNA samples from 812 unrelated white subject (AAA, n = 387; controls, n = 425) were genotyped for 14 polymorphisms in 13 different candidate genes: MMP1(nt-1607), MMP2(nt-955), MMP3(nt-1612), MMP9(nt-1562), MMP10(nt+180), MMP12(nt-82), MMP13(nt-77), TIMP1(nt+434), TIMP1(rs;2070584), TIMP2(rs2009196), TIMP3(nt-1296), TGFBI(nt-509), ELN(nt+422), and COL3A1(nt+581). Odds ratios and P values adjusted for gender and country of origin using logistic regression and stratified by family history of AAA were calculated to test for association between genotype and disease status. Haplotype analysis was carried out for the two TIMP1 polymorphisms; in male subjects.Results: Analyses with one polymorphism per test without interactions showed an association with the two TIMP1 gene polymorphisms (nt+434, P =.0047; rs2070584, P =.015) in male subjects without a family history of AAA. The association remained significant when analyzing TIMP1 haplotypes (x(2) p =.014 and empirical P =.009). In addition, we found a significant interaction between the polymorphism and gender for MMP10 (P=.037) in cases without a family history of AAA, as well as between the polymorphism and country of origin for ELN (P =.0169) and TIMP3 (P =.0023) in cases with a family history of AAA.Conclusions: These findings suggest that genetic variations in TIMP1, TIMP3, MMP10, and ELN genes may contribute to the pathogenesis of AAAs. Further work is needed to confirm the findings in an independent set of samples and to study the functional role of these variants in AAA. It is noteworthy that contrary to a previous study, we did not find an association between the MMP9 (nt-1562) polymorphism and AAA, suggesting genetic heterogeneity of the disease.Clinical Relevance: Abdominal aortic aneurysms (AAAs) are an important cardiovascular disease, but the genetic and environmental risk factors, which contribute to individual's risk to develop an aneurysm, are poorly understood. Histologically, AAAs are characterized by signs of chronic inflammation, destructive remodeling of the extracellular matrix, and depletion of vascular smooth muscle cells. We hypothesized that genes involved in these events could harbor changes that make individuals more susceptible to developing aneurysms. This study identified significant genetic associations between DNA sequence changes in tissue inhibitor of metalloproteinase I (TIMP1), TIMP3, matrix metalloproteinase 10 (MMP10) and elastin (ELN) genes, and AAA. The results will require confirmation using an independent set of samples. After replication it is possible that these sequence changes in combination with other risk factors could be used in the future to identify individuals who are at increased risk for developing an AAA.
BACKGROUND:Clinically evident renal disease (dialysis, history of renal insufficiency, or serum creatinine >2.0 mg/dL) is a known risk factor for mortality after thoracoabdominal aortic aneurysm repair. We extended this concept to the questions of whether subclinical renal disease is also a risk factor and how best to identify subclinical disease. We hypothesized that the glomerular filtration rate (GFR) would be a more sensitive determinant of renal function than serum creatinine alone.METHODS:Between 1991 and 2004, we repaired 1106 thoracoabdominal aortic aneurysms and descending thoracic aortic aneurysms. The median age was 67 years. There were 400 (36%) women and 706 (64%) men. We estimated GFR by using the Cockcroft-Gault equation. We divided baseline serum creatinine and baseline GFR into quartiles and estimated the association of the quartiles with 30-day postoperative mortality by chi2 testing. We further subdivided the population into patients with and without clinically evident renal disease and repeated the analysis in the patients without clinically apparent disease (n = 869).RESULTS:Clinically apparent renal disease was highly associated with 30-day mortality (odds ratio, 3.2; P < .0001). In all patients, serum creatinine quartile and GFR quartile were also both highly significantly associated with 30-day mortality (P < .0001). In patients without clinically apparent renal disease, both creatinine and GFR predicted additional mortality, but GFR was a much stronger predictor (P < .02 for creatinine vs < .0001 for GFR). In these patients, mortality ranged from 5% in the best GFR quartile to 27% in the worst. Taken as continuous variables in logistic regression equations, serum creatinine had no discrimination in patients without clinical disease (P = .73), whereas GFR remained strong (P < .0001).CONCLUSIONS:Preoperative renal function is an important determinant of early mortality even in patients without clinically evident disease. Estimated GFR is a much more powerful determinant of mortality risk than serum creatinine alone.
Background - In the setting of acute coronary syndromes (ACS), nonwhite patients are less likely to undergo invasive cardiac procedures and may have worse clinical outcomes than white patients. Whether the disparate outcomes exist independently of potential biases in treatment patterns remains unclear.Methods and Results - We examined the association between race and outcome in the Treat Angina with Aggrastat and Determine Cost of Therapy With an Invasive or Conservative Strategy - Thrombolysis in Myocardial Infarction 18 study (TACTICS-TIMI 18), a randomized trial of invasive versus conservative treatment strategy in patients with non-ST-elevation ACS. There were 1722 white and 461 nonwhite patients. After adjustment for differences in medical characteristics, nonwhite patients were at significantly increased risk for death, MI, or rehospitalization for ACS (hazard ratio [HR], 1.54; P = 0.003). Rates of protocol-guided angiography and revascularization were similar in both groups. For non-protocol-guided care, however, we found significant disparities, with nonwhite patients less likely to be taking their cardiac medications at follow-up (odds ratio [OR], 0.59; P = 0.0002), to undergo non-protocol-mandated angiography (OR, 0.40; P = 0.03), to receive a stent if undergoing percutaneous coronary intervention (OR, 0.55; P = 0.045), and to have less procedural success after percutaneous coronary intervention (acute gain, 1.40 +/- 0.83 versus 1.81 +/- 0.92 mm; P = 0.004). Nonetheless, an invasive strategy was similarly efficacious in white (HR, 0.66; 95% CI, 0.50 to 0.88) and nonwhite (HR, 0.85; 95% CI, 0.52 to 1.39) patients (P-interaction = 0.52), especially in those with troponin elevation or ST deviation.Conclusions - After adjustment for baseline characteristics, nonwhite patients had a significantly worse prognosis than white patients, regardless of treatment approach. In the absence of protocol guidance, important disparities emerged between the care given the 2 groups. An early invasive strategy is beneficial in and should be considered for all patients, regardless of race.
OBJECTIVES This study sought to investigate the relationship between multiple plaque ruptures, C-reactive protein (CRP), and clinical prognosis in acute myocardial infarction (AMI).BACKGROUND Several studies have demonstrated that ruptured or vulnerable plaques exist not only at the culprit lesion but also in the whole coronary artery in some acute coronary syndrome (ACS) patients. Recent studies have reported that a ruptured plaque at the culprit lesion is associated with elevated CRP, which indicates a poor prognosis in patients with ACS.METHODS We performed intravascular ultrasound in 45 infarct-related arteries and another 84 major coronary arteries in 45 first AMI patients.RESULTS Plaque rupture was observed in 21 patients (47%) at the culprit site. Intravascular ultrasound revealed 17 additional plaque ruptures at remote sites in 11 patients (24%). Patients with multiple risk factors were more frequently found in our multiple-plaque rupture patients compared with single-plaque rupture or nonrupture patients (82% vs. 40% vs. 29%, p = 0.01). High-sensitive CRP levels had a positive correlation with the number of plaque ruptures (p < 0.01). All culprit lesions were successfully treated by percutaneous coronary intervention. Patients with multiple plaque rupture showed significantly poor prognosis compared with others (p = 0.01).CONCLUSIONS Multiple plaque rupture is associated with systemic inflammation, and patients with multiple plaque rupture can be expected to show a poor prognosis. Our results suggest that AMI treatment should focus not only on stabilization of the culprit site but also a systemic approach to systemic stabilization of the arteries. (c) 2005 by the American College of Cardiology Foundation.
OBJECTIVES Changes of ruptured plaques in nonculprit lesions were evaluated using coronary angioscopy.BACKGROUND The concept of multiple coronary plaque ruptures has been established. However, no detailed follow-up studies of ruptured plaques in nonculprit lesions have yet been reported.METHODS Forty-eight thrombi in 50 ruptured coronary plaques in nonculprit lesions in 30 patients were identified by angioscopy. The percent diameter stenosis (%DS) at the target plaques on quantitative coronary angiographic analysis and the serum C-reactive protein (CRP) level were measured.RESULTS The mean angioscopic follow-up period was 13 +/- 9 months. Thirty-five superimposed thrombi still remained at follow-up, and the predominant thrombus color changed from red (56%) at baseline to pinkish-white (83%) at follow-up. The healing rate increased according to the angioscopic follow-up period (23% at > 12 months vs. 55% at > 12 months, p = 0.044). The %DS at the healed plaque increased from baseline to follow-up (12.3 +/- 5.8% vs. 22.7 +/- 11.6%, respectively; p = 0.0004). The serum CRP level in patients with healed plaques (n = 10) was lower than that in those without healed plaques (n = 19; 0.07 +/- 0.03 mg/dl vs. 0.15 +/- 0.11 mg/dI, respectively, p = 0.007).CONCLUSIONS The present study demonstrated that: 1) ruptured plaques in nonculprit lesions tend to heal slowly with a progression of angiographic stenosis; and 2) the serum CRP level might reflect the disease activity of the plaque ruptures. (C) 2005 by the American College of Cardiology Foundation.
Ruta genus is constituted by ten species, of which the most commonly described are R. chalepensis and R. graveolens. Ruta plants are perennial shrubs belonging to the family Rutaceae, which are traditionally used in folk medicine, since ancient times mostly for the treatment of various ailments of the womb.To provide a review of the different uses of Ruta species in traditional medicine, as well as, on their multifactorial biological and pharmacological properties.A search of the literature on genus Ruta and Ruta species was performed using various scientific databases and search engines and the information of articles were reviewed and compiled.Different parts of the plants belonging to Ruta genus are used in folk medicine to treat a wide range of different diseases. The principal use of these is in gynaecological field, but the treatment of pain, fever, nausea, inflammation, infections, nervous disorders, among others, are also described. These plants have been used to fertility regulation, as anti-fertility agent, to control menstrual flux and bleedings, as abortifacient and as contraceptive. The phytochemical composition of these plants consists mainly in essential oil (EO), but phenolic compounds were also reported, like coumarins and flavonoids, as well as alkaloids. Ruta species products like extracts and EOs have shown broad pharmacological activities, such as antimicrobial and antifungal activities, as well as, antiviral and antiparasitic. Moreover, Ruta plants products present antioxidant, neuroprotective, anti-inflammatory, anti-cancer and anti-diabetic activities and demonstrated contraceptive and abortifacient effects. These plants were also tested to be used for non-therapeutic approaches, as bio-insecticides in the control of different insect pests showing to be able to reduce infestation.Ruta species could be a potential source of natural products with biological activities. Ruta extracts, essential oils and isolated compounds have shown a diverse potential for use in the treatment of different diseases, as well as, for pests control, contributing to the valorisation of these plants. Nonetheless, this review indicates that more studies are needed to demonstrate the full potential of Ruta species, and to further explore the toxicology and safety of these plants.
Depression episodes in epilepsy is the most common commorbidity, affecting between 11% and 62% of patients with epilepsy. Although researchers have documented a strong association between epilepsy and psychiatric comorbidities, the nature of this relationship is poorly understood.The manifestation of depression in epilepsy is a complex issue having many interacting neurobiological and psychosocial determinants, including clinical features of epilepsy (seizure frequency, type, foci, or lateralization of foci) and neurochemical or iatrogenic mechanisms. Other risk factors are a family history of psychiatric illness, particularly depression, a lack of control over the seizures and iatrogenic causes (pharmacologic and surgical). In addition, treatment with antiepileptic drugs (AEDs) as well as social coping and adaptation skills have also been recognised as risk factors of depression associated with epilepsy.Epilepsy may foster the development of depression through being exposed to chronic stress. The uncertainty and unpredictability of seizures may instigate sadness, loneliness, despair, low self-esteem, and self-reproach in patients with epilepsy and lead to social isolation, stigmatization, or disability. Often, depression is viewed as a reaction to epilepsy’s stigma and the associated poor quality of life. Moreover, patients with epilepsy display a 4–5 higher rate of depression and suicide compared with healthy population.
Ruta genus is constituted by ten species, of which the most commonly described are R. chalepensis and R. graveolens. Ruta plants are perennial shrubs belonging to the family Rutaceae, which are traditionally used in folk medicine, since ancient times mostly for the treatment of various ailments of the womb.To provide a review of the different uses of Ruta species in traditional medicine, as well as, on their multifactorial biological and pharmacological properties.A search of the literature on genus Ruta and Ruta species was performed using various scientific databases and search engines and the information of articles were reviewed and compiled.Different parts of the plants belonging to Ruta genus are used in folk medicine to treat a wide range of different diseases. The principal use of these is in gynaecological field, but the treatment of pain, fever, nausea, inflammation, infections, nervous disorders, among others, are also described. These plants have been used to fertility regulation, as anti-fertility agent, to control menstrual flux and bleedings, as abortifacient and as contraceptive. The phytochemical composition of these plants consists mainly in essential oil (EO), but phenolic compounds were also reported, like coumarins and flavonoids, as well as alkaloids. Ruta species products like extracts and EOs have shown broad pharmacological activities, such as antimicrobial and antifungal activities, as well as, antiviral and antiparasitic. Moreover, Ruta plants products present antioxidant, neuroprotective, anti-inflammatory, anti-cancer and anti-diabetic activities and demonstrated contraceptive and abortifacient effects. These plants were also tested to be used for non-therapeutic approaches, as bio-insecticides in the control of different insect pests showing to be able to reduce infestation.Ruta species could be a potential source of natural products with biological activities. Ruta extracts, essential oils and isolated compounds have shown a diverse potential for use in the treatment of different diseases, as well as, for pests control, contributing to the valorisation of these plants. Nonetheless, this review indicates that more studies are needed to demonstrate the full potential of Ruta species, and to further explore the toxicology and safety of these plants.
The development of Graves disease (GD) after subacute thyroiditis (SAT) is rare, with approximately 31 reported cases, of which only 5 occurred in men. We describe a case of GD diagnosed based on newly elevated thyroid-stimulating immunoglobulin (TSI) and thyroid-stimulating hormone (TSH) receptor autoantibody (TRAb) levels after SAT.A 32-year-old Chinese man presented with right anterior neck pain, swelling, sore throat, cough, and fever. He had a diffuse tender goiter but no proptosis, lid lag, or stare. His TSH level was 0.03 mIU/mL (normal range [NR] 0.45-5.33 mIU/mL), serum free thyroxine (FT4) level was 2.40 ng/dL (NR 0.61-1.44 ng/dL), total triiodothyronine (TT3) level was 113 ng/dL (NR 87-178 ng/dL), TSI level was <0.10 IU/L (NR < 0.10 IU/L), and erythrocyte sedimentation rate was 21 mm/h (NR < 15 mm/h). After 7 weeks of prednisone, the symptoms resolved, FT4 level was 0.95 ng/dL, and TT3 level was 91 ng/dL. At 11 weeks after SAT onset, the TSH level was <0.01 mIU/mL, TT3 level was 257 ng/dL, FT4 level was 3.03 ng/dL, TSI level was 1.94 IU/L, then 3.42 IU/L 2 weeks later, TRAb level was 8.72 IU/L (NR < 2 IU/L), and erythrocyte sedimentation rate was 4 mm/h. After 1 month of methimazole, the FT4 level was 1.32 ng/dL and TT3 level was 110 ng/dL. Genetic testing revealed human leukocyte antigen-B35 and DRB1∗15:01 positivity.GD after SAT is thought to be due to the activation of thyroid autoimmunity induced by SAT in genetically susceptible individuals.This case illustrates the induction of thyroid autoimmunity after SAT, resulting in GD, supporting TSI and/or TRAb testing if hyperthyroidism recurs. The presence of HLA alleles associated with SAT and GD suggests a genetic contribution to the development of thyroid autoimmunity.
