Long waiting time before tooth extraction may increase delayed wound healing in elderly Japanese.

In osteoporosis patients receiving antiresorptive medications, stopping the drug and delaying tooth extraction has been suggested to reduce the risk of osteonecrosis of the jaw (ONJ). However, postponing tooth extraction for ≥ 2 months was associated with an increased risk of delayed wound healing beyond 8 weeks after extraction, a risk factor for developing ONJ. INTRODUCTION: A long waiting time before tooth extraction could result from concern about a potential increased risk of osteonecrosis of the jaw (ONJ) in osteoporosis patients. We clarified whether a long waiting time before tooth extraction during the past year may be associated with an increased risk of delayed wound healing beyond 8 weeks after tooth extraction, which may be a risk factor of ONJ. METHODS: Of 5639 patients aged ≥ 60 years who visited our 20 clinics or hospitals and answered a structured questionnaire, 426 patients (151 men, 275 women) aged 60-96 years comprised the final participants in this study. Self-reported kyphosis was used as a surrogate marker of vertebral fractures. Stepwise logistic regression analysis, adjusted for covariates, was used to calculate the odds ratio (OR) and the 95% confidence interval (CI) for the presence of delayed wound healing longer than 8 weeks after tooth extraction during the past year based on the duration before extraction. RESULTS: Subjects who had waited > 2 months for tooth extraction had a significantly higher risk of delayed wound healing compared with those whose tooth was extracted within 1 month (OR = 7.23; 95% CI = 2.19-23.85, p = 0.001) regardless if antiresorptive medications for osteoporosis were used. The presence of self-reported kyphosis was significantly associated with an increased risk of delayed wound healing (OR = 5.08; 95% CI = 1.11-23.32, p = 0.036). CONCLUSIONS: A long waiting time before tooth extraction may be a risk factor for delayed wound healing beyond 8 weeks after extraction in patients aged ≥ 60 years.

Issues with the surgical treatment of antiresorptive agent-related osteonecrosis of the jaws.

Antiresorptive agent-related osteonecrosis of the jaw is a rare but significant complication in patients using antiresorptive agents such as bisphosphonates and denosumab. Although the disease is well recognized, and many studies have been performed on the management of this condition, the treatment of severe osteonecrosis is still a challenge. Most recent studies have shown an advantage of surgical treatment over conservative treatment for stage 2/3 patients, but there is no consensus on the appropriate surgical procedures for antiresorptive agent-related osteonecrosis of the jaw. Furthermore, patients with severe systemic conditions may not be appropriate for extensive surgical treatment, and the treatment protocol for such patients has not been established. In this review, issues regarding the current surgical treatment for antiresorptive agent-related osteonecrosis of the jaws are discussed, with an emphasis on the clinical aspects.

Significant improvement of bone mineral density and bone turnover markers by denosumab therapy in bisphosphonate-unresponsive patients.

Bone mineral density (BMD) sometimes cannot be improved by long-term bisphosphonate (BP) therapy in osteoporosis (OP). This study showed that lumbar as well as hip BMD significantly increased after denosumab treatment in patients not responsive to BPs. Thus, denosumab may be a strong OP treatment option for BP-unresponsive patients. INTRODUCTION: BMD sometimes cannot be improved by long-term BP therapy. METHODS: We administered denosumab to osteoporotic patients with a poor response to BPs who had been taking them for 2 years or longer. Ninety-eight women with BP-poor responsive OP were enrolled in this study. Mean (standard deviation [SD]) age was 71.2 (6.9) years and mean (SD) duration of BP treatment was 59.9 (34.3) months. We distinguished BP responders from non-responders based on changes in BMD values at denosumab commencement (baseline) from 2 years beforehand. RESULTS: There were no significant differences in age, duration of BP use, bone turnover markers, or BMD at baseline between the groups. Prior to denosumab, BMD had increased significantly in responders and decreased significantly in non-responders. Bone turnover markers had decreased significantly at 4 months of denosumab treatment (P < 0.001) and lumbar and hip BMD were significantly increased at 1 year of therapy in both groups (P < 0.001). Simple correlation coefficients were -0.337 for lumbar and -0.339 for hip BMD changes (both P = 0.001) before and after denosumab treatment. Both at the lumbar spine and hips, decreased BMD before denosumab therapy was significantly associated with an increase in BMD at 1 year of treatment (spine, t value = -3.502, P = 0.001, R = 0.113; hip, t value = -3.526, P = 0.001, R = 0.115). CONCLUSIONS: These results suggest that denosumab may be a strong OP treatment option for BP-unresponsive patients.

Efficacy and safety of once-yearly zoledronic acid in Japanese patients with primary osteoporosis: two-year results from a randomized placebo-controlled double-blind study (ZOledroNate treatment in Efficacy to osteoporosis; ZONE study).

In a 2-year randomized, placebo-controlled study of 665 Japanese patients with primary osteoporosis, once-yearly administration of zoledronic acid (5 mg) reduced the risk of new morphometric vertebral fractures. INTRODUCTION: The purpose of this study was to determine the efficacy and safety of once-yearly intravenous infusion of ZOL in Japanese patients with primary osteoporosis. METHODS: This was a two-year multicenter, randomized, placebo-controlled, double-blind, parallel-group comparative study (ZONE Study). Subjects were 665 Japanese patients between the ages of 65 and 89 years who had prevalent vertebral fracture. Subjects were randomly assigned to receive once-yearly intravenous infusion of 5 mg of ZOL or placebo at baseline and 12 months. RESULTS: The 2-year incidence of new morphometric vertebral fracture was 3.0 % (10/330 subjects) in the ZOL group and 8.9 % (29/327) in the placebo group (p = 0.0016). The 24-month cumulative incidence of new morphometric vertebral fracture was 3.3 % in the ZOL group versus 9.7 % in the placebo group (log-rank test: p = 0.0029; hazard ratio: 0.35; 95 % confidence interval: 0.17-0.72). The cumulative incidence of any clinical fracture, clinical vertebral fracture, and non-vertebral fracture was significantly reduced in the ZOL group by 54, 70, and 45 %, respectively, compared to the placebo group. At 24 months, ZOL administration increased bone mineral density in the lumbar spine, femoral neck, and total hip (t test: p < 0.0001). No new adverse events or osteonecrosis of the jaw were observed in this study. CONCLUSIONS: Once-yearly administration of ZOL 5 mg to Japanese patients with primary osteoporosis reduced the risk of new morphometric vertebral fractures and was found to be safe.

Panoramic radiography measurements, osteoporosis diagnoses and fractures in Japanese men and women.

OBJECTIVES: The purpose of this study was to investigate the association of the shape of the mandibular cortex on panoramic radiographs with the risk of an osteoporosis diagnosis without prevalent fractures and with the risk of osteoporotic fractures in Japanese men and women. SUBJECTS AND METHODS: One thousand and twenty-one subjects aged 40-89 years, who visited our university hospital and underwent panoramic radiography between 2007 and 2013, participated in this study. Eighty-eight patients received a diagnosis of osteoporosis without prevalent fractures, and 55 were diagnosed with osteoporotic fractures. Blinded to the groupings, we classified the shape of the mandibular cortex on panoramic radiographs as normal, moderately eroded or severely eroded. RESULTS: After adjustment for confounding factors, the odds ratios for an osteoporosis diagnosis associated with moderately eroded and severely eroded mandibular cortices were 1.4 (95% CI, 0.8-2.6) and 2.6 (95% CI, 1.4-5.0), respectively. The odds ratios for an osteoporotic fracture associated with moderately eroded and severely eroded cortices were 0.8 (95% CI, 0.4-1.7) and 1.1 (95% CI, 0.5-2.5), respectively. CONCLUSIONS: Subjects in Japan with eroded mandibular cortices tended to be at increased risk of osteoporosis diagnoses but not of fractures.

Comparing immunocompetent and immunodeficient mice as animal models for bone tissue engineering.

OBJECTIVES: To understand the differences and similarities between immunocompetent and immunodeficient mice as ectopic transplantation animal models for bone tissue engineering. MATERIALS AND METHODS: Osteogenic cells from mouse leg bones were cultured, seeded on ß-TCP granules, and transplanted onto the backs of either immunocompetent or immunodeficient nude mice. At 1, 2, 4, and 8 weeks postoperatively, samples were harvested and evaluated by hematoxylin-eosin staining, tartrate-resistant acid phosphatase (TRAP) staining, and immunohistochemical staining and quantitative PCR. RESULTS: In immunocompetent mice, inflammatory cell infiltration was evident at 1 week postoperatively and relatively higher expression of TNF-α and IL-4 was observed. In immunodeficient mice, new bone area and the number of TRAP-positive cells were larger at 4 weeks than in immunocompetent mice. The volume of new bone area in immunodeficient mice was reduced by 8 weeks. CONCLUSIONS: Bone regeneration was feasible in immunocompetent mice. However, some differences were observed between immunocompetent and immunodeficient mice in the bone regeneration process possibly due to different cytokine expression, which should be considered when utilizing in vivo animal models.

Abundance of calpain and aggrecan-cleavage products of calpain in degenerated human intervertebral discs.

OBJECTIVE: To assess the expression of calpains and calpain-induced aggrecan fragmentation in early and advanced stages of degeneration of human intervertebral discs (IVDs). DESIGN: Disc tissue samples of 55 patients (mean age, 51.2 ± 22.3 years) who underwent intervertebral fusion were divided into groups with early and advanced degeneration based on the Thompson magnetic resonance imaging (MRI) scale. In advanced degeneration group, five patients (mean age, 35.5 ± 11.4 years) of lumbar disc herniation (LDH) were included. Protein levels of m- and µ-calpains and their inhibitor calpastatin were assayed, and immunohistochemical techniques were used to localize and quantify the production of the enzymes. To investigate calpain activity, we assayed purified aggrecan fragmentation in disc tissue by Western blotting and immunohistochemistry with VPGVA antibody, which recognizes the m-calpain generated neo-epitope GVA. RESULTS: Discs at early stages of degeneration expressed low levels of m- and µ-calpains and calpastatin, and few cells expressed degenerative enzymes. At more advanced stages of degeneration, the expression and number of cells immunopositive for m-calpain, µ-calpain and calpastatin were significantly higher. Further finding showed that anti-GVA-reactive aggrecan fragments were significantly higher in discs at advanced compared with early stages of degeneration. Herniated disc samples showed stronger expression and more cells immunopositive for calpains, calpastatin and GVA in the nucleus pulposus than in the annulus fibrous. CONCLUSIONS: The expression of calpains, together with m-calpain-induced degradation products of extracellular matrix, was correlated with the degree of disc degeneration in human IVD tissue. These findings suggest that calpains may be involved in IVD degeneration via proteoglycan (PG) cleavage.

Triage screening for osteoporosis in dental clinics using panoramic radiographs.

Many patients with osteoporosis go undiagnosed because typically no symptoms are present before a fracture. Triage screening to refer patients to appropriate medical professionals for further investigation would be useful to address the increase in the incidence of osteoporotic fractures. Dental clinics may offer a new triage screening pathway because dentists frequently take radiographs of bones in the course of dental treatment. A major premise for such triage screening in dental clinics is that dentists can readily use a screening tool in their dental practice. For example, cortical width and shape of the mandible detected on panoramic radiographs may be appropriate indices for triaging individuals with osteoporosis. To date, several investigators have demonstrated significant associations between cortical indices on panoramic radiographs and bone mineral density of the skeleton generally, such as the spine and femur, biochemical markers of bone turnover and risk of osteoporotic fractures. Further, in two recent Japanese clinical trials, approximately 95% of women who were identified by trained dentists in their clinics using cortical shape findings did have osteopenia or osteoporosis. These findings support the possibility that dental clinics may offer a new triage platform to identify individuals with otherwise undetected osteoporosis.

Decreased circulating CD34+ cells are associated with progression of diabetic nephropathy.

AIMS: Circulating progenitor cells such as CD34+ cells play a key role in maintenance of vascular endothelial function and neovascularization, and a decrease in the number of CD34+ cells is associated with cardiovascular disease. However, the contribution of circulating progenitor cells to microvascular disease, such as diabetic nephropathy, is unclear. This study was therefore designed to clarify the association between diabetic nephropathy and circulating CD34+ cells. METHODS: We measured circulating CD34+ cell numbers in 85 Type 2 diabetic patients aged 40-70 years with normo- and microalbuminuria and determined the association with urinary albumin excretion rate (UAER). RESULTS: The number of circulating CD34+ cells significantly correlated with log UAER (r = -0.289, P = 0.008). Furthermore, in patients with low numbers of CD34+ cells (0.68 > cells/microl, lowest quartile of CD34+ cell number) UAER increased significantly after 12 months compared with baseline [from 34.3 +/- 7.0 to 53.6 +/- 10.8 mg/g creatinine (gCr), P < 0.05], whereas in patients with a high number of CD34+ cells (1.0 < cells/microl, highest quartile of CD34+ cell number) UAER did not change (from 16.7 +/- 4.8 to 20.1 +/- 3.0 mg/gCr). CONCLUSIONS: These results suggest that a decreased number of circulating CD34+ cells is involved in the progression of diabetic nephropathy and may be a predictor of the disease.

Observer performance in diagnosing osteoporosis by dental panoramic radiographs: results from the osteoporosis screening project in dentistry (OSPD).

Mandibular cortical erosion detected on dental panoramic radiographs (DPRs) may be useful for identifying women with osteoporosis, but little is known about the variation in diagnostic efficacy of observers worldwide. The purpose of this study was to measure the accuracy in identifying women at risk for osteoporosis in a worldwide group of observers using DPRs. We constructed a website that included background information about osteoporosis screening and instructions regarding the interpretation of mandibular cortical erosion. DPRs of 100 Japanese postmenopausal women aged 50 years or older who had completed skeletal bone mineral measurements by dual energy X-ray absorptiometry were digitized at 300 dpi. These were displayed on the website and used for the evaluation of diagnostic efficacy. Sixty observers aged 25 to 66 years recruited from 16 countries participated in this study. These observers classified cortical erosion into one of three groups (none, mild to moderate, and severe) on the website via the Internet, twice with an approximately 2-week interval. The diagnostic efficacy of the Osteoporosis Self-Assessment Tool (OST), a simple clinical decision rule based on age and weight, was also calculated and compared with that of cortical erosion. The overall mean sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of the 60 observers in identifying women with osteoporosis by cortical erosion on DPRs were 82.5, 46.2, 46.7, and 84.0%, respectively. Those same values by the OST index were 82.9, 43.1, 43.9, and 82.4%, respectively. The intra-observer agreement in classifying cortical erosion on DPRs was sufficient (weighted kappa values>0.6) in 36 (60%) observers. This was significantly increased in observers who specialized in oral radiology (P<0.05). In the 36 observers with sufficient intra-observer agreement, the overall mean sensitivity, specificity, PPV, and NPV in identifying women with osteoporosis by any cortical erosion were 83.5, 48.7, 48.3, and 85.7%, respectively. The mean PPV and NPV were significantly higher in the 36 observers with sufficient intra-observer agreement than in the 24 observers with insufficient intra-observer agreement. Our results reconfirm the efficacy of cortical erosion findings in identifying postmenopausal women at risk for osteoporosis, among observers with sufficient intra-observer agreement. Information gathered from radiographic examination is at least as useful as that gathered from the OST index.

Bone marrow stromal cell therapy improves femoral bone mineral density and mechanical strength in ovariectomized rats.

BACKGROUND: This study aimed to determine the influence of bone marrow stromal cells (BMSC) on the degree and sustainability of ovariectomy-induced bone loss. METHODS: Allogenic BMSC were injected into either the left or right femur of 15 ovariectomized rats (OVX). Saline was injected into the contralateral femur as a vehicle control. Five rats were killed at 8 weeks and 5 rats at 24 weeks. The other five OVX rats received serial injections 4 weeks after the first injection and were killed 24 weeks after the first injection. To confirm osteoporotic model, five rats received sham operation. Bone mineral density (BMD) was measured using dual-energy X-ray absorptometry. Mechanical properties were evaluated by three-point bending. RESULTS: The OVX rats showed significantly lower BMD compared with that of the sham operated rats. BMD at the femoral mid-shaft was significantly greater in the BMSC-injected bones compared with the control bones. At week 8, ultimate load and stiffness were also improved in the BMSC-injected bones compared with controls. At 24 weeks, the stiffness of control and BMSC-injected bones was statistically indistinguishable. The additional injection aided preservation of both BMD and mechanical properties. DISCUSSION: The present study suggests that bone strength may be improved by direct BMSC injection.

Visualization of intracerebral arteries by synchrotron radiation microangiography.

BACKGROUND AND PURPOSE: Small cerebral vessels are a major site for vascular pathology leading to cerebral infarction and hemorrhage. However, such small cerebral vessels are difficult to visualize by using conventional methods. The goal of our study was the development of methodology allowing visualization of small cerebral arteries in rodents, suitable for experimental models. MATERIALS AND METHODS: Using barium sulfate as a contrast material, we obtained microangiographic images of physiologic and pathologic changes consequent to cerebral infarction in mouse brain by monochromatic synchrotron radiation (SR). To achieve high-resolution and high-contrast images, we used a new x-ray camera with a pixel size of 4.5 microm, and we set the energy level at 37.5 keV, just above the K absorption of barium. RESULTS: Small intracerebral arteries ( approximately 30 microm in diameter) were clearly visualized, as well as the cortical branches (50-70 microm in diameter) at the brain surface. The limit of detection appeared to be vessels approximately 10 microm in diameter. Compared with the noninfarcted side, the number of intracerebral arteries was dramatically decreased in the middle cerebral artery area affected by stroke. CONCLUSIONS: These results indicate the potential of SR for evaluating pathologic changes in small cerebral arteries and for monitoring the impact of pro- and antiangiogenic therapeutic strategies.

Carbon source dependence of transposable element-associated gene activation in Saccharomyces cerevisiae.

Seven cis-dominant mutations leading to the overproduction of the glucose-repressible alcohol dehydrogenase isozyme ADHII (structural gene, ADH2) in Saccharomyces cerevisiae have previously been shown to be due to insertion of a transposable element, Ty, in the 5' regulatory region of the ADH2 gene. We showed that although mating-competent cells (a, alpha, a/a, or alpha/alpha cells) overproduced both ADHII enzyme and ADH2 mRNA, mating-incompetent cells (a/alpha or ste-cells) produced much less ADHII enzyme and ADH2 mRNA. This mating type effect on ADH2 expression was greatest in the presence of a normally derepressing carbon source, glycerol, and much less apparent in the presence of a repressing carbon source, glucose. In addition, Ty insertion led to an aberrant carbon source response in mating-incompetent cells--the normally glucose-repressible ADHII becomes glycerol repressible. The mating type effect and aberrant carbon source response in mating-incompetent cells was specific for Ty-associated mutations in the 5' flanking region of the ADH2 gene in that a non-Ty mutation in the same region did not show these effects. Finally, Ty1 RNA levels also showed a/alpha, suppression, which was apparent only during growth on a nonfermentable carbon source such as glycerol. This suggests that Ty-mediated gene expression is subject to regulation by both mating competence and carbon catabolites.

A chronic encapsulated expanding hematoma that developed 15 years after gamma knife surgery for a cerebral arteriovenous malformation: A case report and review of the literature / Un hematoma encapsulado crónico expansivo que se desarrolló 15 años después de la intervención quirúrgica con bisturí de rayos gamma para tratar una malformación arteriovenosa cerebral: informe de caso y revisión bibliográfica

We report a case of gamma knife surgery (GKS)-induced chronic encapsulated expanding hematoma with extensive literature review. A 17-year-old young man underwent GKS after embolization for arteriovenous malformation (AVM) in the right frontal lobe and the AVM completely disappeared. He developed a generalized convulsion 15 years after GKS. MRI showed a small oedematous change at the AVM site. His epileptic seizure was controlled with anticonvulsant. His epilepsy recurred after three years, and MRI revealed an intracerebral hematoma with extensive surrounding edema at the same lesion. He underwent cerebral angiography and a recurrence of AVM was prevented. The hematoma was surgically removed, and intraoperative finding confirmed an old hematoma with a capsule and capillary hyperplasia, without developing cavernous angioma. The final diagnosis was a secondary chronic encapsulated expanding hematoma after GKS. This is the first report to show the early-stage imaging findings of this late effect after GKS (AU)

Informamos de un caso de hematoma encapsulado crónico expansivo inducido por una intervención quirúrgica con bisturí de rayos gamma (GKS) con una amplia revisión bibliográfica. Un joven de 17 años se sometió a una GKS después de una embolización por malformación arteriovenosa (MAV) en el lóbulo frontal derecho, y la MAV desapareció por completo. Desarrolló una convulsión generalizada 15 años después de la GKS. La resonancia magnética (RM) mostró un pequeño cambio edematoso en la ubicación de la MAV. Su ataque epiléptico se controló con un anticonvulsivo. Su epilepsia se repitió 3 años después, y la RM reveló un hematoma intracerebral con un edema circundante extenso en la misma lesión. Se sometió a una angiografía cerebral y se evitó la recidiva de la MAV. El hematoma se extirpó quirúrgicamente, y el hallazgo intraoperatorio confirmó un antiguo hematoma con una hiperplasia capsular y capilar, sin desarrollo de angioma cavernoso. El diagnóstico final fue un hematoma encapsulado crónico expansivo secundario después de la GKS. Este es el primer informe que muestra los hallazgos del diagnóstico por imagen en la fase temprana de este efecto tardío después de la GKS (AU)

Ectopic expression of constitutively activated Ral GTPase inhibits cell shape changes during Drosophila eye development.

The small GTP-binding protein Ral is activated by RalGDS, one of the effector molecules for Ras. Active Ral binds to a GTPase activating protein for CDC42 and Rac. Although previous studies suggest a role for Ral in the regulation of CDC42 and Rac, which are involved in arranging the cytoskeleton, its in vivo function is largely unknown. To examine the effect of overexpressing Ral on development, transgenic Drosophila were generated that overexpress wild-type or mutated Ral during eye development. While wild-type Ral caused no developmental defects, expression of a constitutively activated protein resulted in a rough eye phenotype. Activated Ral did not affect cell fate determination in the larval eye discs but caused severe disruption of the ommatidial organization later in pupal development. Phalloidin staining showed that activated Ral perturbed the cytoskeletal structure and cell shape changes during pupal development. This phenotype is similar to that caused by RhoA overexpression. In addition, the phenotype was synergistically enhanced by the coexpression of RhoA. These results suggest that Ral functions to control the cytoskeletal structure required for cell shape changes during Drosophila development.

Argos induces programmed cell death in the developing Drosophila eye by inhibition of the Ras pathway.

We studied the role of Ras signaling in the regulation of cell death during Drosophila eye development. Overexpression of Argos, a diffusible inhibitor of the EGF receptor and Ras signaling, caused excessive cell death in developing eyes at pupal stages. The Argos-induced cell death was suppressed by coexpression of the anti-apoptotic genes p35, diap1, or diap2 in the eye as well as by the Df(3L)H99 chromosomal deletion that lacks three apoptosis-inducing genes, reaper, head involution defective (hid) and grim. Transient misexpression of the activated Ras1 protein (Ras1V12) later in pupal development suppressed the Argos-induced cell death. Thus, Argos-induced cell death seemed to have resulted from the suppression of the anti-apoptotic function of Ras. Conversely, cell death induced by overexpression of Hid was suppressed by gain-of-function mutations of the genes coding for MEK and ERK. These results support the idea that Ras signaling functions in two distinct processes during eye development, first triggering the recruitment of cells and later negatively regulating cell death.

Mode of onset of ventricular fibrillation in patients with Brugada syndrome detected by implantable cardioverter defibrillator therapy.

OBJECTIVES: We sought to demonstrate the mode of spontaneous onset of ventricular fibrillation (VF) in patients with Brugada syndrome. BACKGROUND: The electrophysiologic mechanisms of VF in Brugada syndrome have not been fully investigated. METHODS: Nineteen patients (all male, mean age 47 +/- 12 years) with Brugada syndrome were treated with an implantable cardioverter defibrillator (ICD). The implanted devices were capable of storing electrograms during an arrhythmic event. We investigated the mode of spontaneous onset of VF according to the electrocardiographic features during the episode of VF, which were obtained from stored electrograms of ICDs and/or electrocardiographic (ECG) monitoring. RESULTS: During a follow-up of 34.7 +/- 19.4 months (range 14 to 81 months), 46 episodes of spontaneous VF attacks were documented in 7/19 (37%) patients. The event-free period between ICD implantation and the first spontaneous occurrence of VF was 14.6 +/- 12.1 months (range 3.7 to 27.4 months). We investigated 33/46 episodes of VF, for which electrocardiographic features (10 to 20 s before and during VF) were obtained from ICDs and/or ECG monitoring in five patients. A total of 22/33 episodes of VF were preceded by premature ventricular contractions (PVCs), which were almost identical to the initiating PVCs of VF. Furthermore, in three patients who had multiple VF episodes, VF attacks were always initiated by the same respective PVC. The coupling interval of the initiating PVCs of VF was 388 +/- 28 ms. CONCLUSIONS: Spontaneous episodes of VF in patients with Brugada syndrome were triggered by specific PVCs. These findings may provide important insights into the pathophysiological mechanisms causing VF in Brugada syndrome.

Intravascular ultrasound findings after successful primary angioplasty for acute myocardial infarction: predictors of abrupt occlusion.

OBJECTIVES: This study sought to evaluate the intravascular structure as depicted by intravascular ultrasound after successful primary angioplasty (i.e., without thrombolytic therapy) for acute myocardial infarction and to investigate the related predictors of acute coronary occlusion. BACKGROUND: The usefulness of primary angioplasty for acute myocardial infarction is still limited by early reocclusion. There are few data regarding the intravascular ultrasound findings after primary angioplasty. METHODS: Intravascular ultrasound was performed in 27 patients after successful primary angioplasty. Repeat coronary angiography was performed 15 min later, on the following day and 1 month after angioplasty. RESULTS: Abrupt occlusion occurred in 8 of 27 patients. Angiographic variables in patients with versus those without abrupt occlusion were not significantly different. Intravascular ultrasound disclosed a significantly smaller lumen area ([mean +/- SD] 2.49 +/- 0.72 vs. 5.06 +/- 1.52 mm2, p < 0.001) and a significantly greater percent plaque area (80.5 +/- 9.1% vs. 63.7 +/- 7.8%, p < 0.001) in patients with abrupt occlusion. There was no significant difference in external elastic membrane cross-sectional area. We classified the ultrasound appearance of the intravascular structure as smooth, irregular or filled. Abrupt occlusion occurred in none of 6 patients with a smooth intravascular structure, 24% of 17 patients with an irregular structure and in all 4 with a filled structure (p < 0.05). In the latter group, the lumen was filled with bright speckled or low echogenic material, although angiography revealed excellent coronary dilation in all these arteries. CONCLUSIONS: Intravascular ultrasound revealed a narrow lumen in coronary arteries showing abrupt occlusion after successful primary angioplasty, even though angiography disclosed successful dilation. Arteries with a lumen filled with bright speckled or low echogenic material frequently develop abrupt occlusion.

Sympathetic stimulation produces a greater increase in both transmural and spatial dispersion of repolarization in LQT1 than LQT2 forms of congenital long QT syndrome.

OBJECTIVES: The study compared the influence of sympathetic stimulation on transmural and spatial dispersion of repolarization between LQT1 and LQT2 forms of congenital long QT sYndrome (LQTS). BACKGROUND: Cardiac events are more associated with sympathetic stimulation in LQT1 than in LQT2 or LQT3 syndrome. Experimental studies have suggested that the interval between Tpeak and Tend (Tp-e) in the electrocardiogram (ECG) reflects transmural dispersion of repolarization across the ventricular wall. METHODS: We recorded 87-lead body-surface ECGs before and after epinephrine infusion (0.1 microg/kg/min) in 13 LQT1, 6 LQT2, and 7 control patients. The Q-Tend (QT-e), Q-Tpeak (QT-p), and Tp-e were measured automatically from 87-lead ECGs, corrected by Bazett's method (QTc-e, QTc-p, Tcp-e), and averaged among all 87-leads and among 24-leads, which reflect the potential from the left ventricular free wall. As an index of spatial dispersion of repolarization, the dispersion of QTc-e (QTc-eD) and QTc-p (QTc-pD) were obtained among 87-leads and among 24-leads, and were defined as the interval between the maximum and the minimum of the QTc-e and the QTc-p, respectively. RESULTS: Epinephrine significantly increased the mean QTc-e but not the mean QTc-p, resulting in a significant increase in the mean Tcp-e in both LQT1 and LQT2, but not in control patients. The epinephrine-induced increases in the mean QTc-e and Tcp-e were larger in LQT1 than in LQT2, and were more pronounced when the averaged data were obtained from 24-leads than from 87-leads. Epinephrine increased the maximum QTc-e but not the minimum QTc-e, producing a significant increase in the QTc-eD in both LQT1 and LQT2 patients, but not in control patients. The increase in the QTc-eD was larger in LQT1 than in LQT2 patients. CONCLUSIONS: Our data suggest that sympathetic stimulation produces a greater increase in both transmural and spatial dispersion of repolarization in LQT1 than in LQT2 syndrome, and this may explain why LQT1 patients are more sensitive to sympathetic stimulation.