Quality by Design approaches to assessing the robustness of tangential flow filtration for MAb.

Quality by Design (QbD) is a modern approach for quality assurance in pharmaceutical production. This article illustrates a case study of TFF robustness performed for a process characterization of a monoclonal antibody under QbD principles by exploring functional relationships that link the process parameters to quality/process attributes with prior process knowledge, risk assessment, and multivariate experiments. In every case of quality or process attributes, all measured values were in alignment with the allowable specification range, and the developed models were non-significant and had no lack of fit, thus confirming the robustness of the TFF process within the tested ranges of process parameters.

Epigenetic and genetic inactivation of tumor suppressor miR-135a in non-small-cell lung cancer.

BACKGROUND: Despite therapeutic advances, lung cancer prognosis remains poor. Loss of heterozygosity (LOH) in the 3p21 region is well documented in lung cancer, but the specific causative genes have not been identified. MATERIALS AND METHODS: Here, we aimed to examine the clinical impact of miR-135a, located in the 3p21 region, in lung cancer. miR-135a expression was assessed using quantitative real-time polymerase chain reaction. LOH was analyzed at microsatellite loci D3S1076 and D3S1478, and promoter methylation status was determined by pyrosequencing of resected samples of primary non-small-cell lung cancer (NSCLC). The regulation of telomerase reverse transcriptase (TERT) was evaluated in lung cancer cells H1299 by luciferase report assays after treatment with miR-135a mimics. RESULTS: miR-135a was significantly downregulated in squamous cell cancer (SCC) tumor tissues compared to normal tissues (p = 0.001). Low miR-135a expression was more frequent in patients with SCC (p = 2.9 × 10-4 ) and smokers (p = 0.01). LOH and hypermethylation were detected in 27.8% (37/133) and 17.3% (23/133) of the tumors, respectively. Overall, 36.8% (49/133) of the NSCLC cases harbored either miR-135a LOH or promoter hypermethylation. The frequencies of LOH and hypermethylation were significantly associated with SCCs (p = 2 × 10-4 ) and late-stage (p = 0.04), respectively. MiR-135a inhibited the relative luciferase activity of psiCHECK2-TERT-3'UTR. CONCLUSION: These results suggest that miR-135a may act as a tumor suppressor to play an important role in lung cancer carcinogenesis, which will provide a new insight into the translational value of miR-135a. Further large-scale studies are required to confirm these findings.

Presence of conduction abnormalities as a predictor of clinical outcomes in patients with infective endocarditis.

There have been no studies that have assessed the possible correlation between conduction abnormality (CA) and systemic embolism, or the long-term outcomes of patients with infective endocarditis (IE). In this study, 82 consecutive patients with IE and interpretable electrocardiography (ECG) were admitted to Kyungpook National University Hospital from July 2002 to June 2008. ECGs obtained at the time of admission or during hospitalization were analyzed. Patients with CA, which was defined as atrioventricular or intraventricular block, of "new" or "of unknown duration" were considered as those with CA. Composite events were defined as the composite of death and embolic events. Twenty-three (28%) patients had CA classified as new (n = 11) or of unknown duration (n = 12). No significant differences were found between patients with and without CA in terms of age and gender. Mean follow-up duration was 21 ± 23 months. Patients with CA had more frequent embolic events (p = 0.001) and composite events (p = 0.002) during hospitalization, and had more frequent composite events (p < 0.001) during follow-up than those without CA. Kaplan-Meier survival curves showed that patients with CA had a higher composite event rate during follow-up (p = 0.003). However, there was no significant difference between the two groups regarding mortality rates during hospitalization and follow-up. In multivariate analysis, CA was an independent predictor of embolic event rates during hospitalization [odds ratio (OR) 5.198, 95% confidence interval (CI) 1.086-24.867, p = 0.039] and of composite event rates during follow-up (OR 27.168, 95% CI 4.590-160.802, p < 0.001). CA is associated with increased frequency of embolic events during hospitalization and follow-up. Moreover, CA might be a useful predictor of embolic event occurrences during both hospitalization and follow-up.

Prognostic value of standard electrocardiographic parameters for predicting major adverse cardiac events after acute myocardial infarction.

BACKGROUND: The prognostic value of electrocardiographic (ECG) variables in predicting major adverse cardiac events (MACEs) after acute myocardial infarction (AMI) in the era of modern therapy is unclear. This study was conducted to evaluate the prognostic significance of ECG parameters in predicting 1-year MACEs for AMI patients. METHODS: Between January 2006 and January 2008, 529 AMI patients were included. ECG variables were analyzed from the ECG taken on discharge day. The 1-year MACEs were defined as death, nonfatal MI, and revascularization including repeat percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG). Mean follow-up duration was 360 ± 119 days. RESULTS: Of these patients, 497 (94%) patients provided complete follow-up data (355 males; 67 ± 12 years old). The rate of 1-year MACEs was 16%. In univariate analysis, heart rate, corrected QT interval, left ventricular (LV) hypertrophy, voltage (SV(1) + RV(5) ), lateral ST-depression (V(5-6) or I, aVL), pathologic Q wave (V(1-4) , V(5-6) ), ST-elevation (V(1-4) , V(5-6) or I, aVL), and T-wave inversion (V(1-4) , V(5-6) , or I, aVL) had a significant association with 1-year MACEs. In the Cox regression hazard model, lateral ST-depression (hazard ratio [HR] 2.260, 95% confidence interval [CI] 1.204 to 4.241, P = 0.011) and corrected QT interval (HR 1.007, 95% CI 1.002 to 1.011, P = 0.004) were independent predictors of 1-year MACEs. After adjustment for all risk variables, lateral ST-depression (HR 3.781, 95% CI 1.047 to 13.656, P = 0.042) was the only ECG variable that independently predicted 1-year MACEs. CONCLUSION: Lateral ST-depression on discharge day ECG is an independent predictor of 1-year MACEs after AMI.

Incidence of hypertension in Korea: 5-year follow-up study.

Limited data are available about the incidence of hypertension over the 5-yr in non-hypertensive subjects. The study subjects were 1,806 subjects enrolled in a rural area of Daegu, Korea for a cohort study from August to November 2003. Of them, 1,287 (71.3%) individuals had another examination 5 yr later. To estimate the incidence of hypertension, 730 non-hypertensive individuals (265 males; mean age = 56.6 ± 11.1 yr-old) at baseline examination were analyzed in this study. Hypertension was defined as either a new diagnosis of hypertension or self-reports of newly initiated antihypertensive treatment; prehypertension was if the systolic blood pressure was 120-139 mmHg and/or diastolic blood pressure was 80-89 mmHg. During the 5-yr follow-up, 195 (26.7%) non-hypertensive individuals developed incident hypertension. The age-adjusted 5-yr incidence rates of hypertension were 22.9% (95% confidence interval [CI] = 19.9-29.0) in overall subjects, 22.2% (95% CI = 17.2-27.2) in men, and 24.3% (95% CI = 20.4-28.2) in women. The incidence rates of hypertension significantly increased with age. In the multivariate analysis, prehypertension (Odds ratio [OR] 2.25; P < 0.001) and older age (OR 2.26; P = 0.010) were independent predictors for incident hypertension. In this rapidly aging society, population-based preventive approach to decrease blood pressure, particularly in subjects with prehypertension, is needed to reduce hypertension.

Suboptimal use of evidence-based medical therapy in patients with acute myocardial infarction from the Korea Acute Myocardial Infarction Registry: prescription rate, predictors, and prognostic value.

BACKGROUND: Only limited data are available for the recent trend of optimal evidence-based medical therapy at discharge after acute myocardial infarction (AMI) in Asia. We evaluated the predictors for the use of optimal evidence-based medical therapy at discharge and the association between discharge medications and 6-month mortality after AMI. METHODS: Between November 2005 and January 2008, we evaluated the discharge medications among 9,294 post-MI survivors who did not have any documented contraindications to antiplatelet drugs, beta-blockers, angiotensin-converting enzyme inhibitors (ACE-Is)/angiotensin II receptor blockers (ARBs), or statins in the Korea Acute Myocardial Infarction Registry. Optimal evidence-based medical therapy was defined as the use of all 4 indicated medications. RESULTS: Of these patients, 4,684 (50.4%) received all 4 medications at discharge. The discharge prescription rates of antiplatelet drugs, beta-blockers, ACE-Is/ARBs, and statins were 99.0%, 72.7%, 81.5%, and 77.2%, respectively. In multivariate analysis, advanced age, lower systolic blood pressure, higher Killip class at admission, left ventricular systolic dysfunction, higher blood creatinine level, lower total cholesterol levels, and coronary artery bypass grafting during hospitalization were independently associated with less use of optimal evidence-based medical therapy. In contrast, patients who underwent percutaneous coronary intervention were more likely to use optimal medications. In Cox proportional hazards model, optimal evidence-based medical therapy was an independent predictor of 6-month mortality after adjusting clinical characteristics and angiographic and procedural data. CONCLUSIONS: The optimal evidence-based medical therapy is prescribed at suboptimal rates, particularly in patients with high-risk features. New educational strategies are needed to increase the use of these secondary preventive medical therapies.

Eupatilin exhibits a novel anti-tumor activity through the induction of cell cycle arrest and differentiation of gastric carcinoma AGS cells.

In many cases, the process of cancer cell differentiation is associated with the programmed cell death. In the present study, interestingly, we found that eupatilin, one of the pharmacologically active ingredients of Artemisia asiatica that has been reported to induce apoptosis in human gastric cancer AGS cells, also triggers differentiation of these cells. Treatment of AGS cells with eupatilin induced cell cycle arrest at the G(1) phase with the concomitant induction of p21(cip1), a cell cycle inhibitor. This led us to test whether eupatilin may trigger AGS cells to differentiate into the matured phenotypes of epithelial cells and this phenomenon may be coupled to the apoptosis. Eupatilin induced changes of AGS cells to a more flattened morphology with increased cell size, granularity, and mitochondrial mass. It also markedly induced trefoil factor 1 (TFF1), a gene responsible for the gastrointestinal cell differentiation. Eupatilin dramatically induced redistribution of tight junction proteins such as occludin and ZO-1, and F-actin at the junctional region between cells. It also induced phosphorylation of extracellular signal-regulated kinase 2 and p38 kinase. Blockade of ERK signaling by PD098059 or the dominant-negative ERK2 significantly reduced eupatilin-induced TFF1 and p21 expression as well as ZO-1 redistribution, indicating that ERK cascades may mediate eupatilin-induced AGS cell differentiation. Collectively, our results suggest that eupatilin acts as a novel anti-tumor agent by inducing differentiation of gastrointestinal cancer cells rather than its direct role in inducing apoptotic cell death.

RKIKK motif in the intracellular domain is critical for spatial and dynamic organization of ICAM-1: functional implication for the leukocyte adhesion and transmigration.

No direct evidence has been reported whether the spatial organization of ICAM-1 on the cell surface is linked to its physiological function in terms of leukocyte adhesion and transendothelial migration (TEM). Here we observed that ICAM-1 by itself directly regulates the de novo elongation of microvilli and is thereby clustered on the microvilli. However, truncation of the intracellular domain resulted in uniform cell surface distribution of ICAM-1. Mutation analysis revealed that the C-terminal 21 amino acids are dispensable, whereas a segment of 5 amino acids ((507)RKIKK(511)) in the NH-terminal third of intracellular domain, is required for the proper localization and dynamic distribution of ICAM-1 and the association of ICAM-1 with F-actin, ezrin, and moesin. Importantly, deletion of the (507)RKIKK(511) significantly delayed the LFA-1-dependent membrane projection and decreased leukocyte adhesion and subsequent TEM. Endothelial cells treated with cell-permeant penetratin-ICAM-1 peptides comprising ICAM-1 RKIKK sequences inhibited leukocyte TEM. Collectively, these findings demonstrate that (507)RKIKK(511) is an essential motif for the microvillus ICAM-1 presentation and further suggest a novel regulatory role for ICAM-1 topography in leukocyte TEM.

ICAM-1/LFA-1 interaction contributes to the induction of endothelial cell-cell separation: implication for enhanced leukocyte diapedesis.

The basic route and mechanism for diapedesis has not yet to be fully defined. Here we present evidence that "cell-cell separation" between endothelial cells (ECs) may provide a route for leukocyte diapedesis. We unexpectedly found that extensive interaction between peripheral blood leukocytes and ECs that were activated by TNF-alpha induced the opening of EC contacts and, surprisingly, resulted in cell-cell separation. This event was specific to the intercellular adhesion molecules-1 (ICAM-1)/leukocyte function- associated antigen-1 interaction, as demonstrated by the following: (1) ICAM-1 expression correlated with increased EC contraction; and (2) the blocking of ICAM-1 selectively inhibited EC separation. Thus, we suggest that "cell-cell separation" could be a mechanism for diapedesis in situations that may require massive leukocyte infiltration.

A role for Rho-kinase in Ca-independent contractions induced by phorbol-12,13-dibutyrate.

1. Phorbol-12,13-dibutyrate (PDBu) is an activator of protein kinase C (PKC) that causes contractions in both physiological salt solutions and Ca(2+)-depleted solutions. In the present study, we tested the hypothesis that Rho-kinase plays a role in Ca(2+)-independent contractions induced by PDBu in vascular smooth muscles. 2. In Ca(2+)-free solution, 0.1 and 1 micromol/L PDBu induced contraction and myosin light chain (MLC(20)) phosphorylation, both of which were approximately 40% of responses obtained in normal Krebs' solution. Hydroxyfasudil (H1152; 1 micromol/L), an inhibitor of Rho-kinase, but not ML7 (10 micromol/L), an inhibitor of myosin light chain kinase, inhibited Ca(2+)-independent contractions induced by PDBu. 3. In Ca(2+)-free solution, PDBu increased phosphorylation of myosin phosphatase targeting subunit 1 (MYPT1) and CPI-17 (PKC-potentiated inhibitory protein for heterotrimeric myosin light chain phosphatase of 17 kDa). This action was inhibited by H1152, with the phosphorylation of CPI-17 almost completely abolished by 1 micromol/L Ro31-8220, an inhibitor of PKC. 4. In Ca(2+)-free solution, PDBu increased the amount of GTP-RhoA (an activated form of RhoA). This increase was blocked by the PKC inhibitor Ro31-8220, but not by the Rho kinase inhibitor H1152. 5. In conclusion, RhoA/Rho-kinase plays an important role in Ca(2+)-independent contractions induced by PDBu in vascular smooth muscles. The results of the present study suggest that PDBu induces Ca(2+)-independent contractions by inhibiting myosin light chain phospatase (MLCP) through activation of GTP-RhoA and subsequent phosphorylation of MYPT1 and CPI-17.

Correlation between the parameters of signal-averaged ECG and two-dimensional echocardiography in patients with arrhythmogenic right ventricular cardiomyopathy.

BACKGROUND: The correlation between parameters of two-dimensional echocardiography and signal-averaged ECG (SAECG) in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC) is not known well. METHODS: Thirty-three patients (13 females, 40.3 +/- 14.4 years old) were included in this study. Both the right and left ventricular dimensions and systolic function were assessed with two-dimensional echocardiography. The SAECG was performed with high-gain amplification and filtered using bidirectional Butterworth filters between 40 and 250 Hz. We evaluated the correlation between the parameters of the SAECG and two-dimensional echocardiography. RESULTS: The right ventricular (RV) outflow tract was the most frequently (n = 18, 54%) involved segment. Six (18%) patients had only mildly decreased RV systolic function. All the other patients had normal RV systolic function. Although localized left ventricular wall motion abnormalities were observed in 14 (42%) patients, the left ventricular ejection fraction was normal in most (n = 32, 97%). Late potentials were positive in 22 (63%) patients. There was no significant correlation between parameters of the SAECG and two-dimensional echocardiography for the entire patient population. CONCLUSIONS: The SAECG parameters exhibited no correlation to any of two-dimensional echocardiography parameters in the patients with ARVC. Fragmented electrical activity may develop with no significant relation to the anatomical changes in the patients with ARVC.

Intravascular ultrasound guided recanalization of stumpless chronic total occlusion.

BACKGROUND: The recanalization success rate of blunt and vague stump (stumpless) CTO lesions, especially those with a side branch arising from the occlusion, has been significantly lower than that of tapered stump CTO lesions. Intravascular ultrasound (IVUS) may be useful to identify the occlusion point and may facilitate the passage of guide-wires. We evaluated the clinical feasibility of the IVUS-guided wiring technique for stumpless CTO lesions. METHODS: Thirty-one consecutive patients (7 women; mean age: 61.0 ± 8.9 years) with 32 lesions were enrolled. The IVUS catheter was introduced into the side branch and it was withdrawn from the side branch to find the entry point of the occlusion, trying to engage another stiffer guide-wire on the occlusion point with the help of real-time IVUS imaging. RESULTS: The left anterior descending artery was the most common target-lesion location (22 lesions [69%]). CTO lesions were successfully reopened in 26 lesions (81%). IVUS guidance allowed confident navigation of the stiff guide-wires. The entry point could not be identified in one, and full guide-wire passage was impossible in 4 with the IVUS guidance; TIMI 3 flow could not be achieved even after stent deployment in 1. Although procedure-related complications developed in 8 lesions (25%), no events were serious. Emergent operation was not needed and death or fatal myocardial infarction did not develop during or after the procedures. CONCLUSIONS: The IVUS-guided wiring technique is useful and safe for the recanalization of stumpless CTO lesions and might be a valuable tool for the recanalization of complex CTO lesions.

Prevalence of Diabetes Mellitus and Prediabetes in Dalseong-gun, Daegu City, Korea.

BACKGROUND: The aim of the present study was to determine the population-based prevalence of diabetes mellitus (DM) and prediabetes in a rural district of Daegu City, Korea. METHODS: Between August and November 2003, a community-based health survey of adults aged 20 years and older was performed in the rural district of Dalseong-gun in Daegu City. A total of 1,806 of all eligible individuals agreed to participate. Fasting plasma glucose was measured in all participants. Two hour oral glucose tolerance was measured in the 1,773 participants for whom there was neither an established diagnosis of DM nor evidence of DM according to fasting glucose levels. The prevalence of DM and prediabetes was determined according to the 2003 criteria of the American Diabetes Association. Subjects with prediabetes were classified into one of three categories of glucose intolerance: isolated impaired fasting glucose (IFG); isolated impaired glucose tolerance (IGT); or combined IFG and IGT. RESULTS: The prevalence of DM was 12.2%. The highest prevalence rates were observed in subjects in their seventies. A total of 34.7% of all subjects who were assigned a diagnosis of DM in the present study had not been diagnosed previously. The prevalence of prediabetes was 22.7%. The highest prevalence rates were observed in subjects in their fifties. CONCLUSION: The present study identified prevalence rates of 12.2% for DM (age-standardized prevalence rate [ASR], 6.8%), and 22.7% for prediabetes (ASR 18.5%). These results emphasize the need for community health promotion strategies to prevent or delay the onset of DM in individuals with prediabetes.

[Association between gamma-glutamyltransferase and hypertension incidence in rural prehypertensive adults].

OBJECTIVES: Prehypertension is associated with a higher risk of developing hypertension compared with normotension. Yet, factors predicting the development of hypertension among prehypertensive people are ill-understood. This prospective cohort study was performed to examine if serum gamma-glutamyltrasferase (GGT) within a normal range can predict the future risk of hypertension among prehypertensive adults. METHODS: Study subjects were 293 prehypertensive persons >30-years-of-age who participated in a community-based health survey in 2003 and who were followed up in 2008. Sex-specific quartiles of baseline serum GGT were used to examine association with 5-year hypertension incidence. RESULTS: Baseline serum GGT within normal range predicted the risk of developing hypertension for 5 years only in prehypertensive women. Adjusted relative risks were 1.0, 3.7, 3.6, and 6.0 according to quartiles of baseline serum GGT (P for trend <0.01). This pattern was similarly observed in non-drinkers. However, serum GGT was not associated with incident hypertension in men. Different from serum GGT, baseline serum alanine aminotransferase, another well-known liver enzyme, did not predict the risk of incident hypertension in both genders. CONCLUSIONS: Even though baseline serum GGT within normal range strongly predicted the future risk of hypertension, it was observed only in women, Although underlying mechanisms of this association are currently unclear, serum GGT can be used to select a high risk group of hypertension in prehypertensive women.

Electrocardiography patterns and the role of the electrocardiography score for risk stratification in acute pulmonary embolism.

BACKGROUND AND OBJECTIVES: Data on the usefulness of a combination of different electrocardiography (ECG) abnormalities in risk stratification of patients with acute pulmonary embolism (PE) are limited. We thus investigated 12-lead ECG patterns in acute PE to evaluate the role of the ECG score in risk stratification of patients with acute PE. SUBJECTS AND METHODS: One hundred twenty-five consecutive patients (63±14 years, 56 men) with acute PE who were admitted to Kyungpook National University Hospital between November 2001 and January 2008 were included. We analyzed ECG patterns and calculated the ECG score in all patients. We evaluated right ventricular systolic pressure (RVSP) (n=75) and RV hypokinesia (n=80) using echocardiography for risk stratification of acute PE patients. RESULTS: Among several ECG findings, sinus tachycardia and inverted T waves in V(1-4) (39%) were observed most frequently. The mean ECG score and RVSP were 7.36±6.32 and 49±21 mmHg, respectively. The ECG score correlated with RVSP (r=0.277, p=0.016). The patients were divided into two groups {high ECG-score group (n=38): ECG score >12 and low ECG-score group (n=87): ECG score ≤12} based on the ECG score, with the maximum area under the curve. RV hypokinesia was observed more frequently in the high ECG-score group than in the low ECG-score group (p=0.006). Multivariate analysis revealed that a high ECG score was an independent predictor of high RVSP and RV hypokinesia. CONCLUSION: Sinus tachycardia and inverted T waves in V(1-4) were commonly observed in acute PE. Moreover, the ECG score is a useful tool in risk stratification of patients with acute PE.

The impact of circadian variation on 12-month mortality in patients with acute myocardial infarction.

BACKGROUND AND OBJECTIVES: Although circadian variation in the onset of acute myocardial infarction (AMI) has been reported in a number of studies, not much is known about the impact of circadian variation on 12-month mortality. The aim of this study was to investigate the impact of circadian variation on 12-month mortality in patients with AMI. SUBJECTS AND METHODS: Eight hundred ninety two patients (mean age 67±12; 66.1% men) with AMI who visited Kyungpook National University Hospital from November 2005 to December 2007 were included in this study. Patients were divided into groups based on four 6-hours intervals: overnight (00:00-05:59); morning (06:00-11:59); afternoon (12:00-17:59) and evening (18:00-23:59). RESULTS: Kaplan-Meier survival curves showed 12-month mortality rates of 9.6%, 9.1%, 12.1%, and 16.7% in the overnight, morning, afternoon, evening-onset groups, respectively (p=0.012). Compared with the morning-onset AMI group, the serum creatinine levels (p=0.002), frequency of Killip class ≥3 (p=0.004), and prescription rate of diuretics (p=0.011) were significantly higher in the evening-onset AMI group, while the left ventricular ejection fraction (p=0.012) was significantly lower. The proportion of patients who arrived in the emergency room during routine duty hours was significantly lower in evening-onset groups irrespective of the presence or absence of ST-segment elevation (p<0.001). According to univariate analysis, the 12-month mortality rate in the evening group was significantly higher compared to the morning group (hazard ratio 1.998, 95% confidence interval 1.196 to 3.338, p=0.008). CONCLUSION: Patients with evening-onset AMI had poorer baseline clinical characteristics, and this might affect the circadian impact on 12-month mortality. Further studies are needed to clarify the role of circadian variation on the long-term outcome of AMI.

Influence of weather on daily hospital admissions for acute myocardial infarction (from the Korea Acute Myocardial Infarction Registry).

BACKGROUND: We investigated the association between meteorological parameters and hospital admissions for acute myocardial infarction (AMI) in a temperate and continental climate, Korea. METHODS: From the Korean AMI Registry, 2136 Koreans admitted for AMI in four university hospitals in Daegu city from November 2005 to October 2007 were included in this study. We calculated the incidences of AMI per season, per month, and per day-of-week. The meteorological parameters, including air temperature, relative humidity, wind speed, sunshine duration, and a thermo-hydrological index, were provided by the database of the Korea Meteorological Administration. Generalized additive Poisson models were used. RESULTS: Seasonal variations were noted for AMI, characterized by winter peak and summer trough (p<0.001). Monthly occurrence rate of AMI was highest in January and lowest in October (p<0.001). There were significant associations between hospital admissions and meteorological parameters including air temperature, relative humidity, and sunshine duration after controlling for effects of day-of-week, season, and holidays (p<0.05). These associations were stronger in females and the younger age (<65 years) (p<0.01). CONCLUSIONS: The incidence of AMI shows seasonal and monthly variations. Meteorological parameters have a significant influence on the occurrence of AMI, particularly in females and the younger age.

Examining the relationship between triggering activities and the circadian distribution of acute aortic dissection.

BACKGROUND AND OBJECTIVES: There are limited data examining triggering activities and circadian distribution at the onset of acute aortic dissection (AAD) in the context of diagnostic and anatomical classification. The aim of this study was to further investigate this relationship between triggering activities and circadian distribution at the onset of AAD according to diagnostic and anatomic classification. SUBJECTS AND METHODS: A total of 166 patients with AAD admitted to Kyungpook National University Hospital between July 2001 and June 2009 were included. To assess the influence of diagnostic and anatomical classification, we categorized the patients into intramural hematoma (IMH) group (n=67)/non-IMH group (n=99) and Stanford type A (AAD-A, n=94)/type B (AAD-B, n=72). To evaluate circadian distribution, the day was divided into four 6-hour periods: night (00-06 hours), morning (06-12 hours), afternoon (12-18 hours), and evening (18-00 hours). RESULTS: Most (72%) AAD episodes were related to physical (53%) and mental activities (19%), with about one-third occurring during the afternoon, and only 12% occurring at night. No differences in triggering activities or circadian distribution were observed among the groups. Waking hours including morning, afternoon, and evening correlated with triggering activities (p=0.003). These relationships were observed for the non-IMH (p=0.008) and AAD-B (p=0.003) cases. The remaining categories had similar relationships, but did not reach statistical significance. CONCLUSION: Our findings suggest differences in the relationship between triggering activities and the circadian distribution of the onset of AAD according to diagnostic and anatomical classification.

Recurrent catecholamine-induced cardiomyopathy in a patient with a pheochromocytoma.

Pheochromocytomas presents with variable clinical manifestations. Cardiomyopathy caused by a pheochromocytoma is well known. We report the case of a 62-year-old woman with recurrent left ventricular dysfunction, who was subsequently found to have a pheochromocytoma. The patient had two different patterns of cardiomyopathy. Patients with a cardiomyopathy, of non-specific origin, should have a pheochromocytoma ruled out.

Gender differences among korean patients with coronary spasm.

BACKGROUND AND OBJECTIVES: The gender differences among Korean patients with coronary spasm have not been defined. We thus determined the gender differences among Korean patients with coronary spasm. SUBJECTS AND METHODS: Patients with chest pain and/or syncope who were admitted to Kyungpook National University Hospital between January 2001 and August 2008 were included. Provocation of coronary vasospasm with intracoronary ergonovine maleate was performed when baseline coronary angiography showed no significant stenosis or there was a strong clinical suspicion of coronary spasm. The clinical characteristics were analyzed from 104 consecutive patients (56+/-9 years of age; 21 females) who were diagnosed with coronary spasm. RESULTS: Female patients were younger (52+/-7 vs. 57+/-10 years, p=0.046) with lower rates of smoking and alcohol consumption histories than male patients (19% vs. 65%, p<0.001; and 43% vs. 89%, p<0.001, respectively). The other clinical characteristics were not significantly different, except for the triglyceride levels. CONCLUSION: The majority of patients with coronary spasm were males who were smokers and alcohol consumers. The female patients had lower rates of smoking and alcohol consumption, and they were younger than the male patients. Further studies are needed to investigate the relevance of gender differences in the pathogenesis of coronary spasm.