In order to study the effect of muscle exercise on the medical expenditure of the elderly, a three-year exercise program focusing on muscle activity was performed by an intervention group. Individual yearly medical expenditures were collected by 20 participants of the exercise group aver aging 65.2 years of age and 23 control subjects averaging 68.4 years of age with National Health Insurance coverage. Yearly medical expenditures for the exercise group were significantly lower than those of the control group at one and two years after entry. The expenditures increased by 62.6% from 1997 to 1999 in the control group, whereas they increased by only 16.8% for the exer cise group. The results suggest the possibility of the effectiveness of muscle exercise on the reduction in medical expenditure among the elderly.

Objectives Left ventricular systolic dyssynchrony is the most important determinant of response to cardiac resynchronization therapy (CRT), playing a vital role to predict improvement of systolic function or LV reverse remodeling. CardioGRAF is a novel programmer based on the ECG gated single photon emission computed tomography (G-SPECT) imaging to detect LV systolic and diastolic dyssynchrony simultaneously. This study was to investigate the prevalence of systolic and diastolic left ventricular (LV) dyssynchrony in patients with heart failure. Methods We retrospectively studied 69 patients with heart disease, including 31 patients who had symptoms of heart failure (NYHA class Ⅱ-Ⅲ), and 38 patients who had no symptoms of heart failure (NYHA class Ⅰ). G-SPECT data were analyzed by cardiaGRAF, and measurements included the time to end systole (TES), the time to peak ejection (TPE), the time to peak filling (TPF), TES+TPF and maximal difference (MD) of each parameters were obtained, using the 95th percentile of the control group as a cutoffof 150 ms for MD-TES, 139 ms for MD-TPE, 345 ms for MD-TPF and 315 ms for MD-TES+TPF. Results The prevalence of LV systolic dyssynchrony was significantly higher in heart failure patients with reduced LV ejection fraction (LVEF)<45% (72% for MD-TES; 64% for MD-TPE) compared with heart failure patients with preserved LVEF=45% (14% for both MD-TES and MD-TPE; P=0.002, P=0.005, respectively); The prevalence of MD-TES<150 ms was higher in NYHA class Ⅲ patients (64%) compared with NYHA class Ⅱ patients (27%, P=0.049). However, the prevalence of the LV diastolic dyssynchrony were high but not difference between NYHA class Ⅲ(47% for both MD-TPF and MD-TES+TPF) and class Ⅲ(63% for MD-TPF; 69% for MD-TES+TPF; P=NS) patients as well as between patients with preserved LVEF (43% for both MD-TPF and MD-TES+TPF) and patients with reduced LVEF(64% for MD-TPF; 72% for MD-TES+TPF; P=NS). Conclusions The prevalence of LV systolic dyssynchrony was high in heart failure patients with reduced LVEF. Diastolic dyssynchrony was common in patients with heart failure. CardioGRAF maybe a useful method to detect LV dyssynchrony.

A 42-year-old woman with antiphospholipid syndrome (APLS) secondary to systemic lupus erythematosus (SLE) complicated with thrombocytopenic purpura was successfully treated by mitral valve replacement with a mechanical prosthesis and tricuspid valve annuloplasty for mitral valve stenosis and regurgitation due to Libman-Sacks endocarditis. Intraoperative hemorrhagic oozing due to thrombocytopenia was effectively managed with platelet transfusion. Negative microbial culture and pathological examination of the resected mitral valve demonstrated an atypical sterile verrucose lesion, the findings of which were typically characteristic of Libman-Sacks endocarditis in SLE. She was successfully discharged 31 days after the operation without any hemorrhagic or thromboembolic events. However, 100 days after surgery, she suffered from fatal cerebral infarction caused by poor Coumadin compliance. Regarding the prosthetic valve selection, it is reasonable to select the mechanical valve because 1) anticoagulation therapy is necessary for APLS, 2) the risk of the dialysis induction due to the lupus-induced renal failure leading to a high calcium turnover, which results in accelerated bioprosthetic valve calcification. In case of SLE with APLS, in which anticoagulation and antiplatelet therapy is required to prevent the thromboembolic event and thrombocytopenic purpura, after valve replacement, strict management of anticoagulation plays an essential role to prevent thromboembolic complication.

We studied the effects of exercise on the blood fluidity. The subjects were 18 healthy males (21.6±0.8 yr, control : 5, soccer : 9, gymnastics : 4) . We measured the filtration time of whole blood by the Nuclepore filtration method as an index of blood fluidity. The filtration time at rest in the control group, soccer group, and gymnastics group was 59.8±11.9s, 42.5±15.1 s, 28.6±6.7s, respec tively. The filtration time at rest in the soccer group was significantly shorter than that in the control group (p<0.001) . There were no significant differences in filtration time at rest between the control and gymnastics groups, and between the soccer and gymnastics groups. The filtration time after single aerobic exercise was significantly prolonged compared with that before (p<0.001) . The filtration time before and after anaerobic exercise and muscular exercise was not significantly changed. The degree of filtration time prolongation was significantly lower in groups who drank water compared to groups who did not (p<0.001) . The effect of taking a sauna on filtration time was not significant. These results indicates the effect of aerobic exercise on blood fluidity, and the importance of water intake during exercise.

In the EU, signal management guideline is defined as GVP Module Ⅸ “Signal Management”, where the signal management is defined as a set of activities performed to determine whether, based on an examination individual case safety reports (ICSRs), aggregated data from active surveillance systems or studies, scientific literature information or other data sources, there are new risks associated with an active substance or a medicinal product or whether known risks have changed, as well as any related recommendations, decisions, communications and tracking. The EU signal management process includes the following activities : signal detection, signal validation, signal confirmation, signal analysis and prioritisation, signal assessment and recommendation for action.WHO and FDA have also published similar guidance in various documents. Furthermore, the social medial has become another source of signal. It is also very important to review preapproval clinical trial data. This is because, in recent years, there are increased number of drugs with a major problem due to cardiovascular risk or suicide, but such signals often appeared in clinical trial data.Traditional qualitative signal detection method is fundamental to signal detection. However, for regulators that have to monitor all drugs, statistical signal detection and its prioritization are indispensable and various methods have been implemented. For pharmaceutical companies, the need for prioritization itself is small, but the concept is very helpful in the planning of subsequent measures.In signal evaluation, post-authorization safety study in EU and postmarketing requirement in FDA are very important. For regulatory notification of recommended actions, one should consider signal prioritization elements.In Japan, the routine pharmacovigilance activities sufficient within the scope of local GVP as the enforcement regulations of the PMR Law. But for future routine pharmacovigilance activities, we must work on signal detection and evaluation of signals which are difficult to detect including cardiovascular risk, suicide, and carcinogenesis.

OBJECTIVE: A recent study suggested that rs6504340, a polymorphism within the homeobox B (HOXB) gene cluster, is associated with the susceptibility for malocclusions in Europeans. The resulting malocclusions require orthodontic treatment. The aim of this study was to investigate the association of rs6504340 and other dentition-implicated polymorphisms with dental and occlusal traits in Korean and Japanese populations. METHODS: The study participants included 223 unrelated Koreans from the Busan area and 256 unrelated Japanese individuals from the Tokyo metropolitan area. DNA samples were extracted from saliva specimens. Genotyping for rs6504340 and four single nucleotide polymorphisms (SNPs) that have been shown to be associated with the timing of first tooth eruption and the number of teeth at 1 year of age (rs10506525, rs1956529, rs9674544, and rs8079702) was performed using TaqMan assays. The Index of Orthodontic Treatment Need (IOTN), overjet, overbite, arch length discrepancy, crown sizes, and length and width of the dental arches were measured. Spearman's correlation coefficients were calculated to evaluate relationships between rs6504340 and these dental/occlusal traits. RESULTS: We evaluated the aesthetic components and dental health components of the IOTN in the Korean and Japanese populations and found that neither rs6504340 nor the other four SNPs showed any association with dental and occlusal traits in these East Asian populations. CONCLUSIONS: These negative results suggest that further research is needed to identify the genetic determinants of malocclusions in order to reach a consensus.
Asian Continental Ancestry Group* ; Busan ; Consensus ; Crowns ; Dental Arch ; DNA ; Genes, Homeobox ; Genetics ; Humans ; Index of Orthodontic Treatment Need ; Malocclusion ; Multigene Family ; Overbite ; Polymorphism, Single Nucleotide ; Saliva ; Tooth Eruption* ; Tooth*

BACKGROUND/AIMS: The present study aimed to clarify whether virological response within 2 weeks after therapy initiation can predict a null response to pegylated interferon alpha-2b plus ribavirin therapy in patients with high viral load genotype 1b hepatitis C. METHODS: The participants consisted of 72 patients with high viral load genotype 1b. The dynamics of viral load within 2 weeks were measured. RESULTS: Significant differences between null responders and nonnull responders were noted for interleukin (IL)-28B genotype, amino acid 70 substitution, alpha-fetoprotein, low-density lipoprotein cholesterol, hyaluronic acid, and viral response. The area under the curve (AUC) for the receiver operating characteristic curve of the hepatitis C virus (HCV) RNA level decline at 2 weeks (AUC=0.993) was the highest among the factors predicting the null response. When the cutoff value for the HCV RNA level decline at 2 weeks was set at 0.80 log, the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy in predicting a null response were 82%, 96%, 82%, 96%, and 94%, respectively. In comparison, values for the non-TT and mutant type of amino acid 70 substitution were similar to those for HCV RNA level decline at 2 weeks. CONCLUSIONS: Virological response at 2 weeks or the combination of IL-28B and amino acid 70 substitution are accurate predictors of a null response.
Administration, Oral ; Adult ; Aged ; Antiviral Agents/*administration & dosage ; Area Under Curve ; Drug Therapy, Combination ; Female ; Genotype ; Hepatitis C, Chronic/*drug therapy/genetics ; Humans ; Injections, Subcutaneous ; Interferon-alpha/*administration & dosage ; Male ; Medication Adherence ; Polyethylene Glycols/*administration & dosage ; Prospective Studies ; RNA, Viral/metabolism ; Recombinant Proteins/administration & dosage ; Ribavirin/*administration & dosage ; Treatment Outcome ; Viral Load ; Young Adult

OBJECTIVE: This study aimed to evaluate the efficacy of magnetic resonance (MR) imaging in differentiating between cutaneous basal cell carcinoma (cBCC) and cutaneous squamous cell carcinoma (cSCC) in the head and neck region.MATERIALS AND METHODS: Among patients with cutaneous head and neck cancers, 14 with primary cBCCs and 15 with primary cSCCs with a histologic tumor height of ≥ 4 mm underwent MR examinations; the findings were then examined for correlations.RESULTS: cBCCs (71%) occurred more frequently on the nose than cSCCs (13%) (p < 0.01). The maximum diameter (23.5 ± 7.2 mm vs. 12.7 ± 4.5 mm; p < 0.01) and diameter-to-height ratio (2.8 ± 0.9 vs. 1.7 ± 0.4; p < 0.01) were significantly greater in cSCCs than in cBCCs. Superficial ulcer formation (67% vs. 21%; p < 0.05), protrusion into the subcutaneous tissue (60% vs. 21%; p < 0.05), ill-demarcated deep tumor margins (60% vs. 7%; p < 0.01), and peritumoral fat stranding (93% vs. 7%; p < 0.01) were more frequently observed in cSCCs than in cBCCs. Intratumoral T2-hyperintense foci (57% vs. 13%; p < 0.05) were more frequently observed in cBCCs than in cSCCs.CONCLUSION: cBCCs predominantly occurred on the nose with intratumoral T2-hyperintense foci, whereas cSCCs predominantly exhibited a flattened configuration, superficial ulcer formation, protrusion into the subcutaneous tissue, ill-demarcated deep tumor margin, and peritumoral fat stranding.
Carcinoma, Basal Cell ; Carcinoma, Squamous Cell ; Epithelial Cells ; Head ; Humans ; Magnetic Resonance Imaging ; Neck ; Nose ; Skin Neoplasms ; Subcutaneous Tissue ; Ulcer

Methods: HFCs were obtained from patients with LSS who underwent surgery. HFCs were stimulated by tumor necrosis factor-α (TNF-α) and a p38 MAP kinase inhibitor, SB203580. Phosphorylation of the p38 MAP kinase was analyzed by western blotting. The concentration of interleukin-6 (IL-6) in the conditioned medium was measured by enzyme-linked immunoassay and IL-6 messenger RNA expression levels were determined by real-time polymerase chain reaction. Results: TNF-α induced the phosphorylation of p38 MAP kinase in a time-dependent manner, which was suppressed by the p38 MAP kinase inhibitor, SB203580. TNF-α also stimulated IL-6 release in both a time- and dose-dependent manner. On its own, SB203580 did not stimulate IL-6 secretion from HFCs; however, it dramatically suppressed the degree of IL-6 release stimulated by TNF-α from HFCs. Conclusions This is the first report suggesting that TNF-α stimulates the gene expression and protein secretion of IL-6 via p38 MAP kinase in HFCs. A noted association between tissue hypertrophy and inflammation suggests that the p38 MAP kinase inflammatory pathway may be a therapeutic molecular target for LSS.