Efficacy of Cryotherapy and Hangeshashinto for Radiation-induced Oral Stomatitis: Preliminary Study.

BACKGROUND/AIM: Radiation-induced stomatitis is one of the main acute disorders in patients with head and neck cancer. Since its treatment is often delayed or discontinued, the control of perioperative oral function is necessary. It has been reported that Hangeshashinto (Japanese traditional herbal medicine) and cryotherapy (known as frozen therapy) alleviate oral stomatitis and the accompanying pain. In the present study, the combination effect of Hangeshashinto and cryotherapy on radiation-induced stomatitis in patients with head and neck cancers was investigated for the first time. PATIENTS AND METHODS: Fifty patients with head and neck cancer were subjected to radiation therapy with concomitant administration of anticancer drugs. They were separated into two groups, matched according to age, stage of cancer progression, total radiation dose, and type of concomitant anticancer drugs. One group was orally administrated frozen Hangeshashinto, while another group was not. Oral mucosal damage was assessed by the grade classification CTCAE v4.0 of the National Cancer Institute of the United States (Japanese JCOG version). Duration time of radiation-induced stomatitis was determined by the appearance of grade 1 redness to its disappearance. RESULTS: Frozen Hangeshashinto significantly alleviated, delayed the onset, and reduced the duration time of the radiation-induced stomatitis. CONCLUSION: Cryotherapy in combination with Hangeshashinto can be used for the treatment of radiation-induced oral stomatitis.

Rationale and study design of the GOREISAN for heart failure (GOREISAN-HF) trial: A randomized clinical trial.

BACKGROUND: The decongestion strategy using loop diuretics is essential for improving signs and symptoms of heart failure (HF). However, chronic use of loop diuretics in HF has been linked to worsening renal function and adverse clinical outcomes in a dose-dependent manner. Goreisan, a traditional Japanese herbal medicine, has a long history of use in Japan for regulating body fluid homeostasis and has been recognized as causing less adverse outcomes such as dehydration in contrast to loop diuretics in clinical practice. Therefore, we designed the GOREISAN-HF trial to evaluate the long-term effects of a new decongestion strategy adding Goreisan to usual care in patients with HF and volume overload. METHODS: The GOREISAN-HF trial is an investigator-initiated, multicenter, pragmatic, randomized, comparative effectiveness trial in which we will enroll 2,192 patients hospitalized for HF at 68 hospitals in Japan. All study participants will be randomly assigned to either a decongestion strategy that adds Goreisan at a dose of 7.5 g daily on top of usual care or usual care alone. Investigators have the flexibility to change the existing diuretic regimen in both groups. The primary end point is the improvement rate of cardiac edema at 12-month follow-up, and the co-primary end point is a composite of all-cause death or hospitalization up to the end of the planned follow-up period. Secondary end points include longitudinal changes in patient-reported outcomes, loop diuretics dose, and renal function. CONCLUSIONS: The GOREISAN-HF is the first large-scale randomized pragmatic trial to assess the efficacy and safety of a new congestion control strategy adding Goreisan to usual care in patients with HF and volume overload. REGISTRATION NUMBER: NCT04691700.

Kampo medicine for the holistic approach to older adults with heart failure.

Heart failure (HF) is a leading cause of hospitalization, morbidity, and mortality in older adults and represents a significant clinical and economic burden on the health care system. However, there are many challenges in assessing and managing HF in elderly patients, who often have coexisting multimorbidity, frailty, and malnutrition. Therefore, it is often difficult to solve these problems with Western medicine alone, and a holistic approach, including Kampo medicine, can be helpful. In particular, managing volume control and frailty by adding Kampo formulas may help improve health-related quality of life and substantially impact prognosis in HF. This review article summarizes the role of Kampo medicine for older patients with HF and frailty.

Successful Management of Refractory Torsades De Pointes Due to Drug-Induced Long QT Syndrome Guided by Point-of-Care Monitoring of Ionized Magnesium.

Ionized magnesium (iMg) is the physiologically active fraction, although total magnesium (tMg) is often used clinically because a dedicated electrode is required to measure the iMg concentration. The tMg concentration is not correlated with the iMg concentration, especially in severely ill patients. In this report, a case of refractory torsades de pointes (TdP) due to drug-induced long QT syndrome was successfully treated with high-dose magnesium sulfate guided by point-of-care monitoring of the iMg concentration. A woman in her 60s had taken osimertinib for two months to treat lung cancer. TdP occurred after the operation of a thoracic compression fracture under general anesthesia. She was diagnosed with drug-induced long QT syndrome. TdP continued, despite treatment with 6 g magnesium sulfate. The iMg value on the admission to the intensive care unit was 0.92 mmol/L, but TdP occurred intermittently and circulatory dynamics were unstable. After an additional intravenous administration of 1 g magnesium sulfate, continuous intravenous administration was initiated at 1 g/h. TdP terminated when the iMg concentration reached 1.31 mmol/L. Then, the target iMg was set to 1.3 mmol/L. The iMg concentration was measured every two hours to adjust the continuous dose of magnesium sulfate. Magnesium administration was tapered, and she was transferred to a general ward on the third day. She was discharged without complications on the 11th day. Point-of-care monitoring of the iMg concentration and observation of the patient's clinical symptoms were important for the effective and safe treatment of TdP due to drug-induced long QT syndrome.

Changes in self-reported physical activity and health-related quality of life following 3-month astaxanthin supplementation in patients with heart failure: results from a pilot study.

BACKGROUND: Astaxanthin has a strong antioxidant effect. We recently demonstrated that following 3-month astaxanthin supplementation, cardiac contractility and exercise tolerance improved, possibly through the suppression of oxidative stress in a small pilot study involving patients with heart failure with left ventricular systolic dysfunction. This is a sub-study of our pilot study to investigate whether improvements of selfreported physical activity and health-related quality of life were observed following 3-month astaxanthin supplementation. METHODS: We investigated the changes in physical activity by the Specific Activity Scale score and healthrelated quality of life by physical and mental component summary scores in Short Form-8 at baseline and after 3-month astaxanthin supplementation. RESULTS: Data from 17 patients with heart failure were assessed. Following 3-month astaxanthin supplementation, the Specific Activity Scale score increased from the median of 4.5 (interquartile range, 2.0) to 6.5 (interquartile range, 1.1) metabolic equivalent (P=0.001), and the physical and mental component summary scores increased from 46.1±9.2 to 50.8±6.8 (P=0.015) and from 48.9±9.1 to 53.8±4.8 (P=0.022), respectively. There was a linear relationship of the baseline heart rate, or mental component summary score with the percent change in the Specific Activity Scale score (r=0.523, P=0.031 and r=-0.505, P=0.039, respectively). In addition, there was a direct relationship of ischemic etiology with the percent change in the physical component summary score (r=0.483, P=0.049, respectively). Finally, there was a linear relationship between the percent change in the Specific Activity Scale score and that in the mental component summary score (r=0.595, P=0.012). CONCLUSIONS: Following 3-month astaxanthin supplementation, improvements of the self-reported physical activity level and health-related quality of life in both mental and physical components were observed. In patients with heart failure, those with higher baseline heart rate, ischemic etiology, and poorer baseline health-related quality of life have potentials to have greater improvement of physical activity and/or health-related quality of life.

Effects of 3-Month Astaxanthin Supplementation on Cardiac Function in Heart Failure Patients with Left Ventricular Systolic Dysfunction-A Pilot Study.

Astaxanthin has strong antioxidant properties. We conducted a prospective pilot study on heart failure (HF) patients with left ventricular (LV) systolic dysfunction to investigate improvements in cardiac function and exercise tolerance in relation to suppression of oxidative stress by 3-month astaxanthin supplementation. Oxidative stress markers-serum Diacron reactive oxygen metabolite (dROM), biological antioxidant potential (BAP), and urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) concentrations, LV ejection fraction (LVEF), and 6-min walk distance (6MWD) were assessed before and after 3-month astaxanthin supplementation. Finally, the data of 16 HF patients were analyzed. Following 3-month astaxanthin supplementation, dROM level decreased from 385.6 ± 82.6 U.CARR to 346.5 ± 56.9 U.CARR (p = 0.041) despite no changes in BAP and urinary 8-OHdG levels. LVEF increased from 34.1 ± 8.6% to 38.0 ± 10.0% (p = 0.031) and 6MWD increased from 393.4 ± 95.9 m to 432.8 ± 93.3 m (p = 0.023). Significant relationships were observed between percent changes in dROM level and those in LVEF. In this study, following 3-month astaxanthin supplementation, suppressed oxidative stress and improved cardiac contractility and exercise tolerance were observed in HF patients with LV systolic dysfunction. Correlation between suppression of oxidative stress and improvement of cardiac contractility suggests that suppression of oxidative stress by astaxanthin supplementation had therapeutic potential to improve cardiac functioning.

Decreased circulating dihomo-gamma-linolenic acid levels are associated with total mortality in patients with acute cardiovascular disease and acute decompensated heart failure.

BACKGROUND: Polyunsaturated fatty acids (PUFAs) have important roles in the pathogenesis of cardiovascular diseases. However, the clinical significance of omega-6 PUFAs in acute cardiovascular disease remains unknown. METHODS: We enrolled 417 consecutive patients with acute cardiovascular disease admitted to the cardiac intensive care unit at Juntendo University Hospital between April 2012 and October 2013. We investigated the association between serum PUFA levels and long-term mortality. Blood samples were collected after an overnight fast, within 24 h of admission. We excluded patients who received eicosapentaenoic acid therapy and those with malignancy, end-stage kidney disease, chronic hepatic disease, and connective tissue disease. RESULTS: Overall, 306 patients (mean age: 66.4 ± 15.0 years) were analysed. During the follow-up period of 2.4 ± 1.2 years, 50 patients (16.3%) died. The dihomo-gamma-linolenic acid (DGLA) levels, arachidonic acid (AA) levels, and DGLA/AA ratio were significantly lower in the nonsurvivor group than in the survivor group (DGLA: 23.2 ± 9.8 vs. 31.5 ± 12.0 µg/ml, AA: 151.1 ± 41.6 vs. 173.3 ± 51.6 µg/ml, and DGLA/AA: 0.16 ± 0.05 vs. 0.19 ± 0.06, all p < 0.01). Kaplan-Meier curves showed that survival rates were significantly higher in the higher DGLA, AA, and DGLA/AA groups than in their lower counterparts (DGLA and AA; p < 0.01, DGLA/AA; p = 0.01), although omega-3 PUFAs were not associated with prognosis. Furthermore, in patients with acute decompensated heart failure (ADHF), survival rates were significantly higher in the higher DGLA, AA, and DGLA/AA groups than in their lower counterparts (DGLA and AA; p < 0.01, DGLA/AA; p = 0.04). However, among patients with acute coronary syndrome, none of the PUFA levels were associated with prognosis. Among patients with ADHF, after controlling for confounding variables, DGLA and DGLA/AA were associated with long-term mortality [DGLA: hazard ratio (HR), 0.94; 95% confidence interval (CI), 0.88-0.99; p = 0.01 and DGLA/AA: HR, 0.87; 95% CI, 0.77-0.97; p < 0.01], whereas AA was not associated with prognosis. CONCLUSION: Low omega-6 PUFA levels, particularly DGLA, and a low DGLA/AA ratio predict long-term mortality in patients with acute cardiovascular disease and ADHF. TRIAL REGISTRATION: UMIN-CTR; UMIN000007555 .

Anti-inflammatory Activity of Hangeshashinto in IL-1ß-stimulated Gingival and Periodontal Ligament Fibroblasts.

Although a large number of Kampo, Japanese traditional medicines, have been used for the treatment of oral diseases, little is known on their relative potency and endotoxin contamination. In order to obtain basic data for clinical applications, 10 Kampo, and 25 constituent plant extracts were tested for the contamination of lipopolysaccharide (LPS)-like substances, and anti-inflammatory activity. Human gingival (HGF) and periodontal ligament fibroblasts (HPLF) were cultured in 10% fetal bovine serum supplemented with Dulbecco's modified Eagle's medium. Viable cell number was measured by 3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide method. Prostaglandin (PGE2) was determined by enzyme immunoassay. Cyclo-oxygenase (COX)-1 and COX-2 protein expressions were determined by western blot. COX activity was measured using Cox Inhibitor Screening Assay Kit. LPS, quantified by Endotoxin assay kit, was undetectable or relatively low in the test samples except for rikkosan and unseiin. Hangeshashinto potently inhibited PGE2 production by interleukin (IL)-1ß-stimulated HPLFs and HGFs. Hangeshashinto suppressed the expression of COX-2 protein, but not that of COX-1 protein in IL-1ß-induced HGF cells. Hangeshashinto slightly, but not significantly, inhibited both COX-1 and COX-2 activity. The present study provides the basis for clinical application of hangeshashinto for the treatment of stomatitis.

Anti-inflammatory potential of Rikkosan based on IL-1ß network through macrophages to oral tissue cells.

Rikkosan is a traditional Kampo medicine using the control of oral pain caused by dental caries, pulpitis, periodontitis and stomatitis. In order to provide evidence for its clinical effects, we herein investigated whether Rikkosan inhibits the production of pro-inflammatory substances in human and mouse models of inflammation. Rikkosan alone did not induce prostaglandin E2 (PGE2) production, but inhibited interleukin-1ß (IL-1ß) (5 ng/ml)-stimulated PGE2 production in human gingival fibroblasts and human periodontal ligament fibroblasts, with a selectivity index higher than 4.0 and 4.3, respectively. Rikkosan alone dose-dependently stimulated tumor necrosis factor-α (TNF-α) production, reaching a peak level slightly lower than that attained by lipopolysaccharide (LPS) at 0.4 mg/ml in mouse macrophage-like RAW264.7 cells. At a higher concentration of Rikkosan (4 mg/ml), TNF-α production, however, declined significantly regardless of the presence or absence of LPS. Rikkosan dose-dependently inhibited IL-1ß production by LPS-stimulated RAW264.7 cells, with a selective index of 7.6. Five constituent extracts of Rikkosan, either alone or in combination, showed similar effects on TNF-α and IL-1ß productions in activated RAW264.7 cells, but to lower extents than that of Rikkosan. These results demonstrated that Rikkosan inhibited both IL-1ß production by LPS-activated macrophages and PGE2 production by IL-1ß-stimulated human gingival fibroblasts and human periodontal ligament fibroblasts, suggesting that anti-inflammatory effects of Rikkosan may partially be generated by the inhibition of these pro-inflammatory substances via the IL-1ß network through macrophages to oral tissue cells.

Anti-UV activity of Kampo medicines and constituent plant extracts: re-evaluation with skin keratinocyte system.

AIM: In order to search for new biological activity of Kampo medicines and their constituent plant extracts, we investigated their ability to protect the cells from UV irradiation (referred to as 'anti-UV activity') using the human immortalised skin keratinocyte cell line HaCaT. MATERIALS AND METHODS: Anti-UV activity was represented by the selectivity index (SI), defined as the ratio of the concentration that reduced the viable cell number by 50% to the concentration that increased the viability of UV-irradiated cells to 50%. RESULTS: HaCaT cells were highly resistant to UV irradiation, approximately 20% of cells survived even when the exposure time was prolonged to 480 min. Sodium ascorbate, a popular antioxidant, used as positive control, had excellent anti-UV activity (SI=200). Among 10 Kampo medicines, Shosaikoto (SI=34) had the highest anti-UV activity, followed by Hangesyashinto (SI>28), Unseiin (SI>23) and Ninjinyoeito (SI=23), Saireito (SI>19), whereas another four Kampo medicines were much less active (SI<9.6). Among 25 constituent plant extracts, Scutellaria root had the highest anti-UV activity (SI=38), followed by Polyporus sclerotium (SI>26), Gardenia fruit (SI>23), Japanese Gentian (SI>20) and Saposhnikovia root (SI>20). Glycyrrhizin also had potent anti-UV activity (SI=36). The SI values determined with the present HaCaT system were generally one order higher than those obtained with previously reported HSC-2 human oral squamous cell carcinoma system, although there was good correlation between these two systems (R(2)=0.9118). Conclusion. The present study highlights the improved sensitivity of anti-UV activity detection with the HaCaT system, and suggests the possible application of Kampo medicines as a component of sunscreening cosmetics.

Anti-UV/HIV activity of Kampo medicines and constituent plant extracts.

AIM: In order to search for new biological activities of Kampo medicines and their constituent plant extracts, we investigated whether they protect the cells from the cytotoxicity induced by UV irradiation and human immunodeficiency virus (HIV) infection. MATERIALS AND METHODS: Anti-UV/HIV activity (SI value) was evaluated as the ratio of the CC(50) (concentration that reduced the viable cell number by 50%) to the EC(50) (the concentration that increased the viability of UV-irradiated or HIV-infected cells to 50%): SI=CC(50)/EC(50). The content of glycyrrhizin in each sample was determined by high performance liquid chromatography (HPLC). Caspase-3/-7 activity was assayed by cleavage of poly ADP ribose polymerase using western blot analysis. RESULTS: Among 25 plant extracts, Gardenia fruit had the highest anti-UV activity (SI≥8.0), followed by Glycyrrhiza (SI=4.3), Coptis rhizoma (SI=1.5), Cimicifuga rhizoma (SI>1.4), Saposhnikovia root (SI>1.3) and Japanese Gentian (SI>1.1). Among ten Kampo medicines, Unseiin and Hangesyashinto (SI>4.9) had the highest anti-UV activity, followed by Shosaikoto (SI>4.3), Saireito (SI>3.4), Rikkosan (SI>1.2) and Kikyoto (SI=1.1). Glycyrrhiza inhibited UV-induced caspase-3/-7 activation. Only Polyporus sclerotium (SI>4.4), Gardenia fruit (SI>2.7), Atractylodes lancea rhizoma (SI>1.9), Cnidium rhizoma (SI>1.5) and Japanese Angelica root (SI>1.1) exhibited some anti-HIV activity. There was no apparent correlation of their anti-UV/HIV activity and content of glycyrrhizin, a major component of Glycyrrhiza, which exhibited much higher anti-UV activity (SI=20.6) and some anti-HIV activity (SI>2.0). CONCLUSION: The present study suggests the involvement of substances other than glycyrrhizin in the anti-UV/HIV activity of Kampo medicines and their constituent plant extracts.

Respiratory cycle-dependent atrial tachycardia: prevalence, electrocardiographic and electrophysiologic characteristics, and outcome after catheter ablation.

BACKGROUND: Little is known about the tachyarrhythmias relating to respiration. Case reports presented patients with respiratory cycle-dependent atrial tachycardias (RCATs), which cyclically emerge after starting inspiration and cease during expiration. OBJECTIVE: The aim of the present study was to elucidate the prevalence, characteristics, and long-term outcome after radiofrequency catheter ablation (RFCA) of RCATs. METHODS: The electrocardiographic and electrophysiologic properties and results of RFCA were analyzed in 60 patients with a total of 71 focal atrial tachycardias (ATs). RESULTS: Nine RCATs (13%) were observed in 7 patients (12%). RCATs were irregular, with a mean cycle length ranging from 220 to 650 ms, and developed incessantly accounting for 32% ± 14% of the 24-hour heartbeats. The P-wave morphology was positive or biphasic (positive to negative) in V1, and positive in I and II. The electroanatomical mapping demonstrated a centrifugal activation pattern, with the earliest site located at the antrum of the right superior pulmonary vein (RSPV), inside the RSPV, and inside the superior vena cava (SVC) in 4, 2, and 3 RCATs, respectively. Radiofrequency energy delivery at the earliest site or the electrical isolation of the RSPV and SVC suppressed all RCATs. During a follow-up of 25 ± 15 months, 1 RCAT recurred and was eliminated in a second procedure. CONCLUSION: RCATs were observed in 13% of the focal ATs. As presumed from the P-wave morphologies, their foci converged around the RSPV or inside the SVC. RFCA was effective to eliminate RCATs.

Inhibition of prostaglandin E2 production by flavone and its related compounds.

We have previously reported that among 12 major ingredients of Sairei-to, Scutellariae radix inhibited prostaglandin E(2) (PGE(2)) production by lipopolysaccharide (LPS)-activated mouse macrophage-like RAW264.7 cells more efficiently than other ingredients, and wogonin, a major flavonoid from Scutellariae radix, showed greater inhibitory activity and membrane permeability than baicalein and baicalin. Here the effects of six other flavonoids, with similar structures, on membrane permeability and PGE(2) production were investigated. 7-Methoxyflavone inhibited the LPS-stimulated PGE(2) production to the greatest extent, followed by flavone>wogonin (5,7-dihydroxy-8-methoxyflavone)>> 7,8-dimethoxyflavone>chrysin (5,7-dihydroxyflavone)> baicalein (5,6,7-trihydroxyflavone)>>chromone. 7-Methoxyflavone also showed the highest membrane permeability, followed by flavone>chrysin>7,8-dimethoxy-flavone>wogonin>baicalein. When PGE(2) inhibitory activity was expressed per molecule incorporated into the cells, wogonin produced the greatest inhibition, further substantiating its anti-inflammatory potency.

Effect of Scutellariae radix ingredients on prostaglandin E(2) production and COX-2 expression by LPS-activated macrophage.

We previously reported that Sairei-to concentration-dependently modified lipopolysaccharide (LPS)-stimulated prostaglandin E(2) (PGE(2)) production in mouse macrophage-like RAW264.7 cells. Among twelve major ingredients of Sairei-to, Scutellariae radix inhibited the LPS-stimulated PGE(2) production to the greatest extent, followed by Zingiberis rhizoma, Glycyrrhizae radix, Atractylodis lanceae rhizoma and Pinelliae tuber. Scutellariae radix contained several major flavonoids such as baicalin, baicalein and wogonin. We investigated the effect of these flavonoids on PGE(2) production and COX-2 expression by LPS-activated RAW264.7 cells. Wogonin inhibited PGE(2) production most efficiently, followed by baicalein and then baicalin, in the same order as their membrane permeability. It was unexpected that wogonin and all other compounds would fail to inhibit the expression of COX-2 at both protein and mRNA levels, suggesting the importance of re-evaluating the point of action of wogonin.

Effect of Sairei-to and its ingredients on prostaglandin E2 production by mouse macrophage-like cells.

Sairei-to and its twelve ingredients were investigated for their activity to stimulate prostaglandin E2 (PGE2) production by unstimulated and lipopolysaccharide (LPS)-stimulated mouse macrophage-like RAW 264.7 cells. LPS significantly stimulated the production and extracellular secretion of PGE2 by RAW 264.7 cells. Sairei-to concentration-dependently modified the LPS-stimulated PGE2 production. Among Sairei-to ingredients, Scutellariae radix inhibited the LPS-stimulated PGE2 production to the greatest extent, followed by Zingiberis rhizoma, Glycyrrhizae radix, Atractylodis lanceae rhizoma and Pinelliae tuber. On the other hand, Bulpeuri radix, Alismatis rhizoma, Zizyphi fructus, Polyporus, Hoelen, ginseng radix and Cinnamomi cortex further enhanced the LPS-stimulated PGE2 production. Western blot analysis demonstrated that Sairei-to unexpectedly enhanced the expression of cyclooxygenase-2 (COX-2) protein level, but did not significantly affect phospholipase A2 protein level. The present study suggests that the modification of the enzyme activity of COX-2 may be involved in the concentration-dependent effect of Sairei-to on PGE2 production by macrophages.

Bimodal effect of glycyrrhizin on macrophage nitric oxide and prostaglandin E2 production.

Glycyrrhizin is a major constituent of Kanzo, a popular herbal medicine used in food and cosmetics. Glycyrrhizin alone did not stimulate nitric oxide (NO) or prostaglandin E2 (PGE2) production by RAW 264.7 cells, but modified lipopolysaccharide (LPS)-stimulated NO and PGE2 production in a bimodal fashion: it was stimulatory at lower concentrations, whereas it was inhibitory at higher concentrations. Electron-spin resonance spectroscopy showed that glycyrrhizin slightly scavenged the superoxide anion generated by hypoxanthine-xanthine oxidase reaction, but did not scavenge the DPPH and NO radicals. The present study demonstrates the concentration-dependent action of glycyrrhizin on both PGE2 and NO production by activated macrophages.

COX-2 as possible target for the inhibition of PGE2 production by Rikko-san in activated macrophage.

We have previously reported that Rikko-san (RKS) inhibited the lipopolysaccharide (LPS)-stimulated prostaglandin (PG) E2 in mouse macrophage-like RAW264.7 cells without affecting the expression of cyclooxygenase (COX)-2. Here RKS inhibition of the enzyme activity of both COX-1 and COX-2 proteins was investigated. Western blot analysis showed that RKS did not significantly change the S-nitrosylated COX-2 protein level. On the other hand, RKS inhibited the PG production catalyzed by purified COX-2, more effectively than that catalyzed by purified COX-1. These results suggest that RKS inhibits the PGE2 production by selectively inhibiting the COX-2 activity in activated macrophages.

Autologous blood injection into the articular cavity for the treatment of recurrent temporomandibular joint dislocation: a case report.

Autologous blood injection around the articular capsule and/or into the articular cavity, which is one of the treatments for recurrent temporomandibular joint dislocation, was recently reintroduced. Here, we present the management of recurrent temporomandibular joint dislocation by autologous blood injection in an 84-year-old female. After the treatment, although the right condylar process had settled just beneath the articular tubercle, the dislocation had improved and the patient was able to close her mouth without difficulty.

Predictive value of microvolt T-wave alternans for sudden cardiac death in patients with preserved cardiac function after acute myocardial infarction: results of a collaborative cohort study.

OBJECTIVES: We conducted a collaborative cohort study to evaluate the predictive power of microvolt T-wave alternans (TWA) in patients with preserved left ventricular ejection fraction (LVEF) after myocardial infarction (MI). BACKGROUND: There is little information available about the prognostic value of risk stratification markers in this population. Although these patients have a relatively good prognosis, identifying high-risk patients is important in clinical practice. METHODS: This study enrolled 1,041 post-MI patients with an LVEF > or =40% (average 55 +/- 10%). Microvolt TWA testing was performed 48 +/- 66 days after acute MI, and 10 other risk variables were also evaluated. The end points were prospectively defined as sudden cardiac death or life-threatening arrhythmic events. RESULTS: During a follow-up of 32 +/- 14 months, 38 patients (3.7%) died of nonarrhythmic causes and were not considered for analysis. Of the 1,003 evaluable patients, 18 (1.8%) reached an end point. Microvolt TWA was positive in 169 patients (17%), negative in 747 (74%), and indeterminate in 87 (9%). A positive microvolt TWA test, nonsustained ventricular tachycardia, and ventricular late potentials were predictors of events, and percutaneous coronary intervention decreased the risk rate. On multivariate analysis, a positive microvolt TWA test was the most significant predictor, with a hazard ratio of 19.7 (p < 0.0001). This marker had the highest sensitivity and negative predictive value for events. CONCLUSIONS: In patients with preserved cardiac function, the incidence of indeterminate results of microvolt TWA is low, and a positive test result is associated with arrhythmic events. Microvolt TWA could be used for risk stratification in this low-risk population.