Prediction protocol for neurological outcome for survivors of out-of-hospital cardiac arrest treated with targeted temperature management

Aim

To identify patients who can obtain the full benefit from targeted temperature management (TTM) after out-of-hospital cardiac arrest.

Methods

We performed a retrospective observational study of comatose patients treated with TTM after an out-of-hospital cardiac arrest from January 2006 to February 2011. Neurological outcome was evaluated with the Glasgow-Pittsburgh Cerebral Performance category (CPC) at discharge and predictors were determined.

Results

Of 66 patients studied, 40 (60.6%) survived to neurologically intact discharge (CPC 1 or 2). According to multivariate analysis, predictors of good neurological outcome included arrest-to-first cardiopulmonary resuscitation attempt interval ≤5 min, ventricular fibrillation or ventricular tachycardia in the first monitored rhythm, absence of re-arrest before leaving the emergency department, arrest-to-return of spontaneous circulation interval ≤30 min and recovery of pupillary light reflex, which were identifiable in the emergency department. Based on this analysis, we developed a seven-point score (5-R score). If the score was ≥5, it predicted good neurological outcome with a sensitivity of 82.5% (95% confidence interval [CI], 67.2–92.7%) and specificity of 92.3% (95% CI, 74.9–99.1%). The negative predictive value of a score ≥4 was 100% (95% CI, 81.5–100%). Our prediction model was validated internally by a bootstrapping technique.

Conclusions

The prediction protocol using the 5-R score was associated with good neurological outcome of patients treated with TTM. Therefore, it could be helpful in clinical decision making on whether to initiate cooling.     

Leukocyte-depleted terminal blood cardioplegia provides superior myocardial protective effects in association with myocardium-derived nitric oxide and peroxynitrite production for patients undergoing prolonged aortic crossclamping for more than 120 minutes

OBJECTIVES: This study was designed to examine the myocardial protective effect of leukocyte-depleted terminal blood cardioplegia in association with nitric oxide and peroxynitrite production, especially for patients undergoing prolonged aortic crossclamping. METHODS: Fifty-four patients (34 men, 20 women, mean age 56.7 +/- 12.7 years) undergoing aortic valve replacement were randomly allocated to one of two groups; group LDTC (n = 27) received 10 minutes of leukocyte-depleted terminal blood cardioplegic solution, and group CONT (n = 27) served as controls. Each group was subdivided into 2 groups: aortic crossclamping for less than 120 minutes in groups LDTC-S (n = 13) and CONT-S (n = 14); aortic crossclamping for 120 minutes or more in groups LDTC-L (n = 14) and CONT-L (n = 13). RESULTS: After aortic unclamping, group LDTC-L showed higher incidence of spontaneous defibrillation (78.6% vs 30.8%, P =.0213), higher plasma nitrate + nitrite in the coronary sinus effluent (32.5 +/- 4.1 vs 28.7 +/- 3.0 micromol/L, P =.0013), lower differences between coronary sinus effluent and arterial blood in the percentage ratio of nitrotyrosine to tyrosine (myocardium-derived peroxynitrite; 2.987% +/- 0.576% vs 3.951% +/- 0.952%, P =.0036), and plasma polymorphonuclear-elastase (113.9 +/- 21.3 vs 155.5 +/- 41.6 microg/L, P =.0029) and malondialdehyde (2.75 +/- 0.67 vs 4.02 +/- 0.96 micromol/L, P =.0005) than group CONT did. Postoperatively, group LDTC-L showed lower human-heart fatty acid-binding protein (111.4 +/- 25.2 vs 156.4 +/- 38.6 IU/L, P =.0013), lower creatine kinase-muscle and brain (19.2 +/- 4.7 vs 24.8 +/- 6.5 IU/L, P =.0120), and smaller requirement of catecholamine (5.44 +/- 2.29 vs 8.45 +/- 3.42 microg x kg(-1) x min(-1), P =.0122). There were no significant differences in these parameters between groups LDTC-S and CONT-S. CONCLUSIONS: This study demonstrated that leukocyte-depleted terminal blood cardioplegia provided superior myocardial protective effects and regulated myocardial-derived nitric oxide and peroxynitrite production only for patients undergoing aortic crossclamping for more than 120 minutes. The results suggest that prolonged aortic crossclamping deteriorates the tolerance to leukocyte-mediated myocardial injury accompanied by endothelial dysfunction associated with nitric oxide and peroxynitrite production.     

Factors correlating with acoustic radiation force impulse elastography in chronic hepatitis C

AIM: To investigate the factors other than fibrosis stage correlating with acoustic radiation force impulse(ARFI) elastograpy in chronic hepatitis C. METHODS: ARFI elastograpy was performed in 108 consecutive patients with chronic hepatitis C who underwent a liver biopsy. The proportion of fibrosis area in the biopsy specimens was measured by computerassisted morphometric image analysis. RESULTS: ARFI correlated significantly with fibrosis stage(β = 0.1865, P < 0.0001) and hyaluronic acid levels(β = 0.0008, P = 0.0039) in all patients by multiple regression analysis. Fibrosis area correlated significantly with ARFI by Spearman’s rank correlation test but not by multiple regression analysis. ARFI correlated significantly with body mass index(BMI)(β =-0.0334, P = 0.0001) in F 0 or F 1, with γ-glutamyltranspeptidase levels(β = 0.0048, P = 0.0012) in F 2, and with fibrosis stage(β = 0.2921, P = 0.0044) and hyaluronic acid levels(β = 0.0012, P = 0.0025) in F 3 or F 4. The ARFI cutoff value was 1.28 m/s for F ≥ 2, 1.44 m/s for F ≥ 3, and 1.73 m/s for F 4. CONCLUSION: ARFI correlated with fibrosis stage and hyaluronic acid but not with inflammation. ARFI was affected by BMI, γ-glutamyltranspeptidase, and hyaluronic acid in each fibrosis stage.     

Phase I and II study of azacitidine in Japanese patients with myelodysplastic syndromes

Azacitidine, an inhibitor of DNA methyltransferase, is reported to have antileukemic efficacy and is approved for the treatment of myelodysplastic syndromes in Western countries. We have conducted a Phase I/II study of azacitidine in Japanese patients with myelodysplastic syndromes to evaluate its pharmacokinetics, efficacy, and safety. In all, 53 patients received 75 mg/m(2) azacitidine subcutaneously or intravenously once daily for seven consecutive days on a 28-day cycle. The C(max) following intravenous administration was approximately 3.7-fold higher than that following subcutaneous administration, whereas the area under the plasma concentration-time curve from time zero to infinity was comparable for subcutaneous and intravenous administration. The bioavailability of azacitidine following subcutaneous administration was 91.1%, indicating that azacitidine is nearly completely absorbed after subcutaneous administration. The hematologic improvement and hematologic response rates were 54.9% (28/51) and 28.3% (15/53), respectively, and there were no differences between the two routes of administration. Azacitidine was generally well tolerated and clinically manageable in Japanese patients with myelodysplastic syndromes. Adverse events occurred in ≥ 20% of patients included hematologic toxicity, gastrointestinal events, and general disorders, such as malaise. Grade 3/4 adverse events that occurred in ≥ 50% of patients were all due to hematologic toxicity. The safety profile of azacitidine was generally similar for both routes of administration, with the exception of injection site reactions observed following subcutaneous administration. These results indicate that azacitidine can be expected to be a useful therapeutic agent in Japanese patients with myelodysplastic syndromes.     

Presenteeism in college students: reliability and validity of the Presenteeism Scale for Students

Objective

Presenteeism is the impaired work performance due to health problems. We aimed to develop a Presenteeism Scale for Students (PSS), and to reveal the existence of presenteeism among students.

Methods

Students (n = 5,701) in 4 national universities in Japan were recruited via the school-based health examination. Moreover, 122 students participated in a 2-week interval test?Cretest to examine the reliability and criterion-related validity of the PSS.

Results

Of the students, 59.2% indicated some health problems. Allergy was most prevalent health problems, affecting 35.7% of the whole students. Students with emotional problems had higher degree of presenteeism than those with the other problems. The Cronbach??s ?? of the work impairment score of the PSS was 0.90. The Spearman??s coefficient for the test?Cretest score was 0.80 (P < 0.001). Regarding criterion-related validity, Spearman??s coefficient between the work impairment score of the PSS and summary score of the SF-36 was ?0.60 (P < 0.001).

Conclusions

These findings suggest that the PSS can be expected to be useful for assessment of students with presenteeism. Furthermore, we found that the majority of students have some health problems, and proposed that the issue of presenteeism on campus should be addressed.     

Roles of histamine in the pathogenesis of bronchial asthma and reevaluation of the clinical usefulness of antihistamines

Histamine has been reported to play an important role in pathogenesis of bronchial asthma. However, H1-blockers are not recommended as the first drug for asthma therapy in the guidelines. Histamine may play various roles in allergic airway inflammation through the H1 receptor (H1R), H2R, and H4R in immune cells including T lymphocytes and dendritic cells. We therefore evaluated its role in allergic airway inflammation with the use of histamine-deficient mice. The results suggested that histamine plays a role in the prevention of goblet cell hyperplasia. Organic cation transporter-3 (OCT-3) is thought to be a transporter of histamine. Polymorphism of OCT-3 {R120R (T/C)} was associated with the severity of asthma. Recently, it has been proposed that both asthma and allergic rhinitis should be treated as a single airway disease. Comorbidity of asthma and allergic rhinitis is very high (70-80%) and they share similar allergic inflammation. H1-blockers are recommended as first-line drugs to treat allergic rhinitis in the guidelines. Therefore H1-blockers are strongly recommended for patients with both asthma and allergic rhinitis.     

Phenyleneethynylene Macrocycle‐Fused Phenylacetylene Monomers: Synthesis and Polymerization

Phenyleneethynylene macrocycle‐substituted acetylenes were synthesized by repetition of the Sonogashira coupling reaction, and the elimination reaction of the terminal acetylene protecting group. The monomers were polymerized with a rhodium catalyst, [Rh(nbd)Cl]₂, at the terminal acetylene unit, and the polymerization mixtures were purified by precipitating into methanol to yield the corresponding poly(phenylacetylene) derivatives as yellow‐red powders, which had a high degree of polymerization ( ≈ 500) in spite of their steric bulkiness. The trimethylsilyl and pentamethyldisiloxanyl groups of polymers improved their solubility, and the polymers were soluble in common organic solvents, such as toluene, chloroform and tetrahydrofuran.

     

All-trans retinoic acid inhibits KIT activity and induces apoptosis in gastrointestinal stromal tumor GIST-T1 cell line by affecting on the expression of survivin and Bax protein

Background

Imatinib, a selective tyrosine kinase inhibitor, has been used as a standard first-line therapy for irresectable and metastasized gastrointestinal stromal tumor (GIST) patients. Unfortunately, most patients responding to imatinib will eventually exhibit imatinib-resistance, the cause of which is not fully understood. The serious clinical problem of imatinib-resistance demands alternative therapeutic strategy. This study was conducted to investigate the effect of all-trans retinoic acid (ATRA) on GIST cell lines.

Methods

Cell proliferation was determined by trypan blue dye exclusion test. Western blot analysis was performed to test the expression of activated KIT, its downstream proteins, and apoptosis associated proteins. The cytotoxic interactions of imatinib with ATRA were evaluated using the isobologram of Steel and Peckham.

Results and conclusion

In this work, for the first time we have demonstrated that ATRA affected on cell proliferation of GIST-T1 and GIST-882 cell line through inhibition of cell growth in a dose dependent manner and induced apoptosis. High dose of ATRA induced morphologic change in GIST-T1 cells, rounded-up cells, and activated the caspase-3 protein. In further examination, we found that the ATRA-induced apoptosis in GIST-T1 cells was accompanied by the down-regulated expression of survivin and up-regulated expression of Bax protein. Moreover, ATRA suppressed the activity of KIT protein in GIST-T1 cells and its downstream signal, AKT activity, but not MAPK activity. We also have demonstrated that combination of ATRA with imatinib showed additive effect by isobologram, suggesting that the combination of ATRA and imatinib may be a novel potential therapeutic option for GIST treatment. Furthermore, the scracht assay result suggested that ATRA was a potential reagent to prevent the invasion or metastasis of GIST cells.