Neutrophil elastase in amniotic fluid as a predictor of preterm birth after emergent cervical cerclage.

INTRODUCTION: The aim of this study was to investigate neutrophil elastase (NE) in amniotic fluid as a potential marker for predicting pregnancy continuation. MATERIAL AND METHODS: We enrolled 34 pregnant women with bulging fetal membrane during the second trimester who underwent emergent cerclage after confirming the absence of intrauterine infection (amniotic fluid glucose ≥15 mg/dL). Amniotic fluid NE levels were compared between women who completed and did not complete 30, 34, and 36 weeks of gestation, and the optimal cut-off value for predicting pregnancy continuation was estimated. Moreover, the differences in the duration of continued pregnancy were compared between women with NE levels above and below the optimal cut-off value. RESULTS: The optimal cut-off value for NE in amniotic fluid that predicted pregnancy continuation beyond 30, 34, and 36 weeks of gestation was 180 ng/mL; this cut-off value had a sensitivity, specificity, positive predictive value, and negative predictive value of 84.0, 77.8, 91.3, and 63.7% beyond 30 weeks of gestation; 87.5, 80.0, 91.5, and 72.3% beyond 34 weeks of gestation; and 85.0, 71.4, 80.9, and 76.9% beyond 36 weeks of gestation, respectively. The duration of continued pregnancy from emergent cerclage to delivery was significantly longer in women with amniotic fluid NE <180 ng/mL (95.1 ± 5.4 days) than in women with amniotic fluid NE ≥180 ng/mL (44.8 ± 14.3 days). CONCLUSION: The NE levels in amniotic fluid may serve as a useful marker for predicting the duration of continued pregnancy after cervical cerclage.

Prediction of new onset atrial fibrillation through P wave analysis in 12 lead ECG.

It is unknown whether 12-lead ECG can predict new-onset AF. In the present study, we identified patients with new onset AF from our digitally stored ECG database, and the P wave morphologies were analyzed in their preceding sinus rhythm recordings as the precursor state for AF. The P wave was analyzed in the most recent ECG recording of sinus rhythm preceding new onset AF within 12 months. The duration and amplitude of P waves were analyzed in 12 leads and compared between the 2 groups with the other clinical parameters. The study population consisted of 68 patients with new-onset AF and 68 age and sex-matched controls. Multivariate analysis revealed that the P wave amplitude in leads II and V1 (0.157 ± 0.056 versus 0.115 ± 0.057 mV, P = 0.032, and 0.146 ± 0.089 versus 0.095 ± 0.036 mV, P = 0.002) and P wave dispersion (56.9 ± 14.8 versus 33.5 ± 12.9 ms, P = 0.001) were significant independent factors for the prediction of new-onset AF. By using these factors, new-onset AF could be predicted with a sensitivity of 69.1% and specificity of 88.2%. P wave analysis is useful for predicting new onset AF.

Vaginal Myomectomy for Semipedunculated Cervical Myoma during Pregnancy.

Objective Cases of prolapsed myoma in which pregnancy was carried to full term or near term after vaginal myomectomy are very rare. Previously, only two such cases have been reported. In addition, both those patients had a pedunculated leiomyoma, which could be treated by twisting or clamping. Here, we report a case of a patient who was able to carry her pregnancy to term despite vaginal myomectomy for semipedunculated myoma at 13 weeks of pregnancy. Study Design This study is a case presentation. Results The myoma nucleus was removed by making an incision on the surface of the mass. Systemic and transvaginal antibiotics were prescribed after the surgery. Uterine contractions, short cervix, or cervical funneling was not observed in the remaining duration of pregnancy. Conclusion While performing myomectomy during pregnancy, removal of the myoma nucleus is safer than twisting. In addition, postoperative administration of local or systemic antibiotic agents does not adversely affect pregnancy.

Prophylactic statin administration may prevent shortening of the fibrillation cycle length in patients with new-onset atrial fibrillation.

Patients with recently diagnosed atrial fibrillation (AF) tend to exhibit a longer fibrillation cycle length (FCL) than those having a longer clinical history. However, the electrophysiological properties of new-onset AF may vary because of the clinical background of patients. In this study, we evaluated clinical factors to identify the determinants of FCL in new-onset AF. Electrocardiograms (ECGs) recorded from 2008 through 2011 were analyzed using our digital ECG-profiling system. In the 1,578 AF episodes recorded, 466 new-onset AF episodes were identified using clinical referral history and previous ECGs. After evaluating FCL in these new-onset AF episodes, using a customized fibrillation wave analyzer with fast Fourier transform analysis, we divided the patients into a longer-FCL group and a shorter-FCL group using the median FCL (158 ms). Propensity score matching yielded 135 matched pairs of patients with comparable mean ages between the two groups. Four factors (brain natriuretic peptide levels, and use of angiotensin receptor blockers, calcium channel blockers or statins) exhibited a significant difference between the two groups. Multivariate analysis revealed that statin use was the only significant independent predictor of longer FCL (Odds ratio, 3.86; 95% CI, 1.659.63; P = 0.003). Among various clinical parameters, statin use was related to longer FCL at the time of new-onset AF in patients with AF.

Postprandial hyperglycemia and endothelial function in type 2 diabetes: focus on mitiglinide.

The risk of cardiovascular complication in a diabetes patient is similar to that in a nondiabetic patient with a history of myocardial infarction. Although intensive control of glycemia achieved by conventional antidiabetic agents decreases microvascular complications such as retinopathy and nephropathy, no marked effect has been reported on macrovascular complications or all-cause mortality. Evidence from VADT, ACCORD, and ADVANCE would suggest that glycemic control has little effect on macrovascular outcomes. Moreover, in the case of ACCORD, intensive glycemic control may be associated with an increased risk of mortality. There is sufficient evidence that suggests that postprandial hyperglycemia may be an independent risk factor for cardiovascular disease in diabetes patients. However, there are no prospective clinical trials supporting the recommendation that lowering postprandial blood glucose leads to lower risk of cardiovascular outcomes. Mitiglinide is a short-acting insulinotropic agent used in type 2 diabetes treatment. It has a rapid stimulatory effect on insulin secretion and reduces postprandial plasma glucose level in patients with type 2 diabetes. Because of its short action time, it is unlikely to exert adverse effects related to hypoglycemia early in the morning and between meals. Mitiglinide reduces excess oxidative stress and inflammation, plays a cardioprotective role, and improves postprandial metabolic disorders. Moreover, mitiglinide add-on therapy with pioglitazone favorably affects the vascular endothelial function in type 2 diabetes patients. These data suggest that mitiglinide plays a potentially beneficial role in the improvement of postprandial hyperglycemia in type 2 diabetes patients and can be used to prevent cardiovascular diseases. Although the results of long-term, randomized, placebo-controlled trials for determining the cardiovascular effects of mitiglinide on clinical outcomes are awaited, this review is aimed at summarizing substantial insights into this topic.

Coordination by registered dieticians for nutritional and dietary support in disaster in Japan.

PROBLEM: Yamada, a town of Iwate Prefecture in north-eastern Japan, was struck by the tsunami from the Great East Japan Earthquake. In Yamada, it was challenging to manage nutritional and diet support for food aid because these services were unavoidably drawn out for several months in evacuation shelters. CONTEXT: In Japan, food aid in disasters is often provided, divided and distributed erratically due to poor efforts made with regards to dietary support from the perspective of nutrition. The need for nationally registered dieticians to coordinate nutritional and dietary support in evacuation shelters was considered in this disaster. ACTION: A dietary support team was formed of nationally registered dieticians to study the dietary conditions of evacuees in shelters in Yamada and to develop a system to ensure the nutritional and balanced dietary needs of the evacuees. OUTCOME: In this disaster response, model menus were prepared and a menu-food matching system was put in place to order and distribute foods required for balanced meals. Every effort was made to avoid excesses and deficiencies in nutrition; the meals consisted of a staple, main dish, side dish and soup. Along with that, food sanitation and stock management were improved. DISCUSSION: The menu-food matching system put together by the nationally registered dieticians was useful for nutritional and dietary support in this particular disaster. It is recommended that similar nutritional and dietary support coordinated by nationally registered dieticians be considered for disaster management plans where appropriate.

Risks and benefits of combined use of bucolome and warfarin in anticoagulation therapy.

Although bucolome has been used empirically to enhance and stabilize warfarin action in some institutes, the clinical risks and benefits of this combination are unclear. In the present study, warfarin monotherapy (WM) and bucolome combination (BC) therapy were compared in anticoagulation therapy.One hundred and ninety-five patients indicated for anticoagulation therapy were randomly assigned to WM (n = 98) or BC (bucolome 300 mg/day, n = 97). The dosage of warfarin was optimized in each patient to maintain the international normalized ratio (INR) level in the appropriate zone, ie, 1.6-2.6 for lower risk and 2.0-3.0 for higher risk patients. The clinical characteristics, clinical events, and time in therapeutic range (TTR) were evaluated and compared between the two groups. TTR was calculated using Rosendaal's linear interpolation method.The optimal dosage of warfarin was 3.3 ± 1.0 mg/day in WM and 1.4 ± 0.5 mg/day in BC (P < 0.001). During the observation period of 18 ± 6 months, no serious complication was observed and INR was measured 11 ± 3 times in each case. TTR was 0.61 ± 0.13 in WM and 0.62 ± 0.14 in BC (NS), but TTR in the WM subgroup with warfarin > 3 mg (0.58 ± 0.13) was lower than in the WM subgroup with warfarin ≤ 3 mg (0.64 ± 0.13, P = 0.026) and BC (P = 0.042).BC reduced the optimal dosage of warfarin without increasing clinical events. There was no significant difference in TTR between WM and BC, but BC may have benefits in selected cases, such as warfarin resistance.

Effects of ezetimibe add-on therapy for high-risk patients with dyslipidemia.

BACKGROUND: Ezetimibe (Zetia) is a potent inhibitor of cholesterol absorption that has been approved for the treatment of hypercholesterolemia. Statin, an inhibitor of cholesterol synthesis, is the first-choice drug to reduce low-density lipoprotein-cholesterol (LDL-C) for patients with hypercholesterolemia, due to its strong effect to lower the circulating LDL-C levels. Because a high dose of statins cause concern about rhabdomyolysis, it is sometimes difficult to achieve the guideline-recommended levels of LDL-C in high-risk patients with hypercholesterolemia treated with statin monotherapy. Ezetimibe has been reported to reduce LDL-C safely with both monotherapy and combination therapy with statins. RESULTS: To investigate the effect of ezetimibe as "add-on" therapy to statin on hypercholesterolemia, we examined biomarkers and vascular endothelial function in 14 patients with hypercholesterolemia before and after the 22-week ezetimibe add-on therapy. Ezetimibe add-on therapy reduced LDL-C by 24% compared with baseline (p < 0.005), with 13 patients (93%) reaching their LDL cholesterol goals. Of the Ezetimibe add-on therapy significantly improved not only LDL-C, high-density lipoprotein-cholesterol (HDL-C), and apolipoprotein (apo)B levels, but also reduced levels of triglyceride (TG), the ratio of LDL/HDL-C, the ratio of apoB/apoA-I, and a biomarker for oxidative stress (d-ROMs). Furthermore, ezetimibe add-on therapy improved vascular endothelial function in high-risk patients with hypercholesterolemia. CONCLUSION: In conclusion, ezetimibe as add-on therapy to statin might be a therapeutic good option for high-risk patients with atherosclerosis.

Predicting the efficacy of antiarrhythmic agents for interrupting persistent atrial fibrillation according to spectral analysis of the fibrillation waves on the surface ECG.

BACKGROUND: Spectral analysis of the fibrillation waves was performed in patients with persistent atrial fibrillation (PAF) to clarify the usefulness of this method of predicting the efficacy of antiarrhythmic agents. METHODS AND RESULTS: The 59 patients with PAF were randomly assigned to pilsicainide (150 mg/day) or bepridil (200 mg/day) therapy for 4 weeks under optimal anticoagulation therapy. When the first therapy did not interrupt PAF, the drugs were changed in a cross-over manner. The fibrillation cycle length (FCL) was calculated using spectral analysis of the fibrillation waves on the body-surface ECG every 2 weeks. Pilsicainide and bepridil were effective in 19 and 20 patients, respectively. The FCL at the basic state was longest in the pilsicainide-effective group, moderate in the bepridil-effective group and shortest in the failure group (P<0.05). The change in FCL with drug administration (DeltaFCL) was larger in the effective than in the ineffective cases (P<0.01). Successful interruption of the atrial fibrillation (AF) with pilsicainide could be expected for patients with a FCL >148 ms (sensitivity =0.917, specificity =0.612, P=0.007) and DeltaFCL >41 ms (sensitivity =0.875, specificity =0.833, P=0.001). CONCLUSIONS: The FCL reflects the electrophysiological properties of the AF substrate and is considered useful for predicting the efficacy of antiarrhythmic agents.

Effect of oral L-type calcium channel blocker on repetitive paroxysmal atrial fibrillation: spectral analysis of fibrillation waves in the Holter monitoring.

AIMS: The electrical remodelling is considered to play a role in promoting arrhythmogenic substrate of atrial fibrillation (AF), and intracellular calcium overload may play a key role, especially in its early phase. The effect of oral verapamil on repetitive paroxysmal AF (PAF) was evaluated in clinical cases. METHODS AND RESULTS: Thirty-five patients with repetitive PAF (total PAF duration >2/24 h) were divided into two groups with and without verapamil administration (240 mg/day) and they were followed-up for 12 months. Before and after the follow-up period, 24 h Holter ECG was recorded. In each Holter recording, total PAF duration and the longest PAF duration was evaluated and spectral analysis was performed for fibrillation waves in PAF episodes to evaluate the fibrillatory frequency. Total PAF duration was prolonged by 45 +/- 79 min in the control group (n = 18) whereas shortened by 25 +/- 55 min in the verapamil group (n = 17, P = 0.005). The fibrillatory frequency was increased from 5.66 +/- 1.05 to 6.73 +/- 1.02 Hz in the control group and was unchanged in the verapamil group. There was inverse relationship between Deltatotal PAF duration and Deltafibrillatory frequency (P = 0.0002). CONCLUSION: Verapamil prevented the increase in fibrillatory frequency in PAF patients in relatively long-term observation. Verapamil might be effective for prevention of the electrophysiological change and increase in PAF episodes at least in specific type of PAF cases.

Late thrombosis of a drug-eluting stent overlapped in the in-stent restenotic lesion of a bare metal stent.

Late stent thrombosis occurred in the lesion of a sirolimus-eluting stent implanted 6 months previously for an in-stent restenosis lesion in the distal right coronary artery. Seventeen days before admission due to acute myocardial infarction this time, aspirin was discontinued for colon polypectomy. Ticlopidine had been discontinued 3 months before the discontinuation of aspirin. In drug-eluting stent era, the interventional strategy and antiplatelet therapy require long term attention.

Oozing type of left ventricular rupture via subepicardial aneurysm diagnosed 5 months after myocardial infarction.

A 71-year-old man visited our hospital complaining of increasing fatigue and exertional dyspnea. He had had severe epigastric pain for the past 5 months. On admission, chest radiogram showed marked cardiac dilatation and echocardiogram massive pericardial effusion with a small subepicardial aneurysm at the posterior wall of the left ventricle. An urgent pericardiocentesis removed 1300 ml of bloody effusion. The red blood cell count of the pericardial effusion was similar to that of the peripheral blood, and there were no abnormal findings on cytologic and bacteriological examinations. Coronary angiography showed a blunt occlusion of the mid-portion of the circumflex artery. Left ventricular angiogram revealed aneurysmal deformity of the left ventricular posterior wall. These findings suggested that an oozing type of left ventricular rupture via a subepicardial aneurysm had occurred after the onset of myocardial infarction (MI), resulting in massive accumulation of pericardial effusion. The patient is presently doing well without any clinical symptoms 18 months after pericardiocentesis. This is the first case report in which a subepicardial aneurysm with massive pericardial effusion was detected in the chronic stage of MI and successfully managed without surgical repair.

Systolic anterior motion (SAM) of the posterior mitral leaflet: left ventricular outflow tract obstruction in a patient without left ventricular hypertrophy.

Systolic anterior motion (SAM) of the anterior mitral leaflet with mitral-septal contact was generally thought to be a major contributor to dynamic left ventricular outflow tract obstruction in patients with hypertrophic cardiomyopathy. We report an interesting case of SAM of the posterior mitral leaflet in a patient without left ventricular hypertrophy, which led to dynamic left ventricular obstruction.

Arbekacin is actively secreted in the rat intestine via a different efflux system from P-glycoprotein.

This study was undertaken to examine the secretory transport of arbekacin, an aminoglycoside antibiotic, in the rat small intestine and to compare it with those in Caco-2 and LLC-PK1 cells. In vitro permeation of arbekacin was examined using an Ussing chamber technique. Serosal-to-mucosal (secretory)/mucosal-to-serosal (absorptive) permeation ratios of 0.5 mM arbekacin were 2.8 in the jejunum and 7.0 in the ileum, respectively, indicating that arbekacin permeation was highly secretory-oriented. In the ileum, the ratios became smaller with increase in arbekacin concentration applied. When D-glucose was replaced with 3-o-methyl-D-glucose in the experimental medium, the directionality of the arbekacin permeation disappeared almost completely. Absorptive permeation of arbekacin was not significantly influenced by verapamil, cyclosporin A, or probenecid. On the other hand, when gentamicin sulfate was added to the serosal medium, secretory transport of arbekacin was significantly inhibited. The results of this study strongly suggest that a specialized efflux system other than P-glycoprotein and multidrug resistance proteins was involved in the secretory transport of arbekacin in the rat intestine. There was no directionality in arbekacin permeation across Caco-2 cell monolayers, suggesting the absence or very slight expression of the secretory system for arbekacin in this cell line.

In vitro permeation of beta-lactam antibiotics across rat jejunum and its correlation with oral bioavailability in humans.

AIMS: To investigate the correlation between in vitro permeation of 11 beta-lactam antibiotics across rat jejunum and their oral bioavailability in humans. METHODS: The absorptive and secretory permeation across rat jejunum was evaluated and apparent permeability coefficients (P(app)) were determined. RESULTS: A steep, sigmoid-type curve was obtained for the relationship between P(app) in the absorptive permeation and human oral bioavailability. When the ratios of P(app) in the absorptive direction to P(app) in the secretory direction were plotted against human oral bioavailability, a much improved correlation was obtained (r = 0.98, P < 0.001). The addition of glycylglycine to both mucosal and serosal media modified the permeation of ceftibuten and cephalexin from the absorptive to the secretory direction. CONCLUSIONS: For 11 beta-lactam antibiotics rat intestinal permeation correlated well with human oral bioavailability, especially when corrected for secretory transport.