Relation of atrial fibrillation to glomerular filtration rate

Although both atrial fibrillation (AF) and decreasing glomerular filtration rate (GFR) are strongly related to advanced age and share common associated vascular risk factors, few studies have explored the relation between AF and GFR. From residents (age >or=40 years) in Kurashiki City, a total of 41,417 subjects (median age 72 years; 13,956 men) were enrolled in the Kurashiki City Annual Medical Survey from May to December 2006. The estimated overall prevalence of AF was 1.6% (2.8% in the low-GFR tertile, 1.2% in the middle tertile, and 0.9% in the high tertile, p <0.001). After all subjects were categorized into age tertiles (age thresholds 68 and 76 years), AF was identified in 0.9% in the low-GFR tertile, 0.6% in the middle tertile, and 0.5% in the high tertile in the low-age tertile (p = 0.018); 2.6% in the low-GFR tertile, 1.2% in the middle tertile, and 1.1% in the high tertile in the middle-age tertile (p <0.001); and 3.9% in the low-GFR tertile, 2.4% in the middle tertile, and 1.7% in the high tertile in the high-age tertile (p <0.001). The odds ratio for AF adjusted for age, gender, vascular risk factors, cardiac disease, and hemoglobin was 1.91 (95% confidence interval 1.54 to 2.38, p <0.001) for the low-GFR tertile versus the high tertile and 1.12 (95% confidence interval 0.88 to 1.42, p = 0.364) for the middle-GFR tertile versus the high tertile. The prevalence of AF gradually increased with decreasing GFR. In conclusion, AF appears to be associated with decreasing GFR.     

Association of Gln222Arg polymorphism in the deoxyribonuclease I (DNase I) gene with myocardial infarction in Japanese patients.

AIMS: We have recently reported that serum deoxyribonuclease I (DNase I) activity, which may be involved in apoptosis, increases abruptly in the early phase of acute myocardial infarction (MI) [Kawai Y, Yoshida M, Arakawa K, Kumamoto T, Morikawa N, Masamura K, Tada H, Ito S, Hoshizaki H, Oshima S, Taniguchi K, Terasawa H, Miyamori I, Kishi K, Yasuda T. Diagnostic use of serum deoxyribonuclease I activity as a novel early-phase marker in acute myocardial infarction. Circulation 2004;109:2398-2400]. Death of vascular smooth muscle cells, in part because of apoptosis, is postulated to heighten susceptibility to disruption of vulnerable plaque, resulting in onset of MI. The present study evaluated the possibility that Gln222Arg polymorphism of the DNase I gene may be one of the factors involved in predisposition to MI. METHODS AND RESULTS: We assessed 611 Japanese patients: 311 with MI and 300 with stable angina pectoris (AP). Three common phenotypes determined by two common codominant alleles, DNASE1*1 and *2, whose corresponding gene products exhibit different properties, were found in these patient groups. The prevalence of DNASE1*2 was significantly higher in patients with MI than in those with AP (0.543 vs. 0.428, P < 0.001), being confirmed by phenotyping of the second study population. Multiple logistic regression analysis showed that the odds ratio of DNASE1*2 was 1.51 [95% confidence interval (CI) 1.04-2.18]. The association of the DNASE1*2 allele with MI was statistically significant, being independent of other conventional risk factors. CONCLUSION: Our data demonstrate that Gln222Arg polymorphism in the DNase I gene is associated with MI in the Japanese patients.     

Application of one step RT-PCR assay for detection of flavivirus RNA in mosquitoes

The conditions of one step RT-PCR method for detection of virus RNA in field-collected mosquitoes, and preservation period of infected mosquitoes for one step RT-PCR were examined. We compared several virus RNA extraction methods with artificially contaminated mosquito pools with dengue virus (DV), Japanese encephalitis virus (JEV), and yellow fever virus (YFV) with a known amount of plaque forming unit (PFU) to establish the condition of one step RT-PCR. In this study, most effective RNA extraction method was ISOGEN-LS extraction combined with supernatant of centrifuged mosquito homogenates. Detection limit of one step RT-PCR using flavivirus universal primer in ten mosquitoes/tube (pool) was 10 PFU of DV, JEV and YFV, 1 PFU of each viruses using species-specific primer respectively, in one hundred mosquitoes/tube, 100 PFU/tube using universal primer pairs, 10 PFU/tube using species-specific primer pairs respectively. Dengue virus infected single mosquito was mixed with 99 un-infected mosquitoes, and tested by one step RT-PCR. We could detect single infected mosquito in pools containing 99 un-infected mosquitoes. Aedes aegypti and Aedes albopictus were inoculated intrathoracically with a mouse-adapted strain of dengue-1 virus and were kept up to 30 days at different temperature. Then examined by one step RT-PCR to determine the appropriate mosquito handling method and the condition of transportation. Positive result was obtained up to 30 days after the mosquito died naturally. These results suggested that we could detect flavivirus RNA tested not only from live mosquitoes but also dead mosquitoes as well, and could apply one step RT-PCR as a rapid, specific, and highly sensitive tool for flavivirus surveillance.     

Etiology and outcome of community-acquired pneumonia in relation to age and severity in hospitalized adult patients]

The aim of this study was to determine the etiology and outcome of community-acquired pneumonia (CAP) in relation to age and severity in hospitalized patients. Overall, 652 consecutive patients with CAP were studied retrospectively during a 4-year period from 2002. Severity of pneumonia was classified according to the guidelines of the Japanese Respiratory Society (JRS 2005) and American Thoracic Society (ATS 2001). The etiology was identified in 401 of 652 (61.5%) cases. The four most frequent pathogens were Streptococcus pneumoniae (26.2%), influenza virus (12.4%), Mycoplasma pneumoniae (10.9%), and Haemophilus influenzae (5.9%). The most common pathogen in the younger (15-44 years) group and very severe patients (JRS) was Mycoplasma pneumoniae (38.4%) and influenza virus (28.6%), respectively. The three most frequent pathogens in severe CAP patients (ATS) were Streptococcus pneumoniae (29.0%), influenza virus (17.4%), and Legionella species (13.0%). The overall mortality was 6.4%. The mortality of CAP patients among aged 1544, 45-64, 65-74, and 75 years or older was 1.4%, 3.3%, 6.9% and 9.3%, respectively. The mortality of mild, moderate, severe, and very severe patients (RS) was 0%, 4.1%, 15.5%, and 53.6%, respectively. The mortality of non-severe and severe patients (ATS) was 1.8% and 23.9%, respectively. Age and severity had influence on the prevalence of the main microbial pathogens. Streptococcus pneumoniae remained the most important pathogen that needs consideration in initial antibiotic therapy in patients with CAP of all ages and severities. Pathogens identified in patients with severe CAP in Japan were similar to those of Western countries, except for the high incidence of the influenza virus.     

Hemodynamic Changes by Drug Interaction of Adrenaline With Chlorpromazine

Adrenaline (epinephrine) is included in dental local anesthesia for the purpose of vasoconstriction. In Japan, adrenaline is contraindicated for use in patients receiving antipsychotic therapy, because the combination of adrenaline and an antipsychotic is considered to cause severe hypotension; however, there is insufficient evidence supporting this claim. The purpose of the present study was to clarify the changes in hemodynamics caused by drug interaction between adrenaline and an antipsychotic and to evaluate the safety of the combined use of adrenaline and an antipsychotic in an animal study. Male Sprague-Dawley rats were anesthetized with sodium pentobarbital. A catheter was inserted into the femoral artery to measure blood pressure and pulse rate. Rats were pretreated by intraperitoneal injection of chlorpromazine or chlorpromazine and propranolol, and after 20 minutes, saline or 1 of 3 different doses of adrenaline was administered by intraperitoneal injection. Changes in the ratio of mean arterial blood pressure and pulse rate were measured after the injection of adrenaline. Significant hypotension and tachycardia were observed after the injection of adrenaline in the chlorpromazine-pretreated rats. These effects were in a dose-dependent manner, and 100 μg/kg adrenaline induced significant hemodynamic changes. Furthermore, in the chlorpromazine and propranolol–pretreated rats, modest hypertension was induced by adrenaline, but hypotension and tachycardia were not significantly shown. Hypotension was caused by a drug interaction between adrenaline and chlorpromazine through the activation of the β-adrenergic receptor and showed a dose-dependent effect. Low-dose adrenaline similar to what might be used in human dental treatment did not result in a significant homodynamic change.Key Words: Local anesthesia, Drug interaction, Adrenaline, Epinephrine, AntipsychoticsVasoconstrictors are included in local anesthetics to increase the duration of anesthesia, to prevent local anesthesia systemic toxicity, and to promote hemostasis in the local operative field.¹ Adrenaline (epinephrine) is the most common vasoconstrictor that is added to local anesthetics, and lidocaine and articaine with adrenaline are the most widely used local anesthetics for dental treatment. However, adrenaline has drug interactions with some medicines. It is widely believed that the combination of adrenaline with an antipsychotic can cause hypotension because antipsychotics have α-adrenergic blocker effects that can result in decreased peripheral resistance, and adrenaline has been shown to have significant β2-adrenergic mediated vasodilatory effects that also can cause hypotension. Therefore, the combination of adrenaline and an antipsychotic is contraindicated in Japan for fear of causing significant hypotension. However, there is insufficient evidence supporting this claim, and, in clinical settings, there are many situations in which the use of local anesthetics with adrenaline is appropriate for dental treatment of patients receiving antipsychotic therapy. Thus, the purpose of the present study was to clarify the changes in hemodynamics caused by a drug interaction between adrenaline and an antipsychotic and to evaluate the safety of the combined use of adrenaline with an antipsychotic in an animal study.     

Carbon dioxide insufflation during colorectal endoscopic submucosal dissection for patients with obstructive ventilatory disturbance

Purpose

Carbon dioxide (CO₂) insufflation reduces abdominal pain and discomfort after endoscopic procedures; however, there is no previous study focusing the safety of CO₂ insufflation for patients with obstructive ventilatory disturbance. Here, we investigated the safety of CO₂ insufflation during colorectal endoscopic submucosal dissection (ESD) for patients with obstructive disturbance.

Methods

Between January 2010 and January 2013, colorectal ESD was performed using CO₂ insufflation for 385 consecutive patients. End-tidal CO₂ (EtCO₂) and transcutaneous oxygen saturation (SpO₂) were consecutively measured from the time before insertion of the colonoscope to the end of ESD. Patients were monitored by two nurses during the procedure and controlled for clinical symptoms of hypercapnia such as apnea or a depressed level of consciousness. According to their respiratory function, patients were stratified into a normal group and an obstructive disturbance group. We retrospectively compared EtCO₂ and SpO₂ during the procedures and the incidence of symptoms related to CO₂ retention between the two groups.

Results

The obstructive disturbance group consisted of 77 patients. There were similar changes of EtCO₂ in the obstructive disturbance group and normal group and no significant rise in EtCO_2. The maximum EtCO₂ level in any patient was <60 mmHg. In the obstructive disturbance group, there were no symptoms associated with CO₂ retention. There were no significant differences in the median SpO₂ between both groups and no prolonged drop of SpO₂.

Conclusions

CO₂ insufflation during colorectal ESD is safe for patients with obstructive ventilatory disturbance.     

Genetic variant of the renin-angiotensin system and prevalence of type 2 diabetes mellitus: a modest but significant effect of aldosterone synthase

Recent genome-wide association studies have identified multiple variants that confer risk of type 2 diabetes mellitus (DM). However, established associations explain only a part of the heritability. Thus, even at the genome-wide association studies era, candidate gene approach should be still useful. Recent interventional studies against the renin-angiotensin system (RAS) showed reduction in new onset of DM, implying the system is involved in the onset. We substantiated the hypothesis that genetic variants of RAS have significant association with prevalence of DM. We enrolled to the study consecutive 782 subjects who had consulted our hospitals for mainly lifestyle related diseases. They consisted of 282 (36.1 %) diabetes cases. Genotypes were assayed with genomic DNA for conventional four genes of the RAS, i.e., angiotensin converting enzyme (ACE) insertion/deletion variant, angiotensinogen (AGT) M235T variant, angiotensin II type I receptor (AT1) A1166C variant, and aldosterone synthase (CYP11B2) C-344T variant. Association between the genetic variants of the RAS and prevalence of type 2 DM was tested. A significant association of DM and CYP11B2 genotype was obtained. There was no significant association between DM and ACE, AGT and AT1 variants. A multivariate logistic regression showed that age, gender, and CYP11B2 genotype were independent factors for association to diabetes, the DM risk of CC/CT to TT being 1.40 (95 % CI 1.04–1.90, p = 0.029). Thus, it is concluded that a genetic variant of the RAS should have a modest but significant impact on the onset of type 2 diabetes mellitus.     

Expression of N-acetylglucosaminyltransferase V in the subserosal layer correlates with postsurgical survival of pathological tumor stage 2 carcinoma of the gallbladder

Background

N-Acetylglucosaminyltransferase V (GnT-V), an enzyme that catalyzes the β1-6 branching of N-acetylglucosamine on asparagine-linked oligosaccharides of cellular proteins, enhances the malignant behaviors of carcinoma cells in experimental models. The aim of this study was to determine clinical significance of GnT-V expression in human pT₂ gallbladder carcinoma with simple in vitro experiments.

Methods

Ninety patients with pT₂ gallbladder carcinoma were included for this study. The in vitro and in vivo biological effects of GnT-V were investigated using gallbladder carcinoma cells with variable GnT-V expression levels induced by a small interfering RNA.

Results

Of the 90 cases, 57 showed positive staining and the remaining 33 demonstrated negative staining, the subcellular localization in the 57 cases was classified into the granular-type in 31 cases and the diffuse-type in 26 cases. In 76 cases with curative resection, postsurgical survival was significantly poorer in those showing positive staining than in those showing negative staining (P = 0.028). In all of the 76 cases, postsurgical recurrence was significantly more frequent in those showing diffuse-type localization than in those showing negative staining. Experimental analyses demonstrated that the down-regulation of GnT-V expression in gallbladder carcinoma cells induced suppression of cell growth in vitro. The expression levels of GnT-V in the cells were highly correlated with the rapid in vivo growth coupled with the enhanced angiogenesis, and the tendency to form liver metastasis.

Conclusions

GnT-V expression in the subserosal layer of pT₂ gallbladder carcinoma is correlated with the aggressiveness of the disease.