Acetaldehyde production by major oral microbes.

OBJECTIVES: To assess acetaldehyde (ACH) production by bacteria constituting the oral microbiota and the inhibitory effects of sugar alcohols on ACH production. MATERIALS AND METHODS: The predominant bacterial components of the salivary microbiota of 166 orally healthy subjects were determined by barcoded pyrosequencing analysis of the 16S rRNA gene. Bacterial ACH production from ethanol or glucose was measured using gas chromatography. In addition, inhibition by four sugars and five sugar alcohols of ACH production was assayed. RESULTS: Forty-one species from 16 genera were selected as predominant and prevalent bacteria based on the following criteria: identification in ≥95% of the subjects, ≥1% of mean relative abundance or ≥5% of maximum relative abundance. All Neisseria species tested produced conspicuous amounts of ACH from ethanol, as did Rothia mucilaginosa, Streptococcus mitis and Prevotella histicola exhibited the ability to produce ACH. In addition, xylitol and sorbitol inhibited ACH production by Neisseria mucosa by more than 90%. CONCLUSIONS: The oral microbiota of orally healthy subjects comprises considerable amounts of bacteria possessing the ability to produce ACH, an oral carcinogen. Consumption of sugar alcohols may regulate ACH production by oral microbes.

Medium-term results of neoadjuvant systemic chemotherapy using irinotecan, 5-fluorouracil, and leucovorin in patients with locally advanced rectal cancer.

AIMS: The aim of this study was to evaluate the usefulness of neoadjuvant systemic chemotherapy using irinotecan, 5-FU, and leucovorin (LV) for the treatment of locally advanced rectal cancer, which was a powerful ploychemotherapy in those days in Japan. METHODS: Between 2001 and 2004, 26 patients with T3 or T4 and N0-2 non-metastatic resectable rectal cancer were selectively enrolled in this study. Neoadjuvant chemotherapy consisted of two cycles of irinotecan (80 mg/m²), 5-FU (500 mg/m²), and LV (250 mg/m²) on days 1, 8, and 15 for 4 weeks. Surgical resection was performed in all the patients 2-4 weeks after the completion of chemotherapy. RESULTS: Overall down-staging was observed in 15 patients. T level and N level down-staging were observed in 12 and 13 patients, respectively. A pathological complete response was observed in one patients. The median follow-up period was 75 months (range, 8-97 months). Recurrences occurred in 5 patients including pelvic relapses in 3 and distant metastases in 2. The 5-year relapse-free and overall survival rates were 74% and 84%, respectively. CONCLUSIONS: Neoadjuvant systemic chemotherapy comprised of a combination of multi-drugs as irinotecan, 5-FU, and LV may be beneficial to the prognoses of patients with locally advanced rectal cancer.

Stereodynamics in dissociative adsorption of NO on Si(111).

We report results of our study on the surface-temperature dependence of the steric effect in the dissociative adsorption of NO on Si(111)-(7x7). Data presented here show that, at an incident energy of 58 meV, the reactive sticking probability for the N-end collision is larger than that for the O-end collision. Furthermore, this steric preference is quite sensitive to the surface temperature and the surface coverage. This study shows that the transient surface trapping into a shallow precursor well plays a key role in the stereodynamics of the dissociative adsorption at the low energy region.

Anisotropic conduction prolongs ventricular repolarization and increases its spatial gradient in the intact canine heart.

The effects of the activation sequence on ventricular repolarization and its spatial gradient were examined in anesthetized open-chest dogs. Unipolar and bipolar electrograms were recorded from 47 epicardial sites on the anterior left ventricular wall using a mapping electrode. The local QT interval (QT) and the activation time (AT) at each site were measured on the unipolar and bipolar electrograms, respectively. The QT index (QTI) was defined as the QT minus AT interval, and was used as a measure of local repolarization. QTI was longer at each site during propagation that was longitudinal (L) (219+/-21 ms) than during propagation transverse (T) (202+/-22 ms, p<0.001) to the epicardial fiber orientation or during atrial pacing (165+/-20 ms, p<0.001). During L-propagation, the QTI shortened as a function of the distance from the stimulus. The spatial gradient was steeper during T-propagation (p<0.05). Monophasic action potentials (MAP) were also recorded simultaneously at 4 epicardial sites. The MAP duration during ventricular pacing was longer than during atrial pacing at sites within 1.5 cm of the pacing site. This difference disappeared at more distant sites and was attenuated by a simultaneous stimulus from a site symmetrically aligned along the fiber. These findings indicate that anisotropic conduction prolongs ventricular repolarization and increases its spatial gradient in the intact heart. An electrotonic downstream effect appears to be the cause.

Gadolinium suppresses stretch-induced increases in the differences in epicardial and endocardial monophasic action potential durations and ventricular arrhythmias in dogs.

We tested whether acute pressure overloading of the left ventricle (LV) had spatially different effects on repolarization, thereby causing arrhythmias. The effects of gadolinium (Gd3+), a nonspecific blocker of stretch-activated channels were also examined. In anesthetized dogs, 5 s clamping of the ascending aorta (AC), separated by 5-min intervals, was repeated while monophasic action potentials (MAPs) were recorded from the LV endocardium and epicardium. Gd3+ was injected into the left atrium before the second (500 micromol) and third AC (2500 micromol) (n=10). In a separate group (n=7), the effects of Gd3+ in the presence of verapamil were examined. Epicardial MAP durations at 50% and 90% repolarization (APD50; APD90) shortened in response to LV pressure rise and elongation of the segment length induced by the first AC, whereas endocardial MAP durations remained unchanged. Thus, the difference in APD50 and APD90 increased. Consistent with these changes, premature ventricular contractions (PVCs) developed. Gd3+ had no effect on baseline MAP durations, however it prevented an AC-induced increase in the difference by suppressing epicardial MAP shortening. Gd3+ also reduced PVCs in a dose-dependent manner at plasma concentrations of 1-4 micromol/L. The effects were also evident after administration of verapamil. Thus, gadolinium suppressed an increase in the spatial dispersion of repolarization and arrhythmias via a mechanism of action different from that of verapamil.

Ventricular fibrillation and shortening, alternans and after-depolarizations of epicardial monophasic action potentials during coronary occlusion and reperfusion: effect of repetition of ischemia.

The relationship between the occurrence of ventricular fibrillation (VF) and repolarization abnormalities of the ischemic and reperfused myocardium is poorly understood. The present study examined the temporal relationship between ischemia- and reperfusion-induced changes in monophasic action potential (MAP) configurations and the occurrence of VF, and assessed the effects of repetition of ischemia. The left anterior descending coronary artery of 32 anesthetized dogs was occluded twice for 5 min, 30 min apart, during constant atrial pacing while recording MAPs from the epicardial ischemic zone. During the first occlusion, shortening of the MAP duration at 90% repolarization (APD90) and an increase in MAP alternans, defined as the maximal difference in APD90 between 2 consecutive beats, were observed. Afterdepolarizations also occurred transiently in 35% of the animals during occlusion and in 29% upon reperfusion. VF occurred in 28% (9/32 of the dogs) during the first sequence, and the incidence was higher in the subgroups with maximal alternans > or =20 ms (p<0.05), maximal shortening rate > or =30%, and afterdepolarizations. During the second sequence, the incidence of VF was reduced to 9% (3/32, p<0.05), associated with a significant reduction in the MAP changes. Thus, repolarization abnormalities of the ischemic and reperfused myocardium appear to be related to the occurrence of VF. The amelioration of the repolarization abnormalities by repetition of ischemia may be involved in its antifibrillatory effect.

Differential role of epicardial and endocardial K(ATP) channels in potassium accumulation during regional ischemia induced by embolization of a coronary artery with latex.

INTRODUCTION: K(ATP) channels are activated predominantly in the epicardium during regional ischemia. Therefore, the role of K(ATP) channels in ischemia-induced rise of extracellular potassium concentration ([K+]o) might be greater in the epicardium. METHODS AND RESULTS: In 18 anesthetized dogs, the left anterior descending coronary artery (LAD) was ligated, followed by injection of 23-microm latex beads into the occluded artery to interrupt collateral flow, by which accumulated [K+]o might wash out. Epicardial and endocardial [K+]o were measured during a 20-minute period of ischemia using a valinomycin membrane. The dogs were divided into three groups: 6 control dogs (CTRL); 7 dogs pretreated with intravenous glibenclamide (0.3 mg/kg [GLIB]), a blocker of K(ATP) channels; and 5 dogs pretreated with intravenous nicorandil (0.2 to 0.25 mg/kg [NCR]), a K(ATP) channel opener. Before LAD occlusion, there was no difference in [K+]o among the three groups. In the control group, epicardial and endocardial [K+]o were increased to a similar level as a function of time after occlusion (CTRL) at both layers. Ischemia-induced epicardial [K+]o rise was suppressed by GLIB (8.4+/-0.4 vs 6.7+/-0.5 mM, P < 0.05) but augmented by NCR (12.9+/-2.0 mM, P < 0.05). In contrast, endocardial [K+]o rise remained unaffected (7.6+/-0.2 mM CTRL, 7.6+/-1.3 mM GLIB, and 9.4+/-2.2 mM NCR, P = NS). CONCLUSION: Activation of K(ATP) channels plays an important role in epicardial [K+]o rise, but not in endocardial [K+]o rise, during regional ischemia. Another mechanism(s) may be important for endocardial [K+]o accumulation.

Gallbladder disease: appearance of associated transient increased attenuation in the liver at biphasic, contrast-enhanced dynamic CT.

PURPOSE: To evaluate the frequency, location, and appearance of transient increased attenuation in the liver during arterial-phase helical or incremental computed tomography (CT) in patients with gallbladder disease without hepatic extension. MATERIALS AND METHODS: Findings in dynamic CT examinations in 31 patients with surgically proved gallbladder disease not extending into the liver and in 31 control patients without gallbladder disease were retrospectively reviewed and correlated with findings in other imaging examinations. RESULTS: Areas of transient increased hepatic attenuation (n = 27) were identified in 22 of 31 patients with gallbladder disease and in only one of 31 control patients. The difference in these findings was statistically significant (P < .001). In the 27 areas of transient increased hepatic attenuation, these findings were categorized as curvilinear or nodular attenuation adjacent to the gallbladder fossa in 13 (48%), segmental or subsegmental attenuation in segment IV and/or V in seven (26%), lobar attenuation in the left lobe (segments II-IV) in four (15%), and nodular attenuation seen as an early enhancing "pseudolesion" in segment IV in three (11%). Hepatic angiography performed in 10 of the 22 patients showed early depiction of the dilated cystic vein (n = 8) and direct communication with the portal branches (n = 2). CONCLUSION: Transient increased attenuation in the liver had a variable appearance at dynamic arterial-phase CT in most patients with gallbladder disease. This attenuation was most likely due to increased blood flow from the hepatobiliary system.

Different responses of epicardium and endocardium to KATP channel modulators during regional ischemia.

We examined the responses of epicardial (Epi) and endocardial (Endo) layers to ATP-sensitive K+ (KATP) channel modulators during regional ischemia in anesthetized dogs. Five-minute occlusion of the left anterior descending coronary artery was repeated at 30-min interval. Monophasic action potentials (MAPs) and extracellular K+ concentrations ([K+]o) were measured at Epi and Endo layers. 5-Hydroxydecanoate (5-HD, 30 mg/kg iv), a KATP channel blocker, or nicorandil (NCR, 0.2-0.5 mg/kg iv), an opener, was administered before the third or fourth occlusion. Shortening rate of action potential duration at 90% repolarization (APD90) was greater at the Epi layer than at the Endo layer during the first 4 min after the second control occlusion (19.7 +/- 1.5 vs. 13.1 +/- 2.4%, n = 14, P < 0.05). 5-HD suppressed the shortening preferentially at the Epi layer and reduced the difference between the two layers (11.0 +/- 3.5 vs. 11.5 +/- 3.7%, n = 6, NS). In contrast, NCR augmented the shortening preferentially at the Epi layer and increased the difference between the two layers at 4 min (29.0 +/- 2.0 vs. 5.9 +/- 3.0%, n = 6, P < 0.05). The time differentiation of [K+]o rise was similar at the two layers during the control occlusion (0.44 vs. 0.50 mM/min, n = 12). 5-HD reduced the rate of [K+]o rise at both layers (0.34 vs. 0.40 mM/min), whereas NCR augmented the rate at the Epi layer (0.82 vs. 0.50 mM/min). Activation of KATP channels appears to be involved in ischemia-induced APD shortening and [K+]o rise. The different responses of the two layers suggest a lower threshold for activation and/or a denser distribution of KATP channels or other K+ channels at the Epi layer.

[Coronary artery bypass grafting surgery without cardiopulmonary bypass in a patient with calcified aorta].

Coronary artery bypass surgery in a 67-year-old male with severe calcified ascending aorta was performed without cardiopulmonary bypass under beating heart, utilizing the left internal thoracic artery graft. No neurological complication was observed and postoperative angiogram showed good graft patency. We think coronary revascularization without cardiopulmonary bypass can be one of the safe and reliable methods to avoid complications associated with aortic cross clamping and aortic cannulation with severely calcified aorta.

Nicorandil augments regional ischemia-induced monophasic action potential shortening and potassium accumulation without serious proarrhythmia.

Nicorandil is a clinically used nitrovasodilator that has a property as an opener of ATP-sensitive potassium (KATP) channels in vitro. We examined whether nicorandil at a clinically used dose augmented regional ischemia-induced monophasic action potential (MAP) shortening and increase in extracellular potassium concentration ([K+]o), and how it affected arrhythmia occurrence. Five-minute occlusion of a distal site of the left anterior descending coronary artery (LAD) was repeated at 30-min intervals in anesthetized open-chest dogs while recording MAP or measuring [K+]o with a potassium-sensitive valinomycin electrode from the epicardial center of the ischemic myocardium. Nicorandil (0.2-0.5 mg/kg) was administered intravenously (i.v.) 5 min before the third occlusion, and the data were compared with those during the second occlusion (control). During the second occlusion, MAP duration at 90% repolarization (APD90) shortened (mean rate for 5 min, 13 +/- 3%, n = 11) and [K+]o increased from 3.7 +/- 0.1 to 6.2 +/- 0.8 mM at 5 min (n = 12). These changes were reversed < or = 3 min after reperfusion. Before the third occlusion, baseline APD90 and [K+]o were not altered by nicorandil; however, the extent of occlusion-induced shortening of APD90 (25 +/- 4%) and [K+]o increase (7.8 +/- 1.6 mM) was augmented by the pretreatment. The drug effect was attenuated by a concomitant pretreatment with 5-hydroxydecanoate, a specific blocker of KATP channels (n = 2). The prevalence of ventricular fibrillation (VF) during occlusion/reperfusion sequence was reduced after nicorandil (1 of 25 vs. 5 of 25) without de novo VF. These results suggest that nicorandil at a clinical dose facilitates regional ischemia-induced activation of myocardial KATP channels without causing serious proarrhythmia. Such a property might help protect the myocardium against ischemia/reperfusion damage.

Determination of free hydroxyproline and proline in human serum by high-performance liquid chromatography using 4-(5,6-dimethoxy-2-phthalimidinyl)phenylsulfonyl chloride as a pre-column fluorescent labelling reagent.

A fluorescent labelling reagent, 4-(5,6-dimethoxy-2-phthalimidinyl)phenylsulfonyl chloride, was designed for the determination of amines by precolumn HPLC and was applied to the simultaneous determination of hydroxyproline and proline in serum. The reagent reacted with hydroxyproline and proline at 30 degrees C for 10 min to produce the fluorescent derivatives, which were separated on a reversed-phase column by gradient elution with phosphate buffer (1 mmol l-1, pH 7) and acetonitrile and detected by fluorescence measurement at 315 nm (excitation) and 385 nm (emission). The detection limits (signal-to-noise ratio = 3) for both hydroxyproline and proline were 10 fmol per injection. The within-day (n = 10) and day-to-day (n = 5) relative standard deviations using human sera were less than 2.16% and 2.75%, respectively, for hydroxyproline and less than 2.30% and 3.25%, respectively, for proline. The concentrations of free hydroxyproline and proline in normal human sera (n = 13) were 5.6-18.0 and 137.6-252.6 mumol l-1, respectively. The proposed method was also applied to the determination of hydroxyproline and proline in sera from patients with chronic renal failure. The mean concentrations of hydroxyproline and proline in chronic renal failure were about 2.6 and 1.6 times higher, respectively, than those in normal human sera.

Blockade of ATP-sensitive potassium channels by 5-hydroxydecanoate suppresses monophasic action potential shortening during regional myocardial ischemia.

We tested 5-hydroxydecanoate (5-HD), a specific blocker of ATP-sensitive potassium channels (IK.ATP), to determine if mitigates electrophysiologic changes produced by regional myocardial ischemia in vivo. A sequence of 5-minute occlusion of the distal LAD and 30-minute reperfusion was repeated while recording the monophasic action potential (MAP) and bipolar electrogram (EG) from the epicardial center of the ischemic myocardium in anesthetized dogs. 5-HD (30 mg/kg, i.v.) or glibenclamide (0.15 or 0.3 mg/kg, i.v.) was administered before the third occlusion, and the data were compared to the second occlusion data. 5-HD did not affect baseline MAP duration at 90% and 50% repolarization (APD90, APD50) before LAD occlusion but suppressed occlusion-induced shortening of APD90 (16 +/- 2% during the second occlusion vs. 5 +/- 3% during the third occlusion, n = 8, p < 0.01) and APD50 (16 +/- 3% vs. 10 +/- 3%, n = 8, p < 0.05). Pretreatment with glibenclamide also suppressed occlusion-induced MAP shortening and eliminated an additional effect of 5-HD (n = 3). 5-HD did not affect the occlusion-induced increase in duration and activation time of EG. 5-HD, as well as glibenclamide, suppressed regional ischemia-induced MAP shortening, probably by blocking activation of IK.ATP, without affecting conduction delay. These differential effects of 5-HD on repolarization and conduction during the early phase of regional ischemia might have the potential to suppress reentrant ventricular arrhythmias.

[Acute massive pulmonary embolism--report of a case].

A 72-year-old female, who had received medication for hypertension and angina pectoris was hospitalized with complaining of an abrupt dyspnea. Roentgenogram of the chest revealed no abnormal findings except cardiac enlargement. An electrocardiogram showed overloading of the right ventricle. Arterial blood gas analysis of room air showed 55.4 mmHg of PaO2, 25.5 mmHg of PaCO2 and 7.30 of PH, respectively. Acute and massive pulmonary embolism was diagnosed by an emergent pulmonary arteriography. Despite intensive treatment such as infusion of urokinase and heparin for four days, thrombus was still detected in the left main pulmonary artery by a transesophageal echocardiography. By the result of ineffective conservative therapy, embolectomy was performed under cardiopulmonary bypass. However mechanical respiratory support was required for a long time due to the right heart failure, she is doing well for a year after the operation.

Dynamic determinants of left ventricular early diastolic filling in old myocardial infarction.

The determinants of left ventricular early diastolic filling were assessed in 15 patients with old myocardial infarction. The left atrial pressure (LAP) and left ventricular pressure (LVP) were simultaneously measured by a Millar's multisensor micromanometer with the pusled Doppler mitral inflow velocity at baseline and during angiotensin infusion (20 ng/kg/min). Cardiac output was measured by a thermodilution method. LV peak systolic pressure and end-diastolic pressure were significantly (p less than 0.001) increased during angiotensin infusion from 137 +/- 19 to 170 +/- 21 mmHg and from 13.3 +/- 5.9 to 20.4 +/- 6.2 mmHg, respectively. Cardiac index was significantly decreased during angiotensin infusion. Heart rate, diastolic time, and peak positive dP/dt were unchanged. Although the LA-LV peak pressure gradient[(LAP-LVP) max] was unchanged (from 2.8 +/- 1.0 to 3.0 +/- 1.4 mmHg), the pressure gradient interval (the interval between the first and second points of transmitral pressure crossover) was significantly (p less than 0.001) decreased from 154 +/- 38 to 117 +/- 26 msec during angiotensin infusion. Peak early diastolic mitral inflow velocity (peak E) and the time-velocity integral of E wave (Ei) were significantly decreased during angiotensin infusion from 51 +/- 10 to 45 +/- 11 cm/sec (p less than 0.002) and from 7.47 +/- 1.96 to 5.70 +/- 1.66 cm (p less than 0.001), respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Change of left atrial systolic pressure waveform in relation to left ventricular end-diastolic pressure.

The relation between the left atrial systolic pressure waveform and left ventricular end-diastolic pressure was observed in 17 patients who underwent diagnostic cardiac catheterization. Left atrial pressure and left ventricular pressure were simultaneously recorded from a multisensor catheter before and during angiotensin infusion. Left ventricular systolic pressure and left ventricular end-diastolic pressure were 133 +/- 17 and 12.3 +/- 3.2 mm Hg, respectively, before angiotensin infusion and increased to 168 +/- 18 (p less than 0.01) and 19.4 +/- 4.5 mm Hg (p less than 0.01), respectively, during infusion. The left atrial systolic pressure curve consisted of two positive waves--a first wave (A) and a second wave (A'). The A and A' wave pressures were 11.6 +/- 2.3 and 10.2 +/- 3.9 mm Hg, respectively, before angiotensin infusion and 16.5 +/- 2.9 (p less than 0.01) and 18.1 +/- 4.7 mm Hg (p less than 0.01), respectively, during infusion. The ratio of A'/A of left atrial systolic pressure was 0.81 +/- 0.27 before angiotensin infusion and 1.08 +/- 0.14 (p less than 0.01) during infusion. The ratio of A' to A of left atrial systolic pressure was linearly related to left ventricular end-diastolic pressure before and during (p less than 0.01) angiotensin infusion. The amplitude of the A wave exceeded that of the A' wave at normal left ventricular end-diastolic pressures. However, as the left ventricular end-diastolic pressure increased either at rest or during angiotensin infusion, the amplitude of the A' wave increased and often exceeded that of the A wave. These results suggest that the second (A') wave might be attributed to the increased reflection associated with increased left ventricular end-diastolic pressure.

Coronary artery spasm during cardiac angiography.

Unexpected occurrence of coronary artery spasm is sometimes observed during cardiac catheterization. We report here two cases of coronary artery spasm with hypotension and urticaria subsequent to administration of contrast material. The etiology of coronary artery spasm is discussed.

Left atrial conduit function for left ventricular filling dynamics in patient with myocardial infarction.

This study observed the left function in determining filling dynamics of the left ventricle in patients with myocardial infarction. The study consisted of eight control subjects and ten patients with myocardial infarction. The left ventricular filling volume is considered to be composed of the left atrial passive emptying, active emptying, and conduit volumes. The change of left ventricular filling volume was correlated with that of conduit volume (r = .87, P less than .01). However, the change of left ventricular filling volume did not have any correlation to those of left atrial passive emptying and active emptying volumes. These results suggested that the left atrial conduit function was important in determining filling dynamics of the left ventricle.

[A case of miliary tuberculosis with intracranial tuberculoma].

A case of miliary tuberculosis with intracranial tuberculoma was reported. Homogenous or ring-like enhancing lesions surrounded with edema were seen after administration of contrast material on CT examination. However, CT is considered very useful method of evaluating the effect of antituberculous therapy.

[CT findings of malignant lymphoma of the anterior mediastinum--differentiation from invasive thymoma].

CT findings were compared retrospectively between 9 cases with malignant lymphoma of the anterior mediastinum and 8 cases with invasive thymoma. CT findings of malignant lymphoma were as follows: 1) The majority of the tumors were bilateral and extended beyond the anterior mediastinum to the other mediastinum compartments. 2) Their margin was either smooth or lobulated. 3) Their density was either homogeneous or heterogeneous. In the case with heterogeneous density, ring, triangle and/or band-like low density areas, just like interspace of fused lymph nodes, were demonstrated. Calcification or cysts could not be shown. 4) Patent inherent vessels without deviation were occasionally demonstrated running through the tumors. 5) The tumors faced and contacted widely to anterior chest wall and often pressed the lung laterally at the anterior parietomediastinal pleural reflection. 6) Pleural implants were not demonstrated.