Antioxidative Pseudoenzymatic Mechanism of NAD(P)H Coexisting with Oxyhemoglobin for Suppressed Methemoglobin Formation.

Oxyhemoglobin (HbO2) coexisting with equimolar NADH retards autoxidation and oxidant-induced metHb formation based on the pseudocatalase (CAT) and pseudosuperoxide dismutase (SOD) activities. In this work, we compared the effects of NADH with those of NADPH and estimated the binding site of NAD(P)H to HbO2 to elucidate the antioxidative mechanisms. The results clarified that pseudo-CAT and pseudo-SOD activities of HbO2 coexisting with NADPH were similar to activities obtained with NADH. Prompt MetHb formation (<40 min) facilitated by oxidants (H2O2, NO, and NaNO2) was hindered by NADPH. These effects were similar to those of NADH. However, we found that NADPH is thermally unstable compared to NADH and that NADPH cannot sustain antioxidative effects for a long period of autoxidation to metHb such as 24 h. Lineweaver-Burk plots clarified that the Michaelis constants of these pseudoenzymatic activities are in the millimolar range. Addition of inositol hexaphosphate (IHP) and 2,3-diphosphoglycerate (DPG), which are known to bind not only with deoxyHb but also weakly with HbO2, showed competitive inhibition of pseudoenzymatic activities. These results suggest that the binding site of NADH and NADPH on HbO2 is the same as those of IHP and DPG. 31P nuclear magnetic resonance definitively showed 1:1 stoichiometric binding of NADH to HbO2. High-performance liquid chromatography analysis showed that NADH preferentially inhibited autoxidation of α-subunit heme. Docking simulations also predicted that the binding site of relaxed-state HbO2 with NAD(P)H is the same as those with IHP and DPG. Collectively, the pseudoenzymatic activities of HbO2 coexisting with NAD(P)H are induced by the 1:1 stoichiometric binding of NAD(P)H to HbO2.

Prognostic Value of BNP Reduction During Hospitalization in Patients With Acute Heart Failure.

BACKGROUND: Prognostication of patients discharged after acute heart failure (AHF) hospitalization remains challenging. Body weight (BW) reduction is often used as a surrogate marker of decongestion despite the paucity of evidence. We thought to test the hypothesis that B-type natriuretic peptide (BNP) reduction during hospitalization has independent prognostic value in AHF. METHODS AND RESULTS: We studied the prognostic predictability of percentage BNP reduction achieved during hospitalization in patients from the REALITY-AHF study. Percentage BNP reduction was defined as (BNP on admission - BNP at discharge) / BNP on admission × 100. The primary endpoint was 1-year all-cause death. In 1028 patients (age, 77 ± 13 years; 57% male; left ventricular ejection fraction, 47 ± 16%) with AHF, median BNP level at admission was 747 ng/L (interquartile range, 439-1367 ng/L) and median percentage BNP reduction was 62.5% (interquartile range, 36.5-78.5%). The smallest percentage BNP reduction quartile had more than 2-fold higher risk of all-cause death than the greatest quartile (23.0% vs 9.7%, P< .001). After adjusting for covariates including BNP at discharge, the percentage BNP reduction was significantly associated with all-cause death (hazard ratio 0.96, 95% confidence interval 0.93-0.99, P= .032), whereas percentage BW reduction was not. Percentage BNP reduction was more predictive in patients with heart failure with reduced ejection fraction than in those with preserved ejection fraction. CONCLUSIONS: The prognostic value of percentage BNP reduction during hospitalization was superior to that of percentage BW reduction and was independent of other risk markers, including BNP at discharge.

Ring-Opening Polymerization of Hemoglobin.

Hemoglobin (Hb), an oxygen-carrying protein, has an α2ß2 tetrameric structure that dissociates reversibly into two αß dimers (α2ß2 ⇄ 2αß). We synthesized a cyclic Hb-ring monomer with two ß subunits bound through a 10 kDa polyethylene glycol (PEG) chain. The monomer induced ring-opening polymerization to produce a supramolecular polymer via intersubunit interaction of αß dimers of an Hb molecule at the PEG terminals. Both the ring-closed monomer and the ring-opened supramolecular polymer were then fixed covalently by intramolecular cross-linking of two ß subunits. Quantification of fixed products at various monomer concentrations revealed the equilibrium constant ( K), a ratio of propagation and depropagation rate constants, as 5.68 mM-1. The average degree of polymerization ([Formula: see text]) increased proportionally, concomitantly with the initial monomer concentration. Hb polymer with [Formula: see text] = 13.2 ( Mn = ca. 1 MDa) was obtained by cross-linking at 2.33 mM. Our novel strategy of ring-opening polymerization of Hb will eventually realize a highly aligned and efficiently polymerized Hb for creating artificial oxygen carriers for a clinical use.

Visit-to-Visit B-Type Natriuretic Peptide Variability during the Previous Year Has Independent Prognostic Value in Patients with Stable Chronic Heart Failure.

BACKGROUND: There is wide variability of visit-to-visit (V2V) B-type natriuretic peptide (BNP) in patients with chronic heart failure (CHF), even when they are stable. The prognostic significance of V2V-BNP variability has not been investigated. We aimed to test whether V2V-BNP variability during the stable period of CHF has prognostic value regardless of BNP level. METHODS: In 278 stable outpatients (75 ± 10 years, 65% male) with CHF, we studied V2V-BNP variability, which was defined as the coefficient of variance of BNP values measured during 1 year before enrollment. All-cause death and rehospitalization due to HF were considered the primary endpoint. RESULTS: The median V2V-BNP variability was 25.7% (IQR: 19.2-34.4%). During the follow-up period (median 3.2 years), 100 patients reached the endpoint and those with high V2V-BNP variability (≥25.7%) had a significantly higher rate of events (p = 0.001). CHF severity in terms of BNP level and MAGGIC risk score was not significantly different between those with high and low V2V-BNP variability. Multivariable analysis showed that high V2V-BNP variability was independently associated with increased event rates even after adjustment for other known prognostic predictors, including BNP (hazard ratio 1.90, p = 0.003), or for MAGGIC risk score and BNP (hazard ratio 1.72, p = 0.010). The hazard for the outcome consistently increased as V2V-BNP variability increased, with a marked increase up to about 30%. CONCLUSIONS: Even in the stable phase of CHF, V2V-BNP variability was associated with worse long-term outcomes, independent of BNP level.

Analysis of Dimeric αß Subunit Exchange between PEGylated and Native Hemoglobins (α2ß2 Tetramer) in an Equilibrated State by Intramolecular ßß-Cross-Linking.

Various chemical modifications of hemoglobin (Hb) including PEGylation have been investigated to produce red blood cell substitutes. Some of those modifications are designed on the premise that the α2ß2 tetrameric structure of Hb is fundamentally stable and that it rarely dissociates into two αß dimers in a physiological condition. However, in the present work using the "clipping" method we detected and quantitatively analyzed the considerable degree of exchange reaction of αß subunits between ß93Cys-bis-PEGylated and native Hbs through dissociation into αß dimers and restructuring to α2ß2 tetramer in a physiological condition. The equilibrium constant ( Keq) of subunit exchange reactions increased from 0.82 to 2.86 with increasing molecular weight of PEG from 2 to 40 kDa, indicating that longer PEG chains enhanced such exchange reaction. The results suggest that the exchange might occur for other modified Hbs even at a practically high concentration for use as a red blood cell substitute.

Prolapse Volume to Prolapse Height Ratio for Differentiating Barlow's Disease From Fibroelastic Deficiency.

BACKGROUND: As mitral valve (MV) repair for Barlow's disease remains surgically challenging, it is important to distinguish Barlow's disease from fibroelastic deficiency (FED) preoperatively. We hypothesized that the prolapse volume to prolapse height ratio (PV-PH ratio) may be useful to differentiate Barlow's disease and FED.Methods and Results:In 76 patients with MV prolapse who underwent presurgical transesophageal echocardiography, the 3D MV morphology was quantified: 19 patients were diagnosed with Barlow's disease and 57 with FED. The patients with Barlow's disease had greater prolapse volume and height than the patients with FED, as well as greater PV-PH ratio (0.61±0.35 vs. 0.17±0.10, P<0.001). Receiver-operating characteristic analysis revealed that with a cutoff value of 0.27, the PV-PH ratio differentiated Barlow's disease from FED with 84.2% sensitivity and 84.2% specificity. Net reclassification improvement showed that the differentiating ability of the PV-PH ratio was significantly superior to prolapse volume (1.30, P<0.001). After being adjusted by each of prolapse volume and height, annular area and shape, and the number of prolapsed segments, the PV-PH ratio had an independent association with Barlow's disease. CONCLUSIONS: The PV-PH ratio was able to differentiate Barlow's disease from FED with high accuracy. 3D quantification including this value should be performed before MV repair.

Efficacy and Accuracy of Novel Automated Mitral Valve Quantification: Three-Dimensional Transesophageal Echocardiographic Study.

BACKGROUND: Previous studies indicated that the three-dimensional features of the mitral valve (MV) have a significant impact on MV disease. However, quantification of MV with manual tracing software was too time-consuming for routine clinical practice. This study was performed to investigate the efficacy and accuracy of MV quantification with a novel highly automated commercially available software package developed for this purpose. METHODS: Using the manual tracing and automated package, two expert sonographers and one cardiologist individually analyzed three-dimensional datasets acquired with transesophageal echocardiography from 74 patients (15 with functional mitral regurgitation, 32 with MV prolapse, and 27 normal subjects) retrospectively. Time for analysis and inter-observer agreement were compared between the two methods, and agreement of measurements was analyzed using Cronbach's α. RESULTS: Time for analysis using the automated package was significantly shorter than manual tracing (whole cohort, 260 ± 65 vs. 381 ± 68 seconds, P < 0.001; functional mitral regurgitation, 234 ± 42 vs. 378 ± 64 seconds, P < 0.001; MV prolapse, 293 ± 69 vs. 407 ± 67 seconds, P < 0.001; normal controls, 235 ± 52 vs. 351 ± 60 seconds, P < 0.001). There was good agreement among all three observers using both methods, and measurements with the automated package agreed well with the manual tracing values. CONCLUSIONS: The novel automated software package reduced time for quantification of MV with similar accuracy compared to the manual method. Automated quantification is useful and may be a key to widespread adoption of three-dimensional quantification in clinical practice.

Olmesartan reduces inflammatory biomarkers in patients with stable coronary artery disease undergoing percutaneous coronary intervention: results from the OLIVUS trial.

The OLmesartan on the progression of coronary atherosclerosis: evaluation by IntraVascular UltraSound (OLIVUS) trial demonstrated that an angiotensin II receptor blocker, olmesartan, reduces the rate of coronary atheroma progression as evaluated by intravascular ultrasound in patients with stable angina pectoris undergoing percutaneous coronary intervention. This substudy examined the impact of olmesartan on serum biomarkers and the relationship between biomarker changes and atheroma progression. Patients in the OLIVUS trial (n = 247) were randomly assigned to a control group or the olmesartan group. A subgroup of these patients (n = 135, 55 %) was analyzed at baseline and at 14 months. Patients' characteristics and blood-pressure control were identical between the control group (n = 65) and the olmesartan group (n = 70), and also between the subpopulation and total population. The change in the level of high-sensitivity C-reactive protein (hs-CRP) (mg/l) and adiponectin (µg/ml) was significantly greater in the olmesartan group than in the control group (between-group differences: 0.5 and -0.7; 95 % confidence interval: 0.2-0.8 and -1.3 to -0.1; P = 0.001 and 0.02, respectively). Multiple regression analysis revealed that the nominal changes in total atheroma volume and percent atheroma volume were significantly associated with the nominal change in hs-CRP in the olmesartan group but not in the control group. Olmesartan reduced hs-CRP in patients with stable angina, and this correlated with the change in coronary atheroma.

Characteristics of postural muscle activation patterns induced by unexpected surface perturbations in elite ski jumpers.

[Purpose] This study investigated the characteristics of postural control following postural disturbance in elite athletes. [Subjects] Ten elite ski jumpers and ten control subjects participated in this study. [Methods] Subjects were required to maintain balance without stepping following unexpected horizontal surface perturbation in a forward or backward direction. [Results] A lower and reproducible peak magnitude of the center of mass velocity was shown in the athlete group compared to the control group. Cross-correlation analyses showed longer time lags at the moment of peak correlation coefficient between trunk flexor and extensor muscle activities, and shorter time lags and higher correlations between ankle flexor and extensor muscle activities were shown in the athlete group than in the control group. [Conclusion] The elite ski jumpers showed superior balance performance following surface perturbations, more reciprocal patterns in agonist-antagonist pairs of proximal postural muscles, and more co-contraction patterns in distal postural muscles during automatic postural responses than control individuals. This strategy may be useful in sports requiring effective balance recovery in environments with a dynamically changing surface, as well as in rehabilitation.

Two weeks administration of tranexamic acid for acute intracerebral hemorrhage: A hospital-based pilot study.

Background: A previous report suggested that functional status does not differ between patients who received tranexamic acid and those who received placebo within the early hours of intracerebral hemorrhage (ICH). Our pilot study tested the hypothesis that 2 weeks administration of tranexamic acid would contribute to functional improvement. Methods: Consecutive patients with ICH were administered 250 mg tranexamic acid 3 times a day continuously for 2 weeks. We also enrolled historical control consecutive patients. We collected clinical data that involved hematoma size, level of consciousness, and Modified Rankin Scale (mRS) scores. Results: Univariate analysis showed that the mRS score on day 90 was better in the administration group (P = 0.0095). The mRS scores on the day of death or discharge suggested a favorable effect of the treatment (P = 0.0678). Multivariable logistic regression analysis also showed that the treatment was associated with good mRS scores on day 90 (odds ratio [OR] = 2.81, 95% confidence interval [CI]: 1.10-7.21, P = 0.0312). In contrast, ICH size was associated with poor mRS scores on day 90 (OR = 0.92, 95% CI: 0.88-0.97, P = 0.0005). After propensity score matching, there was no difference in the outcomes between the two groups. We did not detect mild and serious adverse events. Conclusion: The study could not show the significant effect of 2 weeks administration of tranexamic acid on functional outcomes of ICH patients after the matching; however, suggested that this treatment is at least safe and feasible. A larger and adequately powered trial is needed.

Comprehensive validation of a wearable foot sensor system for estimating spatiotemporal gait parameters by simultaneous three-dimensional optical motion analysis.

BACKGROUND: Use of a wearable gait analysis system (WGAS) is becoming common when conducting gait analysis studies due to its versatility. At the same time, its versatility raises a concern about its accuracy, because its calculations rely on assumptions embedded in its algorithms. The purpose of the present study was to validate twenty spatiotemporal gait parameters calculated by the WGAS by comparison with simultaneous measurements taken with an optical motion capture system (OMCS). METHODS: Ten young healthy volunteers wore two inertial sensors of the commercially available WGAS, Physilog®, on their feet and 23 markers for the OMCS on the lower part of the body. The participants performed at least three sets of 10-m walk tests at their self-paced speed in the laboratory equipped with 12 high-speed digital cameras with embedded force plates. To measure repeatability, all participants returned for a second day of testing within two weeks. RESULTS: Twenty gait parameters calculated by the WGAS had a significant correlation with the ones determined by the OMCS. Bland and Altman analysis showed that the between-device agreement for twenty gait parameters was within clinically acceptable limits. The validity of the gait parameters generated by the WGAS was found to be excellent except for two parameters, swing width and maximal heel clearance. The repeatability of the WGAS was excellent when measured between sessions. CONCLUSION: The present study showed that spatiotemporal gait parameters estimated by the WGAS were reasonably accurate and repeatable in healthy young adults, providing a scientific basis for applying this system to clinical studies.

Relationship between scapular control during isometric shoulder flexion and scapular motion during baseball pitching: a cross-sectional study.

BACKGROUND: A baseball pitcher with decreased scapular control may not be able to achieve suitable scapular motion at maximum shoulder external rotation (MER) of baseball pitching during the pitching action. It is common clinically to compare scapular control of the throwing and non-throwing arms to detect side-to-side differences. However, it remains unclear whether scapular control is different between the throwing and non-throwing arms. Moreover, no data exist on the relationship between scapular control and scapular motion at MER of pitching. Primarily, this study aimed to compare scapular control during isometric shoulder flexion between the throwing and non-throwing arms. Secondly, this study aimed to investigate the relationship between scapular control during isometric shoulder flexion and scapular motion at MER of pitching. METHODS: Fifteen healthy collegiate baseball pitchers (age, 20.2 ± 1.9 years; height, 1.76 ± 0.05 m; body mass, 73.3 ± 6.7 kg) were recruited. An optical motion tracking system was used to assess scapular motion. Scapular control was defined as the amount of change in the scapular internal rotation angle, downward rotation angle, and anterior tilt angle during isometric shoulder flexion. We assessed scapular position at MER of pitching. RESULTS: No significant differences were detected for any of the scapular angles during isometric shoulder flexion between the throwing and non-throwing arms. The amount of change in the scapular internal rotation angle, scapular downward rotation angle, and scapular anterior tilt angle during isometric shoulder flexion had a significant relationship with the scapular downward rotation angle at MER. CONCLUSIONS: No side-to-side difference was noted in scapular control during isometric shoulder flexion in healthy collegiate baseball pitchers at the group level. Further studies are required to understand the side-to-side differences at the individual level. Additionally, there was a relationship between scapular control during isometric shoulder flexion and scapular position at MER. These findings suggest that clinicians may consider using isometric shoulder flexion to assess scapular control in baseball pitchers.

Numerical study of transient aerodynamic forces acting on a ski jumper considering dynamic posture change from takeoff to landing.

This study was designed to develop a computational fluid dynamics (CFD) method for unsteady analysis of a series of ski jump movements with attitude changes, and to analyse the aerodynamic characteristics of an expert jumper over the entire ski jump movement. Two ski jumpers participated in this study. A sensor-based motion capture suit was used to capture the jumper's posture during the actual ski jump. A three-dimensional computer graphics animation was created by superimposing the joint angles obtained from the motion measurements of the 3D shape of the athlete. The unsteady aerodynamic forces acting on the ski jumper, from the takeoff to the landing, were then calculated using CFD. A time-varying spatially uniform flow was specified as the inflow boundary condition of the computational domain. The results indicated that both the lift and drag forces of the expert jumper increase rapidly during the initial flight when the jumper's posture changes drastically. Thereafter, drag force decreased considerably, but the decrease in the lift force was less drastic. Later in the flight phase, the lift force acting on the expert jumper increased, and throughout the flight phase, the lift-drag ratio of the expert jumper remained higher than that of the unskilled jumper.

Structural insights into the substrate specificity of IMP-6 and IMP-1 metallo-ß-lactamases.

IMP-type metallo-ß-lactamases confer resistance to carbapenems and a broad spectrum of ß-lactam antibiotics. IMP-6 and IMP-1 differ by only a point mutation: Ser262 in IMP-1 and Gly262 in IMP-6. The kcat/Km values of IMP-1 for imipenem and meropenem are nearly identical; however, for IMP-6, the kcat/Km for meropenem is 7-fold that for imipenem. In clinical practice, this may result in an ineffective therapeutic regimen and, consequently, in treatment failure. Here, we report the crystal structures of IMP-6 and IMP-1 with the same space group and similar cell constants at resolutions of 1.70 and 1.94 Å, respectively. The overall structures of IMP-6 and IMP-1 are similar. However, the loop region (residues 60-66), which participates in substrate binding, is more flexible in IMP-6 than in IMP-1. This difference in flexibility determines the substrate specificity of IMP-type metallo-ß-lactamases for imipenem and meropenem. The amino acid at position 262 alters the mobility of His263; this affects the flexibility of the loop via a hydrogen bond with Pro68, which plays the role of a hinge in IMP-type metallo-ß-lactamases. The substitution of Pro68 with a glycine elicited an increase in the Km of IMP-6 for imipenem, whereas the affinity for meropenem remained unchanged.

Association of elevated plasma B-type natriuretic peptide levels with paroxysmal atrial fibrillation in patients with nonobstructive hypertrophic cardiomyopathy.

OBJECTIVES: To investigate the relationship between the plasma B-type natriuretic peptide (BNP) level and the occurrence of atrial fibrillation (AF) in nonobstructive hypertrophic cardiomyopathy (HCM) patients. METHODS: Patients (n=97) were classified into chronic AF (CAF; n=14), paroxysmal AF (PAF; n=18) and normal sinus rhythm (NSR; n=65) groups. The plasma BNP values were analyzed with logarithmic transformation. RESULTS: The PAF group showed significantly higher plasma BNP levels than the NSR group [mean (range; -l SD and +1 SD); 248.3 (143.5, 429.5) vs. 78.2 (27.9, 218.8 ng/L), p<0.0001]. The CAF group also showed significantly higher plasma BNP levels than the NSR group [291.1 (161.4, 524.8 ng/L), p<0.0001]. Multivariate analysis with other clinical factors selected association of PAF as one of the factors that increased the plasma BNP level. CONCLUSIONS: The present study indicated that plasma BNP level is clinically useful for identification of nonobstructive HCM patients who have a risk of PAF.

Higher incidence and serum levels of minor cardiac biomarker elevation in sirolimus-eluting stent (Cypher) than bare metal stent implantations.

OBJECTIVES: Minor cardiac biomarker elevation after percutaneous coronary intervention has long-term prognostic significance. The sirolimus-eluting stent (Cypher) has been reported to require high postinflation pressure for optimal implantation. We examined the incidence of minor cardiac biomarker elevation induced by Cypher implantation. METHODS: We measured the serum concentration of cardiac troponin-I (cTnI) 24 h after stenting and those of creatine kinase isoenzyme MB and creatine kinase before, immediately after, and 6, 12 and 24 h after implantation in patients who underwent Cypher stent (CS group; n=53) or bare metal stent (BMS group; n=57) implantation. RESULTS: No significant difference in clinical background was observed between the two groups. When a cutoff cTnI value of 0.50 ng/ml was used, the CS group showed a significantly higher incidence of cTnI elevation (35.8%, 19/53) than the BMS group (14.0%, 8/57) (P<0.05). Similarly, the incidence of cTnI > or = 0.03 ng/ml tended to be higher in the CS group (88.7%, 47/53) than in the BMS group (73.7%, 42/57: 0.05

Crystallization and preliminary X-ray analysis of isomaltase from Saccharomyces cerevisiae.

Isomaltase from Saccharomyces cerevisiae is an oligo-1,6-glucosidase that preferentially hydrolyzes isomaltose, with little activity towards isomaltotriose or longer oligosaccharides. An amino-acid sequence analysis of the isomaltase revealed that it belongs to glucoside hydrolase family 13. Recombinant isomaltase was purified and crystallized by the hanging-drop vapour-diffusion method with PEG 3350 as the precipitant. The crystals belonged to space group C2, with unit-cell parameters a = 95.67, b = 115.42, c = 61.77 A, beta = 91.17 degrees . X-ray diffraction data were collected to 1.35 A resolution from a single crystal on a synchrotron-radiation source.

A Rare Case of Thyrotropin-Secreting Pituitary Adenoma Coexisting with Papillary Thyroid Carcinoma Presenting with Visual Disturbance without Hyperthyroidism.

BACKGROUND: Thyroid-stimulating hormone-secreting pituitary adenomas (TSHomas) are uncommon, and majority of the patients present with symptoms of hyperthyroidism. Herein, we report the first case of TSHoma with differentiated thyroid carcinoma (DTC) that presented with visual disturbance without any clinical feature of hyperthyroidism. CASE DESCRIPTION: A 57-year-old man presented with left temporal hemianopsia of his left eye without any sign of hyperthyroidism. A mass lesion in the sellar and suprasellar region compressing the optic nerves was identified via magnetic resonance imaging. Free thyroxine and free triiodothyronine levels were slightly elevated, whereas the serum level of thyroid-stimulating hormone remained within normal range. Further endocrinologic examination led to the preoperative diagnosis of TSHoma. Ultrasonography and 111In-octreotide scan showed a mass lesion in left lobe of the thyroid gland, and subsequent thyroid aspiration biopsy confirmed the diagnosis of papillary thyroid carcinoma. After administration of short-acting octreotide to prevent thyrotoxic crisis in the perioperative period, the tumor was removed via endoscopic transnasal-transsphenoidal surgery, and the pathologic diagnosis of TSHoma was made. His visual acuity improved, and free triiodothyronine and free thyroxine levels normalized. He underwent thyroidectomy 3 months later after endoscopic transnasal-transsphenoidal surgery. CONCLUSIONS: Herein, we report the first case of TSHoma with DTC that presented with visual disturbance without any clinical feature of hyperthyroidism and reviewed the 13 reported cases of TSHoma coexisting with DTC. The optimal treatment strategy in patients with TSHoma and coexistent DTC has not been established, and individualized therapeutic strategies are needed.

[A surgically treated case of ileus caused by small intestinal tuberculosis during treatment for pulmonary tuberculosis].

A 44-year-old man consulted medical clinic, complaining of cough and sputum. Then he was admitted to our hospital, because of positive acid-fast bacilli in his sputum and positive PCR (polymerase chain reaction) for Mycobacterium tuberculosis. Combined use of isoniazid (INH), rifampicin (RFP), ethambutol (EB) and pyrazinamide (PZA) was started. But 4 days after starting treatment, we had to suspend tuberculosis chemotherapy because of hepatopathy. Since then he started to complain epigastralgia and vomiting. Plain abdominal X-ray and abdominal computed tomography (CT) led to a diagnosis of ileus. Inspite of insertion of ileus tube symptoms of ileus did not improve. Small bowl series showed severe stenosis at ileum end, necessitating jejunectomy. Macroscopic study revealed a ring ulcer and multiple epithelioid cell granuloma with Langhans' giant cells was detected histopathologically. PCR for M. tuberculosis of extracts from ileum was positive. Therefore the patient was diagnosed small intestinal tuberculosis. Treatment was continued by the combination of INH, RFP, EB, and the symptoms markedly improved. There have been no sign of recurrence since the end of the 6-month treatment for tuberculosis.

Insufficient Leaflet Remodeling in Patients With Atrial Fibrillation: Association With the Severity of Mitral Regurgitation.

BACKGROUND: The relationship between annular dilatation caused by atrial fibrillation (AF) and mitral regurgitation (MR) remains controversial. We hypothesized that the small ratio of total leaflet area/annulus area (TLA/AA), reflecting insufficient leaflet remodeling to annular dilatation, is a main component of MR in patients with AF. METHODS AND RESULTS: Three-dimensional transesophageal echocardiographic data of the mitral valve were analyzed in 28 AF patients with moderate or severe MR (MR group), age- and sex-matched 56 AF patients with mild or less MR (non-MR group), and 16 control subjects. AA was significantly greater in both the MR (645±126 mm2/m2, P<0.001) and non-MR groups (568±121 mm2/m2, P=0.001) compared with control subjects (444±108 mm2/m2). However, TLA/AA was significantly smaller in the MR (1.29±0.10, P<0.001), but not in the non-MR group (1.65±0.24, P>0.99), compared with control subjects (1.70±0.29). In linear regression analysis, TLA/AA was inversely associated with the effective regurgitant orifice (r=-0.73, P<0.001). The area under the receiver-operating-characteristics curve of TLA/AA was significantly greater than that of AA (0.95 versus 0.72, P<0.001). Multivariable analysis revealed that small TLA/AA (P<0.001) was independently associated with significant MR, while AA was not (P=0.26). CONCLUSIONS: In patients with AF, insufficient leaflet remodeling to annular dilatation, rather than crude annular dilatation, was strongly associated with the severity of MR.