Fecal eosinophil granule-derived proteins reflect disease activity in inflammatory bowel disease

OBJECTIVES: The aims of this study were: 1) to examine whether the fecal levels of eosinophil granule-derived proteins reflect disease activity in inflammatory bowel disease (IBD); and 2) to examine the extracellular release of these proteins from eosinophils and their stability in feces by an in vitro study. METHODS: We investigated 42 patients with ulcerative colitis (UC), 37 patients with Crohn's disease (CD), and 29 control subjects. The stool samples were collected at 4 degrees C over 48 h and were homogenized. The fecal levels of eosinophil cationic protein (ECP) and eosinophil protein X (EPX) were measured by radioimmunoassay. Fecal Hb (Hb), alpha1-antitrypsin (AT), and lactoferrin (Lf) were also measured by ELISA. RESULTS: Fecal ECP and EPX concentrations were significantly increased in both active UC and active CD compared to inactive UC and inactive CD, respectively. Fecal EPX concentration correlated with the fecal Hb, AT, and Lf concentrations more closely than fecal ECP concentration. Even in the inactive stage, CD patients who relapsed within the following 3 months showed higher fecal ECP and EPX concentrations compared to the patients who did not. EPX was released extracellularly more efficiently than ECP (18.6% vs 6.3%, after incubation for 15 min at 25 degrees C). EPX was more stable in the feces than ECP. CONCLUSIONS: The measurement of eosinophil granule-derived proteins in feces is useful for evaluating disease activity and predicting relapse in patients with IBD. EPX may be more suitable than ECP as a fecal eosinophil marker.     

Effects of Dobutamine Infusion on Mitral Regurgitation

Both intensity of mitral regurgitant murmur and color-coded Doppler regurgitant signal area have been reported to correlate with the degree of regurgitation. To evaluate the relationship between the intensity of regurgitant murmur and severity of mitral regurgitation, phonocardiography, echocardiography, and Doppler ultrasound were performed in 18 patients with mitral regurgitation before and during dobutamine infusion. Mitral regurgitation was due to mitral valve prolapse with ruptured chordae tendineae in 8 patients, rheumatic change in 5 patients, and dilated cardiomyopathy in 5 patients. With intravenous dobutamine infusion, heart rate (77–103 beats/min), systolic blood pressure (119–144 mmHg), peak mitral regurgitant jet velocity (4.5–5.4 m/sec), intensity of mitral regurgitant murmur (to 201% of that before infusion in early systole) increased, while left ventricular end-diastolic volume (124–102 mm), left ventricular end-systolic volume (57–42 mm), mitral anular diameter (33–28mm), and color Doppler mitral regurgitant signal area (704–416 mm²) decreased (P < 0.05). Total (forward + backward) left ventricular stroke volume (66–61 mL/beat) showed no change. Dobutamine decreased mitral regurgitant flow/beat, regardless of etiology of mitral regurgitation, which was probably due to the decrease of left ventricular size and mitral annular diameter. Although total (forward + backward) left ventricular stroke volume was unchanged, dobutamine effectively increased forward left ventricular stroke volume by decreasing backward regurgitation. Mitral regurgitant murmur became louder despite the decrease of mitral regurgation, indicating the uselessness of auscultation in the grading of the severity of mitral regurgitation.     

Anteroposterior and varus–valgus laxity of the knee increase after stair climbing in patients with mild osteoarthritis

The aim of this study was to measure exercise-induced changes in knee joint laxity in patients with knee osteoarthritis (OA). The study subjects were 46 female patients with OA and 22 age- and sex-matched normal controls. Radiographs of the knee were taken in all subjects, and the disease severity was graded according to the Kellgren and Lawrence (K-L) grading system. The K-L grade of the control subjects (non-OA group) was 0-1. The OA patients were divided into those with mild OA (K-L grade 2, n = 20) and advanced OA (K-L grade 3-4, n = 26). The subject climbed up and down 8 steps on a staircase apparatus over a period of 10 min. The anteroposterior (A-P) translation was measured with KT2000 arthrometer, and varus-valgus (V-V) rotation was measured on stress radiographs before and after the stair climbing. The Δchange in A-P translation after the exercise was significantly larger in mild OA group than other groups (P < 0.005). The Δchange in V-V rotation after exercise was significantly larger in mild and advanced OA groups than the control (P < 0.003). There were no significant differences in A-P laxity and V-V laxity before exercise among the non-OA, mild OA and advanced OA groups. Exercise resulted in significant changes in A-P knee joint laxity in patients with mild OA relative to the control. The results suggest that daily physical activities (e.g., knee bending or squatting) play a role in the development of knee laxity, particularly in patients with mild OA, and that progression of knee OA seems to correlate with increments of A-P knee joint laxity.     

Prognostic impact of left ventricular noncompaction in patients with Duchenne/Becker muscular dystrophy — Prospective multicenter cohort study

Background

The reported prevalence of left ventricular noncompaction (LVNC) varies widely and its prognostic impact remains controversial. We sought to clarify the prevalence and prognostic impact of LVNC in patients with Duchenne/Becker muscular dystrophy (DMD/BMD).

Methods

We evaluated the presence of LNVC in patients with DMD/BMD aged 4–64 years old at the study entry (from July 2007 to December 2008) and prospectively followed-up their subsequent courses (n = 186). The study endpoint was all-cause death and the presence of LVNC was blinded until the end of the study (median follow-up: 46 months; interquartile range: 41–48 months).

Results

There were no significant differences in baseline characteristics between patients with LVNC (n = 35) and control patients without LVNC (n = 151), with the exception of LV function. Patients with LVNC showed, in comparison with patients without LVNC, a significant negative correlation between age and LVEF (R = − 0.7 vs. R = − 0.4) at baseline; and showed a significantly greater decrease in absolute LVEF (− 8.6 ± 4.6 vs. − 4.3 ± 4.5, p < 0.001) during the follow-up. A worse prognosis was observed in patients with LVNC (13/35 died) than in patients without LVNC (22/151 died, Log-rank p < 0.001). Multivariate Cox analysis revealed that LVNC is an independent prognostic factor (relative hazard 2.67 [95% CI: 1.19–5.96]).

Conclusion

LVNC was prevalent in patients with DMD/BMD. The presence of LVNC is significantly associated with a rapid deterioration in LV function and higher mortality. Neurologists and cardiologists should pay more careful attention to the presence of LVNC.     

Persistent elevation of exhaled nitric oxide and modification of corticosteroid therapy in asthma

BackgroundPersistent airway inflammation, detected by fractional exhaled nitric oxide (FE_NO), is occasionally observed in asthmatic patients, even in those treated with inhaled corticosteroids (ICS). However, improvement in residual airway inflammation and pulmonary function through modification of corticosteroid therapy has not been proven.MethodsThirteen asthmatic patients whose FE_NO levels were over 40 parts per billion (ppb), despite dry-powder ICS therapy, were enrolled. A 3-step change in steroid treatment was undertaken until FE_NO was less than 40 ppb. In the first step, the powder formula was changed to an ultra-fine particle compound as an equipotent ICS dose. In the second step, the ICS dose was doubled. In the third step, oral corticosteroids were added. We measured pulmonary function and FE_NO and alveolar NO concentrations (CAlvNO).ResultsDoubling the ICS dose and changing the ICS formula significantly improved FVC (p<0.001), FEV1 (p<0.05), the slope of the single nitrogen washout curve (dN₂) (p<0.01), FE_NO (p<0.001), and CAlvNO (p<0.05), relative to baseline. The reductions in FE_NO were significantly associated with the improvement in airflow limitation assessed by dN₂ (r=0.73, p=0.007). The remaining FE_NO elevation, even after doubling the ICS dose, did not decrease after oral corticosteroid administration.ConclusionsThese results suggest that modification of ICS therapy can suppress residual FE_NO elevation, and that reduction in FE_NO levels is associated with improvement in airflow limitation. However, steroid-resistance mechanisms may exist in some asthmatic patients with sustained FE_NO elevations.     

Bactericidal activity of cefclidin (E1040) against Pseudomonas aeruginosa under conditions simulating plasma pharmacokinetics: lack of development of chromosomally-mediated resistance to beta-lactams.

The bactericidal activity of cefclidin (E1040), a new cephalosporin, against Pseudomonas aeruginosa was compared with that of ceftazidime and imipenem in an in-vitro model in which antibiotic concentration was varied continuously. A two-compartment open in-vitro model was used to simulate the plasma pharmacokinetics of each antibiotic in man for 12 h after a 1 h infusion of 1 g iv. The bactericidal activity of each antibiotic was observed for 6 h; however, it was diminished or absent after 6 h when the antibiotic concentration fell near to the MIC. With ceftazidime and imipenem, marked regrowth was observed after 6 h. Moreover, selection of resistant variants was observed with ceftazidime, and these variants produced 200 to 500 times more beta-lactamase than the corresponding wild-type strains. With cefclidin neither marked regrowth nor emergence of resistant variants was observed. The affinity of cefclidin for the chromosomal beta-lactamase produced by P. aeruginosa was much lower than the affinities of other new beta-lactams, and cefclidin was hydrolyzed more slowly than ceftazidime at a low concentration (2 microM). The high activity of cefclidin against P. aeruginosa, which results mainly from the low affinity of cefclidin for the pseudomonal beta-lactamase, and may play a major role in the absence of regrowth and lack of selection of resistant variants.     

Effect of upper gastrointestinal endoscopy on circulation in the elderly.

BACKGROUND: Upper gastrointestinal endoscopy in the elderly is increasingly becoming more common, despite the possibility that a minimal load on the circulation can cause serious complications such as shock and cardiac arrest. OBJECTIVE: The effects of endoscopy on the heart and the possibility of predicting circulatory accidents were studied using natriuretic peptide levels. METHODS: The patients were randomly chosen according to their age and divided into an elderly group (over 60 years of age, 64 patients) and a young group (under 30 years of age, 20 patients). The patients in the elderly group were further subdivided into two groups based on the presence or absence of circulatory complications (46 patients with circulatory complications and 18 without complications). The load on the heart was evaluated by measuring human atrial natriuretic peptide (hANP) and human brain natriuretic peptide (hBNP) which are secreted by the myocardial cells in response to cardiac load. Specimens were obtained before and after endoscopy. RESULTS: The hANP level was significantly higher after endoscopy in the elderly group, regardless of the presence or absence of circulatory complications. No significant difference was observed in the hBNP level. No significant increase in hANP or hBNP levels was observed after endoscopy in the young group. CONCLUSIONS: These observations suggest an increased atrial load during endoscopy in the elderly. The increase in pulse rate during endoscopy is one possible cause of atrial load. Therefore, the risk of circulatory system damage must be recognized when endoscopy is performed in the elderly. The measurement of plasma hANP and hBNP levels may provide effective indices for evaluating cardiac load during endoscopy.     

A CASE OF CHOLESTEROSIS OF THE COMMON BILE DUCT DIAGNOSED BY PERORAL CHOLANGIOSCOPY

We experienced a case of cholesterosis of the common bile duct in which peroral cholangioscopy (POCS) was very useful for making a diagnosis. The patient was a 66‐year‐old man. He was admitted for examination of an asymptomatic mass in the pancreas. The mass was diagnosed as a serous cystic tumor of the pancreas. While examining the tumor, endoscopic retrograde cholangiopancreatography (ERCP) incidentally revealed a 7 mm irregular filling defect in the distal common bile duct. EST was then performed, followed by POCS, which revealed a clump of yellowish‐white Ip or Isp polyps in the distal bile duct. Histological examination of biopsy specimens taken under direct vision gave a diagnosis of cholesterol polyps containing foamy cells. POCS was useful for allowing direct observation of the characteristic color of cholesterol polyps, and for obtaining biopsy specimens under direct vision.