Sacroiliitis in inflammatory bowel disease on abdominal computed tomography: prevalence, misses, and associated factors.

OBJECTIVE: To evaluate the prevalence and rate of a missed diagnosis of sacroiliitis on abdominal computed tomography (CT) in patients with inflammatory bowel disease (IBD). Factors associated with sacroiliitis were also assessed. METHOD: This retrospective study included 210 patients with IBD (mean age 31.1 years) who underwent abdominal CT. Based on a validated abdominal CT scoring tool, bilateral sacroiliac (SI) joints on abdominal CT in the whole study population were retrospectively reviewed. Subsequently, patients were classified into the 'patients with sacroiliitis' group and the 'patients without sacroiliitis' group. Univariate and multivariate regression analyses were used to clarify the factors associated with sacroiliitis. RESULTS: Sacroiliitis was identified in 26 out of 210 patients (12.4%). However, sacroiliitis was recognized on the primary reading in only five of these 26 patients (19.2%) and was missed on the initial report in the remaining 21 patients (80.8%). Among the 21 patients, 20 (95.2%) were finally diagnosed with axial spondyloarthritis (axSpA). There was a higher prevalence of female sex (p = 0.04), upper gastrointestinal involvement (p = 0.04), and back pain (p < 0.01) in patients with sacroiliitis than in those without sacroiliitis. However, on multivariate analysis, back pain was the only factor associated with sacroiliitis (p = 0.01). CONCLUSION: Physicians should carefully evaluate SI joints on abdominal CT in patients with IBD to enable early detection of sacroiliitis, potentially leading to an early diagnosis of axSpA. In addition, if patients with IBD present with back pain, the possibility of sacroiliitis should be considered.

PTI-125 Reduces Biomarkers of Alzheimer's Disease in Patients.

BACKGROUND: The most common dementia worldwide, Alzheimer's disease is often diagnosed via biomarkers in cerebrospinal fluid, including reduced levels of Aß1-42, and increases in total tau and phosphorylated tau-181. Here we describe results of a Phase 2a study of a promising new drug candidate that significantly reversed all measured biomarkers of Alzheimer's disease, neurodegeneration and neuroinflammation. PTI-125 is an oral small molecule drug candidate that binds and reverses an altered conformation of the scaffolding protein filamin A found in Alzheimer's disease brain. Altered filamin A links to the α7-nicotinic acetylcholine receptor to allow Aß42's toxic signaling through this receptor to hyperphosphorylate tau. Altered filamin A also links to toll-like receptor 4 to enable Aß-induced persistent activation of this receptor and inflammatory cytokine release. Restoring the native shape of filamin A prevents or reverses filamin A's linkages to the α7-nicotinic acetylcholine receptor and toll-like receptor 4, thereby blocking Aß42's activation of these receptors. The result is reduced tau hyperphosphorylation and neuroinflammation, with multiple functional improvements demonstrated in transgenic mice and postmortem Alzheimer's disease brain. OBJECTIVES: Safety, pharmacokinetics, and cerebrospinal fluid and plasma biomarkers were assessed following treatment with PTI-125 for 28 days. Target engagement and mechanism of action were assessed in patient lymphocytes by measuring 1) the reversal of filamin A's altered conformation, 2) linkages of filamin A with α7-nicotinic acetylcholine receptor or toll-like receptor 4, and 3) levels of Aß42 bound to α7-nicotinic acetylcholine receptor or CD14, the co-receptor for toll-like receptor 4. DESIGN: This was a first-in-patient, open-label Phase 2a safety, pharmacokinetics and biomarker study. SETTING: Five clinical trial sites in the U.S. under an Investigational New Drug application. PARTICIPANTS: This study included 13 mild-to-moderate Alzheimer's disease patients, age 50-85, Mini Mental State Exam ≥16 and ≤24 with a cerebrospinal fluid total tau/Aß42 ratio ≥0.30. INTERVENTION: PTI-125 oral tablets (100 mg) were administered twice daily for 28 consecutive days. MEASUREMENTS: Safety was assessed by electrocardiograms, clinical laboratory analyses and adverse event monitoring. Plasma levels of PTI-125 were measured in blood samples taken over 12 h after the first and last doses; cerebrospinal fluid levels were measured after the last dose. Commercial enzyme linked immunosorbent assays assessed levels of biomarkers of Alzheimer's disease in cerebrospinal fluid and plasma before and after treatment with PTI-125. The study measured biomarkers of pathology (pT181 tau, total tau and Aß42), neurodegeneration (neurofilament light chain and neurogranin) and neuroinflammation (YKL-40, interleukin-6, interleukin-1ß and tumor necrosis factor α). Plasma levels of phosphorylated and nitrated tau were assessed by immunoprecipitation of tau followed by immunoblotting of three different phospho-epitopes elevated in AD (pT181-tau, pS202-tau and pT231-tau) and nY29-tau. Changes in conformation of filamin A in lymphocytes were measured by isoelectric focusing point. Filamin A linkages to α7-nicotinic acetylcholine receptor and toll-like receptor 4 were assessed by immunoblot detection of α7-nicotinic acetylcholine receptor and toll-like receptor 4 in anti-filamin A immunoprecipitates from lymphocytes. Aß42 complexed with α7-nicotinic acetylcholine receptor or CD14 in lymphocytes was also measured by co-immunoprecipitation. The trial did not measure cognition. RESULTS: Consistent with the drug's mechanism of action and preclinical data, PTI-125 reduced cerebrospinal fluid biomarkers of Alzheimer's disease pathology, neurodegeneration and neuroinflammation from baseline to Day 28. All patients showed a biomarker response to PTI-125. Total tau, neurogranin, and neurofilament light chain decreased by 20%, 32% and 22%, respectively. Phospho-tau (pT181) decreased 34%, evidence that PTI-125 suppresses tau hyperphosphorylation induced by Aß42's signaling through α7-nicotinic acetylcholine receptor. Cerebrospinal fluid biomarkers of neuroinflammation (YKL-40 and inflammatory cytokines) decreased by 5-14%. Biomarker effects were similar in plasma. Aß42 increased slightly - a desirable result because low Aß42 indicates Alzheimer's disease. This increase is consistent with PTI-125's 1,000-fold reduction of Aß42's femtomolar binding affinity to α7-nicotinic acetylcholine receptor. Biomarker reductions were at least p ≤ 0.001 by paired t test. Target engagement was shown in lymphocytes by a shift in filamin A's conformation from aberrant to native: 93% was aberrant on Day 1 vs. 40% on Day 28. As a result, filamin A linkages with α7-nicotinic acetylcholine receptor and toll-like receptor 4, and Aß42 complexes with α7-nicotinic acetylcholine receptor and CD14, were all significantly reduced by PTI-125. PTI-125 was safe and well-tolerated in all patients. Plasma half-life was 4.5 h and approximately 30% drug accumulation was observed on Day 28 vs. Day 1. CONCLUSIONS: PTI-125 significantly reduced biomarkers of Alzheimer's disease pathology, neurodegeneration, and neuroinflammation in both cerebrospinal fluid and plasma. All patients responded to treatment. The magnitude and consistency of reductions in established, objective biomarkers imply that PTI-125 treatment counteracted disease processes and reduced the rate of neurodegeneration. Based on encouraging biomarker data and safety profile, approximately 60 patients with mild-to-moderate AD are currently being enrolled in a Phase 2b randomized, placebo-controlled confirmatory study to assess the safety, tolerability and efficacy of PTI-125.

Rheumatoid factor and immunoglobulin M mark hepatitis C-associated mixed cryoglobulinaemia: an 8-year prospective study.

OBJECTIVES: The prevalence and factors of hepatitis C virus (HCV) -associated mixed cryoglobulinaemia in Asia remain elusive, and we aimed to investigate these topics. METHODS: An 8-year prospective cohort study was conducted in 678 consecutive Taiwanese individuals with chronic HCV infection (438 completed an anti-HCV therapy course). RESULTS: Of 678 individuals, 437 (64.5%) had mixed cryoglobulinaemia and 20 (2.9%) had mixed cryoglobulinaemic syndrome. At baseline, IgM (cut-off >122 mg/dL), triglycerides and IgG levels, and HCV genotype 3 were independently associated with mixed cryoglobulinaemia. Rheumatoid factor (RF) levels were associated with mixed cryoglobulinaemic syndrome (cut-off >12.2 IU/mL). At 24 weeks post-therapy, the 362 individuals with a sustained virological response (SVR) had higher cured (106/362 (29.3%) versus 10/76 (13.2%), p = 0.003) and lower persistent (100/362 (27.6%) versus 33/76 (43.4%), p = 0.003) mixed cryoglobulinaemia rates than non-SVR patients. Among SVR patients, compared with baseline levels, RF, IgG and IgM levels decreased, except in individuals with new mixed cryoglobulinaemia. Pre-therapy IgM levels were associated with 24-week post-therapy new (95% CI of OR 1.002-1.023) and persistent (95% CI of OR 1.004-1.015) mixed cryoglobulinaemia in SVR patients. After up to 8 years, 24-week post-therapy IgM levels were associated with mixed cryoglobulinaemia in SVR patients (9/51; 17.64%; 95% CI of HR 1.004-1.011). Among 17 SVR patients with pre-therapy mixed cryoglobulinaemic syndrome, 5 (29.4%) had long-term mixed cryoglobulinaemia and 4 (23.5%) had mixed cryoglobulinaemic syndrome. CONCLUSIONS: Over 60% of chronic HCV-infected individuals had mixed cryoglobulinaemia, and 17.64% of SVR patients had mixed cryoglobulinaemia 8 years post-therapy. Pre-therapy RF and IgM levels marked HCV-associated mixed cryoglobulinaemic syndrome and mixed cryoglobulinaemia, respectively.

Curvature measurement of human bilateral cochleae.

OBJECTIVE: This study aimed to characterise the geometry of the human bilateral spiral cochlea by measuring curvature and length. METHOD: Eight subjects were recruited in this study. Magnetic resonance imaging was used to visualise the right and left cochlea. Visualisation of the cochlear spiral was enhanced by T2 weighting and further processing of the raw images. The spirals were divided into three segments: the basal turn, the middle turn and the apex turn. The length and curvature of each segment were non-invasively measured. RESULTS: The mean left and right cochlear lengths were 3.11 cm and 3.95 cm, respectively. The measured lengths of the cochlear spiral are consistent with data in the literature derived from anatomical dissections. Overall, the apex turn segment of the cochlea had the greatest degree of curvature (p < 0.05). The mean apex turn segment curvatures for left and right cochleae were 9.65 cm(-1) and 10.09 cm(-1), respectively. CONCLUSION: A detailed description of the cochlear spiral is provided, using measurements of curvature and length. These data will provide a valuable reference in the development of cochlear implantation procedures for minimising the potential damage during implantation.

Relationship between socioeconomic status and anemia prevalence in adolescent girls based on the fourth and fifth Korea National Health and Nutrition Examination Surveys.

BACKGROUND/OBJECTIVES: We studied the relationship between socioeconomic status (SES), represented by household income, and the prevalence of anemia and iron deficiency anemia (IDA) among adolescent girls in Korea. SUBJECTS/METHODS: The samples were based on the data from a four-year (2008-2011) collection for the Korea National Health and Nutrition Examination Survey (1312 girls, age 10-18 years). The survey included demographic, anthropometric, biochemical and nutritional parameters. A multiple regression analysis after adjusting for age, body mass index (BMI), red blood cell count, white blood cell count and red meat intake was performed. Anemia was defined as hemoglobin level lower than 11.5 g/dl for ages 10-11 years and 12.0 g/dl for ages 12-14 years. Iron deficiency was defined as serum ferritin level below 15 µg/l. RESULTS: The prevalences of anemia and IDA in Korean girls were 5.3 and 4.2%, respectively. Girls with anemia were older, taller, weighed more, had higher BMI, had higher portion of menarche experience and consumed less red meat than girls without anemia. Girls with higher income had lower anemia prevalence and consumed more iron and vitamins. Logistic regression analysis showed a decreasing trend in anemia prevalence as household income increased. Correlation analysis demonstrated that there is a relationship between household income and serum hemoglobin and ferritin levels (P=0.003 and P=0.026, respectively). CONCLUSIONS: Higher SES leads to lower prevalence of anemia and IDA in Korean adolescent girls. This may be due to the fact that higher SES individuals consume more iron and vitamin C.

Duganella sacchari sp. nov. and Duganella radicis sp. nov., two novel species isolated from rhizosphere of field-grown sugar cane.

Two strains, designated Sac-22(T) and Sac-41(T), were isolated from rhizosphere soil and rhizoplane of field-grown sugar cane clone Co86032. Comparative 16S rRNA gene sequence analysis showed a clear affiliation of these two bacteria with the class Betaproteobacteria, their closest relatives being Pseudoduganella violaceinigra and Duganella zoogloeoides with 16S rRNA gene sequence pairwise similarities of 96.4-97.2 % to the two novel strains. Strains Sac-22(T) and Sac-41(T) shared a 16S rRNA gene sequence similarity value of 97.6 %. Cells of the two strains were Gram-reaction-negative, aerobic, motile and rod-shaped. Ubiquinone (Q-8) was the respiratory quinone and the predominant polar lipids consisted of phosphatidylglycerol and phosphatidylethanolamine. The main cellular fatty acids were C16 : 0, C16 : 1ω7c/iso-C15 : 0 2-OH, C17 : 0 cyclo, C10 : 0 3-OH and C12 : 0. The DNA G+C content of the genomic DNA was 56.4 mol% for strain Sac-22(T) and 54.9 mol% for strain Sac-41(T). Based on the results of 16S rRNA gene sequence analysis and physiological and biochemical characterization, that differentiated strains Sac-22(T) and Sac-41(T) from all recognized species of the genus Duganella, it was concluded that strains represent two novel species in the genus Duganella for which the names Duganella sacchari sp. nov. (type strain Sac-22(T) = KCTC 22381(T) = NCIMB 14475(T)) and Duganella radicis sp. nov. (type strain Sac-41(T) = KCTC 22382(T) = NCIMB 14476(T)) are proposed.

The development of bone mineral lateralization in the arms.

UNLABELLED: Bone mineral content (BMC) is known to be greater in the dominant arm after the age of 8 years. We studied a group of children and found that BMC sidedness gradually increased up to the age of 6 years and then remained stable into late adolescence. INTRODUCTION: Bone mineral content (BMC) exhibits sidedness in the arms after the age of 8 years, but it is not known whether BMC is greater in the dominant arm from birth or whether lateralization develops in early childhood. To address this, we examined bone mineral status in relation to handedness and age. METHODS: Subjects (N = 158) were children recently initiating glucocorticoids for underlying disease (leukemia 43 %, rheumatic conditions 39 %, nephrotic syndrome 18 %). Handedness was determined by questionnaire and BMC by dual-energy X-ray absorptiometry. RESULTS: Median age was 7.2 years (range, 1.5 to 17.0 years), 49 % was male, and the spine BMD Z-score was -0.9 (SD, 1.3). By linear regression, BMC sidedness in the arms was significantly related to age (r = 0.294, p = 0.0005). Breakpoint analysis revealed two lines with a knot at 6.0 years (95 % CI, 4.5-7.5 years). The formula for the first line was: dominant:nondominant arm BMC ratio = 0.029 × age [in years] + 0.850 (r = 0.323, p = 0.017). The slope of the second line was not different from 0 (p = 0.332), while the slopes for the two lines were significantly different (p = 0.027). CONCLUSIONS: These results show that arm BMC sidedness in this patient group develops up to age 6 years and then remains stable into late adolescence. This temporal profile is consistent with mechanical stimulation of the skeleton in response to asymmetrical muscle use as handedness becomes manifest.

Methylobacillus rhizosphaerae sp. nov., a novel plant-associated methylotrophic bacterium isolated from rhizosphere of red pepper.

A novel plant-associated obligate methylotrophic bacterium, designated strain Ca-68(T), was isolated from the rhizosphere soil of field-grown red pepper from India. The isolates are strictly aerobic, Gram negative, motile rods multiplying by binary fission and formaldehyde is assimilated via the ribulose monophosphate pathway. A comparative 16S rRNA gene sequence-based phylogenetic analysis placed the strain in a clade with the species Methylobacillus flagellatus, Methylobacillus glycogens and Methylobacillus pratensis, with which it showed pairwise similarity of 97.8, 97.4 and 96.2 %, respectively. The major fatty acids are C(16:0), C(10:0) 3OH and C(16:1) ω7c. The G+C content of the genomic DNA is 59.7 mol%. The major ubiquinone is Q-8. Dominant phospholipids are phosphatidylethanolamine, phosphatidylglycerol and diphosphatidylglycerol. Based on 16S rRNA gene sequence analysis and DNA-DNA relatedness (14-19 %) with type strains of the genus Methylobacillus, the novel isolate was classified as a new species of this genus and named Methylobacillus rhizosphaerae Ca-68(T) (=KCTC 22383(T) = NCIMB 14472(T)).

The effect of pre-procedure anxiety on sedative requirements for sedation during colonoscopy.

This study investigated the effects of pre-procedural anxiety (assessed using the Beck Anxiety Inventory) on sedative requirements in 135 patients undergoing sedation for colonoscopy. Deep sedation was defined as loss of consciousness and no response to colonoscopy, and was achieved by target-controlled infusion of propofol. Patients' characteristics, baseline haemodynamic profiles, Beck Anxiety Inventory scores, effect-site propofol concentration at loss of consciousness and characteristics of recovery were recorded. No correlations were found between Beck Anxiety Inventory scores and effect-site propofol concentration at loss of consciousness or baseline haemodynamic profiles. There was no statistical difference in the characteristics of recovery among patients with different levels of anxiety. In conclusion, in patients receiving deep sedation for colonoscopies, the level of pre-procedural anxiety did not relate to the sedative requirement or post-procedural recovery characteristics.

Irradiated allogeneic cells enhance umbilical cord blood stem cell engraftment in immunodeficient mice.

Umbilical cord blood (UCB) is a readily available source of hematopoietic stem cells for transplantation. UCB hematopoietic SCT for average- and large-sized patients is often limited by the number of cells available in a single unit. To address this limitation, we performed experiments to determine if adjunctive therapy with third-party human allogeneic cells enhances the engraftment of human UCB in immunodeficient mice. UCB cells with or without sequential infusion of irradiated third-party allogeneic cells were used in transplantation studies of NOD/SCID and NOD/SCID-IL2Rγ null mice. We studied the impact of irradiated allogeneic cells on colony formation in vitro using long-term culture assays also. Our studies demonstrate that short- and long-term UCB engraftment of immunodeficient mice is enhanced by irradiated allogeneic cells. Secondary transplants demonstrate the durability of engraftment. These preclinical studies support the further development of irradiated allogeneic cells as an adjunct to single UCB transplantation when limiting numbers of cells are available.

Prosthetic endocarditis treated by repeated heart transplantation: report of a successful case.

The treatment of recurrent prosthetic valve endocarditis is extremely difficult. Heart transplantation (HT) may save the patient's life. Recurrent endocarditis, however, can occur after HT. This report described a patient who had under gone four conventional valve surgeries and three HTs successfully. In May 2000, a 14-year-old boy suffered from endocarditis with severe aortic valve regurgitation. He underwent aortic valve replacement (AVR) at another hospital. Due to prosthetic valve endocarditis, he displayed a severe paravalvular leakage and was transferred to our hospital where he underwent Bentall's operation in October 2000. Despite a full antibiotic course, he experienced a relapse of the prosthetic endocarditis with significant deterioration of the heart function and a progressively more severe paravalvular leak. Considering the difficulties of repair and the poor heart function, he underwent an HT in June 2003 and recovered well. Unfortunately, endocarditis with aortic valve regurgitation attacked him again after 3 years. Remarkably, all blood cultures were negative. A second AVR was performed in October 2006 with a Second Bentall's procedure 1 year later in 2007. In November 2009, the patient suddenly displayed cardiogenic shock with collapse. He was transferred to our hospital and needed extracorporcal membrane oxygenation (ECMO) support. Two days later, he underwent a second HT. However, the donor heart was nonfunctional due to the prolonged ischemia time. ECMO support was continuously needed after the HT. A third HT was performed successfully 10 days later. Due to previous reported experiences of culture-negative endocarditis, minocycline was prescribed twice daily continuously after the third HT/seventh cardiac surgery. The patient was discharged 2 months later. To date he takes minocycline every day and lives a healthy life.

Anatomical distribution of vertebral fractures: comparison of pediatric and adult spines.

SUMMARY: We compared the distribution of vertebral fractures in adults and children and found that fractures occurred in different locations in the two age groups. This likely relates to the different shape of the immature spine. INTRODUCTION: We hypothesized that the anatomical distribution of vertebral fractures (VF) would be different in children compared to adults. METHODS: We compared the distribution of VF defined using the Genant semi-quantitative method (GSQ method) in adults (N = 221; 545 fractures) and in children early in the course of glucocorticoid therapy (N = 44; 94 fractures). RESULTS: The average age in the adult cohort was 62.9 years (standard deviation (SD), 13.4 years), 26% was male, the mean lumbar spine Z-score was -1.0 (SD, 1.5), and the corresponding T-score was -2.4 (SD, 1.4). The pediatric cohort median age was 7.7 years (range, 2.1-16.6 years), the mean lumbar spine Z-score was -1.7 (SD, 1.5), 52% was male, and disease categories were acute lymphoblastic leukemia (66%), rheumatological conditions (21%), and nephrotic syndrome (14%). The VF distribution was biphasic in both populations, but the peaks differed in location. In adults, the peaks were at T7/T8 and at T12/L1. In children, the focus was higher in the thoracic spine, at T6/T7, and lower in the lumbar spine, at L1/L2. When children were assessed in two age-defined sub-groups, a biphasic VF distribution was seen in both, but the upward shift of the thoracic focus to T6 was observed only in the older group, with the highest rates of fracture present between ages 7 and 10 years. CONCLUSIONS: These results suggest that the anatomical distribution of VF differs between children and adults, perhaps relating to the different shape of the immature spine, notably the changing ratio of kyphosis to lordosis.

The accuracy of clinical kyphosis examination for detection of thoracic vertebral fractures: comparison of direct and indirect kyphosis measures.

OBJECTIVE: To compare the accuracies of two simple physical examination maneuvers for detecting the presence of thoracic vertebral fractures (VF) diagnosed by radiography: direct measurement of kyphosis angle (KA, in degrees) and indirect measurement using wall-occiput distance (WOD, in cm). METHODS: Subjects were 280 women (average age, 54.5 years; range, 18-92) referred for assessment of osteoporosis. KA was measured from T4 to T12 using a digital inclinometer while WOD was measured with the patient in a standardized position. VF were diagnosed on radiographs using semi-quantitative morphometry. RESULTS: KA and WOD were moderately correlated (r = 0.72, p<10(-11)). KA increased by 3.7(o) (95% CI, 2.6-4.8(o)) for each VF (p = 4x 10(-11)) and WOD rose 1.3 cm (95% CI, 0.8-1.7 cm) per VF (p = 2 x 10(-11)). The areas under the receiver operating characteristic curves were 0.72 (95% CI, 0.65-0.79) for KA and 0.76 (95% CI, 0.69-0.82) for WOD, which were not significantly different (p = 0.13). CONCLUSIONS: Given similar performances of direct and indirect measures of kyphosis, we propose that WOD should be used in clinical practice, with a clinical threshold of WOD>4.0 cm as an indication to consider spine radiography. At this WOD threshold, sensitivity was 41% (95% CI, 31-52%) and specificity was 92% (95% CI, 87-95%). WOD should be considered for use in the clinical assessment of osteoporosis patients.

Modeling the formation of in vitro filopodia.

Filopodia are bundles of actin filaments that extend out ahead of the leading edge of a crawling cell to probe its upcoming environment. In vitro experiments (Vignjevic et al. in J Cell Biol 160:951-962, 2003) have determined the minimal ingredients required for the formation of filopodia from the dendritic-like morphology of the leading edge. We model these experiments using kinetic aggregation equations for the density of growing bundle tips. In mean field, we determine the bundle size distribution to be broad for bundle sizes smaller than a characteristic bundle size above which the distribution decays exponentially. Two-dimensional simulations incorporating both bundling and cross-linking measure a bundle size distribution that agrees qualitatively with mean field. The simulations also demonstrate a nonmonotonicity in the radial extent of the dendritic region as a function of capping protein concentration, as was observed in experiments, due to the interplay between percolation and the ratcheting of growing filaments off a spherical obstacle.

Identification of the novel allele HLA-B*13:01:03 by sequence-based typing method in a Taiwanese individual.

A new human leukocyte antigen (HLA)-B allele, B*13:01:03 (B*130103), has been found in a Taiwanese individual. It differs from B*13:01:01 (B*130101) by a synonymous substitution at codon 113 (CAT->CAC).

Identification of HLA-B*5410 in Taiwan.

A new human leukocyte antigen-B allele, B*5410, has been detected in Taiwan. It has one nucleotide change from B*5401 at codon 156 (CTG-->CGG), resulting in one amino acid change (L-->R).

Tricuspid valve regurgitation and endomyocardial biopsy after orthotopic heart transplantation.

OBJECTIVE: Tricuspid valve regurgitation (TR) after heart transplantation (HTx) has been reported to be caused by endomyocardial biopsy (EMB), acute cellular rejection (ACR), or atrial anastomosis. We performed a prospective study of this problem among our HTx cohort. METHODS: From 1988 to 2006, we performed 274 HTx. Excluding cases within 1 year (2006), there were 178 patients in whom we had records of EMB dates, ACR grades (International Society for Heart and Lung Transplantation [ISHLT], 1990), echocardiography-measured TR, and time-to-TR. Statistical analyses were performed using nonparametric comparisons, Spearman correlation, Kaplan-Meier time to failure curves, and Cox regression model. RESULTS: All 178 patients underwent a biatrial anastomosis and underwent 2631 EMB (median, 15 times per patient; range, 0-42). The median follow-up duration was 66 months (range 2 days-194 months). Up to December 31, 2006, there were 47 patients (47/178 = 26.4%) who developed moderate-to-severe TR, which differed significantly from the prevalence rate (24/39 = 61.5%) reported by another cardiac team (P = .001) that performed bicaval anastomoses in half of the cases (20/39 = 51%). Our 1-, 3-, and 10-year Kaplan-Meier incidence rates of remarkable TR were 14.7% (10.2%-20.8%), 19.4% (14.2%-26.2%), and 36.3% (27.2%-47.3%), respectively. A positive correlation was shown between each patient's EMB times and ACR but not TR grades, in terms of mean, maximum, or minimum over time (all P < .001 for null hypothesis of noncorrelation). Each patient's EMB times and number of definite ACRs (> or = ISHLT grade II) did not differ significantly between the two groups of remarkable versus nonremarkable TR. Remarkable TR was negatively predicted by each patient's EMB times (hazard ratio = 0.93; P = .010) but not by the ACR grades or the numbers of definite ACRs. CONCLUSION: Our cohort demonstrated that biatrial anastomosis, ACR, or EMB were not associated with the risk of remarkable TR. The protective effect of EMB on remarkable TR needs further investigation.

Extending donor source with bench coronary angiography: a case report.

This report proposes a safer, economical method to examine the marginal donor heart for a better chance of use, which also delivers comparable image quality of catheterization (CathLab) without creating potential damage to the kidney. Currently the examination of the coronary system mainly relies on the CathLab, which is not commonly accessible, and also results in nephrotoxic effects. Therefore, bench coronary angiography is hereby proposed because it is commonly available and economical as well as able to indicate coronary lesions for surgeons as well as the CathLab study. These benefits altogether provide a better chance to select usable hearts from older donors to help relieve the organ shortage.

Detection of the p53 response in zebrafish embryos using new monoclonal antibodies.

The zebrafish has many advantages as a vertebrate model organism and has been extensively used in the studies of development. Its potential as a model in which to study tumour suppressor and oncogene function is now being realized. Whilst in situ hybridization of mRNA has been well developed in this species to study gene expression, antibody probes are in short supply. We have, therefore, generated a panel of anti-zebrafish p53 monoclonal antibodies and used these to study the p53 response in zebrafish embryos. By immunohistochemistry, we show that the exposure of zebrafish embryos to p53-activating agents such as R-roscovitine and gamma-irradiation results in the accumulation of p53 protein in the gut epithelium, liver and pancreas. A combination of R-roscovitine and gamma-irradiation results in massive p53 induction, not only in the pharyngeal arches, gut region and liver but also in brain tissues. Induction of apoptosis and expression of p53 response genes are seen in regions that correspond to sites of p53 protein accumulation. In contrast, although zebrafish tp53(M214K) mutant embryos showed a similar accumulation of p53 protein, a complete lack of a downstream p53-dependent response was observed. In this system the p53 gene is identified as a p53-responsive gene itself. Our results demonstrate that zebrafish p53 protein can readily be induced in embryos and detected using these new antibody tools, which will increase the usefulness of zebrafish as a model in compound-based screening for novel drugs in cancer research.

Nocturnal wrist movements are correlated with objective clinical scores and plasma chemokine levels in children with atopic dermatitis.

BACKGROUND: Atopic dermatitis (AD) is a distressing disease associated with pruritus and sleep disturbance. Scratching due to pruritus is an important mechanism in the exacerbation of AD but is difficult to document in the home environment. OBJECTIVES: To evaluate whether nocturnal wrist activities, defined as average acceleration in the early hours of sleep, were correlated with components of the SCORing Atopic Dermatitis (SCORAD) index and various AD-associated chemokine markers. METHODS: Patients with AD aged under 18 years were recruited and the severity of eczema was assessed with the SCORAD index. Concentrations of plasma AD-associated chemokines [cutaneous T-cell attracting cytokine (CTACK); macrophage-derived chemokine (MDC); thymus and activation regulated chemokine (TARC)], interleukin (IL)-18, serum total IgE, and eosinophil counts were measured in these patients. Healthy children with noninflammatory and nonitchy skin conditions as well as healthy children of staff volunteers were recruited as controls. All children were instructed to wear the DigiTrac monitor on their dominant wrist before sleeping. The monitor was programmed to record limb motion between 22.00 and 08.00 h the following morning. RESULTS: Twenty-four Chinese children with AD (mean +/- SD age 12.6 +/- 3.7 years) and 15 normal children (mean +/- SD age 11.9 +/- 3.4 years) were recruited. The median (interquartile range) SCORAD was 54.8 (32.8-70.2). Plasma concentrations in pg mL(-1) of CTACK, MDC, TARC and IL-18 in the patients were 105 (92-172), 1648 (973-4214), 258 (100-850) and 415 (304-539), respectively. When compared with controls, most wrist activities occurred at frequencies between 1 and 3 Hz. These activities were most consistent over the first 3 h of sleeping and correlated significantly with disease severity, extent, intensity, and AD-associated chemokine markers CTACK, MDC and TARC. However, there was no significant correlation between wrist activities and the subjective symptom of pruritus or sleep loss. CONCLUSIONS: This is the first study to demonstrate that wrist activities, nonintrusively measured by the DigiTrac monitor at home, are closely correlated with the objective clinical scores and levels of peripheral blood chemokine markers for AD but not with the reported symptoms of pruritus or sleep loss. We propose that wrist activities between 1 and 3 Hz for the first 3 h are a good indicator of AD severity in children and should substitute for the pruritus and sleep-loss components of the SCORAD.