BackgroundPerianal infection is a common problem for patients with acute leukemia. However, neutropenia and bleeding tendency are relatively contraindicated to surgical intervention. The epidemiology, microbiology, clinical manifestations and outcomes of perianal infection in leukemic patients are also rarely discussed.MethodThe medical records of 1102 adult patients with acute leukemia at a tertiary medical center in Taiwan between 2001 and 2010 were retrospectively reviewed and analyzed.ResultThe prevalence of perianal infection was 6.7% (74 of 1102) in adult patients with acute leukemia. Twenty-three (31%) of the 74 patients had recurrent episodes of perianal infections. Patients with acute myeloid leukemia had higher recurrent rates than acute lymphoblastic leukemia patients (p = 0.028). More than half (n = 61, 53%) of the perianal infections were caused by gram-negative bacilli, followed by gram-positive cocci (n = 36, 31%), anaerobes (n = 18, 15%) and Candida (n = 1, 1%) from pus culture. Eighteen patients experienced bacteremia (n = 24) or candidemia (n = 1). Overall 41 (68%) of 60 patients had polymicrobial infection. Escherichia coli (25%) was the most common micro-organism isolated, followed by Enterococcus species (22%), Klebsiella pneumoniae (13%), and Bacteroides species (11%). Twenty-five (34%) of 74 patients received surgical intervention. Acute leukemia patients with surgically managed anal fistulas tended to have fewer recurrences (p = 0.067). Four (5%) patients died within 30 days after diagnosis of perianal infection. Univariate analysis of 30-day survival revealed the elderly (≧ 65 years) (p = 0.015) and patients with shock (p<0.001) had worse outcome. Multivariate analysis showed septic shock to be the independent predictive factor of 30-day crude mortality of perianal infections (p = 0.016).ConclusionPerianal infections were common and had high recurrence rate in adult patients with acute leukemia. Empirical broad-spectrum antibiotics with anaerobic coverage should be considered. Shock independently predicted 30-day crude mortality. Surgical intervention for perianal infection remains challenging in patients with acute leukemia.
Gene duplication and sequence divergence are driving forces toward establishing protein families. To examine how sequence changes affect carbohydrate specificity, the two closely related proto-type chicken galectins CG-14 and CG-16 were selected as models. Binding properties were analyzed using a highly sensitive solid-phase assay. We tested 56 free saccharides and 34 well-defined glycoproteins. The two galectins share preference for the II (Galb1-4GlcNAc) versus I (Galb1-3GlcNAc) version of b-galactosides. A pronounced difference is found owing to the reactivity of CG-14 with histo-blood group ABH active oligosaccharides and A/B active glycoproteins. These experimental results prompted to determine activitystructure correlations by modeling. Computational analysis included consideration of the flexibility of binding partners and the presence of water molecules. It provided a comparative description of complete carbohydrate recognition domains, which had so far not been characterized in animal galectins. The structural models assigned II, I selectivity to a region downstream of the central Trp moiety. Docking revealed that the tetrasaccharides can be accommodated in their free-state low-energy conformations. CG-14's preference for A versus B epitopes could be attributed to a contact between His124 and the Nacetyl group of GalNAc. Regarding intergalectin comparison, the Ala53/Cys51 exchange affects the interaction potential of His54/His52. Close inspection of simulated dynamic interplay revealed reorientation of His124 at the site of the His124/Glu123 substitution, with potential impact on ligand dissociation. In summary, this study identifies activity differences and provides information on their relation to structural divergence, epitomizing the value of this combined approach beyond galectins.
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