Characterization of CD33 as a new member of the sialoadhesin family of cellular interaction molecules

CD33 is a member of the Ig superfamily that is restricted to cells of the myelomonocytic lineage but whose functions and binding properties are unknown. It shares sequence similarity with sialoadhesin, CD22, and the myelin-associated glycoprotein, which constitute the Sialoadhesin family of sialic acid-dependent cell adhesion molecules. In the present study, we show that CD33 is a fourth member of this family. As a model for sialic acid-dependent binding, human erythrocytes were derivatized with N-acetylneuraminic acid (NeuAc) in different linkages. A recombinant soluble form of CD33, Fc-CD33, bound red blood cells with a specificity similar to that of sialoadhesin, preferring NeuAc alpha 2,3Gal in N- and O-glycans over NeuAc alpha 2,6Gal in N-glycans. Fc- CD33 also bound selectively to the myeloid cell lines HL-60 and U937. However, CD33 was unable to mediate cell binding after transient expression in COS cells, despite high levels of surface expression. Pretreatment of the CD33-transfected cells with sialidase rendered them capable of mediating sialic acid-dependent binding. These results show that CD33 can function as a sialic acid-dependent cell adhesion molecule and that binding can be modulated by endogenous sialoglycoconjugates when CD33 is expressed in a plasma membrane.     

Management of skeletal-related events in patients with advanced prostate cancer and bone metastases: Incorporating new agents into clinical practice

Skeletal-related events (SREs) are a common complication of bone metastases, and have serious negative consequences for patients with castrate-resistant prostate cancer (CRPC). SREs can lead to severe pain, increased risk of death, increased health care costs and reduced quality of life. Until recently, zoledronic acid has been the sole standard of care for the prevention of SREs in men with CRPC with bone metastases. Denosumab, a receptor activator of nuclear factor kappa-B ligand (RANK-L) inhibitor, has been recently approved for use in Canada for this indication, thus presenting another option for these patients. Denosumab was shown to be superior to zoledronic acid in delaying the time to first or subsequent SREs in CRPC patients with bone metastases. This review discusses current and previous trials examining agents designed to prevent SREs in men with CRPC and bone metastases. It also discusses the practical aspects of administering a bone-targeted therapy, including choosing a bone-targeted therapy, monitoring at the onset and during therapy, switching from one therapy to another, and assessing potential complications.     

Antibiotics for Treatment of Clostridium difficile Infection in Hospitalized Patients with Inflammatory Bowel Disease

Patients with inflammatory bowel disease (IBD), namely ulcerative colitis (UC) and Crohn''s disease (CD), have worse outcomes with Clostridium difficile infection (CDI), including increased readmissions, colectomy, and death. Oral vancomycin is recommended for the treatment of severe CDI, while metronidazole is the standard of care for nonsevere infection. We aimed to assess treatment outcomes of CDI in IBD. We conducted a retrospective observational study of inpatients with CDI and IBD from January 2006 through December 2010. CDI severity was assessed using published criteria. Outcomes included readmission for CDI within 30 days and 12 weeks, length of stay, colectomy, and death. A total of 114 patients met inclusion criteria (UC, 62; CD, 52). Thirty-day readmissions were more common among UC than CD patients (24.2% versus 9.6%; P = 0.04). Same-admission colectomy occurred in 27.4% of UC patients and 0% of CD patients (P < 0.01). Severe CDI was more common among UC than CD patients (32.2% versus 19.4%; P = 0.12) but not statistically significant. Two patients died from CDI-associated complications (UC, 1; CD, 1). Patients with UC and nonsevere CDI had fewer readmissions and shorter lengths of stay when treated with a vancomycin-containing regimen compared to those treated with metronidazole (30-day readmissions, 31.0% versus 0% [P = 0.04]; length of stay, 13.62 days versus 6.38 days [P = 0.02]). Patients with UC and nonsevere CDI have fewer readmissions and shorter lengths of stay when treated with a vancomycin-containing regimen relative to those treated with metronidazole alone. Patients with ulcerative colitis and CDI should be treated with vancomycin.     

Biliary stricture dilatation: multicenter review of clinical management in 73 patients

Eighty-nine biliary strictures in 73 patients who had undergone percutaneous balloon dilatation were reviewed to determine long-term patency rates and clinical management problems. The majority of dilatations were performed in patients with anastomotic strictures (n = 44), iatrogenic strictures (n = 28), and strictures associated with sclerosing cholangitis (n = 17). Patency rates after 36 months or more were 67%, 76%, and 42%, respectively. Complications, mostly minor, occurred in less than 7% of patients. Of patients with significant biliary obstruction, 15% had little or no intrahepatic biliary duct dilatation demonstrated by cross-sectional imaging and/or direct cholangiography. No definite conclusions could be drawn about the utility of long-term internal/external stenting.     

Asymptomatic neonatal colonisation by Clostridium difficile

In a prospective survey of infants born in a single maternity unit, asymptomatic faecal colonisation by Clostridium difficile occurred in 31 (47%) of 66 babies who provided a faecal sample during week one of life and at age 14 and 28 days, and in 46 (30.7%) of the total of 150 babies for whom at least one faecal sample was obtained during the month of study. There was no evidence for acquisition of the organism from the mother during delivery and colonisation was unrelated to the means of delivery, infant sex, means of feeding, duration of hospital stay, or antibiotic treatment. New colonisation occurred throughout the month of the study and further evidence for environmental acquisition was obtained by the finding of a similar strain of C difficile in 7 babies from one ward together with positive environmental cultures. Colonisation was frequently transient and occasionally intermittent; most infants kept the same strain during their period of carriage. Twenty two (47.8%) babies colonised by C difficile had low titres of cytopathic faecal toxin but none had symptomatic diarrhoea or features of necrotizing enterocolitis. The in vitro toxigenic potential of 57 toxigenic isolates from 36 babies was low and 12 babies carried non-toxigenic strains. Transient colonisation by C difficile in early life is almost certainly more common than is generally recognized and the neonate provides an important reservoir of potential infection.     

Aortopulmonary window lesions: detection with chest radiography

A retrospective morphologic study of 80 cases was undertaken to determine factors affecting detectability of computed tomographically (CT) proved aortopulmonary (AP) window lesions on conventional posteroanterior (PA) and lateral chest radiographs. Criteria used for determining abnormality were: solitary lymph node enlargement over 1.5 cm or three or more 1-cm nodes and obvious large masses or vascular anomalies. CT scans and corresponding PA and lateral radiographs were analyzed for lesion detectability, size, and location. In 49% of cases there was no detectable lesion in the AP window on radiographs; a definite AP window lesion was seen in 41%, and 10% were equivocal. Major contributing factors to low detectability of AP window lesions on radiographs include size and, more important, location of the lesion. An additional 45 cases of CT-proved normal AP windows were retrospectively reviewed to determine the false-positive rate of PA and lateral radiographs in detection of AP window lesions: 43 (96%) were classified as negative, the remaining two (4%) as equivocal. Although the AP window is a small space, it is the site of many pathologic conditions; the study results indicate that CT may be an essential procedure for its evaluation.