Evaluation of angiogenic signaling molecules associated with reactive thrombocytosis in an iron-deficient rat model.

BACKGROUND: Iron deficiency anemia (IDA)-induced reactive thrombocytosis can occur in children and adults. The underlying mechanism for this phenomenon is indeterminate. Traditional cytokines such as thrombopoietin (TPO), interleukin-6 (IL-6), and IL-11 involved in megakaryopoiesis have not been shown to be the cause. Recent studies suggest that growth factors and signaling molecules involved with angiogenesis influence the proliferation and differentiation of megakaryocytes. METHODS: We investigated the possible association between angiogenic cytokines with reactive thrombocytosis due to IDA in an iron-deficient (ID) rat model. Complete blood count, iron panels, and TPO levels were measured at baseline and 5 weeks later in both control (C) and ID rats. Angiogenic cytokines were evaluated in the bone marrow in all rats. RESULTS: We successfully induced IDA in our rats by phlebotomy and reduced iron diet. We did not find an increase of TPO in ID rats. A review of the bone marrow showed an increase in the number of megakaryocytes, vascular structures, as well as increased intensity of stain for vascular endothelial growth factor (VEGF), and CXC chemokine receptor 4 (CXCR4) in rats with IDA compared to controls. CONCLUSIONS: Our results of histological bone marrow data suggest an important role for angiogenesis in the development of IDA-induced thrombocytosis. IMPACT: Thrombocytosis is common with IDA in both children and adults, but the mechanism is unclear. We confirmed that TPO is not the major driver of iron deficiency-associated thrombocytosis. We confirmed the increase in the number of megakaryocytes in the bone marrow despite stable TPO levels. We provided evidence supporting an important role of angiogenesis in megakaryocytopoiesis/thrombopoiesis with increased vascular structures and angiogenic cytokines in the bone marrow of iron-deficient rats. The demonstration that angiogenesis may play an important role in secondary thrombocytosis could lead to a new approach in treating symptomatic reactive thrombocytosis by targeting angiogenesis.

Acquisition of high-level mupirocin resistance and its fitness cost among methicillin-resistant Staphylococcus aureus strains with low-level mupirocin resistance.

We investigated whether methicillin (meticillin)-resistant Staphylococcus aureus (MRSA) isolates with low-level mupirocin resistance can serve as recipients of a pSK41-like plasmid conferring high-level mupirocin resistance without substantial fitness cost. Our results suggest that acquisition of the plasmid conferring high-level mupirocin resistance was not necessarily associated with fitness cost in some MRSA recipients with low-level mupirocin resistance.

Epidemiology of community-onset Staphylococcus aureus infections in pediatric patients: an experience at a Children's Hospital in central Illinois.

BACKGROUND: The nation-wide concern over methicillin-resistant Staphylococcus aureus (MRSA) has prompted many clinicians to use vancomycin when approaching patients with suspected staphylococcal infections. We sought to characterize the epidemiology of community-onset S. aureus infections in hospitalized children to assist local clinicians in providing appropriate empiric antimicrobial therapy. METHODS: From January 2005-June 2008, children (0-18 years old) admitted to the Children's Hospital of Illinois with community-onset S. aureus infections were identified by a computer-assisted laboratory-based surveillance and medical record review. RESULTS: Of 199 patients, 67 (34%) had invasive infections, and 132 (66%) had skin and soft tissue infections (SSTIs). Among patients with invasive infections, S. aureus isolates were more likely to be susceptible to methicillin (MSSA 63% vs. MRSA 37%), whereas patients with SSTIs, S. aureus isolates were more likely to be resistant to methicillin (MRSA 64% vs. MSSA 36%). Bacteremia and musculoskeletal infections were the most common invasive infections in both groups of S. aureus. Pneumonia with empyema was more likely to be caused by MRSA (P = 0.02). The majority (approximately 90%) of MRSA isolates were non-multidrug resistant, even in the presence of healthcare-associated risk factors. CONCLUSION: Epidemiological data at the local level is important for antimicrobial decision-making. MSSA remains an important pathogen causing invasive community-onset S. aureus infections among hospitalized children. In our hospital, nafcillin in combination with vancomycin is recommended empiric therapy in critically ill patients with suspected invasive staphylococcal infections. Because up to 25% of MSSA circulating in our area are clindamycin-resistant, clindamycin should be used cautiously as empiric monotherapy in patients with suspected invasive staphylococcal infections.

Simultaneous carriage of multiple genotypes of Staphylococcus aureus in children.

The co-existence of multiple genotypes in colonization by Staphylococcus aureus has not been fully investigated. The aim of this study was to evaluate the heterogeneity of S. aureus carriage in children. We evaluated 125 nasal and perianal swab samples that were positive for S. aureus from 76 children scheduled for elective surgery. For each sample, at least four colonies with the same or different morphotypes were selected for analysis. Multiple-locus variable-number tandem-repeat fingerprinting was used to determine the genetic relatedness and to characterize the clonality of the S. aureus strains. Of the 125 swabs, 91 (73 %) contained meticillin-sensitive S. aureus (MSSA), 8 (6 %) contained meticillin-resistant S. aureus (MRSA), and 26 (21 %) contained MSSA and MRSA simultaneously. A total of 738 S. aureus strains were evaluated with a mean of 6 colonies (range 4-15) picked from each culture. Of the 125 swabs, 32 (26 %) samples contained two genetically distinct S. aureus strains and 6 (5 %) contained three different genotypes. Multiple S. aureus strains simultaneously carried by individual children were genetically unrelated to each other. We concluded that the co-existence of multiple genotypes of S. aureus was common. The significance of multiple carriage is yet to be determined, but this intraspecies interplay could be important to pathogenicity and virulence in S. aureus.

Molecular surveillance of Staphylococcus aureus colonization in a neonatal intensive care unit.

In a survey of staphylococcal colonization, Staphylococcus aureus was detected in 7 of 67 infants (10%). Two of the infants (3%) carried methicillin-resistant S aureus (MRSA), revealing an unsuspected transmission of MRSA within the neonatal intensive care unit. Molecular surveillance of S aureus provided useful information to improve infection control practices.

A prospective study of methicillin-resistant Staphylococcus aureus colonization in children scheduled for elective surgery.

BACKGROUND: Staphylococcus aureus is a major cause of surgical wound infections. To obtain contemporary data on S aureus, we performed a prospective study of colonization and infection in children scheduled for elective surgical procedures. METHODS: A nasal swab and clinical information were obtained at the presurgical outpatient visit. At operation, nasal and perianal swabs were obtained. S aureus were isolated and characterized. RESULTS: We enrolled 499 patients from June 2005 to April 2007. Wound classes were 1 (73%), 2 (22%), 3 (5%), and 4 (0.2%). Prophylactic antibiotics were administered for 153 (31%). Postoperative length of stay ranged from 0 (77%) to 6 days, with 19 (4%) staying 4 days or more. Screening cultures grew S aureus for 186 procedures (36.6%); of these, 141 were methicillin-resistant S aureus (MRSA) (76% of all staphylococcal cultures or 28% of all procedures). Most MRSA had Staphylococcal Chromosomal Cassette mec type II and resistance to clindamycin-typical for hospital-associated strains. There were 10 (2%) surgical site infections, including 4 methicillin-sensitive S aureus, 1 MRSA, 2 with no growth, and 2 with no cultures. CONCLUSION: Methicillin-resistant S aureus colonization was common in asymptomatic children. Most strains appeared to be health care-associated and resistant to clindamycin. Wound infection rate remained low despite the high prevalence of staphylococcal colonization.

CD62 expression during thrombus formation.

A large right atrial mass was discovered in a 16-year-old female patient receiving chemotherapy treatment for Hodgkin disease. The patient was participating in a platelet function research study. During laboratory examination of platelet activation, increasing CD62 and CD63 expression were found to mirror the clot formation. Further investigation of platelet expression of CD62 and CD63 by flow cytometry might reveal it to be a valuable tool in predicting impending thrombus formation.

Differences in adhesion receptor expression between immature and older platelets and red blood cells of neonates and adults.

PURPOSE: To examine the hypothesis that reticulated platelets and reticulocytes show elevated adhesion receptor expression compared with mature cells in both adult and neonatal cells. METHODS: Flow cytometry was used to examine laminin, fibronectin (VLA-6), and thrombospondin (glycoprotein IV [GPIV]) expression in reticulated red cells, reticulated platelets, and older peripherally circulating mature red cells and mature platelets in seven newborn cord blood samples and blood samples from eight adult volunteers. RESULTS: The difference in the neonatal reticulated platelet percentage of 9.2+/-14.8% was not statistically significant from the adult reticulated platelet percentage of 5.0+/-1.5% in this small population. There was a statistically significant difference between the reticulated cord blood red cell mean of 7.7+/-1.8% and the adult mean of 3.1+/-0.43%. Mean expression of VLA-6 was 96% in adult reticulated platelets, 79% in adult mature platelets, 81% in cord reticulated platelets and 65% in cord mature platelets. Mean expression of GPIV was similar, with corresponding values of 90%, 71%, 78%, and 57%. Reticulated red cells in adults averaged 44% VLA-4 and 46% GPIV; cord reticulocytes were 9% and 15%, respectively. CONCLUSIONS: Reticulated cells newly released from the bone marrow express more adhesive receptors than mature cells in both groups. Cord blood samples showed hypoexpression of both receptor types in red blood cells and platelets.