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Objectives: To determine the distribution of and risk factors for colonization and infection with vancomycin-resistant enterococci; to evaluate the molecular epidemiology of these strains; and to assess the effect of interventions, including 1) strict adherence to infection control procedures and 2) restricted use of vancomycin.Design: Problem identification based on descriptive studies, point-prevalence surveys, and case-control studies and followed by specific interventions and evaluation of the response to these interventions.Setting: University medical center.Participants: All patients hospitalized between May 1992 and June 1994 (59,196 admissions).Main Results: 75 active infections attributed to vancomycin-resistant enterococci were identified. Thirty-one patients (41%) had bloodstream infections and 6 (8%) died. The incidence of active infection was highest in the organ transplantation unit (13.2 infections/1000 admissions). In the point-prevalence studies, vancomycin-resistant enterococci were isolated from 20% of a random sample of hospitalized patients in July, August, and September 1993 (adjusted prevalence, 16.9%). Case-control studies showed significant associations between colonization and infection and 1) receipt of antimicrobial agents, particularly vancomycin, and 2) severity of illness. Although several small case clusters had isolates with identical banding patterns on pulsed field gel electrophoresis, at least 45 different banding patterns were noted among medical center isolates. Interventions took place in November and December 1993. Vancomycin restriction policies resulted in a 59% decrease in intravenous vancomycin use and an 85% decrease in oral vancomycin use. Point-prevalence surveys done in April, May, and June 1994 showed a consistent 20% level of colonization with vancomycin-resistant enterococci strains (adjusted prevalence, 18.7%). No significant changes were seen in rates of vancomycin-resistant enterococci infection.Conclusions: Vancomycin-resistant enterococci are an important cause of illness and death in the study institution, particularly among organ transplant recipients and other seriously ill persons; they have also become a common intestinal colonizer among hospitalized patients. The diversity of isolates (based on molecular typing studies) suggests that resistant organisms have been introduced from multiple sources. Interventions that effectively lower the overall level of colonization with vancomycin-resistant enterococci must still be identified. [ABSTRACT FROM AUTHOR]

Objective: To test the following hypotheses: (1) Children entering foster care report more depressive symptoms and have a higher prevalence of clinically significant depressive symptoms than children not in care. (2) Demographic and historical data can predict which children in foster care are at highest risk for depression. Design: Cross-sectional study, including a comparison group. Setting: Foster Care Health Program in Baltimore, Maryland, and Baltimore City Public Schools. Methods: We administered the Children's Depression Inventory (CDI) to 160 school-age children entering foster care and to a comparison group of 60 urban, African-American school children. Results: Children entering foster care had higher mean CDI scores than children in published norms (p < 0.03). A similar difference in CDI scores between children in foster care and urban, African-American children did not reach statistical significance. Prevalence of clinically significant depressive symptoms did not differ significantly between the children in foster care, published norms, and comparison group (13.8, 10 and 8.3%, respectively). Depressive symptoms in children entering foster care were associated with age, but not with gender or ethnicity; parental history of affective disorder or substance abuse; history of abuse or neglect; or previous foster care or mental health treatment. Conclusions: Children entering foster care report more depressive symptoms than children in published norms. The prevalence of clinically significant depressive symptoms is similar for children in foster care, published norms, and urban, African-American children. Depressive symptoms in children entering foster care are associated with age, but not with other demographic and historical variables. Implications for Practice: Children entering foster care should be a particular priority for mental health screening, with early mental health treatment when indicated. [ABSTRACT FROM AUTHOR]

There are no clinically relevant treatments available that improve function in the growing population of very preterm infants (less than 32 weeks' gestation) with neonatal brain injury. Diffuse white matter injury (DWMI) is a common finding in these children and results in chronic neurodevelopmental impairments. As shown recently, failure in oligodendrocyte progenitor cell maturation contributes to DWMI. We demonstrated previously that the epidermal growth factor receptor (EGFR) has an important role in oligodendrocyte development. Here we examine whether enhanced EGFR signalling stimulates the endogenous response of EGFR-expressing progenitor cells during a critical period after brain injury, and promotes cellular and behavioural recovery in the developing brain. Using an established mouse model of very preterm brain injury, we demonstrate that selective overexpression of human EGFR in oligodendrocyte lineage cells or the administration of intranasal heparin-binding EGF immediately after injury decreases oligodendroglia death, enhances generation of new oligodendrocytes from progenitor cells and promotes functional recovery. Furthermore, these interventions diminish ultrastructural abnormalities and alleviate behavioural deficits on white-matter-specific paradigms. Inhibition of EGFR signalling with a molecularly targeted agent used for cancer therapy demonstrates that EGFR activation is an important contributor to oligodendrocyte regeneration and functional recovery after DWMI. Thus, our study provides direct evidence that targeting EGFR in oligodendrocyte progenitor cells at a specific time after injury is clinically feasible and potentially applicable to the treatment of premature children with white matter injury.

This study tested the hypothesis that there are consistent individual differences in the relationship between glycated hemoglobin (HbA1c) and mean blood glucose (MBG) levels in individuals with similar preceding blood glucose levels. Blood glucose data were collected for up to 2.3 years by 128 children and adolescents with type 1 diabetes. HbA1c values were date-matched with MBG levels calculated from an average of 85 self-monitored blood glucose measurements collected in the previous 30 days. There was significant linear correlation between MBG and HbA1c (HbA1c=0.027xMBG+5.8, n=682, r=.71, P<.0001) but also wide variability in the population HbA1c response to MBG. We calculated a hemoglobin glycation index (HGI=observed HbA1c-predicted HbA1c) to quantify the magnitude and direction of the difference between each patient's set of observed and predicted HbA1c results. Likelihood ratio tests and t statistics showed that mean HGI were significantly different among individuals, and that 29% of the patients had HbA1c levels that were statistically significantly higher or lower than predicted by the regression equation. The observed individual differences in the relationship between MBG and HbA1c were not related to erythrocyte age and there was no evidence of analytical artifact. We interpret these results as possible evidence of high and low hemoglobin glycation phenotypes within the population. We conclude that MBG and HbA1c are not necessarily interchangeable estimates of glycemic control and that hemoglobin glycation phenotype may be important for the clinical assessment of diabetic patients.

Background: Gram-positive organisms, including vancomycin-resistant enterococci (VRE), have emerged as major pathogens on the organ transplant service at our institution. We hypothesized that our use of vancomycin as part of routine surgical prophylaxis increased the risk of VRE colonization and infection; conversely, there was concern that failure to use vancomycin prophylaxis would increase peri-operative morbidity due to gram-positive organisms., Methods: Renal transplant recipients (n = 88) were randomized to receive either a) vancomycin/ceftriaxone or b) cefazolin; and pancreas transplants (n = 24) to receive either a) vancomycin/gentamicin or b) cefazolin/gentamicin. Stool samples or rectal swabs were obtained for culture for enterococci within 24 h of transplantation and weekly while hospitalized., Results: Enterococci were isolated on stool culture from 38 (34%) of 102 patients at the time of transplantation; 4 (11%) of the isolates were VRE. The percentage of patients who subsequently acquired VRE was low (1-7% per wk) but remained constant during hospitalization. There was no association between new VRE detection and vancomycin use for either prophylactic or therapeutic purposes. Forty-four patients (39%) had a post-operative infection with 46% of these infections due to gram-positive organisms; rates were unaffected by prophylactic vancomycin use. Pancreas transplant patients who did not receive vancomycin prophylaxis had a significantly longer initial hospitalization (p = 0.03); however, differences were not statistically significant when total length of stay (LOS) within the first 90 d of transplantation was compared., Conclusions: Vancomycin surgical prophylaxis does not appear to have an effect on VRE colonization or infection, or on rates of infection with gram-positive bacteria. Elimination of vancomycin prophylaxis in renal transplant patients may be a reasonable part of an overall program to limit vancomycin usage, although as a single measure, its impact may be minimal. Vancomycin surgical prophylaxis may be of greater importance in pancreas transplants.

Background: The risk associated with transplantation of renal allografts from hepatitis B virus core antibody-positive (HBcAb(+)), hepatitis B virus surface antigen-negative (HBsAg(-)) donors is not well defined., Methods: Over 4 years, we performed 45 kidney transplants from IgG HBcAb(+), IgM HBcAb(-), HBsAg(-) donors into recipients with a history of prior hepatitis B virus (HBV) infection or reported vaccination. We examined HBV-related outcomes in these 45 patients, in comparison with 45 recipients of allografts from HBcAb(-) donors (matched for transplant type, date, and pretransplant HBV antibodies). We sought evidence for HBV transmission by testing posttransplant sera for the presence of HBcAb, hepatitis B virus surface antibody, and HBsAg. Additionally, we analyzed alanine aminotransferase profiles and allograft survival rates for all patients., Results: No patient receiving an allograft from an HBcAb(+) donor developed clinical HBV infection. No patient receiving an allograft from an HBcAb(+) donor had HBsAg detected through retrospective testing of stored sera or through prospective routine clinical evaluation and care. However, among the HBcAb(+) kidney recipients, 27% developed new HBcAb and/or hepatitis B virus surface antibody after transplant; in contrast, only 4% of control patients developed new antibody responses (relative risk=4.94; confidence interval 1.07-22.83). Among the recipients of HBcAb(+) organs, 18% developed elevated transaminases after transplant, in comparison with 36% of the controls. No association was found between "seroconverter" status and elevated alanine aminotransferase profiles in either group., Conclusions: Transplantation of renal allografts from HBcAb(+), HBsAg(-) donors was not associated with clinically detectable HBV disease or antigenemia. However, recipients had a significantly increased risk of HBV seroconversion, consistent with exposure to HBV antigen. These results suggest that HBcAb(+) kidneys can be safely used if transplanted into appropriate recipients, but highlight the need for effective HBV vaccination and vaccine-response monitoring in potential recipients.

A cohort study was conducted in a cancer center to identify risk factors for bacteremia with vancomycin-resistant enterococci (VRE) in neutropenic cancer patients colonized with VRE. There were 10 patients with VRE bacteremia among 56 colonized with VRE, of whose charts 51 were available for review. One hundred percent of patients with VRE bacteremia (10 of 10) vs. 56% of patients without VRE bacteremia (23 of 41) had acute leukemia (P = .01, Fisher's exact test). Four of the 10 patients with VRE bacteremia had a positive Clostridium difficile toxin assay within 6 days of their first positive VRE blood culture. Both C. difficile infection and antimicrobial (vancomycin and ciprofloxacin) use during VRE colonization were significant risk factors for VRE bacteremia in univariate analysis. When a Cox proportional hazards model was used to account for differences in follow-up time, C. difficile infection was the only statistically significant risk factor (risk ratio, 8.2; P = .007) for VRE bacteremia in VRE-colonized patients with acute leukemia.

Growth hormone (GH)-binding protein (GHBP) and GH secretion are potential mediators of linear growth in children. To study the relationship between these variables, we measured GHBP activity, peak stimulated GH (PKGH), and 24-hour integrated GH concentration (ICGH) in 76 children referred for evaluation of growth. Linear growth was expressed as an age- and sex-specific growth rate standard deviation score (GRSD), which was calculated from sequential height measurements in the 6-month period immediately before GH testing. Using multiple regression models, we found that the relationship between GHBP and growth (GRSD) depended on height (height standard deviation [HGTSD] expressed as an age- and sex-specific z score) controlling for ICGH or PKGH. In further analysis of this relationship, we divided the subjects by HGTSD in subsequent analyses. In 19 children of normal stature (HGTSD > -2), GRSD increased with GH concentration (measured both as PKGH and ICGH: P <.013,R2 = .56) but decreased with higher levels of GHBP (P < .005,R2 = .62). In contrast, for 57 subjects with severe short stature (HGTSD < or = -2), GRSD could not be predicted from GHBP, GH secretion, HGTSD, or interaction involving these variables. These data suggest the hypothesis that under normal conditions, GHBP and GH level may be important predictors of growth rate in children.

Objective: To assess the usefulness of specific cardiovascular reflex tests in childhood and to estimate the prevalence of cardiovascular reflex abnormalities among children with IDDM. In adults, abnormal cardiovascular reflexes are a frequent complication of diabetes, associated with increased morbidity and mortality., Research Design and Methods: We measured heart-rate responses to deep breathing and standing in ambulatory children with and without IDDM between 6-19 yr of age. A subgroup of the IDDM patients was retested after 1 yr., Results: We found the best techniques for detecting cardiovascular reflex abnormality in children were as follows: to record heart-rate responses to deep breathing either as the change in heart rate corrected for inspiratory heart rate or as the ratio of R-R intervals during expiration and inspiration; and to use the Maximum-minimum ratio for heart-rate responses to standing. HR-DBc was lower in diabetic than nondiabetic children (28.6 +/- 9.2% [n = 248] vs. 33.6 +/- 6.8% [n = 60]; P < 0.0005). Similarly, E:I was lower in children with IDDM than control subjects (1.42 +/- 0.19 [n = 248] vs. 1.52 +/- 0.15 [n = 60]; P < 0.0005). In the IDDM group, 21% of the children had abnormal HR-DBc or E:I responses. HR-STND M/m was lower in children with IDDM than control subjects (1.28 +/- 0.20 [n = 167] vs. 1.38 +/- 0.22 [n = 45]; P < 0.014). Among children with IDDM, 11.4% had abnormal HR-STND M/m responses. Overall, 29% of IDDM children tested abnormal in either HR-DBc or HR-STND M/m; 3% were abnormal in both tests. We found no correlation of HbA1c levels (n = 74) or duration of diabetes with either HR-DB, expiration to inspiration (n = 248), or HR-STND M/m (n = 167). In patients who were reevaluated after 1 yr we found a high correlation of the first and repeat HR-DBc tests (r = 0.47, n = 75, P < 0.0001), E:I (r = 0.53, n = 75, P < 0.0001), and HR-STND M/m (r = .49, n = 37, P < 0.002), but no evidence of an increased number of children with cardiovascular reflex abnormality., Conclusions: With easily performed HR-DB and HR-STND tests, we detected cardiovascular reflex abnormality in 29% of children with IDDM. We found no correlation of changes in HR-DB and HR-STND with HbA1c or duration of diabetes. These tests provide an objective clinical measurement to monitor autonomic neuropathy in children with diabetes.

The critical elements of the change process were designed into the strategic planning process and the pilot project for the Integrated Academic Information Management System (IAIMS) at the University of Maryland. These elements were: Support by the institutional leadership; a critical mass of interested participants from diverse groups across the organization, committed to the project and with ownership of the plan; a motivating level of dissatisfaction with the status quo; the construction of a scenario describing the desired future and an assessment of needs to achieve it; technical and consulting help; a pilot project with replicable features to demonstrate the concept and feasibility of the approach; and participation of opinion leaders initially with later identification of additional opinion leaders who would become part of the pattern of acceptance of the innovation and diffusion of the technology across the campus.

We examined changes in spontaneously secreted growth hormone with aging by studying the 24-h integrated concentration of GH (IC-GH) of 173 nonobese subjects (height, greater than or equal to 5%; 7-65 yr of age). There was no significant difference in IC-GH on repeat testing of 13 men or in 23 women studied in the follicular and again in the luteal phase of the menstrual cycle. The level of IC-GH was strongly effected by age; children had the highest mean IC-GH, and there was a decline in IC-GH with increasing age after the second decade of life. The correlation of IC-GH with age was highly significant (r = 0.73; P less than 0.0001). There was no difference in IC-GH between males and females when matched for age. The mean IC-GH at Tanner stage 5 of puberty (7.4 +/- 2.0 ng/ml) was higher than that at stages 2-4 (5.7 +/- 1.4; P less than 0.0005) or that in prepubertal children (5.8 +/- 1.4; P less than 0.001). Thus, age and pubertal status must be carefully considered when interpreting the IC-GH for patients suspected of having deficient or excessive secretion of GH.