A DNA prime-modified vaccinia virus ankara boost vaccine encoding thrombospondin-related adhesion protein but not circumsporozoite protein partially protects healthy malaria-naive adults against Plasmodium falciparum sporozoite challenge.

The safety, immunogenicity, and efficacy of DNA and modified vaccinia virus Ankara (MVA) prime-boost regimes were assessed by using either thrombospondin-related adhesion protein (TRAP) with a multiple-epitope string ME (ME-TRAP) or the circumsporozoite protein (CS) of Plasmodium falciparum. Sixteen healthy subjects who never had malaria (malaria-naive subjects) received two priming vaccinations with DNA, followed by one boosting immunization with MVA, with either ME-TRAP or CS as the antigen. Immunogenicity was assessed by ex vivo gamma interferon (IFN-gamma) enzyme-linked immunospot assay (ELISPOT) and antibody assay. Two weeks after the final vaccination, the subjects underwent P. falciparum sporozoite challenge, with six unvaccinated controls. The vaccines were well tolerated and immunogenic, with the DDM-ME TRAP regimen producing stronger ex vivo IFN-gamma ELISPOT responses than DDM-CS. One of eight subjects receiving the DDM-ME TRAP regimen was completely protected against malaria challenge, with this group as a whole showing significant delay to parasitemia compared to controls (P = 0.045). The peak ex vivo IFN-gamma ELISPOT response in this group correlated strongly with the number of days to parasitemia (P = 0.033). No protection was observed in the DDM-CS group. Prime-boost vaccination with DNA and MVA encoding ME-TRAP but not CS resulted in partial protection against P. falciparum sporozoite challenge in the present study.

Prevalence of nosocomial infections in neonatal intensive care unit patients: Results from the first national point-prevalence survey.

OBJECTIVES: Patients admitted to neonatal intensive care units (NICUs) are at high risk of nosocomial infection. We conducted a national multicenter assessment of nosocomial infections in NICUs to determine the prevalence of infections, describe associated risk factors, and help focus prevention efforts. STUDY DESIGN: We conducted a point prevalence survey of nosocomial infections in 29 Pediatric Prevention Network NICUs. Patients present on the survey date were included. Data were collected on underlying diagnoses, therapeutic interventions/treatments, infections, and outcomes. RESULTS: Of the 827 patients surveyed, 94 (11.4%) had 116 NICU-acquired infections: bloodstream (52.6%), lower respiratory tract (12.9%), ear-nose-throat (8.6%), or urinary tract infections (8.6%). Infants with infections were of significantly lower birth weight (median 1006 g [range 441 to 4460 g] vs 1589 g [range 326 to 5480 g]; P <.001) and had longer median durations of stay than those without infections (88 days [range 8 to 279 days] vs 32 days [range 1 to 483 days]; P <.001). Most common pathogens were coagulase-negative staphylococci and enterococci. Patients with central intravascular catheters (relative risk = 3.81, CI 2.32-6.25; P <.001) or receiving total parenteral nutrition (relative risk = 5.72, CI 3.45-9.49; P <.001) were at greater risk of bloodstream infection. CONCLUSIONS: This study documents the high prevalence of nosocomial infections in patients in NICUs and the urgent need for more effective prevention interventions.

Nosocomial infection rates in US children's hospitals' neonatal and pediatric intensive care units.

BACKGROUND: Few data are available on nosocomial infections (NIs) in US children's hospitals' neonatal or pediatric intensive care units. The Pediatric Prevention Network (PPN) was established to improve characterization of NIs in pediatric patients and to develop and test interventions to decrease NI. METHODS: Fifty participating children's hospitals were surveyed in 1998 to determine NI surveillance methods used and neonatal intensive care unit (NICU) and pediatric intensive care unit (PICU) 1997 NI rates. Data were collected on standardized forms and entered and analyzed by using SPSS for Windows. RESULTS: Forty-three (86%) children's hospitals returned a completed questionnaire. All reported conducting NICU and PICU NI surveillance (range, 2-12; median, 12 months). Nineteen children's hospitals provided NICU NI rate data in one or more formats suitable for comparison. Denominators used for NICU NI rate calculations varied: 17 reported overall NI by patient-days; 19 reported bloodstream infection (BSI) by central venous catheter (CVC)-days, and 8 reported BSI by patient-days. Sixteen (16) children's hospitals reported NICU BSI data stratified by CVC-days and birth-weight cohort, and ventilator-associated pneumonia (VAP) by birth weight cohort was reported by 12. Twenty-four children's hospitals reported PICU NI rate data in one or more formats suitable for comparison. Denominators used for PICU NI rate calculations also varied: 20 reported overall NI rates by patient-days; 23 reported BSI rates by CVC-days, and 10 reported BSI rates by patient-days; 24 reported VAP by ventilator-days; and 15 reported urinary tract infections (UTIs) by urinary catheter-days. Median overall NI rates per 1000 patient days were 8.9 in NICUs and 13.9 in PICUs. Median NICU NI device-associated rates by birth weight (>2500 g, 1501-2500 g, 1001-1500 g, and

The Internet: a practical example of the use of new technology in the assessment of vancomycin use in pediatrics. The Pediatric Prevention Network.

BACKGROUND: The rapid emergence of both new infections and new technologies has revolutionized health care during the past 50 years. Increased use of the Internet has enabled health care professionals to educate, interact, and collaborate throughout the world in ways never before possible. Increased use of vancomycin has been associated with the emergence of organisms with decreased susceptibility to vancomycin, such as Enterococcus and staphylococcal species. The purpose of this article is to describe our experience using Internet technology to assess vancomycin use at children's hospitals in the United States. METHODS: A Web-based evaluation was developed and distributed on the Internet to 57 Pediatric Prevention Network hospitals. The evaluation was structured to collect summary statistics on vancomycin use and admissions data by service for 1997 and 1998. RESULTS: Twenty-four hospitals were able to provide archived vancomycin use and patient admissions data; completed evaluations were returned from 15 hospitals (62.5% response rate). Personnel at 6 (40%) hospitals completed the evaluation directly on the Internet. CONCLUSIONS: In our study, Internet technology facilitated a more efficient evaluation of vancomycin use, but fewer than half of the personnel at Pediatric Prevention Network hospitals completed the evaluation directly on the Internet. It is unclear whether personnel at these hospitals were limited in Internet access, support, or understanding. Efforts should be directed to educate health care personnel on the advantages of the Internet. Furthermore, many of the pharmacy databases used in our assessment were not standardized across hospitals nor systematically validated. Understanding that limitations still remain-within the source of the data studied, the health care system sampled, and the Internet tools available-is essential because the Internet offers health care professionals today a tool both to protect patients and to improve quality throughout the world.

Drinking and HIV: knowledge and context.

AIDS: The unique role of alcohol consumption on the AIDS epidemic is examined, as are the gaps in knowledge that exist among patients, practitioners, and researchers. Research on how alcohol abuse enhances unsafe sex practices and nonadherence to AIDS medication regimens is discussed. In addition, the effects of drinking, with respect to HIV infection and the need for interventions, which may be particularly important to women, particularly to women of color, reasons why male-oriented intervention models may not be appropriate for alcohol-abusing women, and the need for effective interventions to include issues such as child care, family and partner roles, and other potential barriers are discussed. Other topics include treatment problems among seropositive alcohol abusers, and the needs of populations at high risk for alcohol abuse and HIV infection such as prison inmates, homeless youth, and women with histories of victimization to be addressed.^ieng

Irreversibility of birth-related changes in the pulmonary circulation.

We hypothesized that establishing conditions of hypoxia and fluid filling of the airways in lungs of newborns would reproduce the high levels of pulmonary vascular resistance (PVR) observed in the fetal state. We assessed the hemodynamics of the left pulmonary circulation of 1- to 3-day-old lambs during a variety of airway states while attempting to reestablish fetal conditions. Eleven animals were studied during both normoxemia and hypoxemia in a baseline airway state with a positive end-expiratory pressure (PEEP) of 4 cm H2O, and in experimental airway states, of atelectasis, and fluid filling to 15 and 30 mL/kg and with PEEP of 12 cm H2O. PVR increased while pulmonary blood flow decreased with all airway state changes as compared to baseline, suggesting a passive mechanism for these changes. With the addition of hypoxemia there was a further increase in PVR in all states accompanied by an increase in pulmonary blood flow, indicating that active vasoconstriction was responsible for the increase in PVR. The combined effects of hypoxemia and fluid filling, designed to approximate the fetal state, increased PVR to only 20-30% of fetal values. Thus, additional factors appear to be important in maintaining the high PVR of the fetal state. We speculate that ventilation of the lungs at birth irreversibly alters these factors.

Dopamine beta-hydroxylase immunoreactivity in human cerebrospinal fluid: properties, relationship to central noradrenergic neuronal activity and variation in Parkinson's disease and congenital dopamine beta-hydroxylase deficiency.

1. Dopamine beta-hydroxylase is stored and released with catecholamines by exocytosis from secretory vesicles in noradrenergic neurons and chromaffin cells. Although dopamine beta-hydroxylase enzymic activity is measurable in cerebrospinal fluid, such activity is unstable, and its relationship to central noradrenergic neuronal activity in humans is not clearly established. To explore the significance of cerebrospinal fluid dopamine beta-hydroxylase, we applied a homologous human dopamine beta-hydroxylase radioimmunoassay to cerebrospinal fluid, in order to characterize the properties and stability of cerebrospinal fluid dopamine beta-hydroxylase, as well as its relationship to central noradrenergic neuronal activity and its variation in disease states such as hypertension, renal failure, Parkinsonism and congenital dopamine beta-hydroxylase deficiency. 2. Authentic, physically stable dopamine beta-hydroxylase immunoreactivity was present in normal human cerebrospinal fluid at a concentration of 31.3 +/- 1.4 ng/ml (range: 18.5-52.5 ng/ml), but at a 283 +/- 27-fold lower concentration than that found in plasma. Cerebrospinal fluid and plasma dopamine beta-hydroxylase concentrations were correlated (r = 0.67, P = 0.001). Some degree of local central nervous system control of cerebrospinal fluid dopamine beta-hydroxylase was suggested by incomplete correlation with plasma dopamine beta-hydroxylase (with an especially marked dissociation in renal disease) as well as the lack of a ventricular/lumbar cerebrospinal dopamine beta-hydroxylase concentration gradient. 3. Cerebrospinal fluid dopamine beta-hydroxylase was not changed by the central alpha 2-agonist clonidine at a dose that diminished cerebrospinal fluid noradrenaline, nor did cerebrospinal fluid dopamine beta-hydroxylase correspond between subjects to cerebrospinal fluid concentrations of noradrenaline or methoxyhydroxyphenylglycol; thus, cerebrospinal fluid dopamine beta-hydroxylase concentration was not closely linked either pharmacologically or biochemically to central noradrenergic neuronal activity. 4. Cerebrospinal fluid dopamine beta-hydroxylase was not changed in essential hypertension. In Parkinson's disease, cerebrospinal fluid dopamine beta-hydroxylase was markedly diminished (16.3 +/- 2.9 versus 31.3 +/- 1.4 ng/ml, P < 0.001) and rose by 58 +/- 21% (P = 0.02) after adrenal-to-caudate chromaffin cell autografts. In congenital dopamine beta-hydroxylase deficiency, lack of detectable dopamine beta-hydroxylase immunoreactivity in cerebrospinal fluid or plasma suggests absent enzyme (rather than a catalytically defective enzyme) as the origin of the disorder. 5. We conclude that cerebrospinal fluid dopamine beta-hydroxylase immunoreactivity, while not closely linked to central noradrenergic neuronal activity, is at least in part derived from the central nervous system, and that its measurement may be useful in both the diagnosis and treatment of neurological disease.

Acute splenic sequestration crisis in sickle cell disease: early detection and treatment.

Acute splenic sequestration crisis (ASSC) in children with various forms of sickle cell disease can result in life-threatening circulatory collapse due to the loss of circulating blood volume. Over a 6-year period we have treated 12 patients ranging in age from 5 1/2 months to 7 years presenting with acute sequestration crisis. Eleven had homozygous sickle cell disease and the other had sickle-thalassemia. One patient died of acute circulatory collapse. Eight patients underwent splenectomy after a major episode of sequestration with no serious infectious complications up to 5 years following splenectomy. Three patients with minor episodes have been followed with no recurrences. To foster early detection of this potentially lethal complication of sickle cell disease, an educational program in our Comprehensive Sickle Cell Center instructs the parents to examine the spleen and bring their child in for evaluation if the spleen enlarges. A newly developed videotape describes the common symptoms of ASSC and illustrates the technique of palpating the spleen. With early detection of sickle cell disease by neonatal screening and the educational program, the morbidity and mortality from this complication of sickle cell disease can be reduced.

Homologous radio-immunoassay of human plasma dopamine-beta-hydroxylase: analysis of homospecific activity, circulating plasma pool and intergroup differences based on race, blood pressure and cardiac function.

We used a homologous human dopamine-beta-hydroxylase (DBH) radio-immunoassay (RIA) to explore reported differences in plasma DBH enzymatic activity among patient groups stratified for race, blood pressure and cardiac function, as well as to determine plasma immunoreactive DBH protein pool and the relative activity of the enzyme in plasma versus human chromaffin tissue storage vesicles. Plasma DBH activity was lower in patients with congestive heart failure than in control subjects (19.9 +/- 4.0 versus 34.4 +/- 5.9 iu/l, P less than 0.05), paralleled by lower immunoreactive plasma DBH protein concentration (3.50 +/- 0.73 versus 6.34 +/- 1.05 micrograms/ml, P less than 0.05). All subject groups had similar plasma DBH homospecific activity (plasma DBH enzymatic activity/immunoreactive plasma DBH protein), ranging from 5.03 +/- 0.28 to 5.84 +/- 0.44 iu/mg. For the entire subject group, there was a significant relationship between plasma DBH activity and plasma DBH immunoreactive protein (r = 0.89, n = 78, P less than 0.01) from which no subgroup deviated systematically. Black hypertensives had lower plasma DBH activity than white hypertensives (23.0 +/- 5.2 versus 42.9 +/- 4.8 iu/l, P less than 0.01), though their plasma DBH homospecific activities and activity/immunoreactive protein plots were indistinguishable. Total circulating plasma DBH pools were large (from 13.1 +/- 3.7 to 27.5 +/- 4.8 mg).(ABSTRACT TRUNCATED AT 250 WORDS)