Cooking fuel type, household ventilation, and the risk of acute lower respiratory illness in urban Bangladeshi children: a longitudinal study.

UNLABELLED: Acute lower respiratory illnesses (ALRI) are the leading cause of death among children <5 years. Studies have found that biomass cooking fuels are an important risk factor for ALRI. However, few studies have evaluated the influence of natural household ventilation indicators on ALRI. The purpose of this study was to assess the association between cooking fuel, natural household ventilation, and ALRI. During October 17, 2004-September 30, 2005, children <5 years living in a low-income neighborhood of Dhaka, Bangladesh, were assessed weekly for ALRI and surveyed quarterly about biomass fuel use, electric fan ownership, and natural household ventilation (windows, ventilation grates, and presence of a gap between the wall and ceiling). Bivariate and multivariate analyses were performed using generalized estimating equations. Six thousand and seventy-nine children <5 years enrolled during the study period (99% participation) experienced 1291 ALRI. In the multivariate model, ≥2 windows [OR = 0.75, 95% CI = (0.58, 0.96)], ventilation grates [OR = 0.80, 95% CI = (0.65, 0.98)], and not owning an electric fan [OR = 1.50, 95% CI = (1.21, 1.88)] were associated with ALRI; gap presence and using biomass fuels were not associated with ALRI. Structural factors that might improve household air circulation and exchange were associated with decreased ALRI risk. Improved natural ventilation might reduce ALRI among children in low-income families. PRACTICAL IMPLICATIONS: The World Health Organization has stated that controlling pneumonia is a priority for achieving the fourth Millennium Development Goal, which calls for a two-third reduction in mortality of children <5 years old compared to the 1990 baseline. Our study represents an important finding of a modifiable risk factor that might decrease the burden of respiratory illness among children living in Bangladesh and other low-income settings similar to our study site. We found that the existence of at least two windows in the child's sleeping room was associated with a 25% decreased ALRI risk. Increasing available natural ventilation within the household in similar settings has the potential to reduce childhood mortality because of acute lower respiratory illnesses.

Rainfall, household crowding, and acute respiratory infections in the tropics.

SUMMARYAcute respiratory infections (ARI) are the leading cause of death worldwide in children aged <5 years, and understanding contributing factors to their seasonality is important for targeting and implementing prevention strategies. In tropical climates, ARI typically peak during the pre-rainy and rainy seasons. One hypothesis is that rainfall leads to more time spent indoors, thus increasing exposure to other people and in turn increasing the risk of ARI. A case-crossover study design in 718 Bangladeshi children aged <5 years was used to evaluate this hypothesis. During a 3-month period with variable rainfall, rainfall was associated with ARI [odds ratio (OR) 2·97, 95% confidence interval (CI) 1·87-4·70]; some evidence of an increased strength of association as household crowding increased was found (≥3 people/room, OR 3·31, 95% CI 2·03-5·38), but there was a lack of association in some of the most crowded households (≥5 to <6 people/room, OR 1·55, 95% CI 0·54-4·47). These findings suggest that rainfall may be increasing exposure to crowded conditions, thus leading to an increased risk of ARI, but that additional factors not captured by this analysis may also play a role.

Effect of setting a maximum milking time, from peak lactation, on production, milking time and udder health.

AIM: To examine the effect of setting a maximum milking time, from peak lactation until drying-off, on production, duration of milking, and udder health of dairy cows. METHODS: Forty cows were assigned in twin-pairs to be either milked until cups were removed at a milk flow-rate threshold of 0.35 kg/minute (Control), or until cups were removed at a milk flow-rate threshold of 0.35 kg/minute, or maximum time, whichever came first (MaxT). The maximum time was set by determining the milking time of the 70th percentile cow when ranked from fastest to slowest, irrespective of yield. The milking routine was typical of that practised on dairy farms in New Zealand, and involved no pre-milking preparation. The study began at peak lactation (68 (SD 7) days in milk; DIM) and continued for 26 weeks. Duration of milking and milk yield were measured for each milking. Composition of milk was determined from weekly herd tests, and milk quality from fortnightly somatic cell counts (SCC). Completeness of milking and teat condition were assessed during the study. The bacterial status of quarter milk samples was determined at the beginning and end of the study, and all treated cases of clinical mastitis recorded. ANOVA was used to examine the effect of treatment group on variables of interest. RESULTS: Total milk, fat and protein yields during the study period did not differ between treatments. On average, 30.3% of the morning and 27.6% of the afternoon milkings of MaxT cows reached the maximum time at which cups were removed, and were therefore shortened. While the average milking time of the slowest-milking cow was longer for the Control compared with MaxT group in Weeks 1-18, the average milking time did not differ between treatments. There was no difference in overall SCC, and the incidence of clinical mastitis, or the percentage of infected quarters at drying-off, was similar for the MaxT and Control cows. CONCLUSION: The results show that setting a maximum milking time can reduce the milking time of slower-milking cows in a herd without compromising overall herd production and udder health. CLINICAL RELEVANCE: Although the numbers of cows in the study were small there was no evidence of a major increase in SCC, or subclinical or clinical mastitis when a maximum milking time was set for slower-milking cows.

Quantitative analysis and molecular fingerprinting of methicillin-resistant Staphylococcus aureus nasal colonization in different patient populations: a prospective, multicenter study.

OBJECTIVES: To better understand the prevalence of methicillin-resistant Staphylococcus aureus (MRSA) colonization or infection in different patient populations, to perform quantitative analysis of MRSA in nasal cultures, and to characterize strains using molecular fingerprinting. DESIGN: Prospective, multicenter study. SETTING: Eleven different inpatient and outpatient healthcare facilities. PARTICIPANTS: MRSA-positive inpatients identified in an active surveillance program; inpatients and outpatients receiving hemodialysis; inpatients and outpatients with human immunodeficiency virus (HIV) infection; patients requiring cardiac surgery; and elderly patients requiring long-term care. METHODS. Nasal swab samples were obtained from January 23, 2006, through July 27, 2007; MRSA strains were quantified and characterized by molecular fingerprinting. RESULTS: A total of 444 nares swab specimens yielded MRSA (geometric mean quantity, 794 CFU per swab; range, 3-15,000,000 CFU per swab). MRSA prevalence was 20% for elderly residents of long-term care facilities (25 of 125 residents), 16% for HIV-infected outpatients (78 of 494 outpatients), 15% for outpatients receiving hemodialysis (31 of 208 outpatients), 14% for inpatients receiving hemodialysis (86 of 623 inpatients), 3% for HIV-infected inpatients (5 of 161 inpatients), and 3% for inpatients requiring cardiac surgery (6 of 199 inpatients). The highest geometric mean quantity of MRSA was for inpatients requiring cardiac surgery (11,500 CFU per swab). An association was found between HIV infection and colonization with the USA300 or USA500 strain of MRSA (P < or = .001). The Brazilian clone was found for the first time in the United States. Pulsed-field gel electrophoresis patterns for 11 isolates were not compatible with known USA types or clones. CONCLUSION: Nasal swab specimens positive for MRSA had a geometric mean quantity of 794 CFU per swab, with great diversity in the quantity of MRSA at this anatomic site. Outpatient populations at high risk for MRSA carriage were elderly residents of long-term care facilities, HIV-infected outpatients, and outpatients receiving hemodialysis.

Longitudinal analysis of community health workers' adherence to treatment guidelines, Siaya, Kenya, 1997-2002.

OBJECTIVES: To investigate community health workers' (CHW) adherence over time to guidelines for treating ill children and to assess the effect of refresher training on adherence. METHODS: Analysis of 7151 ill-child consultations performed by 114 CHWs in their communities from March 1997-May 2002. Adherence was assessed with a score (percentage of recommended treatments that were prescribed), calculated for each consultation. Recommended treatments were those that were indicated based on CHW assessments. We used piecewise regression models to evaluate adherence before and after training. RESULTS: The average adherence score was 79.4%. Multivariable analyses indicate that immediately after the first refresher training, the mean adherence level improved for patients with a severe illness, but worsened for patients without severe illness. Adherence scores declined rapidly during the 6 months after the second refresher training. CONCLUSIONS: The first refresher was partially effective, the second refresher had an effect contrary to that intended, and patient characteristics had a strong influence on adherence patterns. Longitudinal studies are useful for monitoring the dynamics of CHW performance and evaluating effects of quality improvement interventions.

The influence of observation and setting on community health workers' practices.

OBJECTIVE: To determine whether results from an evaluation that involved observation of community health workers while they performed patient consultations in a hospital reflected normal everyday practices. DESIGN: Comparison of two samples of ill-child consultations: (i) consultations performed during an evaluation in which we observed community health workers in a hospital in-patient and outpatient department from February to March 2001 and (ii) consultations performed under no observation in villages and documented in clinical registers within the 90 days before the hospital evaluation. SETTING: Siaya District Hospital and villages in Kenya. STUDY PARTICIPANTS: Community health workers. MAIN OUTCOME MEASURE: Treatment error indicator, defined as the percentage of consultations where at least one recommended treatment (where recommended treatments were those that were indicated based on community health worker assessments of the child's condition) was not prescribed. RESULTS: We analyzed data on 1132 consultations (372 from the hospital evaluation and 760 from the community) performed by 103 community health workers. For all types of consultations combined, the difference between treatment error indicators (hospital minus community) was -16.4 [95% confidence interval (CI): -25.6, -7.1]. CONCLUSIONS: We found that community health workers made treatment errors less frequently when they were observed in a hospital in-patient or outpatient department than when they were not observed in the community. Evaluations that involve the observation of community health workers in a hospital setting might overestimate the quality of care that they normally give in their villages.

Debate-guidelines for control of glycopeptide-resistant enterococci (GRE) have not yet worked.

Glycopeptide-resistant enterococci (GRE) have become a focus of concern in many countries because options for antimicrobial therapy of GRE infection are limited. Several guidelines for the control and prevention of GRE colonization and infection have been developed for healthcare settings, and occasional journal articles now report "control" (usually relative reduction of incidence or prevalence rate rather than elimination) of GRE infections. Yet, rates of infection and colonization with GREcontinue to climb in many parts of the world, showing that true control has not been achieved. Programmes to control GRE will be effective only when they (1) are less expensive to implement; (2) are shown to be cost-effective despite the fact that they merely reduce prevalence levels rather than eradicating the problem; (3) do not require almost perfect implementation to be effective; (4) are shown to be sustainable; (5) are shown to work in acute-care settings other than selected academic centres; and (6) are shown to work in non-acute care settings. Until then, it is clear that guidelines for control of GRE have not worked. New guidelines that truly control GRE must be developed, and this must be done quickly.

Validation of Vitek version 7.01 software for testing staphylococci against vancomycin.

We tested 143 isolates of staphylococci with vancomycin by the National Committee for Clinical Laboratory Standards broth microdilution (BMD) reference method and compared the results to those generated using the Vitek automated system (GPS-105 and GPS-107 cards and version 7.01 software). For ten isolates, the vancomycin MICs by BMD were 8 microg/ml. By Vitek, the vancomycin MICs ranged from 2 to 16 microg/ml. Vancomycin MICs of > or =32 microg/ml were reported for two additional isolates by Vitek; however, the MICs decreased to < or =0.5 microg/ml on retesting. By BMD, the vancomycin MICs for both isolates were 1 microg/ml. While the modal vancomycin MIC results by BMD for S. aureus and coagulase-negative staphylococci (CoNS) were both 1 microg/ml, Vitek results showed a mode of < or =0.5 microg/ml for S. aureus, and a mode of 2 microg/ml for CoNS. Vitek did not report vancomycin MICs of 1 or 4 microg/ml for any of the isolates tested. While the sensitivity of detecting staphylococci with reduced susceptibility to vancomycin appears to be improved with Vitek version 7.01 software, when compared to earlier software versions, laboratories may notice an overall shift in MIC data toward higher vancomycin MICs, although for the most part, this does not affect the categorical interpretations of the results.

Tuberculosis treatment in nepal: a rapid assessment of government centers using different types of patient supervision.

SETTING: Urban and periurban government tuberculosis (TB) treatment clinics in Nepal. OBJECTIVE: To assess TB treatment supervision strategies and outcomes. DESIGN: Three types of treatment centers were selected according to intensity of treatment supervision: Group A-all patients supervised by directly observed therapy (DOT) at the treatment center during the intensive phase; Group B-flexible DOT where patient-nominated treatment supervisors include community or family members; Group C-drugs dispensed monthly and no supervised treatment. The cohort studied comprised all new patients starting treatment during a 5-month period in 1996 (n = 759). RESULTS: At group A treatment centers, 100% of patients had daily DOT supervised by treatment center staff during the intensive phase. At group B sites, 75% of nominated supervisors were family or community members and 13% of patients had no supervisor. At group C sites 93% of patients were unsupervised. Bacteriologically confirmed cure rates for smear-positive patients were 91% (95%CI 80.3-97.2) for A sites, 57% (95%CI 48.8-64.0) for B, and 34% (95%CI 25.1-40.4) for C. Treatment centers with the best results had good access to laboratory facilities, uninterrupted drug supply, longer clinic hours, standardized TB case management, and support from a non-governmental organization. CONCLUSION: At government facilities in Nepal, only group A treatment centers achieved World Health Organization global targets for cure. Group B treatment centers showed better outcomes than unsupervised therapy but did not achieve cure targets. Rapid low-cost assessments to collect data that are not routinely reported can improve the evaluation of program aspects such as supervision strategies.

Measuring the economic costs of antimicrobial resistance in hospital settings: summary of the Centers for Disease Control and Prevention-Emory Workshop.

Health systems administrators and clinicians need refined calculations of the attributable cost of infections due to drug-resistant microorganisms to develop and assess cost-effective prevention strategies that deal with these infections. To date, however, efforts to provide this information have yielded widely variable and often conflicting estimates. This lack of reproducibility is largely attributable to problems in study design and in the methods used to identify and measure costs. Addressing these methodological issues was the focus of a workshop that included participants from a broad range of backgrounds, including economics, epidemiology, health care management, health care outcomes research, and clinical care. This workshop summary presents the advantages and disadvantages of various research designs as well as particular methodological issues related to the measurement of the economic cost of resistance in health care settings. Suggestions are made for needed common definitions and approaches, study areas for future research are considered, and priority investigations are identified.

The effect of vancomycin and third-generation cephalosporins on prevalence of vancomycin-resistant enterococci in 126 U.S. adult intensive care units.

BACKGROUND: Patient-specific risk factors for acquisition of vancomycin-resistant enterococci (VRE) among hospitalized patients are becoming well defined. However, few studies have reported data on the institutional risk factors, including rates of antimicrobial use, that predict rates of VRE. Identifying modifiable institutional factors can advance quality-improvement efforts to minimize hospital-acquired infections with VRE. OBJECTIVE: To determine the independent importance of any association between antimicrobial use and risk factors for nosocomial infection on rates of VRE in intensive care units (ICUs). DESIGN: Prospective ecologic study. SETTING: 126 adult ICUs from 60 U.S. hospitals from January 1996 through July 1999. PATIENTS: All patients admitted to participating ICUs. MEASUREMENTS: Monthly use of antimicrobial agents (defined daily doses per 1000 patient-days), nosocomial infection rates, and susceptibilities of all tested enterococci isolated from clinical cultures. RESULTS: Prevalence of VRE (median, 10%; range, 0% to 59%) varied by type of ICU and by teaching status and size of the hospital. Prevalence of VRE was strongly associated with VRE prevalence among inpatient non-ICU areas and outpatient areas in the hospital, ventilator-days per 1000 patient-days, and rate of parenteral vancomycin use. In a weighted linear regression model controlling for type of ICU and rates of VRE among non-ICU inpatient areas, rates of vancomycin use (P < 0.001) and third-generation cephalosporin use (P = 0.02) were independently associated with VRE prevalence. CONCLUSIONS: Higher rates of vancomycin or third-generation cephalosporin use were associated with increased prevalence of VRE, independent of other ICU characteristics and the endemic VRE prevalence elsewhere in the hospital. Decreasing the use rates of these antimicrobial agents could reduce rates of VRE in ICUs.

Characterization of clinical isolates of Klebsiella pneumoniae from 19 laboratories using the National Committee for Clinical Laboratory Standards extended-spectrum beta-lactamase detection methods.

Extended-spectrum beta-lactamases (ESBLs) are enzymes found in gram-negative bacilli that mediate resistance to extended-spectrum cephalosporins and aztreonam. In 1999, the National Committee for Clinical Laboratory Standards (NCCLS) published methods for screening and confirming the presence of ESBLs in Klebsiella pneumoniae, Klebsiella oxytoca, and Escherichia coli. To evaluate the confirmation protocol, we tested 139 isolates of K. pneumoniae that were sent to Project ICARE (Intensive Care Antimicrobial Resistance Epidemiology) from 19 hospitals in 11 U.S. states. Each isolate met the NCCLS screening criteria for potential ESBL producers (ceftazidime [CAZ] or cefotaxime [CTX] MICs were > or =2 microg/ml for all isolates). Initially, 117 (84%) isolates demonstrated a clavulanic acid (CA) effect by disk diffusion (i.e., an increase in CAZ or CTX zone diameters of > or =5 mm in the presence of CA), and 114 (82%) demonstrated a CA effect by broth microdilution (reduction of CAZ or CTX MICs by > or =3 dilutions). For five isolates, a CA effect could not be determined initially by broth microdilution because of off-scale CAZ results. However, a CA effect was observed in two of these isolates by testing cefepime and cefepime plus CA. The cefoxitin MICs for 23 isolates that failed to show a CA effect by broth microdilution were > or =32 microg/ml, suggesting either the presence of an AmpC-type beta-lactamase or porin changes that could mask a CA effect. By isoelectric focusing (IEF), 7 of the 23 isolates contained a beta-lactamase with a pI of > or =8.3 suggestive of an AmpC-type beta-lactamase; 6 of the 7 isolates were shown by PCR to contain both ampC-type and bla(OXA) genes. The IEF profiles of the remaining 16 isolates showed a variety of beta-lactamase bands, all of which had pIs of < or =7.5. All 16 isolates were negative by PCR with multiple primer sets for ampC-type, bla(OXA), and bla(CTX-M) genes. In summary, 83.5% of the K. pneumoniae isolates that were identified initially as presumptive ESBL producers were positive for a CA effect, while 5.0% contained beta-lactamases that likely masked the CA effect. The remaining 11.5% of the isolates studied contained beta-lactamases that did not demonstrate a CA effect. An algorithm based on phenotypic analyses is suggested for evaluation of such isolates.

Antimicrobial resistance prevalence rates in hospital antibiograms reflect prevalence rates among pathogens associated with hospital-acquired infections.

To determine whether routine antibiograms (summaries reporting resistance of all tested isolates) reflect resistance rates among pathogens associated with hospital-acquired infections, we compared data collected from 2 different surveillance components in the same 166 intensive care units (ICUs). ICUs reported data during the same months to both the infection-based surveillance and the laboratory-based surveillance. Paired comparisons of the percentage of isolates resistant were made between systems within each ICU. No significant differences existed (P>.05) between the percentage of isolates resistant from the infection-based system and laboratory-based system for all antimicrobial-resistant organisms studied, except methicillin resistance in Staphylococcus species. The mean difference in percentage resistance was higher from the infection-based system than the laboratory-based system for S. aureus (mean difference, +8%, P<.001) and coagulase-negative staphylococci (mean difference, +9%, P<.001). Overall, hospital antibiograms reflected susceptibility patterns among isolates associated with hospital-acquired infections. Hospital antibiograms may underestimate the relative frequency of methicillin resistance among Staphylococcus species when associated with hospital-acquired infections.

Increasing threat of Gram-positive bacterial infections in the intensive care unit setting.

The effects of resistance are being noted on an increasing scale in the intensive care unit (ICU). Around the world, new epidemiologic patterns of ICU occurrence are being observed for Gram-positive multidrug-resistant organisms. Current problems include the appearance of insusceptibility to vancomycin and other glycopeptides in Staphylococcus aureus organisms that are virulent enough to cause infection in patients with normal host defenses. In addition, multidrug-resistant organisms like methicillin-resistant S.aureus are spreading from healthcare to community settings, and community organisms like Streptococcus pneumoniae are spreading to healthcare settings. Focal persistence and subsequent worldwide spread of enterococci resistant to vancomycin and other glycopeptides and multiple-resistance mechanisms in the same organism also require attention. Strategies such as multidisciplinary management of infections, appropriate infection control measures, and surveillance of resistance patterns are necessary to address the problem of resistance. Intensivists have been prominent in research and control efforts in this field and should continue to lead future efforts.

Applying economic principles to health care.

Applying economic thinking to an understanding of resource use in patient care is challenging given the complexities of delivering health care in a hospital. Health-care markets lack the characteristics needed to determine a "market" price that reflects the economic value of resources used. However, resource allocation in a hospital can be analyzed by using production theory to determine efficient resource use. The information provided by hospital epidemiologists is critical to understanding health-care production processes used by a hospital and developing economic incentives to promote antibiotic effectiveness and infection control.

Economic impact of antimicrobial resistance.

One reason antimicrobial-drug resistance is of concern is its economic impact on physicians, patients, health-care administrators, pharmaceutical producers, and the public. Measurement of cost and economic impact of programs to minimize antimicrobial-drug resistance is imprecise and incomplete. Studies to describe and evaluate the problem will have to employ new methods and be of large scale to produce information that is broadly applicable.

Ability of laboratories to detect emerging antimicrobial resistance in nosocomial pathogens: a survey of project ICARE laboratories.

A proficiency testing project was conducted among 48 microbiology laboratories participating in Project ICARE (Intensive Care Antimicrobial Resistance Epidemiology). All laboratories correctly identified the Staphylococcus aureus challenge strain as oxacillin- resistant and an Enterococcus faecium strain as vancomycin-resistant. Thirty-one (97%) of 32 laboratories correctly reported the Streptococcus pneumoniae strain as erythromycin-resistant. All laboratories testing the Pseudomonas aeruginosa strain against ciprofloxacin or ofloxacin correctly reported the organism as resistant. Of 40 laboratories, 30 (75%) correctly reported resistant MICs or zone sizes for the imipenem- and meropenem-resistant Serratia marcescens. For the extended-spectrum beta-lactamase (ESBL)-producing strain of Klebsiella pneumoniae, 18 (42%) of 43 laboratories testing ceftazidime correctly reported ceftazidime MICs in the resistant range. These results suggest that current testing generally produces accurate results, although some laboratories have difficulty detecting resistance to carbapenems and extended-spectrum cephalosporins. This highlights the need for monitoring how well susceptibility test systems in clinical laboratories detect emerging resistance.

The impact of changing pathogens of serious infections in hospitalized patients.

New epidemiological patterns are being observed for multidrug-resistant nosocomial organisms. Current problems include the appearance of resistance determinants in organisms that are virulent enough to cause infection in patients with normal host defenses. In addition, multidrug-resistant organisms are spreading from health care to community settings, and organisms from the community are spreading to health care settings. The appearance and spread of resistance can be examined both at a molecular level and on a larger scale involving several pathways. Potential pathways within institutions include the following: introduction of new strains from outside sources (e.g., patients or health care workers from other institutions); exchange of resistance determinants via genetic mutation or transfer of genetic material; emergence or selection of resistant strains following exposure to antimicrobials; and clonal dissemination. Strategies such as multidisciplinary management of infections, appropriate infection control measures, and surveillance of resistance patterns are necessary to address the problem of resistance.

Effects of deferoxamine, a chelator of free iron, on NA(+), K(+)-ATPase activity of cortical brain cell membrane during early reperfusion after hypoxia-ischemia in newborn lambs.

Free iron chelation after hypoxia-ischemia can reduce free radical-induced damage to brain cell membranes and preserve electrical brain activity. We investigated whether chelation of free iron with deferoxamine (DFO) preserved cortical cell membrane activity of Na(+),K(+)-ATPase and electrocortical brain activity (ECBA) of newborn lambs during early reperfusion after severe hypoxia-ischemia. Hypoxia was induced in 16 lambs by decreasing the fraction of inspired oxygen to 0.07 for 30 min, followed by a 5-min period of hypotension (mean arterial blood pressure <35 mm Hg). ECBA (in microvolts) was measured using a cerebral function monitor. Immediately after hypoxia and additional ischemia, eight lambs received DFO (2.5 mg/kg, i.v.), and seven lambs received a placebo (PLAC). Two lambs underwent sham operation. One hundred eighty minutes after completion of hypoxia and ischemia, the brains were obtained and frozen. Na(+),K(+)-ATPase activity was measured in the P(2) fraction of cortical tissue. Na(+),K(+)-ATPase activity was 35.1 +/- 7.4, 42.0 +/- 7.6, and 40.7 +/- 1.4 micromol inorganic phosphate/mg protein per hour in PLAC-treated, DFO-treated, and sham-operated lambs, respectively (p < 0.05: DFO versus PLAC). ECBA was 11.2 +/- 6.1, 14.8 +/- 4.8, and 17.5+/-.0.5 microV in PLAC-treated, DFO-treated, and sham-operated lambs, respectively (p = 0.06: DFO versus PLAC). Na(+),K(+)-ATPase activity correlated with ECBA at 180 min of reperfusion (r = 0.85, p < 0.001). We conclude that Na(+),K(+)-ATPase activity of cortical brain tissue was higher in DFO-treated lambs compared with PLAC-treated animals during the early reperfusion phase after severe hypoxia-ischemia, suggesting a reduction of free radical formation by DFO. Furthermore, a positive relationship was found between Na(+),K(+)-ATPase activity and ECBA.

Effect of dexamethasone treatment on maturational changes in the NMDA receptor in sheep brain.

The objective of the present study was to examine the effect of antenatal or postnatal treatment with corticosteroids on the NMDA receptor, one of the mediators of both normal brain development and hypoxic-ischemic injury, by determining the characteristics of the receptor MK-801 binding site in untreated and corticosteroid-treated fetal and newborn lambs. (3)H-MK-801 binding was performed in cerebral cortical cell membranes from fetal sheep at 88, 120, and 136 d gestation (term = 150 d), and from 5-d-old lambs and adult ewes. Animals were randomized to receive dexamethasone [fetuses: 6 mg, i.m. every 12 hr for four doses to mother; lambs: 0.01 mg/kg (low dose) or 0.25 mg/kg (high dose) every 12 hr for four doses] or placebo. During development, B(max) (apparent number of receptors) increased, reaching a maximum in 5-d-old lambs (p < 0.05) and decreasing in the adult brain. K(d) (dissociation constant) did not change, suggesting that receptor affinity was not altered during maturation. Dexamethasone treatment had no effect on MK-801 binding in the fetus or adult, but in lambs was associated with a significant decrease in B(max) from 2.17 +/- 0.18 pmol/mg protein in placebo-treated animals to 1.65 +/- 0.8 and 1.62 +/- 0.07 pmol/mg protein in low-dose and high-dose animals, respectively. Affinity for (3)H-MK-801 decreased 20% after dexamethasone treatment in lambs only (p < 0.05). Thus, dexamethasone treatment appears to modify the NMDA receptor only during a specific period of brain development.