Metal mixtures and oral health among children and adolescents in the National Health and Nutrition Examination Survey (NHANES), 2017-2020.

INTRODUCTION: Dental caries is the most common non-communicable human disease, yet little is known about the role of environmental metals, despite teeth consisting of a hard matrix of trace elements. We conducted a cross-sectional study of associations between environmental metals and objective assessment of dental caries and subjective assessments of oral health among a representative sample of U.S. children and adolescents. METHODS: Data were from the 2017-March 2020 pre-pandemic data file of the National Health and Nutrition Examination Survey (NHANES). To account for metal mixtures, we used weighted quantile sum (WQS) regression to estimate the joint impact of multiple trace elements assessed in blood and urine with oral disease outcomes. RESULTS: The blood metal mixture index was associated with a 32% (95% CI: 1.11, 1.56) increased risk of decayed surfaces while the urine metal mixture index was associated with a 106%, RR (95% CI = 2.06 (1.58, 2.70) increased caries risk. For both blood and urine, Mercury (Hg) had the largest contribution to the mixture index followed by Lead (Pb). The WQS blood metal mixture index was also significantly associated with poorer self-rated oral health, although the magnitude of the association was not as strong as for the objective oral disease measures, RR (95% CI) = 1.04 (1.02, 1.07). DISCUSSION: Increased exposure to a metal mixture was significantly related to poorer objective and subjective oral health outcomes among U.S. children and adolescents. These are among the first findings showing that metal mixtures are a significant contributor to poor oral health.

Prenatal Pb exposure is associated with reduced abundance of beneficial gut microbial cliques in late childhood: an investigation using Microbial Co-occurrence Analysis (MiCA).

Background: Many analytical methods used in gut microbiome research focus on either single bacterial taxa or the whole microbiome, ignoring multi-bacteria relationships (microbial cliques). We present a novel analytical approach to identify multiple bacterial taxa within the gut microbiome of children at 9-11 years associated with prenatal Pb exposure. Methods: Data came from a subset of participants (n=123) in the Programming Research in Obesity, Growth, Environment and Social Stressors (PROGRESS) cohort. Pb concentrations were measured in maternal whole blood from the second and third trimesters of pregnancy. Stool samples collected at 9-11 years old underwent metagenomic sequencing to assess the gut microbiome. Using a novel analytical approach, Microbial Co-occurrence Analysis (MiCA), we paired a machine-learning algorithm with randomization-based inference to first identify microbial cliques that were predictive of prenatal Pb exposure and then estimate the association between prenatal Pb exposure and microbial clique abundance. Results: With second-trimester Pb exposure, we identified a 2-taxa microbial clique that included Bifidobacterium adolescentis and Ruminococcus callidus, and a 3-taxa clique that added Prevotella clara. Increasing second-trimester Pb exposure was associated with significantly increased odds of having the 2-taxa microbial clique below the 50th percentile relative abundance (OR=1.03,95%CI[1.01-1.05]). In an analysis of Pb concentration at or above vs. below the United States and Mexico guidelines for child Pb exposure, odds of the 2-taxa clique in low abundance were 3.36(95%CI[1.32-8.51]) and 6.11(95%CI[1.87-19.93]), respectively. Trends were similar with the 3-taxa clique but not statistically significant. Discussion: Using a novel combination of machine-learning and causal-inference, MiCA identified a significant association between second-trimester Pb exposure and reduced abundance of a probiotic microbial clique within the gut microbiome in late childhood. Pb exposure levels at the guidelines for child Pb poisoning in the United States, and Mexico are not sufficient to protect against the potential loss of probiotic benefits.

Non-linear and non-additive associations between the pregnancy metabolome and birthweight.

BACKGROUND: Birthweight is an indicator of fetal growth and environmental-related alterations of birthweight have been linked with multiple disorders and conditions progressing into adulthood. Although a few studies have assessed the association between birthweight and the totality of exogenous exposures and their downstream molecular responses in maternal urine and cord blood; no prior research has considered a) the maternal serum prenatal metabolome, which is enriched for hormones, and b) non-linear and synergistic associations among exposures. METHODS: We measured the maternal serum metabolome during pregnancy using an untargeted metabolomics approach and birthweight for gestational age (BWGA) z-score in 410 mother-child dyads enrolled in the PRogramming of Intergenerational Stress Mechanisms (PRISM) cohort. We leveraged a Bayesian factor analysis for interaction to select the most important metabolites associated with BWGA z-score and to evaluate their linear, non-linear and non-additive associations. We also assessed the primary biological functions of the identified proteins using the MetaboAnalyst, a centralized repository of curated functional information. We compared our findings with those of a traditional metabolite-wide association study (MWAS) in which metabolites are individually associated with BWGA z-score. RESULTS: Among 1110 metabolites, 46 showed evidence of U-shape associations with BWGA z-score. Most of the identified metabolites (85%) were lipids primarily enriched for pathways central to energy production, immune function, and androgen and estrogen metabolism, which are essential for pregnancy and parturition processes. Metabolites within the same class, i.e. steroids and phospholipids, showed synergistic relationships with each other. CONCLUSIONS: Our results support that the aspects of the maternal metabolome during pregnancy contribute linearly, non-linearly and synergistically to variation in newborn birthweight.

Association between prenatal immune phenotyping and cord blood leukocyte telomere length in the PRISM pregnancy cohort.

BACKGROUND: Environmental exposures including air pollutants, toxic metals, and psychosocial stress have been associated with shorter telomere length (TL) in newborns. These exposures have in turn been linked to an enhanced inflammatory immune response. Increased inflammation during pregnancy may be a central biological pathway linking environmental factors with reduced TL at birth. Approaches that more comprehensively characterize the prenatal inflammatory milieu rather than targeting specific individual cytokines in relation to newborn TL may better elucidate inflammatory mechanisms. METHODS: Analyses included 129 mother-child dyads enrolled in the PRogramming of Intergenerational Stress Mechanisms (PRISM) pregnancy cohort. We measured 92 inflammation related proteins during pregnancy in maternal serum using the Olink protein array and quantified cord blood relative leukocyte TL (rLTL) via qPCR. We leveraged a tree-based machine learning algorithm to select the most important inflammatory related proteins jointly associated with rLTL. We then evaluated the combined association between the selected proteins with rLTL using Bayesian Weighted Quantile Sum (BWQS) Regression. Analyses were adjusted for gestational week of serum collection, maternal race/ethnicity, age, and education, and fetal sex. We evaluated major biological function of the identified proteins by using the UniProtKB, a centralized repository of curated functional information. RESULTS: Three proteins were negatively and linearly associated with rLTL (CASP8 ß: -0.22 p = 0.008, BNGF ß: -0.43 p = 0.033, TRANCE ß: 0.38 p = 0.004). Results from BWQS regression showed a significant overall decrease in rLTL (ß: -0.26 95%CrI: -0.43, -0.07) per quartile increase of the mixture, with CASP8 contributing the greatest weight (CASP8 50%; BNGF 27%, and TRANCE 23%). The identified proteins were involved in the regulation of apoptotic processes and cell proliferation. CONCLUSIONS: This proteomics approach identifies novel maternal prenatal inflammatory protein biomarkers associated with shortened rLTL in newborns.

Blood lead level among Palestinian schoolchildren: a pilot study.

In Palestine, chronic exposure to lead has not been adequately addressed as a problem for children. To assess the exposure of Palestinian schoolchildren, we surveyed blood lead levels in 3 schools in Nablus city and collected demographic and clinical data. Blood samples were collected from 178 children (140 boys, 38 girls), age range 6-8 years. The overall mean blood lead level was 3.2 (SD 2.4) microg/dL, and 4.5% of children had levels above 10 microg/dL. Blood lead levels were significantly higher among children living in refugee camps near industrial/high traffic regions than among children living in residential areas of the city. Blood lead levels were positively correlated with family size (r = 0.15) and negatively correlated with household area (r = -0.18). Blood lead levels among these Palestinian schoolchildren were higher than those of other countries where leaded gasoline has been banned and seemed to be higher in more economically deprived children.

Blood lead level among Palestinian schoolchildren: a pilot study

In Palestine, chronic exposure to lead has not been adequately addressed as a problem for children. To assess the exposure of Palestinian school children, we surveyed blood lead levels in 3 schools in Nablus city and collected demographic and clinical data. Blood samples were collected from 173 children [140 boys/38 girls], age range 6-8 years. The overall mean blood lead level was 3.2 [SD 2.4] microg/dL, and 4.5% of children had levels above 10 microg/dL Blood lead levels were significantly higher among children living in refugee camps near industrial high traffic regions than among children living in residential areas of the city. Blood lead levels were positively correlated with family size [r = 0.15] and negatively correlated with household area [r =0.18]. Blood lead levels among these Palestinian schoolchildren were higher than those of other countries where leaded gasoline has been banned and seemed to be higher in more economically deprived children

Manganese exposure and cognitive deficits: a growing concern for manganese neurotoxicity.

This symposium comprised five oral presentations dealing with recent findings on Mn-related cognitive and motor changes from epidemiological studies across the life span. The first contribution highlighted the usefulness of functional neuroimaging of the central nervous system (CNS) to evaluate cognitive as well as motor deficits in Mn-exposed welders. The second dealt with results of two prospective studies in Mn-exposed workers or welders showing that after decrease of Mn exposure the outcome of reversibility in adverse CNS effects may differ for motor and cognitive function and, in addition the issue of plasma Mn as a reliable biomarker for Mn exposure in welders has been addressed. The third presentation showed a brief overview of the results of an ongoing study assessing the relationship between environmental airborne Mn exposure and neurological or neuropsychological effects in adult Ohio residents living near a Mn point source. The fourth paper focused on the association between blood Mn and neurodevelopment in early childhood which seems to be sensitive to both low and high Mn concentrations. The fifth contribution gave an overview of six studies indicating a negative impact of excess environmental Mn exposure from air and drinking water on children's cognitive performance, with special attention to hair Mn as a potential biomarker of exposure. These studies highlight a series of questions about Mn neurotoxicity with respect to cognitive processes, forms and routes of exposure, adequate biomarkers of exposure, gender differences, susceptibility and exposure limits with regard to age.

Ozone exposure, antioxidant genes, and lung function in an elderly cohort: VA normative aging study.

BACKGROUND: Ozone (O3) exposure is known to cause oxidative stress. This study investigated the acute effects of O(3) on lung function in the elderly, a suspected risk group. It then investigated whether genetic polymorphisms of antioxidant genes (heme oxygenase-1 (HMOX1) and glutathione S-transferase pi (GSTP1)) modified these associations. METHODS: 1100 elderly men from the Normative Aging Study were examined whose lung function (forced vital capacity (FVC) and forced expiratory volume in 1 second (FEV1)) was measured every 3 years from 1995 to 2005. The study genotyped the GSTP1 Ile105Val and Ala114Val polymorphisms and the (GT)n repeat polymorphism in the HMOX1 promoter, classifying repeats as short (n<25) or long (n> or =25). Ambient O(3) was measured continuously at locations in the Greater Boston area. Mixed linear models were used, adjusting for known confounders. RESULTS: A 15 ppb increase in O(3) during the previous 48 h was associated with a 1.25% decrease in FEV(1) (95% CI: -1.96% to -0.54%). This estimated effect was worsened with either the presence of a long (GT)n repeat in HMOX1 (-1.38%, 95% CI: -2.11% to -0.65%) or the presence of an allele coding for Val105 in GSTP1 (-1.69%, 95% CI: -2.63% to -0.75%). A stronger estimated effect of O(3) on FEV(1) was found in subjects carrying both the GSTP1 105Val variant and the HMOX1 long (GT)n repeat (-1.94%, 95% CI: -2.89% to -0.98%). Similar associations were also found between FVC and O(3) exposure. CONCLUSIONS: Our results suggest that O(3) has an acute effect on lung function in the elderly, and the effects may be modified by the presence of specific polymorphisms in antioxidant genes.

Association of black carbon with cognition among children in a prospective birth cohort study.

While studies show that ultrafine and fine particles can be translocated from the lungs to the central nervous system, the possible neurodegenerative effect of air pollution remains largely unexplored. The authors examined the relation between black carbon, a marker for traffic particles, and cognition among 202 Boston, Massachusetts, children (mean age = 9.7 years (standard deviation, 1.7)) in a prospective birth cohort study (1986-2001). Local black carbon levels were estimated using a validated spatiotemporal land-use regression model (mean predicted annual black carbon level, 0.56 mug/m(3) (standard deviation, 0.13)). The Wide Range Assessment of Memory and Learning and the Kaufman Brief Intelligence Test were administered for assessment of cognitive constructs. In analysis adjusting for sociodemographic factors, birth weight, blood lead level, and tobacco smoke exposure, black carbon (per interquartile-range increase) was associated with decreases in the vocabulary (-2.2, 95% confidence interval (CI): -5.5, 1.1), matrices (-4.0, 95% CI: -7.6, -0.5), and composite intelligence quotient (-3.4, 95% CI: -6.6, -0.3) scores of the Kaufman Brief Intelligence Test and with decreases on the visual subscale (-5.4, 95% CI: -8.9, -1.9) and general index (-3.9, 95% CI: -7.5, -0.3) of the Wide Range Assessment of Memory and Learning. Higher levels of black carbon predicted decreased cognitive function across assessments of verbal and nonverbal intelligence and memory constructs.

Delta-aminolevulinic acid dehydratase polymorphism and the relation between low level lead exposure and the Mini-Mental Status Examination in older men: the Normative Aging Study.

OBJECTIVE: To determine whether a polymorphism the in delta-aminolevulinic acid dehydratase (ALAD) gene modifies the neurotoxicity of lead in older adults. METHODS: The authors studied men participating in the Department of Veterans Affairs' Normative Aging Study, assessing their recent exposure to lead by measuring blood lead (n = 915) at each triennial clinic visit, and, beginning in 1991, assessing their cumulative exposure by measuring lead levels in tibia (n = 722) and patella (n = 720), using K-shell x ray fluorescence. Starting in 1993 and again at each triennial visit, the authors administered the Mini-Mental State Examination (MMSE) to assess their cognitive functioning. The relation of the lead biomarkers to MMSE score was evaluated and this association was compared among men who carried the variant allele, ALAD-2, versus men without the allele. RESULTS: Sixteen per cent of men carried the ALAD-2 allele. Median tibia and patella lead levels (first-third quartile) were 19 (13-28) and 27 (18-39) microg/g. Blood lead levels were consistent with non-occupational exposure: only 6% of men had levels > or =10 microg/dl. In multivariable adjusted analyses, higher levels of blood lead were associated with poorer performance on the MMSE. This association was most pronounced among ALAD-2 carriers, among whom a 3 microg/dl increment in blood lead (the interquartile range) was associated with a 0.26 point lower mean MMSE score (95% CI -0.54 to 0.01), compared with a 0.04 point lower score (95% CI -0.16 to 0.07) among non-carriers. The modest 0.22 point difference in these associations did not attain statistical significance, however (p(interaction) = 0.13). The associations between bone lead levels and MMSE score did not vary by ALAD-2 status. CONCLUSIONS: Although not statistically significant, these findings suggest that ALAD genotype may modify blood lead's adverse association with cognition among older men who had community exposures to lead. However, despite a relatively large sample size and the use of sensitive methods for measuring lead burden, the evidence overall was fairly weak.

Response to child abuse in the pediatric emergency department: need for continued education.

BACKGROUND: Child abuse is a leading pediatric public health problem. Pediatric emergency physicians are on the front line to identify and respond to child abuse. The physician's response to suspected child abuse cases is influenced by educational content and experience. OBJECTIVE: To determine pediatric emergency medicine Fellows' level of preparedness to respond to suspected child abuse, and to assess obstacles and attitudinal barriers to effective response. STUDY DESIGN: Self-reported written survey. METHODS: A 30-item anonymous questionnaire was mailed to 162 pediatric emergency medicine Fellows in the United States and Canada in 1995. A response rate of 77.2% (n = 125) was achieved. RESULTS: Prior to fellowship, 97.6 % of the responding Fellows reported having had some pre-fellowship instruction, including formal courses, conferences, and direct patient contact, on child abuse during medical school and residency. Whereas the majority (61.4%) received > or =10 hours of child abuse response instruction before fellowship, most (70.1 %) reported <10 hours of child abuse response instruction during their fellowship; 17.1 % reported they had no child abuse response training during their fellowship. Prior experience was also determined by reported involvement with managing child abuse cases during their medical training to date. Before fellowship, the median level of child abuse case involvement was 15 (mode 20) compared with a median of 10 cases (mode 10) reported during fellowship training. More than one third (48/125) noted the lack of organized lectures or conferences on child abuse available during fellowship training. While the majority (107/125) reported the opportunity to do a rotation in child protection/ abuse during fellowship training; the rotation was required for only 32.7% (35/107); among Fellows who reported an elective rotation in child abuse (72/107), one half (36/72) reported that they were unlikely to participate. Factors most frequently selected as perceived obstacles to responding to child abuse included lack of formal training on the topic (33.6%), lack of experience handling these cases (37.6%), personal discomfort (41.6%), and perceived lack of response by local protective services (42.4%) and police (25.6%). Sixty percent (75/125) had a protocol in the pediatric emergency department to facilitate response to child abuse. Many felt ill-prepared to interact with Child Protective Services (52.8%) and police (42.4 %). Prior experience managing child abuse cases and educational content during fellowship training were independently predictive of frequency of identifying cases of child abuse during fellowship. CONCLUSIONS: Significant training gaps in postgraduate medical education on response to child abuse for the pediatric emergency subspecialist are identified, as well as perceived obstacles to effective response, which may have implications for designing future curricula.

Methemoglobinemia: etiology, pharmacology, and clinical management.

Methemoglobin (MHb) may arise from a variety of etiologies including genetic, dietary, idiopathic, and toxicologic sources. Symptoms vary from mild headache to coma/death and may not correlate with measured MHb concentrations. Toxin-induced MHb may be complicated by the drug's effect on other organ systems such as the liver or lungs. The existence of underlying heart, lung, or blood disease may exacerbate the toxicity of MHb. The diagnosis may be complicated by the effect of MHb on arterial blood gas and pulse oximeter oxygen saturation results. In addition, other dyshemoglobins may be confused with MHb. Treatment with methylene blue can be complicated by the presence of underlying enzyme deficiencies, including glucose-6-phosphate dehydrogenase deficiency. Experimental antidotes for MHb may provide alternative treatments in the future, but require further study.

Association between iron deficiency and low-level lead poisoning in an urban primary care clinic.

OBJECTIVES: The purpose of this study was to examine the association between iron deficiency and low-level lead poisoning. METHODS: Data were collected in an urban primary care clinic from 3650 children aged 9 to 48 months. Iron deficiency was defined as a red cell mean corpuscular volume (MCV) of less than 70 fL and a red cell distribution width (RDW) of more than 14.5 in children younger than 2 years, and an MCV of less than 73 fL and RDW of more than 14.5 in those 2 years or older. RESULTS: After adjustment for age, hemoglobin concentration, and insurance status, the odds ratios for iron deficiency predicting blood lead levels greater than or equal to 5 micrograms/dL and greater than or equal to 10 micrograms/dL were 1.63 (95% confidence interval [CI] = 1.29, 2.04) and 1.44 (95% CI = 1.004, 2.05). CONCLUSIONS: Iron deficiency is significantly associated with low-level lead poisoning in children aged 9 to 48 months.

The role of iron therapy in childhood plumbism.

Iron deficiency and lead poisoning share common environmental risk factors and both are causes of neurocognitive toxicity. Despite their links epidemiologically, little is known of the effects of iron supplements on lead kinetics and toxicity. Nevertheless, iron is routinely prescribed in children with lead poisoning. Most of the existing data focus on the effects of preexisting iron deficiency on lead absorption. Animal studies demonstrate that iron-deficient animals have increased lead absorption. Lead-poisoned iron-deficient animals treated with iron supplements have demonstrated decreased lead excretion, a factor that might exacerbate lead toxicity while mitigating the effects of iron deficiency. Iron supplements given to children with iron deficiency and lead poisoning have been demonstrated to improve developmental assessment scores, an effect that is independent of blood lead concentration, suggesting that it is solely due to reversal of iron deficiency. Improvements in developmental assessment scores and decreases in blood lead in iron-replete children with lead poisoning secondary to iron supplements have not been demonstrated in clinical studies. Given these factors, the use of iron supplements in lead poisoning should be individualized, and the supplements should be provided only to patients who are iron deficient or who continue to live in lead-exposed housing.

Effect of metoclopramide dose on preventing emesis after oral administration of N-acetylcysteine for acetaminophen overdose.

OBJECTIVE: To determine the effect of the metoclopramide dose on the prevention of vomiting of N-acetylcysteine in acetaminophen overdose. METHODS: Patients with acetaminophen ingestions receiving metoclopramide prior to emergency department administration of N-acetylcysteine were included. Emergency Department and poison center records were reviewed for administration of metoclopramide pre-N-acetylcysteine and incidence of subsequent vomiting. The treatment group was defined as patients receiving high-dose metoclopramide (20-50 mg intravenously) prior to the loading dose of N-acetylcysteine. Controls were patients receiving standard-dose (< 20 mg intravenously) metoclopramide prior to loading dose of N-acetylcysteine. Outcome was vomiting within 60 minutes of N-acetylcysteine administration. RESULTS: Twelve of 19 patients (63%) receiving standard-dose metoclopramide vomited N-acetylcysteine. Only 5 of 23 patients (22%) receiving high-dose metoclopramide vomited N-acetylcysteine (crude odds ratio: 6.2; 95% CI [1.3-30.3]). After controlling for confounding in the logistic regression model, the effect of high-dose metoclopramide in preventing vomiting of N-acetylcysteine remained significant (adjusted odds ratio: 17.0; 95% CI [2.6-110.0]). CONCLUSION: This study supports the efficacy of high-dose metoclopramide to prevent emesis after the oral loading dose of N-acetylcysteine.

Effect of iron deficiency anemia on lead distribution after intravenous dosing in rats.

OBJECTIVE: To determine the effect of iron deficiency anemia on blood and tissue lead distribution. METHODS: 24 weanling rats were divided into 2 groups. One group received an iron replete diet (200 ppm); the other received a low iron diet (20 ppm). After 24 days, each group was further subdivided into two doses of lead (5 mg/kg and 10 mg/kg) which was administered intravenously. Rats were continued on their respective diets for 7 days post-lead injection to allow tissue distribution, then sacrificed and blood and tissue lead concentration measured. RESULTS: Prior to lead administration, baseline blood lead concentrations were not significantly different between groups. At sacrifice, whole blood lead levels were significantly higher in iron deficient animals than in iron replete at both 5 and 10 mg/kg administered lead. Iron deficient animals had comparable lead concentrations to iron replete animals in brain, kidney and liver. Femur lead concentrations were higher at 10 mg/kg administered lead. CONCLUSION: Iron deficiency alters lead distribution such as that increased lead is found in blood for a given exposure.

Baclofen overdose: drug experimentation in a group of adolescents.

BACKGROUND: Baclofen, a lipophilic analog of gamma-aminobutyric acid, is clinically used to control spasticity. We report a mass exposure to baclofen in adolescents seeking intoxication; toxicokinetic data are included. CASE SERIES: A group of adolescents became symptomatic after ingesting 3 to 30 20-mg tablets of baclofen during a party at a suburban Boys' Club. Several children were noted to be very lethargic by chaperones, ingestion was suspected, and paramedics were called. Some white tablets were found in a couch at the site of the party. The Massachusetts Poison Control Center was called, and the tablets were identified as baclofen (20 mg). Fourteen patients were taken to local hospitals; 9 required intubation. Eight adolescents were transferred to our institution. In these 8 patients, symptoms were noted within 1 to 2 hours after overdose. The most common clinical findings included coma (7), hypothermia (6), bradycardia (5), hypertension (4), and hyporeflexia (8). Mean length of mechanical ventilation was 40 hours. Three patients had unifocal premature ventricular contractions. Two patients had tonic-clonic seizures. A single dose of activated charcoal was given to all patients. Drugs administered included nifedipine (1), flumazenil (1), naloxone (1), lorazepam (2), and phosphenytion (2). All patients recovered and were discharged home within 5 days of ingestion. Serial serum baclofen levels were obtained in all intubated patients (range, 0.049 to 6.0; normal, 0.08 to .40 microgram/mL). Levels obtained 14 hours after ingestion showed a linear correlation with length of mechanical ventilation (R2 = 0.9863). Persistent symptoms were noted in some patients, despite nondetectable baclofen levels. Toxicologic screening for drugs of abuse was negative except in 2 patients with ethanol levels, both < 5 mg/dL. CONCLUSION: Baclofen overdose may result in coma, apnea, autonomic disturbances, cardiac conduction abnormalities, and seizures. Levels obtained shortly after overdose correlate with length of mechanical ventilation.

N-acetylcysteine reduces methemoglobin in an in-vitro model of glucose-6-phosphate dehydrogenase deficiency.

OBJECTIVE: To determine whether N-acetylcysteine (NAC) reduces methemoglobin (MHB) in an in-vitro model of glucose-6-phosphate dehydrogenase (G6PD) deficiency, given that methylene blue is an ineffective MHB antidote in G6PD deficiency. METHODS: Five volunteers donated blood, which was divided equally into 2 test tubes, centrifuged, and washed with Tris-Mopps buffer (pH 7.4, 15 mmol/L glucose). Both tubes were incubated with epiandrosterone (EA) (400 micromol), a specific inhibitor of G6PD. After 75 microL of 0.18 mol hydroxylamine (HA) was added to induce MHB formation, 150 microL of NAC (20 mg/mL) was added to tube 1 and 150 microL of phosphate-buffered saline (PBS) was added to tube 2 as a volume control. Serial MHB levels are reported as a percentage of total hemoglobin (Hb). G6PD activity was measured at baseline, 15 minutes after EA, and at 5 hours. RESULTS: Mean G6PD activity at baseline was 9.2+/-2.9 U/g Hb (normal >4.6 U/g Hb); 15 minutes after EA was 3.0+/-1.0 U/g Hb; and at experiment's end was 2.3+/-0.7 U/g Hb. The mean (+/-SD) areas under the concentration-time curves (AUCs) of NAC-EA-HA and PBS-EA-HA samples were compared using an unpaired t-test and were significantly different: PBS-EA-HA, 20,400+/-1,100 % min, vs NAC-EA-HA, 10,400+/-1,000 % min, respectively (p < 0.05). CONCLUSION: In this in-vitro model of G6PD deficiency, NAC efficiently reduced MHB.

Pulsus paradoxus: an objective measure of severity in croup.

We used a noninvasive monitor of arterial pressure to determine the utility of pulsus paradoxus (PP) as an objective severity measure in croup. We performed a prospective, blinded comparison of PP in children with croup versus healthy control subjects, analyzed the relationship between PP and Westley croup score (WCS), and observed the effect of racemic epinephrine (RE) on PP and WCS in a subgroup of patients with severe croup. The PP and WCS were measured at presentation and in severe patients after treatment with RE. Mean PP was 6.1 +/- 1.8 (SD) mm Hg (n = 29) in control subjects compared with a mean of 17.8 +/- 11.2 (SD) mm Hg (n = 28) in patients with croup (p < 0.00001). There was significant concordance between baseline WCS and PP (Spearman's rho: 0.68; p = 0.0001). The mean decrease in PP after RE was 7.5 +/- 11.8 (SD) mm Hg (p = 0.05; n = 12). The magnitude of decrease in PP after RE has significant concordance with the concurrent decrease in WCS (Spearman's rho: 0.73; p < 0.007). PP is elevated in children with croup, and the magnitude of elevation correlates with severity as measured by the WCS. PP may have utility as a research tool to objectively measure the severity of upper airway obstruction in croup.