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.

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.

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.

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 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.

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.

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.

Continuous, noninvasive measurement of pulsus paradoxus in patients with acute asthma.

OBJECTIVE: To evaluate a continuous, noninvasive measurement technique for pulsus paradoxus (PP) as an objective asthma severity indicator. DESIGN: Prospective, masked assessment of the relationship between PP, peak expiratory flow rate, oxygen saturation, clinical scoring, and admission decisions. SETTING: An urban pediatric emergency department. PATIENTS: Children with acute asthma. INTERVENTIONS: Standardized treatment per National Heart, Lung, and Blood Institute guidelines. MAIN OUTCOME MEASURES: Peak expiratory flow rate, oxygen saturation, pulmonary index score, and masked disposition decision. RESULTS: Significant positive correlations existed between PP and the pulmonary index score at the initial evaluation (r = 0.44; P < .001) and after 30 minutes (r = 0.51; P < .001) and 60 minutes (r = 0.45; P < .001). Significant negative correlations existed between PP and the percent predicted peak expiratory flow rate (r = -0.31; P = .01) and the oxygen saturation (r = -0.30; P = .02). The mean PP was significantly greater in patients who were admitted for further treatment at all time points (P = .003 or P = .002). At 30 minutes after presentation, a PP greater than 15 mm Hg predicted admission for further treatment or relapse; the sensitivity was 0.42, the specificity was 0.89, and the likelihood ratio was 3.86. CONCLUSIONS: Our measurement technique for PP is a useful objective indicator of the severity of asthma. Pulsus paradoxus correlates with clinical score, peak expiratory flow rate, and oxygen saturation. Furthermore, an elevated PP is associated with the decision to admit a patient for further treatment. These results suggest that this technique may represent a useful research tool for the assessment of acute, severe asthma. Further development of the technology may allow for a clinical application.

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.

Evaluation of pre- and posttreatment pulse oximetry in acute childhood asthma.

OBJECTIVE: To evaluate the utility of pre- and posttreatment O2 saturation (SpO2) for prediction of admission or relapse after ED release in acute asthma exacerbations using a standardized treatment protocol. DESIGN: A prospective, double-blind, observational study was performed at a pediatric ED. Children with acute asthma were enrolled upon ED presentation. SpO2 was measured prior to treatment and after disposition decision. Two experienced physicians determined disposition based on history and physical examination alone, while blinded to SpO2. Relapse of released patients was determined by telephone follow-up. RESULTS: A pretreatment room-air SpO2 of < or = 91% had a sensitivity of 0.24, a specificity of 0.86, and a likelihood ratio of 1.77 to predict admission/relapse. A posttreatment room-air SpO2 of < or = 91% had a sensitivity of 0.34, a specificity of 0.98, and a likelihood ratio of 16.43 to predict admission/relapse. CONCLUSIONS: As opposed to some previous studies, this study found pretreatment SpO2 to be a relatively poor predictor of admission. A posttreatment SpO2 of < or = 91% occurred in a minority (32%) of patients, but increased the odds of admission 16-fold and may be used as an adjunct to objectively confirm the need for admission.

Continuous noninvasive determination of pulsus paradoxus: a pilot study.

OBJECTIVE: To evaluate two methods of continuous, noninvasive monitoring of pulsus paradoxus (PP). METHODS: A single-subject, nonblind assessment was conducted of the ability of noninvasive monitoring techniques to measure experimentally induced PP. Variable degrees of PP were induced in a healthy adult breathing through a one-way valve to which a series of external airway resistances were added. Intra-arterial pressure (IAP), finger arterial blood pressure (FINAP), pulse oximeter pulse waveform, and chest wall motion were continuously recorded. For each resistance, PP was calculated from the IAP (PPIAP) and the FINAP (PPFINAP) recordings. PP was measured manually (PPmanual) in the opposite arm. The percentage pulse waveform decrease on inspiration (%PWDpleth) was derived from the oximeter pulse waveform. These measurements were compared with the PPIAP. Bias was assessed as the mean difference between PP measures. RESULTS: PPFINAP was highly correlated with PPIAP (r = 0.96; 95% CI 0.93 to 0.98; p < 0.0001). There was a weak correlation between PPmanual and PPIAP (r = 0.27; 95% CI -0.05 to 0.55; p = 0.0963). The %PWDpleth correlated with PPIAP (r = 0.59, 95% CI 0.32 to 0.78; p = 0.0002). Bias was -1.515 +/- 5.6 mm Hg between PPIAP and PPFINAP; and -4.508 +/- 23.4 mm Hg between PPIAP and PPmanual. CONCLUSION: An accurate and continuous PP can be measured noninvasively using a FINAP monitor. This method has much better agreement with IAP measurements than do manual measurements. The qualitative information provided by the oximeter pulse waveform is less accurate than that provided by the FINAP monitor, but is a potentially useful screening tool for detection of significant PP.

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.

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.

Response to battered mothers in the pediatric emergency department: a call for an interdisciplinary approach to family violence.

BACKGROUND: Child abuse and wife abuse are linked. Studies indicate 30% to 59% of mothers of children reported for child abuse also are battered. In homes where domestic violence occurs, the children are at increased risk of physical abuse or neglect. Children who witness battering of their mothers are at risk for psychosocial sequelae including developmental delays and posttraumatic stress disorder. OBJECTIVE: To determine pediatric emergency medicine fellows' level of preparedness to respond to battered mothers, and to assess obstacles and attitudinal barriers to their 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: Before fellowship, 97.6% of respondents had training (including formal courses, conferences, and direct patient contact) on child abuse/neglect although only 29.6% received similar instruction on woman battering. There was a marked disparity between patient contact experience for child abuse/neglect and woman battering throughout training. Before fellowship, 89/122 (73%) reported direct involvement in at least 10 cases of child abuse/neglect. Seventy-one (57.3%) of 124 fellows had not handled any cases of woman battering before fellowship; 106/124 (85.5%) had been directly involved in fewer than 10 cases. During fellowship 81 (67.5%) of 120 respondents had been involved in at least 10 cases of child abuse/neglect and 46/120 (38.3%) had handled at least 20 cases. In contrast, 72 (73.5%) of the 98 responding fellows had not handled any cases of woman battering during fellowship. Furthermore, 86/100 fellows reported no formal training on woman battering in their fellowship curricula. Only 5/118 (4.2%) reported having protocols in place for responding to battered women in the pediatric emergency department. Items most frequently selected from a list of potential obstacles to responding to battered women included: lack of a protocol (82/113), lack of formal training in the field (103/118), and lack of experience with woman battering cases (100/117). The majority, 75/118 (63.6%), believed that responding to battered mothers did not belong in the preview of pediatrics. Potential attitudinal barriers confirmed with the greatest frequency included: frustration that nothing could be done and lack of time to respond appropriately to battered mothers in the pediatric emergency department. CONCLUSIONS: Battered mothers are rarely identified in the pediatric emergency department even though the physicians report handling a significant number of child abuse/neglect cases. Education on domestic violence, including the implications of woman battering for childrens' health, should be incorporated in the training curricula of pediatric emergency department physicians to raise awareness of the need to explore for the presence of concurrent abuse in both children and their mothers. Identifying battered women through their children will impact greatly on the welfare of both mother and child.

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.

Use of infrared thermometry to measure lavage and intravenous fluid temperature.

A study was conducted to determine the accuracy of tympanic thermometers for measuring the temperature of warmed fluids in fluid bags and in tubing at the delivery site (ie, beside the intravenous [IV] catheter). One-liter 0.9% saline bags were warmed in a microwave oven. A thermocouple electronic temperature probe was then used to measure the reference temperature. The probe was inserted into each bag and bathed in the fluid. Temperature changes were recorded simultaneously over a 20-minute period using the probe and a First Temp Tympanic Thermometer (Intelligent Medical Systems, Inc, Carlsbad, CA). The warmed fluid was then allowed to run through microdrip IV tubing. Temperature of the effluent was measured in the tubing using the tympanic thermometer externally and the probe internally at the same point. The two measures were compared using linear regression and Student's t tests. Overall, the correlation between the two probes was r = 0.99 for both the fluid bags and the IV tubing. The overall mean differences were small, 0.7 degrees C and 1.2 degrees C for the bags and tubing, respectively, but they were statistically different (P > .05). Data were analyzed in three temperature ranges: < 36 degrees C, 36 degrees C to 41 degrees C, and 41 degrees C. Again, small differences were found on the order of 1 degree C. It was concluded that infrared thermometry is an accurate method for measuring the initial and delivery temperature of warmed fluids. Although tympanic thermometer measurements were statistically different from reference readings in certain temperature ranges, these differences were small and not clinically significant.(ABSTRACT TRUNCATED AT 250 WORDS)

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.

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.

Hemolysis after acetaminophen overdose in a patient with glucose-6-phosphate dehydrogenase deficiency.

CASE REPORT: A sixteen year-old-male with a history of glucose-6-phosphate dehydrogenase deficiency ingested an unknown amount of acetaminophen and presented to an emergency department 7.5 h later. He was afebrile. His serum acetaminophen level was 184 micrograms/mL, and his urine toxicologic screen was otherwise negative. Vomiting led to enrollment in a experimental protocol of intravenous N-acetylcysteine. He developed no evidence of subsequent chemical hepatitis but did develop a significant Coomb's negative hemolytic anemia. Hemoglobin on presentation was 14 g/dL and reached a nadir of 9.4 g/dL on admission day 4. CONCLUSION: Patients with glucose-6-phosphate dehydrogenase deficiency who overdose with acetaminophen should be monitored for the possible development of subsequent drug-induced hemolysis.