Ultra-high-field (9.4 T) MRI Analysis of Contrast Agent Transport Across the Blood-Perilymph Barrier and Intrastrial Fluid-Blood Barrier in the Mouse Inner Ear.

HYPOTHESIS: Effective paramagnetic contrast agent for the penetration of the perilymphatic spaces of the scala tympani, scala vestibuli, and scala media of the mouse inner ear can be determined using intravenous injection of various gadolinium (Gd) complexes and ultra-high-field magnetic resonance imaging (MRI) at 9.4 Tesla. BACKGROUND: A number of contrast agents have been explored in experimental high-field MRI to determine the most effective Gd complex for ideal signal-to-noise ratio and maximal visualization of the in vivo mammalian inner ear in analyzing the temporal and spatial parameters involved in drug penetration of the blood-perilymph barrier and intrastrial fluid-blood barrier in the mouse model using MRI. METHODS: Gadoteric acid (Dotarem), Gadobutrol (Gadovist), Gadodiamide (Omniscan), Gadopent acid (Magnevist), and Mangafodipir (Teslascan) were administered intravenously using the tail vein of 60 Balb/C mice. High-resolution T1 images of drug penetration were acquired with a horizontal 9.4 T Agilent magnet after intravenously injection. Signal intensity was used as a metric of temporal and spatial parameters of drug delivery and penetration of the perilymphatic and endolymphatic spaces. RESULTS: ANOVA analysis of the area under the curve of intensity enhancement in perilymph revealed a significant difference (p < 0.05) in the scalae uptake using different contrast agents (F (3,25) = 3.54, p = 0.029). The Gadoteric acid complex Dotarem was found to be the most effective Gd compound in terms of rapid, morphological enhancement for analysis of the temporal, and spatial distribution in the perilymphatic space of the inner ear. CONCLUSION: Gadoteric acid (Dotarem) demonstrated efficacy as a contrast agent for enhanced visualization of the perilymphatic spaces of the inner ear labyrinthine in the mouse, including the scala tympani and scala vestibuli of the cochlea, and the semicircular canals of the vestibular apparatus. These findings may inform the clinical application of Gd compounds in patients with inner ear fluid disorders and vertigo.

Middle Ear Function and Pathophysiology in Andean Children Living at High Altitudes.

Counter, S. Allen, Leo H. Buchanan, Fernando Ortega, Anthony B. Jacobs, and Göran Laurell. Middle ear function and pathophysiology in Andean children living at high altitudes. High Alt Med Biol. 18:163-170, 2017.-The extent of altitude-related middle ear disorders in children native to high altitudes is unclear. This study examined middle ear pathophysiology in two groups of children living in high-altitude Ecuadorian Andean communities by investigating middle ear pressure (MEP), tympanic membrane compliance (TMC), and ear canal volume (ECV) using tympanometry, and by otological examination. Altitude I Group lived at 2850 m, and Altitude II Group resided at around 4000 m. The two high-altitude groups were compared with a reference group of children residing at sea level. Mean MEP was -3.6 daPa (SD: 39.2), 3.5 daPa (SD: 28.7), and 1.3 daPa (SD: 13.6) for Altitude I Group, Altitude II Group, and the Sea Level Group, respectively. The MEP was not significantly different among the three groups. Mean TMC was 0.63 cm3 (SD: 0.51), 0.60 cm3 (SD: 0.43), and 0.60 cm3 (SD: 0.24) for Altitude I Group, Altitude II Group, and the Sea Level Group, respectively. The TMC was not significantly different among the three groups. Mean ECV was 1.1 (SD: 0.26), 1.2 (SD: 0.26), and 1.0 (SD: 0.23) for Altitude I Group, Altitude II Group, and the Sea Level Group, respectively. The difference in ECV between Altitude I Group and Altitude II Group was significant (p = 0.043), as was the difference between Altitude II Group and the Sea Level Group (p = 0.001). ECV did not differ significantly between Altitude I Group and the Sea Level Group. Otological examination revealed a low incidence of ear canal and middle ear pathology. In conclusion, tympanometric and otological findings did not reveal a high incidence of middle ear pathophysiology in children living at altitudes as high as around 4000 m.

Assessment of the Brainstem-Mediated Stapedius Muscle Reflex in Andean Children Living at High Altitudes.

Counter, S. Allen, Leo H. Buchanan, Fernando Ortega, Anthony B. Jacobs, and Göran Laurell. Assessment of the brainstem-mediated stapedius muscle reflex in Andean children living at high altitudes. High Alt Med Biol. 18:37-45, 2017.-This study examined the physiological thresholds, amplitude growth, and contraction duration of the acoustic stapedius reflex (ASR) in Andean children aged 2-17 years living at altitudes of 2850 m (Altitude I Group) and 3973 m (Altitude II Group) as part of a general medical assessment of the health status of the children. The brainstem-mediated ASR reveals the integrity of the neuronal components of the auditory reflex arc, including the cochlea receptors, eight cranial nerves, and brainstem neural projections to the cochlear nuclei, bilateral superior olivary nuclei, facial nerve nuclei, and facial nerve and its stapedius branch. Uncrossed (ipsilateral) and crossed (contralateral) ASR thresholds (ASRT), ASR amplitude growth (ASRG) function, and ASR muscle contraction duration (decay/fatigue) (ASRD) were measured noninvasively with 500, 1000 Hz and broadband (bandwidth = 125-4000 Hz) noise stimulus activators using a middle ear immittance system. Oxygen saturation (SaO2) level and heart rate were measured in a subsample of the study group. Statistical analyses revealed that the Altitude I and Altitude II groups had ASRT, ASRG function, and ASRD rates comparable to children at sea level and that the two groups were not significantly different for any of the ASR measures. No significant association was found between SaO2 or heart rate and ASRT, growth, and muscle fatigue rate. In conclusion, the assessment of the ASR in children in the high-altitude groups revealed normal function. Furthermore, the results indicate no adverse oto-physiological effects of altitude on the brainstem-mediated ASR at elevations between 2850 and 4000 m and suggest normal middle ear and auditory brainstem function.

Experimental Fusion of Contrast Enhanced High-Field Magnetic Resonance Imaging and High-Resolution Micro-Computed Tomography in Imaging the Mouse Inner Ear.

OBJECTIVE: Imaging cochlear, vestibular, and 8th cranial nerve abnormalities remains a challenge. In this study, the membranous and osseous labyrinths of the wild type mouse inner ear were examined using volumetric data from ultra high-field magnetic resonance imaging (MRI) with gadolinium contrast at 9.4 Tesla and high-resolution micro-computed tomography (µCT) to visualize the scalae and vestibular apparatus, and to establish imaging protocols and parameters for comparative analysis of the normal and mutant mouse inner ear. METHODS: For in vivo MRI acquisition, animals were placed in a Milleped coil situated in the isocenter of a horizontal 9.4 T Varian magnet. For µCT examination, cone beam scans were performed ex vivo following MRI using the µCT component of a nanoScan PET/CT in vivo scanner. RESULTS: The fusion of Gd enhanced high field MRI and high-resolution µCT scans revealed the dynamic membranous labyrinth of the perilymphatic fluid filled scala tympani and scala vestibule of the cochlea, and semicircular canals of the vestibular apparatus, within the µCT visualized contours of the contiguous osseous labyrinth. The ex vivo µCT segmentation revealed the surface contours and structural morphology of each cochlea turn and the semicircular canals in 3 planes. CONCLUSIONS: The fusion of ultra high-field MRI and high-resolution µCT imaging techniques were complementary, and provided high-resolution dynamic and static visualization of the complex morphological features of the normal mouse inner ear structures, which may offer a valuable approach for the investigation of cochlear and vestibular abnormalities that are associated with birth defects related to genetic inner ear disorders in humans.

Lead levels in the breast milk of nursing andean mothers living in a lead-contaminated environment.

Concentrations of lead (Pb) in breast milk (PbM) and blood (PbB) were measured in a current cohort of lactating mothers living in Andean communities where women of childbearing age engage in the occupational use of Pb, and compared to results obtained in earlier studies. Mean PbM concentration in the current group of breastfeeding mothers tested in 2012/2013 was 3.73 µg/L (SD: 7.3; range: 0.049-28.04), and significantly lower than the 9.83 µg/L (SD: 12.75; range: 0.2-49) previously observed in breastfeeding mothers in the study area from 1999 to 2007. Breastfeeding women in the current cohort showed an average PbM/PbB ratio of 3.6%, which is in agreement with other studies. The mean PbB level obtained for the current cohort was 7.8 µg/dl (SD: 5.2; range: 1.4-21), and significantly lower than the mean PbB level of 20.8 µg/dl (SD: 16.4; range: 4-73) obtained for the comparison group of breastfeeding mothers tested between 1999 and 2007. A correlation of .687 between paired PbM and maternal PbB was found, indicating that maternal PbB level is a significant predictor of PbM. Current PbM levels remain higher than international averages, but indicate that maternal Pb exposure has declined over time in the environmentally Pb-contaminated study area. The current reduction in Pb in milk and blood of breastfeeding mothers may be due to adherence to a Pb-exposure education and prevention program initiated by the authors in the study area years earlier, as well as recent improvements in local health care delivery.

Magnetic resonance imaging of the middle and inner ear after intratympanic injection of a gadolinium-containing gel.

OBJECTIVE: To investigate the distribution and elimination of a gadolinium containing high viscosity formulation of sodium hyaluronan (HYA gel) after injection to the middle ear. MATERIALS AND METHODS: The T1 contrast agent gadolinium-diethylenetriamine pentaacetic acid-bis methylamine (Gd-DTPA-BMA) was added to HYA gel and delivered to the middle ear of 13 albino guinea pigs by 3 different ways of injection. Magnetic resonance imaging was performed with a 4.7 T MRI system using a T1-weighted 3-dimentional rapid acquisition with relaxation enhancement sequence. RESULTS: An injection technique where the Gd-DTPA-BMA-containing HYA gel was delivered to the middle ear through a percutaneous injection through the auditory bulla after a small incision had been made in the tympanic membrane gave the best filling of the middle ear, covering the cochlea and the region of the round window niche for 24 hours in a majority of the ears studied. Ears injected without an incision in the tympanic membrane showed an immediate uptake of Gd-DTPA-BMA in the inner ear as a sign of rupture of the round window membrane. CONCLUSION: A percutaneous injection of a HYA gel into the tympanic bulla is distributed in a predictable way and gives a good filling of the middle ear cavity. The HYA gel remains in close vicinity to the RWM for more than 24 hours. Injection should be performed after an incision of the tympanic membrane has been made to prevent rupture of the round window membrane.

Tracking blood lead and zinc protoporphyrin levels in Andean adults working in a lead contaminated environment.

The purpose of this study was to investigate current blood lead (PbB) and zinc protoporphyrin (ZPP) levels in adults presently living in environmentally Pb-contaminated Andean communities, and to compare the findings with the PbB and ZPP levels of Pb-exposed adult cohorts from the same study area tested between 1996 and 2007. Blood samples from 39 adults were measured for PbB and ZPP concentrations. The current mean PbB level (22.7 µg/dl) was significantly lower than the mean (37.9 µg/dl) of the initial 1996 cohort. PbB levels for the 1997, 1998, 2003, and 2006 cohorts were also significantly lower than the levels for the 1996 group. Elevated ZPP/heme ratios of 103.3, 128.4, and 134.2 µmol/mol were not significantly different for the 2006, 2007, and 2012 groups, indicating chronic Pb exposure. While ZPP levels of Andean Ecuadorian Pb-glazing workers have remained elevated, PbB levels declined. Lead exposure of the workers needs to be continually monitored.

MRI evidence of endolymphatic impermeability to the gadolinium molecule in the in vivo mouse inner ear at 9.4 tesla.

OBJECTIVE: Previous in vivo experimental magnetic resonance imaging (MRI) investigations of the mammalian inner ear at 4.7 Tesla have indicated that intravenously injected gadolinium (Gd) penetrates the perilymphatic labyrinth, but not the endolymphatic membranous labyrinth. In the present study, high field MRI at 9.4T was used to visualize the in vivo mouse vestibulo-cochlea system, and to determine whether the endolymphatic system is permeable to a Gd complex. METHODS: A 9.4 T Varian magnet equipped with a 12 cm inner diameter gradient system with maximum gradient strength of 600 mT/m, a millipede coil (Varian design) and a Gd contrast agent were used for image acquisition in the normal C57 BL-6 mouse. RESULTS: High-resolution 2D and 3D images of the mouse cochlea were acquired within 80 minutes following intravenous injection of Gd. Gd initially permeated the perilymphatic scala tympani and scala vestibuli, and permitted visualization of both cochlear turns from base to apex. The superior, inferior and lateral semicircular canals were subsequently visualized in 3 planes. The membranous endolymphatic labyrinth was impermeable to intravenously injected Gd, and thus showed no apparent uptake of Gd at 9.4T. CONCLUSION: The 9.4T field strength MRI permitted acquisition of high resolution images of anatomical and physiological features of the normal, wild type mouse perilymphatic inner ear in vivo, and provided further evidence that the endolymphatic system is impermeable to intravenously injected Gd.

Brainstem auditory evoked responses in children living at high altitude in the andes mountains.

OBJECTIVES: This neurophysiological study compared brainstem auditory evoked responses (BAER) in children living at high elevations (2800 to 3000 meters) in the Andes Mountains of Ecuador with a reference group of children living at sea level in the U.S. METHODS: BAER absolute latencies of waves I through V; interpeak latencies I-III, III-V, and I-V; amplitudes of waves I and V; and the V/I amplitude ratio were measured by scalp electrodes at acoustic click stimulus rates of 10 and 50 pulses per second (pps). RESULTS: Statistical analysis showed that the high-altitude group had significantly longer absolute and interpeak BAER latencies than the sea-level reference group at both the 10 and 50 pps stimulus rates for most wave peaks. The amplitudes of waves I and V were significantly reduced for the high-altitude group at 10 and 50 pps, suggesting blood O2 saturation effects. CONCLUSIONS: The BAER of children in the high-altitude group suggested physiological anomalies in auditory neural conduction and summation compared with the sea-level group. The results further suggest that small physiological effects of altitude on BAER, especially at elevations near 3000 meters and higher, should be taken into consideration in the evaluation of brainstem auditory function.

Declining blood lead and zinc protoporphyrin levels in Ecuadorian Andean children.

OBJECTIVES: To investigate current lead (Pb) exposure in children living in Andean Ecuadorian communities. Blood Pb (PbB) and zinc protoporphyrin (ZPP) levels were used respectively as biomarkers of acute and chronic Pb poisoning. The current PbB-ZPP levels were compared with previous pediatric PbB-ZPP levels recorded over years in the study area. DESIGN AND METHODS: Samples of whole blood were collected from 22 Andean children of Quechua and Mestizo backgrounds and measured for PbB concentrations by graphite furnace atomic absorption spectroscopy. ZPP/heme ratio and ZPP whole blood (ZPP WB) levels were measured with a hematofluorometer. RESULTS: The mean PbB level for children in the current study group was 14.5 µg/dL, which was significantly lower than the mean PbB level of 41.1 µg/dL found in the same study area in the 1996-2000 test period, and lower than the 22.2 µg/dL mean level found in the 2003-2007 period. The current mean ZPP/heme ratio was 102.1 µmol/mol, and the mean ZPP WB level was 46.3 µg/dL, both lower than values previously found in children in the study area. CONCLUSION: While the current pediatric PbB-ZPP levels in the study area remain elevated in some children, the overall levels indicate a decline relative to levels observed in the same Pb-contaminated area in the period between 1996 and 2007. The elevated ZPP levels suggest a history of chronic Pb exposure, and potential iron deficiency in some children. The overall reduction in PbB-ZPP levels suggests a positive outcome of a Pb-exposure education and prevention program, and the therapeutic intervention of succimer chelation therapy.

Association of hemoglobin levels and brainstem auditory evoked responses in lead-exposed children.

OBJECTIVES: Decreased blood hemoglobin (HbB) levels and anemia have been associated with abnormal brainstem auditory evoked responses (BAER). Lead (Pb) exposure has also been associated with anemia and aberrant BAER. This study investigated the relationship between HbB level and BAER wave latency and amplitude in Pb-exposed Andean children. DESIGN AND METHODS: Sixty-six children aged 2 to 15 years (mean age: 9.1; SD: 3.3) living in Pb-contaminated villages were screened for HbB levels, blood Pb (PbB) levels and BAER latencies and amplitudes. RESULTS: The mean HbB level observed in the study group was 11.9 g/dL (SD: 1.4; range: 8.6-14.8 g/dL). The mean HbB level corrected for altitude was 10.3g/dL (SD: 1.4; range: 6.9-13.1 g/dL), and suggestive of anemia. The mean PbB level was 49.3 µg/dL (SD: 30.1; range: 4.4-119.1 µg/dL) and indicative of Pb poisoning. Spearman rho correlation analyses revealed significant associations between the BAER absolute latencies and HbB level, indicating that as the HbB level decreased, the BAER wave latency increased. Children with low HbB levels (≤11 g/dL) showed significantly prolonged absolute latencies of waves I, II, III, IV and V compared to the children with normal HbB levels. Although a significant relationship between HbB and BAER waves was observed, no significant associations between PbB level and BAER parameters were found. CONCLUSION: Low hemoglobin levels may diminish auditory sensory-neural function, and is therefore an important variable to consider when assessing BAER in children with anemia and/or Pb exposure.

Acoustic stapedius muscle reflex in mercury-exposed Andean children and adults.

CONCLUSION: The results suggested mercury (Hg)-induced anomalies in the brainstem-mediated acoustic stapedius muscle reflex in children. OBJECTIVES: Hg exposure has been associated with hearing impairment and brainstem anomalies. Acoustic stapedius reflex (ASR) thresholds, growth functions, decay/adaptation times, and behavioral auditory thresholds were used to screen Andean children and adults for Hg-induced auditory brainstem and facial nerve impairment. METHODS: Fifty-one participants, which included 22 children (aged 6-17 years) and 29 adults (aged 19-83 years) living in gold mining areas of Ecuador where Hg is widely used in amalgamation, were screened using ASR immittance procedures. RESULTS: Mean blood mercury (HgB) level in the children was 15.6 µg/L (SD, 21.3; median, 7 µg/L; range, 2.0-89 µg/L), and in the adults 8.5 µg/L (SD, 7.1; median, 6 µg/L; range, 2.0-32 µg/L). Mean contralateral ASR thresholds (ASRT) for the screening frequency of 2000 Hz in the children (39 ears) was 92.9 dB HL (SD, 6.1; range, 80-105 dB HL), and in the adults (53 ears) 90.0 dB HL (SD, 6.4; range, 65-105 dB HL). The ASRT in the children increased significantly with HgB level (rho = 0.433; p = 0.008).

Environmental lead exposure and otoacoustic emissions in Andean children.

Studies relating sensory hearing impairment to lead (Pb) exposure in children have presented inconsistent results. The objective of this study was to measure distortion product otoacoustic emissions (DPOAE), sounds emanating from the outer hair cells of the inner ear, in Pb-exposed children to determine the effects of Pb poisoning on the inner ear. DPOAE were recorded for 9 f(2) frequencies from 1187 to 7625 Hz on 102 ears of 53 Pb-exposed children (aged 6-16 yr) residing in Pb-contaminated environments in the Andes Mountains of Ecuador where Pb glazing of ceramics is the primary livelihood. Blood lead (PbB) levels ranged from 4.2 to 94.3 µg/dl (mean: 37.7; SD: 25.7; median: 36.4). The median PbB level was markedly higher than the Centers for Disease Control and Prevention (CDC) and World Health Organization (WHO) 10-µg/dl action level. Spearman rho correlation analyses of the relation between PbB level and DPOAE amplitude and between PbB level and DPOAE signal-to-noise ratio revealed no significant associations at any of the f(2) frequencies tested. In addition, no significant correlation (Spearman rho) between PbB level and hearing sensitivity for 6 pure-tone test frequencies from 1000 to 8000 Hz was found. Although the study group was found to have abnormally elevated PbB levels, in contrast to some earlier reports, the results of the current study showed no consistent Pb-induced sensory effects on the cochlea of Pb-intoxicated children.

Neurocognitive screening of lead-exposed andean adolescents and young adults.

This study was designed to assess the utility of two psychometric tests with putative minimal cultural bias for use in field screening of lead (Pb)-exposed Ecuadorian Andean workers. Specifically, the study evaluated the effectiveness in Pb-exposed adolescents and young adults of a nonverbal reasoning test standardized for younger children, and compared the findings with performance on a test of auditory memory. The Raven Coloured Progressive Matrices (RCPM) was used as a test of nonverbal intelligence, and the Digit Span subtest of the Wechsler IV intelligence scale was used to assess auditory memory/attention. The participants were 35 chronically Pb-exposed Pb-glazing workers, aged 12-21 yr. Blood lead (PbB) levels for the study group ranged from 3 to 86 microg/dl, with 65.7% of the group at and above 10 microg/dl. Zinc protoporphyrin heme ratios (ZPP/heme) ranged from 38 to 380 micromol/mol, with 57.1% of the participants showing abnormal ZPP/heme (>69 micromol/mol). ZPP/heme was significantly correlated with PbB levels, suggesting chronic Pb exposure. Performance on the RCPM was less than average on the U.S., British, and Puerto Rican norms, but average on the Peruvian norms. Significant inverse associations between PbB/ZPP concentrations and RCPM standard scores using the U.S., Puerto Rican, and Peruvian norms were observed, indicating decreasing RCPM test performance with increasing PbB and ZPP levels. RCPM scores were significantly correlated with performance on the Digit Span test for auditory memory. Mean Digit Span scale score was less than average, suggesting auditory memory/attention deficits. In conclusion, both the RCPM and Digit Span tests were found to be effective instruments for field screening of visual-spatial reasoning and auditory memory abilities, respectively, in Pb-exposed Andean adolescents and young adults.

Neurophysiologic and neurocognitive case profiles of Andean patients with chronic environmental lead poisoning.

This report presents case profiles of three siblings in a family of lead (Pb) glazing workers living in a Pb-contaminated Andean village who presented with extreme plumbism (blood Pb levels: 47 to 128 microg/dl) from childhood to adolescence. These cases are examples of persons who have chronic Pb poisoning as a result of prolonged occupational and environmental exposure in a Pb-glazing ceramic cottage industry in the study area. Using behavioral and physiological techniques for measuring the integrity of the peripheral and central auditory systems, including otoacoustic emissions, and replicated auditory brainstem electrophysiological potentials, the authors found normal auditory neurosensory function in each patient, thus ruling out hearing impairment as a basis for adverse neurocognitive outcomes. This finding is contrary to the prevailing view regarding the detrimental effects of Pb poisoning on the cochlear and auditory brainstem of children. Performance on tests of visual spatial intelligence and auditory memory/attention was below average in these patients, which may underlie their reported learning disabilities. In two of the cases, there was an improvement in cognitive performance following a lowering of PbB levels from chelation therapy and Pb prevention education, suggesting some level of reversibility of their neurocognitive deficits. Nevertheless, these case profiles suggest that if the patients persist in Pb-glazing activities, in spite of repeated chelation therapy and family counseling, they may continue to be re-intoxicated and remain at risk for learning disabilities and other neurological impairments.

Zinc protoporphyrin levels, blood lead levels and neurocognitive deficits in Andean children with chronic lead exposure.

OBJECTIVES: To investigate the relationship between blood lead (PbB), zinc protoporphyrin (ZPP) levels and performance on a test of auditory memory in Andean children and adolescents with chronic lead (Pb) exposure. DESIGN AND METHODS: PbB and ZPP levels were measured in blood samples from 166 participants (aged 6-16 yrs.) exposed to Pb in a local ceramic glazing cottage industry in Ecuadorian villages. PbB levels and ZPP/heme ratios were analyzed in relation to performance on the Digit Span subtest of the Wechsler IV intelligence scale, a test of auditory memory. RESULTS: Mean PbB level for the study group was 18.0 microg/dL (S.D.: 15.1; range: 3.0-86.0), and the mean ZPP/heme ratio was 105.7 mumol/mol (S.D.: 100.9; range: 36.0-592.0). There was no significant difference in PbB and ZPP levels between the 84 females and the 82 males. The mean Digit Span scale score (DS SS) for the study group was 6.81 (S.D.: 2.95; range: 1.0-17.0), which is below the average score of 10 for the test, with the females performing significantly better than males (t=2.435; p=0.01). Regression analyses revealed statistically significant inverse associations between DS SS and PbB level (r=0.251, p=0.001), and between DS SS and ZPP/heme ratio (r=0.246, p=0.001). CONCLUSION: Elevated PbB levels, representing acute exposure, and ZPP levels, reflecting chronic Pb exposure in this cohort of Andean inhabitants were associated with poor performance on a test of auditory memory, suggesting that the children and adolescents in the study area have neurocognitive deficits that may affect learning.

Comparative analysis of zinc protoporphyrin and blood lead levels in lead-exposed Andean children.

OBJECTIVES: The objective of this study was to investigate the zinc protoporphyrin/heme ratio (ZPP/heme) as a biomarker for chronic lead (Pb) poisoning in children with a history of high Pb exposure. DESIGN AND METHODS: ZPP/heme ratio was measured in blood samples from 78 children (44 females and 34 males) with persistent Pb exposure from Pb glazing of ceramics in a local cottage industry in the Andes Mountains of Ecuador. RESULTS: Mean blood lead (PbB) level was 26.4 microg/dL (SD: 23.2; range: 4.0-107.0), and the mean ZPP/heme ratio was 152.4 micromol/mol (SD: 190.6; range: 36.0-1064.0). A regression analysis of PbB level and ZPP/heme ratio revealed a significant association (r=0.761, p= <0.0001), with the logZPP showing a higher correlation with PbB (r=0.869, p= <0.0001). The ZZP/heme ratio decreased significantly with increasing age (ANOVA, p=0.030). The mean ZPP/heme ratios for females and males were 139.6 and 169.0 micromol/mol, respectively, and were not statistically different (t-test, p=0.504). CONCLUSION: The elevated ZPP/heme ratios, coupled with high PbB levels observed in this cohort of Andean children of Pb-glazing workers, suggest chronic Pb intoxication and probable iron deficiency.

Brainstem mediation of the stapedius muscle reflex in hydranencephaly.

Hydranencephaly is a rare condition in which the cerebral hemispheres are absent at birth and are replaced by membranous sacs in a cerebrospinal fluid-filled cranium. Surviving hydranencephalic patients have a functional brainstem and possible remnants of the cerebral cortex. This case report examines hearing function and the integrity of the brainstem mediated stapedius muscle reflex (SMR) in an adult with hydranencephaly, using middle ear impedance change measures. The brainstem mediated ipsilateral and cross-brainstem contralateral SMRs were elicited in the right ear at normal threshold levels for noise bands of 0.25-1.0, 1.0-4.0, and 0.25-4.0 kHz (broadband), and at the sinusoidal frequencies of 0.5, 1.0, and 2.0 kHz. The ipsilateral and contralateral SMR decay rates were normal. The growth in the SMR amplitude in response to noise and pure tone stimuli from threshold to saturation over a 15-20 dB range was normal and showed essentially sigmoidal curves. The normal ipsilateral and crossed brainstem contralateral electrophysiological SMR in this hydranencephalic patient demonstrated the preservation of peripheral hearing reception and functional brainstem auditory afferent and efferent tracts and nuclei in the absence of corticofugal influence.

Lead concentrations in maternal blood and breast milk and pediatric blood of Andean villagers: 2006 follow-up investigation.

OBJECTIVE: To determine the current lead (Pb) concentration in blood (PbB) and breast milk (PbM) of mothers and the PbB of children living in Andean Ecuadorian villages with high Pb contamination. METHODS: Samples of whole blood from 93 participants (74 children and 19 adult women) were analyzed for Pb concentration by graphite furnace atomic absorption spectroscopy with Zeeman background correction, and milk samples from nursing mothers were analyzed by inductively coupled plasma-mass spectrometry (ICP-MS). RESULTS: Mean PbB concentration in children in 2006 was 26.7 microg/dL (SD: 23.0), and significantly lower than the mean PbB level in 1996 to 2000, but similar to the PbB level found in 2003. The mean PbB level of 22.0 microg/dL (SD: 20.6) for the 19 women in the 2006 study group did not differ significantly from the women in the 1996 to 2000 or 2003 study group. The PbM levels (range: 1-49 microg/L) of nursing mothers in the 2006 group were similar to the PbM values observed in the breast milk of nursing mothers in the same study area in 2003, and matched high PbB levels in some mother-infant pairs. CONCLUSION: This study found elevated, but stable, PbB and PbM levels in mothers and elevated, but stable, PbB levels in children in 2006 that were consistent with the levels observed in 2003 in the same Andean villages.

Neurocognitive screening of mercury-exposed children of Andean gold miners.

Performance on Raven's Coloured Progressive Matrices (RCPM) test of visual-spatial reasoning was used to evaluate the effects of mercury (Hg) exposure on 73 Andean children aged 5 to 11 years (mean: 8.4) living in the Nambija and Portovelo gold mining areas of Ecuador, where Hg is widely used in amalgamation. Mean levels of Hg found in blood (Hg(B)), urine (Hg(U)), and hair (Hg(H)) samples were 5.1 microg/L (SD: 2.4; range: 1-10 microg/L), 13.3 microg/L (SD: 25.9; range: 1-166 microg/L), and 8.5 microg/g (SD: 22.8; range: 1-135 microg/g), respectively. Of the children in the Nambija area 67-84.9% had abnormal RCPM standard scores (i.e., < or = 25%tile), depending on the test norm used in the data analysis. Higher standard scores for Peruvian (t = 4.77; p = < 0.0001) and Puerto Rican (t = 4.51; p = < 0.0001) norms than for U.S. norms suggested a linguistic influence. No difference was found between Peruvian and Puerto Rican norms (t = 0.832; p = < 0.408), which showed a significant positive correlation (r = 0.915, p = < 0.0001). Children with abnormal Hg(B) and Hg(H) levels had significantly lower scores on the RCPM subtest B than did children with nontoxic Hg levels (t = -2.16; p = < 0.034). These results suggest that a substantial number of Hg-exposed children in the Nambija study area have neurocognitive deficits in visual-spatial reasoning.