Trace-metal contamination in the glacierized Rio Santa watershed, Peru.

The objective of this research is to characterize the variability of trace metals in the Rio Santa watershed based on synoptic sampling applied at a large scale. To that end, we propose a combination of methods based on the collection of water, suspended sediments, and riverbed sediments at different points of the watershed within a very limited period. Forty points within the Rio Santa watershed were sampled between June 21 and July 8, 2013. Forty water samples, 36 suspended sediments, and 34 riverbed sediments were analyzed for seven trace metals. The results, which were normalized using the USEPA guideline for water and sediments, show that the Rio Santa water exhibits Mn concentrations higher than the guideline at more than 50% of the sampling points. As is the second highest contaminating element in the water, with approximately 10% of the samples containing concentrations above the guideline. Sediments collected in the Rio Santa riverbed were heavily contaminated by at least four of the tested elements at nearly 85% of the sample points, with As presenting the highest normalized concentration, at more than ten times the guideline. As, Cd, Fe, Pb, and Zn present similar concentration trends in the sediment all along the Rio Santa.The findings indicate that care should be taken in using the Rio Santa water and sediments for purposes that could affect the health of humans or the ecosystem. The situation is worse in some tributaries in the southern part of the watershed that host both active and abandoned mines and ore-processing plants.

Access to care for children with symptoms of sleep disordered breathing.

OBJECTIVES: To determine if children with sleep disordered breathing who have Medicaid insurance encounter more difficulty accessing an otolaryngologist than those with private insurance. DESIGN: Retrospective study. SETTING: Urban tertiary care pediatric hospital. PATIENTS: Children referred for evaluation of sleep disordered breathing (SDB). INTERVENTION: Survey of patients' parents and guardians. MAIN OUTCOME MEASURE: Timely access to an otolaryngologist in their community. RESULTS: Ninety-seven patients were included. Fifty patients had private insurance, 47 had Medicaid. The mean age was 5 years for those with private insurance and 5.6 years for those with Medicaid (p=0.27). The symptoms of SDB in both groups were similar. It took an average of 1.97 weeks for the children in the private insurance group to get an appointment versus 10.8 weeks for those with Medicaid (p=0.002). The mean distance traveled by the children in the private insurance group was 9.86 miles compared to 18.05 miles for those with Medicaid (p=0.001). CONCLUSION: Children who were referred for evaluation of SDB were of similar age and had similar symptoms regardless of insurance type. Children with Medicaid wait longer and travel farther to see an otolaryngologist than children with private insurance.

Synchronous airway lesions in children younger than age 3 years undergoing adenotonsillectomy.

OBJECTIVE: Determine the prevalence of synchronous airway lesions (SALs) in children younger than age 3 years undergoing adenoidectomy or adenotonsillectomy for sleep-disordered breathing (SDB) at Children's Memorial Hospital. DESIGN: Case series with chart review. SETTING: Tertiary care pediatric hospital. CHILDREN: One hundred ten children 3 years of age or younger who underwent adenoidectomy or adenotonsillectomy along with a full-airway evaluation that included flexible fiber-optic laryngoscopy, direct laryngoscopy, and rigid bronchoscopy for SDB from January 2003 to January 2009. OUTCOME MEASURES: Prevalence of SALs and rate of SALs that required intervention. RESULTS: Sixty-seven percent of children were found to have at least 1 SAL. Four children required surgical intervention for a SAL. There was no significant difference in preoperative respiratory distress index (RDI) between children with normal airway examinations compared with children with a SAL. There was no significant difference in the rate of SALs between children younger than 18 months old and those 18 to 36 months old. CONCLUSIONS: There is a high incidence of SALs in children younger than 3 years old with SDB. There was no significant difference in the rate of SALs in children younger than 18 months old compared with children 18 to 36 months old. The RDI determined by a polysomnography was not predictive of the presence of a SAL. Tracheal cobblestoning was the most common SAL discovered.

MRI of orbital cellulitis and orbital abscess: the role of diffusion-weighted imaging.

OBJECTIVE: Our aims were to describe the role of diffusion-weighted imaging (DWI) in detecting abscess as a complication of orbital cellulitis and to assess whether abscess can be diagnosed with a combination of conventional unenhanced sequences and whole-brain DWI with parallel acquisition. Nine cases of orbital cellulitis imaged with MRI were retrospectively reviewed, including six cases with pyogenic abscess. CONCLUSION: In this preliminary study, DWI improved diagnostic confidence in nearly all cases of orbital abscess when used in conjunction with contrast-enhanced imaging. DWI also confirmed abscess in a majority of cases without contrast-enhanced imaging, which may be of particular use when contrast material is contraindicated.

Enantiomeric propanolamines as selective N-methyl-D-aspartate 2B receptor antagonists.

Enantiomeric propanolamines have been identified as a new class of NR2B-selective NMDA receptor antagonists. The most effective agents are biaryl structures, synthesized in six steps with overall yields ranging from 11-64%. The compounds are potent and selective inhibitors of NR2B-containing recombinant NMDA receptors with IC 50 values between 30-100 nM. Potency is strongly controlled by substitution on both rings and the centrally located amine nitrogen. SAR analysis suggests that well-balanced polarity and chain-length factors provide the greatest inhibitory potency. Structural comparisons based on 3D shape analysis and electrostatic complementarity support this conclusion. The antagonists are neuroprotective in both in vitro and in vivo models of ischemic cell death. In addition, some compounds exhibit anticonvulsant properties. Unlike earlier generation NMDA receptor antagonists and some NR2B-selective antagonists, the present series of propanolamines does not cause increased locomotion in rodents. Thus, the NR2B-selective antagonists exhibit a range of therapeutically interesting properties.

Subunit-specific mechanisms and proton sensitivity of NMDA receptor channel block.

We have compared the potencies of structurally distinct channel blockers at recombinant NR1/NR2A, NR1/NR2B, NR1/NR2C and NR1/NR2D receptors. The IC50 values varied with stereochemistry and subunit composition, suggesting that it may be possible to design subunit-selective channel blockers. For dizocilpine (MK-801), the differential potency of MK-801 stereoisomers determined at recombinant NMDA receptors was confirmed at native receptors in vitro and in vivo. Since the proton sensor is tightly linked both structurally and functionally to channel gating, we examined whether blocking molecules that interact in the channel pore with the gating machinery can differentially sense protonation of the receptor. Blockers capable of remaining trapped in the pore during agonist unbinding showed the strongest dependence on extracellular pH, appearing more potent at acidic pH values that promote channel closure. Determination of pK(a) values for channel blockers suggests that the ionization of ketamine but not of other blockers can influence its pH-dependent potency. Kinetic modelling and single channel studies suggest that the pH-dependent block of NR1/NR2A by (-)MK-801 but not (+)MK-801 reflects an increase in the MK-801 association rate even though protons reduce channel open probability and thus MK-801 access to its binding site. Allosteric modulators that alter pH sensitivity alter the potency of MK-801, supporting the interpretation that the pH sensitivity of MK-801 binding reflects the changes at the proton sensor rather than a secondary effect of pH. These data suggest a tight coupling between the proton sensor and the ion channel gate as well as unique subunit-specific mechanisms of channel block.

Postoperative pain management after craniotomy: evaluation and cost analysis.

OBJECTIVE: Patients undergoing craniotomies have traditionally received opiates for the management of their postoperative pain. The use of narcotic pain medications can be costly, can decrease early walking, can lengthen hospital stay, and can alter a patient's neurological examination results. The use of alternative pain medications such as cyclooxygenase-2 (COX-2) inhibitors may benefit patients by resolving many of these issues. Compared with traditional nonsteroidal anti-inflammatory drugs, these anti-inflammatory medications may be used safely in neurosurgical patients because of their selective inhibition of the COX-2 enzyme, which avoids the platelet dysfunction caused by other nonsteroidal anti-inflammatory drugs. METHODS: A randomized, single-blinded prospective study was used to evaluate the efficacy of alternative pain management strategies for patients who have undergone craniotomy. Twenty-seven patients were randomly assigned to a control group (n = 13) receiving narcotics alone or an experimental group (n = 14) receiving a COX-2 inhibitor in addition to narcotic pain medications. RESULTS: The narcotics group was noted to have statistically significantly higher visual analog scale scores, increased length of stay, and increased narcotic use compared with the COX-2 group. The narcotics group also had increased hospitalization costs when compared with the COX-2 group. CONCLUSION: The use of scheduled atypical analgesics, such as COX-2 inhibitors, in addition to narcotics for the management of postoperative pain after craniotomy may provide better pain control, may decrease side effects associated with narcotic pain medications, may encourage earlier walking, and may reduce total hospitalization costs.

Serum protein profile analysis in patients with head and neck squamous cell carcinoma.

OBJECTIVES: To analyze surface-enhanced laser desorption and ionization time-of-flight mass spectrometry (SELDI-TOF-MS) protein profiles of patients with head and neck squamous cell carcinoma (HNSCC) and healthy controls and to determine the sensitivity and specificity of SELDI assay for HNSCC detection before and after treatment. DESIGN: Proteomic analysis and comparison of serum samples. SETTING: Tertiary care academic medical center. SUBJECTS: Seventy-eight patients with HNSCC and 68 healthy controls. MAIN OUTCOME MEASURES: Serum samples were prospectively collected from 78 patients with HNSCC and 68 healthy control volunteers. SELDI-TOF-MS was performed on serum samples to identify protein peaks in the range of 0 to 100 kDa. Classification analysis of the spectral data was performed and used to classify the disease status of the patients. RESULTS: The SELDI-TOF-MS assay generated serum protein profiles ranging from 0 to 100 kDa. After background subtraction, mass calibration, and normalization, 545 protein peaks were identified. Classification tree analysis based on peak expression correctly classified patients with HNSCC with 82% sensitivity and 76% specificity. Subgroup analysis correctly classified 83% of oral cavity tumors, 81% of oropharyngeal tumors, and 88% of laryngeal tumors. Pretreatment and posttreatment samples were available from 12 patients, and the posttreatment samples were correctly classified in 86% of the patients at 3 months and 75% of the patients at 6 months. CONCLUSIONS: Proteomic SELDI-TOF-MS analysis of serum protein profiles distinguishes patients with HNSCC from controls with a high degree of sensitivity and specificity. Further investigation into the clinical utility of this technology in HNSCC detection and surveillance is warranted.

Molecular determinants of proton-sensitive N-methyl-D-aspartate receptor gating.

Extracellular protons inhibit N-methyl-D-aspartate (NMDA) receptors with an IC50 value in the physiological pH range. To identify the molecular determinants of proton sensitivity, we used scanning mutagenesis of the NR1 subunit to search for residues that control proton inhibition of NMDA receptors. Homology modeling of the extracellular domains suggested that residues at which mutations perturbed pH sensitivity were localized in discrete regions. The majority of mutations that strongly affected proton sensitivity were clustered in the extracellular end of the second transmembrane domain (M3) and adjacent linker leading to the S2 portion of the glycine-binding domain of NR1. Mutations in NR2A confirmed that the analogous region controls the pH sensitivity of this subunit and also identified the linker region between the third transmembrane domain (M4) and the S2 portion of the NR2 glutamate binding domain as an additional determinant of proton sensitivity. One mutant receptor, NR1(A649C)/NR2A(A651T), showed a 145-fold reduction in the IC50 for protons (IC50, 17.3 microM corresponding to pH 4.9). The M3-S2 linker region has been suggested to control NMDA receptor gating, leading to the hypothesis that the proton sensor and receptor gate may be structurally and functionally integrated.

Interactions between opioids and cocaine on locomotor activity in rats: influence of an opioid's relative efficacy at the mu receptor.

RATIONALE: Cocaine and mu opioid agonists increase central dopamine concentrations and produce robust interactions at both neurochemical and behavioral levels. Although the interactions between cocaine and high-efficacy mu opioids have been well characterized, the interactions between cocaine and lower efficacy opioids have not been as extensively examined. OBJECTIVE: The purpose of this study was to examine the interactions between cocaine and opioids possessing a range of relative efficacy at the mu receptor. METHODS: Male, Long-Evans rats were habituated to an open-field, locomotor activity chamber, and the effects of cocaine and various opioids were tested under a cumulative dosing procedure. In this procedure, a selected dose of an opioid was administered during the first component of a session, with increasing doses of cocaine administered during subsequent components. RESULTS: When administered alone, cocaine produced dose-dependent increases in locomotor activity that was stable across 5 weeks of behavioral testing. The high-efficacy mu opioid levorphanol, and the low-efficacy opioids buprenorphine, butorphanol, nalbuphine and (-)-pentazocine, dose-dependently enhanced the effects of cocaine at doses that did not alter locomotor activity when administered alone. In contrast, the opioid antagonist naloxone, and to a lesser extent, the kappa opioid spiradoline attenuated the effects of cocaine at doses that did not alter locomotor activity when administered alone. Across an extensive dose range, the low-efficacy opioid nalorphine failed to alter cocaine's locomotor-activating effects. CONCLUSIONS: These data suggest that low-efficacy opioids possessing significant mu-agonist activity (e.g. buprenorphine, butorphanol, nalbuphine, (-)-pentazocine) may potentiate the effects of cocaine in a manner similar to that typically observed with high-efficacy mu opioids.

Age-related differences in sensitivity to the antinociceptive effects of kappa opioids in adult male rats.

RATIONALE: Significant differences in the potency and effectiveness of opioid analgesics have been reported in subject populations differing in age. Although the relationship between aging and sensitivity to the antinociceptive effects of mu opioids has been examined extensively, relatively few studies have examined this relationship in kappa opioids. OBJECTIVES: The purpose of the present investigation was to examine the antinociceptive effects of selected kappa and mixed-action opioids in young (3 months) and aged (21 months) male rats. METHODS: In a warm-water, tail-withdrawal procedure, rats were restrained and the latencies to remove their tails from 50 degrees C (low temperature) and 55 degrees C (high temperature) water were measured. Selected kappa (U69,593, U50,488) and mixed-action (butorphanol, nalbuphine) opioids were tested alone, and in combination with the high-efficacy, kappa-opioid spiradoline. RESULTS: All test drugs were more effective (i.e., produced a greater maximal effect) in aged rats than in young rats at both water temperatures. In drug combination tests, U69,593 and U50,488 enhanced the effects of spiradoline under conditions in which they failed to produce high levels of antinociception when administered alone. In contrast, butorphanol and nalbuphine antagonized the effects of spiradoline under conditions in which they failed to produce high levels of antinociception when administered alone. CONCLUSIONS: These data may be taken as evidence that: (1) aged male rats are more sensitive than young male rats to the antinociceptive effects of kappa opioids, (2) U69,593 and U50,488 display agonist activity in the warm-water, tail-withdrawal procedure under some conditions in which they fail to produce antinociceptive effects, and (3) butorphanol and nalbuphine possess only limited agonist activity at the kappa receptor.