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BACKGROUND: Animal studies have demonstrated that low paraoxonase-1 (PON1) status (i.e., low catalytic efficiency and/or low plasma PON1 activity) is associated with neurotoxic effects after exposure to several organophosphate (OP) [...]

BACKGROUND: Mixtures of organophosphate and carbamate pesticides are commonly detected in freshwater habitats that support threatened and endangered species of Pacific salmon (Oncorhyncus sp.). These pesticides inhibit the activity of [...]

Hydrogen atoms constitute about half of all atoms in proteins and play a critical role in enzyme mechanisms and macromolecular and solvent structure. Hydrogen atom positions can readily be determined by neutron diffraction, and as such, neutron diffraction is an invaluable tool for elucidating molecular mechanisms. Joint refinement of neutron and X-ray diffraction data can lead to improved models compared with the use of neutron data alone and has now been incorporated into modern, maximum-likelihood based crystallographic refinement programs like CNS. Joint refinement has been applied to neutron and X-ray diffraction data collected on crystals of diisopropyl fluorophosphatase (DFPase), a calcium-dependent phosphotriesterase capable of detoxifying organophosphorus nerve, agents. Neutron omit maps reveal a number of important features pertaining to the mechanism of DFPase. Solvent molecule W33, coordinating the catalytic calcium, is a water molecule in a strained coordination environment, and not a hydroxide. The smallest Ca-O-H angle is 53[degrees], well beyond the smallest angles previously observed. Residue Asp-229, is deprotonated, supporting a mechanism involving nucleophilic attack by Asp-229, and excluding water activation by the catalytic calcium. The extended network of hydrogen bonding interactions in the central water filled tunnel of DFPase is revealed, showing that internal solvent molecules form an important, integrated part of the overall structure. enzyme mechanism | H/D exchange

BACKGROUND: The widespread use of organophosphorus (OP) pesticides has led to frequent exposure in adults and children. Because such exposure may cause adverse health effects, particularly in children, the sources and patterns of exposure need to be studied further. OBJECTIVES: We assessed young urban/suburban children's longitudinal exposure to OP pesticides in the Children's Pesticide Exposure Study (CPES) conducted in the greater Seattle, Washington, area, and used a novel study design that allowed us to determine the contribution of dietary intake to the overall OP pesticide exposure. METHODS: Twenty-three children 3-11 years of age who consumed only conventional diets were recruited for this 1-year study conducted in 2003-2004. Children switched to organic diets for 5 consecutive days in the summer and fall sampling seasons. We measured specific urinary metabolites for malathion, chlorpyrifos, and other OP pesticides in urine samples collected twice daily for a period of 7, 12, or 15 consecutive days during each of the four seasons. RESULTS: By substituting organic fresh fruits and vegetables for corresponding conventional food items, the median urinary metabolite concentrations were reduced to nondetected or close to nondetected levels for malathion and chlorpyrifos at the end of the 5-day organic diet intervention period in both summer and fall seasons. We also observed a seasonal effect on the OP urinary metabolite concentrations, and this seasonality corresponds to the consumption of fresh produce throughout the year. CONCLUSIONS: The findings from this study demonstrate that dietary intake of OP pesticides represents the major source of exposure in young children. KEY WORDS: children, chlorpyrifos, dietary exposure, longitudinal pesticide exposure, malathion, organic diet, organophosphorus pesticides, urinary biomonitoring. Environ Health Perspect 116:537-542 (2008). doi:10.1289/ehp.10912 available via http://dx.doi.org/ [Online 15 January 2008], Organophosphorus (OP) pesticides, a group of cholinesterase-inhibiting insecticides, have been widely used both in residential and agricultural environments because of their broad spectrum of insecticidal activity and effectiveness. The widespread [...]

Several genome-wide analyses are conducted to explain the connection of the organophosphorus (OP) compounds with the motor neuron disease (MND). The MND is caused by the neuropathy target esterase (NTE) that is usually inhibited by the OP compounds.

BACKGROUND: Recent epidemiologic studies have identified organophosphorus pesticides (OPs) as environmental factors potentially contributing to the increase in asthma prevalence over the last 25 years. In Support of this hypothesis, [...]

We report on the creation of a high surface area, chemically selective material for the efficient adsorption of organophosphate and organophosphonate species. Using silica microparticles in conjunction with gold nanoparticles and surface modification chemistry, we have demonstrated a material with a binding constant for organophosphonates and organophosphates (OPPs) ofK = 2 x [10.sup.6] [M.sup.-1]. The binding of OPPs to the modified gold nanoparticles appears as a speclral shift in the gold nanoparticle resonance. The sensitivity of this technique is limited by scattering losses of suspensions of the particles, and we report on how this sensitivity can be recovered to a significant extent by the use of solvents with a refractive index close to that of the silica particles.

Organophosphates induce bronchoobstruction in guinea pigs, and salbutamol only transiently reverses this effect, suggesting that it triggers additional obstructive mechanisms. To further explore this phenomenon, in vivo (barometric plethysmography) and in vitro (organ baths, including ACh and substance P concentration measurement by HPLC and immunoassay, respectively; intracellular [Ca.sup.2+] measurement in single myocytes) experiments were performed. In in vivo experiments, parathion caused a progressive bronchoobstruction until a plateau was reached. Administration of salbutamol during this plateau decreased bronchoobstruction up to 22% in the first 5 min, but thereafter airway obstruction rose again as to reach the same intensity as before salbutamol. Aminophylline caused a sustained decrement (71%) of the parathion-induced bronchoobstruction. In in vitro studies, paraoxon produced a sustained contraction of tracheal rings, which was fully blocked by atropine but not by TTX, [omega]-conotoxin (CTX), or epithelium removal. During the paraoxon-induced contraction, salbutamol caused a temporary relaxation of ~50%, followed by a partial recontraction. This paradoxical recontraction was avoided by the [M.sub.2-] or neurokinin-1 (N[K.sub.1])-receptor antagonists (methoctramine or AF-DX 116, and L-732138, respectively), accompanied by a long-lasting relaxation. Forskolin caused full relaxation of the paraoxon response. Substance P and, to a lesser extent, ACh released from tracheal rings during 60-min incubation with paraoxon or physostigmine, respectively, were significantly increased when salbutamol was administered in the second half of this period. In myocytes, paraoxon did not produce any change in the intracellular [Ca.sup.2+] basal levels. Our results suggested that: 1) organophosphates caused smooth muscle contraction by accumulation of ACh released through a TTX- and CTX-resistant mechanism; 2) during such contraction, salbutamol relaxation is functionally antagonized by the stimulation of [M.sub.2] receptors; and 3) after this transient salbutamol-induced relaxation, a paradoxical contraction ensues due to the subsequent release of substance P. albuterol; [[beta].sub.2]-adrenoceptor agonist; parathion; paraoxon; tachykinins; physostigmine; airway smooth muscle

The directed evolution of organophosphorus hydrolase (OPH) to improve the hydrolysis of a poorly hydrolyzable substrate, chlopyrifos is described. The results indicate that the directed evolution of OPH and related enzymes may lead to potential biological solutions for efficient decontamination and detection of neurotoxic nerve agents.

How to cite this article: Wadia RS. Treatment of Organophosphate Poisoning. Indian J Crit Care Med 2003;7:85-87 How to cite this URL: Wadia RS. Treatment of Organophosphate Poisoning. Indian J [...]

Abstract Organophosphate compound (OPC) poisoning with suicidal intent is common in Indian ICUs. The effect of OPCs is to produce a persistent depolarization of the neuromuscular junction leading to muscle [...]

Research describes the synthesis, isolation, and structural characterization and magnetic/electron paramagnetic resonance analyses of a complex between cobalt(II) and the diphosphonate ligand, imino-bis(methylphosphonic acid). Data indicate that the complex possesses solid-state properties of the metal organophosphonate material and mononuclear Co(II) sites.

Research describes the synthesis of 5-carbaphosphatranes that exhibit a nearly ideal trigonal bipyramidal structure of 1-hydro-5-carbaphosphatrane with electronegative oxygens at equatorial sites. Data indicate that the transannular bond in 5-caraphosphatrane is twice stronger than phosphatrane and more than three times that of silatrane.

Researchers have isolated an organophosphate hydrolase from Plesiomonas sp. strain M6 that can convert methyl parathion to para-nitrophenol. The gene for this enzyme could be expressed in Escherichia coli and used to biodegrade organophosphate pesticides such as parathion, methyl parathion, and methamidophos.

The Cu(I) complexes, [([Ph.sub.3]P).sub.2]CuL (L = [[S.sub.2]P [Me.sub.2]]-, [[OSPR.sub.2]]- (R = Me, Ph), [([XPR.sub.2]) ([YPR.sub.2])N]- (X, Y, R, R' = O, O, Ph, Ph; O, S, Ph, Ph; O, S, OEt, Pr; S, S, Me, Me)) and Cu(II) complexes, Cu[L.sub.2] (L = [([XPR.sub.2])([YPR'.sub.2])N]- (X, Y, R, R' = O, O, Ph, Ph; O, S, Ph, Ph)), have been prepared. The Cu(I) derivatives were characterized by multinuclear NMR spectroscopy and in two cases by X-ray crystallography. [([Ph.sub.3]P).sub.2]Cu[[S.sub.2]P[Me.sub.2]] (1) crystallizes in the orthorhombic space group [P2.sub.1][2.sub.1] [2.sub.1] (No. 19) with cell parameters a = 9.782(2), b = 17.808(4), c = 20.216(4) [Angstrom] V = 3521(6) [[Angstrom].sup.3] and Z = 4, and [([Ph.sub.3]P).sub.2]Cu[(OP[Ph.sub.2]).sub.2]N] (4) in the triclinic space group P[bar 1] (No. 2) with cell parameters a = 9.8079(2), b = 12.9141(3), c = 22.5666(5) [Angstrom], [alpha] = 75.714(2), [beta] = 79.465(2), [gamma] = 68.2770(8)[degrees], V = 2559.9(1) [[Angstrom].sup.3] and Z = 2. In both cases the phosphorus ligands are bidentate, thus resulting in monomeric molecules that contain tetrahedral Cu[P.sub.2][S.sub.2] and Cu[P.sub.2][O.sub.2] cores. The molecular structures of two of the Cu(II) derivatives were also determined. Cu[[[(OP[Ph.sub.2]).sub.2]N].sub.2] (8) and Cu [(OP[Ph.sub.2])[(SP[Ph.sub.2])N].sub.2] (9) crystallize in the triclinic space group P[bar 1] (No. 2) with cell parameters a = 8.887(2), b = 10.739(2), c = 12.477(3) [Angstrom] [alpha] = 77.61(3), [beta] = 76.15(5), [gamma] = 79.46(3)[degrees], V = 1118.3(4) [[Angstrom].sup. 3] and Z = 1 for 8, and a = 9.626(2), b = 14.151(3), c = 24.752(5) [Angstrom], [alpha] = 88.23(3), [beta] = 79.93(3), [gamma] = 89.77(3)[degrees], V = 3181(1) [[Angstrom].sup.3] and Z = 3 for 9. The molecule of Cu[[[[(OP[Ph.sub.2]).sub.2]N].sub.2] (8) has a planar Cu[O.sub.4] core, while in Cu[(OP[Ph.sub.2])[(SP [Ph.sub.2])N].sub.2] (9) both planar and tetrahedral copper cores are observed in a ratio of 1:2. Key words: structure, copper, thiophosphinates, oxo- and thio-imidodiphosphinates.

Research is presented concerning the development of a technique which uses enzyme-linked immunosorbent assay and solid phase extraction to measure the levels of chlorphrifos in the tissues of fish. The method was tested on 19 samples.

The comparison of experimental and ab initio predicted absorption and VCD spectra indicates that (-)-tert-butylphenylphosphine oxide is of (S)-configuration, in agreement with the known absolute configuration, only one tautomeric structure and one conformation is predominant for (-)-tert-butylphenylphosphine oxide in CHCl3 and CDCl3 solutions.

The phosphatidylcholine-preferring phospholipase C from Bacillus cereus is inhibited by the cyclic N,N' -dihydroxyureas 6-10. This class of inhibitors is thought to function by the bidentate chelation of the N,N' -dihydroxyurea array to one or more of the zinc ions at the active site of the enzymes.

Research into the development of a ring-closing metathesis strategy for incorporating sulfone groups into polybicyclic molecules is presented.

A bacterium that can degrade the insecticide fenitrothion has been discovered. It appears to be a species of Burkholderia and its fenitrothion-degrading ability resides on two plasmids, pNH1 and pNF2.

The synthesis and characterization of a series of xanthene-based rhodium complexes of a series of amphiphilic diphosphines with pendant groups -C6H4O(CH2)nC6H4SO3Na- (n= 0,3,6) is reported.

Isomerism of aurated phosphine sulfides, thiophosphinates, thiophosphonates, and thiophosphates is discussed based on structural and quantum chemical studies. In phosphine sulfides, in which the negative charge at the sulfur atom is neutralized by the neighboring phosphonium center and that should bring on reduction of formal charge at the aurated sulfur center and influence acceptor properties. There is greater choice of donor sites for auration in trithiophosphonates and -phosphates and they have been studied now. Theoretical studies of the diauration of the (H(sub.2)PS(sub.2))(super.-) anion and of the stepwise triauration of phosphine sulfide as a model substrate have been carried out.

Metallic palladium was observed to catalyze the deep oxidation of a broad range of functional organics by dioxygen at 80-90 degrees C in water and in the presence of carbon monoxide or dihydrogen. Several classes or organic compounds were studied: benzene, pheno and substituted phenols, nitro and halo organics, organophosphorus, and organosulfur compounds. For all cases, deep oxidation to CO, CO2 and water occurred in high yields, resulting in up to several hundred turnovers over a 24 hr period.

A study on gallium phosphide as a semiconductor investigated 12 neutral or ionic gallium phosphorus hydrides in terms of their relative energies, harmonic vibrational frequencies and equilibrium structures using three different techniques. It is apparent from these structures that gallium and phosphorus can form strong double bonds although unsaturation at gallium leads to the formation of weaker than expected bonds. Experimental methods and other findings are discussed.

An amperometric biosensor based on the immobilization of organophosphorus hydrolase (OPH) onto screen-printed carbon electrodes is shown useful for the rapid, sensitive, and low-cost detection of organophosphate (OP) nerve agents. The sensor relies upon the sensitive and rapid anodic detection of the enzymatically generated p-nitrophenol product at the OPH/Nafion layer immobilized onto the thick-film electrode in the presence of the OP substrate. The amperometric signals are linearly proportional to the concentration of the hydrolyzed paraoxon and methyl parathion substrates up to 40 and 5 [[micro]molar], showing detection limits of 9 x [10.sup.-8] and 7 x [10.sup.-8] M, respectively. Such detection limits are substantially lower compared to the (2-5) x [10.sup.-6] M values reported for OPH-based potentiometric and fiber-optic devices. The high sensitivity is coupled to a faster and simplified operation, and the sensor manifests a selective response compared to analogous enzyme inhibition biosensors. The applicability to river water sampling is illustrated. The attractive performance and greatly simplified operation holds great promise for on-site monitoring of OP pesticides.

A reaction of stoichiometric amounts of CuI, red P, and Se in evacuated silica ampules was used to prepare pure orange (CuI)3P4Se4. Single crystals at room temperature were used to determine the crystal structure. (CuI)3P4Se4 crystallized in the hexagonal system, space group P6(sub 3)cm with a=19.601(2) angstroms, c=-6.7196(6) angstroms, and Z=6. The compound consisted of beta-P4Se4 cages that were embedded between columns of copper iodide. These columns were considered as sections of wurtzite-type structure which was not yet known for copper iodide

P-tris-(dimethylamino)-C-dimethylphosphonium ylide was studied to determine if it could replace P4-t-Bu. In addition, the possibility of immobilizing an ylide on resins was investigated to make more attractive the use of ylides as strong nonnucleophilic bases. A suspension of Merryfield's resin and phosphine in DCE was stirred under reflux for five days to prepare a strongly hindered nonnucleophilic supported base. The results showed that ylide had a nonnucleophilic strong base which was comparable but cheaper than P-4-t-Bu.

Electron correlated, ab-initio theoretical and density functional theory methods were used in a study on phosphinines to investigate the 24 possible valence isomers of diphosphinine P2(C-H)4. It appears that three planar isomers are distinctly more stable than others. The various families of isomers have distinct ranges of stabilities which virtually do not overlap at the MP2 level. Other experimental results and conclusions are discussed.

The intramolecular nondissociative ligand exchange of (4+)-coordinate phosphorus compounds has been investigated. The results of dynamic 1H NMR studies showed that these compounds undergo intramolecular ligand exchange which are similar to those already found for the silicon compounds. The DeltaG values for this process were found to lie in the range 56.2-61.7 kJ mol-1. Another isomerization process in the 1,2 adjacent ligand shift was also observed with the phosphane sulfide.

The syntheses and characterization of four In-thiolates are presented. The scheme involves the electrochemical oxidation of anodic indium metal in an acetonitrile solution of phosphinothiol ligands. Structural analysis showed that all four In-thiols exhibited six-coordinate geometries based on (InS3P3), (InS3P2O) and (InS4P2) cores. The In-P bond distances were found to be anomalously long, as a result of steric crowding.

The binding of trivalent lanthanide cations Mn+ (Mn = La3+, Eu3+, Yb3+, Sr2+ and Na=) to three important classes of ligands used to complex lanthanide or actinide ions were investigated by ab initio quantum mechanics. These ligands are the substituted amides, pyridines, and the phosphoryl-containing OPPh3 ligand. The results showed that the interaction energies follow trends expected from the cation hardness and ligand basicity or softness in the amide series.

The replacement of histidine by leucine at amino acid position 257 and by arginine at position 254 of the dimeric bacterial enzyme organophosphorous hydrolase (OPH) resulted in the creation of three altered enzymes. The resultant changes in substrate specificity upon the application of the enzymes to analogues of chemical warfare agents VX and soman, proves that OPH's specificity can be substantially enhanced through site-specific changes. It is also suggested that metal requirement modifications can affect catalytic attributes.

The reactions of primary amines, secondary amines, amino acids and model peptides with hydroxymethylphosphines were explored. Results showed that the reactions of these multifunctional phosphines with excess amino acids led to unexpectedly produced monomeric products. The new compounds created were characterized by a combination of spectroscopic and analytical methods and their molecular structures confirmed using single-crystal x-ray diffraction.

Two extended uranyl organophosphorus compounds, linear-chain uranyl phenylphosphinate UO(sub 2)(O(sub 2)PHC(sub 6)H(sub 5))(sub 2) and layered uranyl methylphosphonate UO(sub 2)(O(sub 3)PCH(sub 3)), have been synthesized and structurally characterized. The compounds crystallize in the triclinic space group P1 with different unit cell parameters. The uranyl ions, linked by the phosphonate anions, form parallel inorganic layers, and the methyl groups point perpendicularly between the layers.

A fiber-optic microbial biosensor suitable for direct measurement of organophosphate nerve agents was developed. The unique features of this novel microbial biosensor were the recombinant Escherichia coli cells expressing the enzyme organophosphorus hydrolase on the cell surface and the optical detection of the products of enzyme-catalyzed organophosphate hydrolysis. The use of cells with the metabolic enzyme expressed on the cell surface as a biological sensing element provides advantages of no resistance to mass transport of the analyte and product across the cell membrane and low cost due to elimination of enzyme purification, over the conventional microbial biosensors based on cells expressing enzyme intracellularly and enzyme-based sensors, respectively. The use of an optical transducer allows the detection of different organophosphates in a mixture, presently not feasible with acetylcholinesterase-based biosensors. E. coli cells expressing organophosphorus hydrolase (OPH) on the cell surface were immobilized in low melting temperature agarose on a nylon membrane and attached to the common end of a bifurcated fiber-optic bundle. OPH-expressing E. coli cells catalyzed the hydrolysis of organophosphorus pesticides to form stoichiometric amounts of chromophoric products that absorb light at specific wavelengths. The backscattered radiation of the specific wavelength incident light was measured using a photomultiplier detector and correlated to the organophosphate concentration. The best sensitivity and response time were obtained using a sensor constructed with 1.5 mg of cells operating in pH 9, 50 mM HEPES buffer with 100 mM NaCl and 0.05 mM Co[Cl.sub.2] at 30 [degrees]C. At optimized conditions, the biosensor measured paraoxon, parathion, and coumaphos pesticides with high selectivity against triazine and carbamate pesticides in approximately 10 min. The lower detection limits were 3 [[micro]molar] for paraoxon and parathion and 5 [[micro]molar] for coumaphos. When stored in the buffer at 22 [degrees] C, the biosensor was stable for over a 1-month period and showed no decline in the response for over 75 repeated usages. The new fiber-optic microbial biosensor is an ideal tool for on-line monitoring of the detoxification process for organophosphate pesticides-contaminated wastewaters but may not be suitable for environmental monitoring.

Mercury salts have been found to enhance the chemical hydrolysis of organophosphate compounds (OPs), particularly parathion-methyl. The rate of OPs' hydrolysis is increased as the pH is increased and with the metal acting as a nucleophile. An increased rate in the hydrolysis of OPs can be seen with decreasing pH when the mechanism is dominated by the metal acting as an electrophile.

Serum paraoxonase (PON1) is an esterase linked with high-density lipoproteins (HDLs) in plasma, involved in detoxification of organophosphate insecticides. The role of PON1 was studied in vivo, with the creation of PON1-knockout mice by gene targeting. PON1-deficient mice were sensitive to chlorpyrifos oxon toxicity, and HDLs isolated from them could not prevent low-density lipoprotein oxidation. PON1-null mice became more susceptible to atherosclerosis when fed on a high fat, high cholesterol diet, than wild type littermates.

Organophosphoric compounds (OPCs) belong to a class of pesticides in use around the world. They account for a large number of poisonings in humans and pose hazards for the environment. Thus, microbial degradation of the compounds are of great interest for researchers. In an effort to better understand the metabolic process behind the microbial utilization of OPCs. spontaneous organophosphate utilization mutants of the Escherichia coli K-12 strain was investigated. Two genes responsible for the mutation were then identified using cloning experiments.

The C-H**S and C-H**O hydrogen bonds were found to be one of the factors contributing to the molecular packing of 1,6-anhydro-2-O-(tosyl)-4-S-(5,5-dimethyl-2-thioxa-1,3,2-dioxaphosphorinan-2 -yl)-beta-D-glucopyranose molecules in the solid phase. On the other hand, the O-H***S interaction was observed to be responsible for the inclusion of a 2-propanol molecule into the solvate structure.

The reaction of organophosphorus boranes with amine pentacarbonyltungsten complexes were observed to result into the corresponding chiral and achiral W(CO)5(PR3) complexes in 63-92% yields by a one-step synthesis. This reaction occurs under mild conditions through a ligand exchange between the borane and tungsten complexes. The stereochemistry of the production of pentacarbonyltungsten complexes with tertiary chiral organophosphorus compounds has high stereoselectivity and retention of configuration at the chiral P center.

The synthesis and crystal structure of the linear chain zirconium organophosphonate (NH4)Zr(F2)(H3(O3PCH2NH(CH2CO2)2)2)*3H2O*NH4Cl are presented. The novel zirconium phosphonate compound was derived from the reaction of zirconyl chloride with N-(phosphonomethyl)iminodiacetic acid in the presence of HF. It is the first example of a linear chain structure in the zirconium phosphate of phosphonate systems since the formation of such linear chains is unusual for zirconium phosphonates which usually present layered structures.

Originally utilized or developed as human poisons, anticholinesterase compounds are among the most widely used pesticides in the world and non-target wildlife are frequently exposed. Because these compounds primarily act by inhibiting acetylcholinesterase at synapses within the central and peripheral nervous systems, the potential for altering physiological and behavioral responses essential for survival and reproduction in exposed animals is great. We review the effects of acute but sublethal exposure to organophosphates and carbamates on thermoregulation (hypothermia), food consumption (anorexia and altered foraging behavior), and reproduction (altered hormone levels, reductions in clutch and litter size, and alterations in reproductive behavior), and the mechanisms believed to cause them. We believe these are the direct toxic effects most likely to reduce populations of free-living birds and mammals within treated areas. Data from studies of captive birds and laboratory mammals and free-living individuals given controlled dosages are included with an emphasis on information published within the last 5 years. The limitations of existing data for determining the biological and regulatory significance of these effects are discussed.

The magnitudes and relative orientations of chemical shielding dipolar and J coupling tensors for isolated (super31)P-(supe31)P spin pairs was studied using iterative fitting of (super)31P magic-angle spinning (MAS) nuclear magnetic resonance (NMR) spectra. Results showed that iterative fitting of (super31)P MAS NMR spectra present in transition-metal phosphine complexes can accurately determine parameters for isotropic and anisotropic interactions of isolated (super31)P-(super31)P spin pairs. These further demonstrated that the orientation of the chemical shielding tensors relative to each other and relative to the internuclear axis can be accurately measured.