Assessment of adenoidal obstruction in children: clinical signs versus roentgenographic findings

OBJECTIVE: As part of a comprehensive study of indications for tonsillectomy and adenoidectomy, we investigated the reliability of standardized clinical assessments and standardized roentgenographic assessments of adenoidal obstruction of the nasopharynx, and the degree of correlation between clinical assessments and roentgenographic assessments. METHODS: We rated the degree of patients' mouth breathing and patients' speech hyponasality on a 4-point scale (none = 1; mild = 2; moderate = 3; marked = 4), we averaged the ratings for each child to obtain a Nasal Obstruction Index, and we determined levels of interobserver agreement concerning the ratings. We classified lateral soft-tissue roentgenograms of the nasopharynx, based on assessments of adenoid size and of nasopharyngeal airway patency, as showing either no obstruction, borderline obstruction, or obstruction, and we determined levels of inter- and intraobserver agreement concerning the classifications. Finally, we determined correlations in individual patients between clinical ratings and roentgenographic ratings of nasal/nasopharyngeal obstruction, and calculated the predictive values of clinical ratings based on roentgenographic ratings as the gold standard. RESULTS: In sets of paired examinations, weighted kappa values for interobserver agreement concerning mouth breathing (total, 235 children) and speech hyponasality (total, 648 children) ranged from 0.84 to 0.91. The value for interobserver agreement concerning roentgenographic assessment of nasopharyngeal airway status (207 children) was 0.92, and for intraobserver agreement (191 children) 0.88. The Kendall's tau b value for concordance between Nasal Obstruction Index values and roentgenographic ratings (1033 children) was 0.51. Nasal Obstruction Index values at the lower and upper extremes--i.e., 1.0 and > or = 3.5, respectively--were highly predictive of concordant roentgenographic ratings. CONCLUSIONS: We conclude that standardized clinical ratings of the degree of children's mouth breathing and speech hyponasality provide reliable and reasonably valid assessments of the presence and degree of adenoidal obstruction of the nasopharyngeal airway. These clinical assessments are particularly valid at the extremes of either marked obstruction or no obstruction. Clinical assessment alone may be insufficient to establish the presence of adenoidal obstruction, but clinical assessment alone when findings are unequivocally negative can suffice to rule out adenoidal obstruction with a high degree of confidence.     

Identification of three candidate mutations causing type IIA von Willebrand disease using a rapid, nonradioactive, allele-specific hybridization method

Type IIA von Willebrand disease (vWD), the most common type II vWD variant, is characterized by decreased binding of von Willebrand factor (vWF) to platelet glycoprotein Ib (Gplb) and by a decrease in large and intermediate vWF multimers. Mutations reported to cause vWD type IIA are clustered within the A2 domain of vWF, which is encoded by exon 28. Genomic DNA from affected members of 12 unrelated families with type IIA vWD were screened for these mutations by a rapid, nonradioactive, allele-specific oligonucleotide (ASO) hybridization method. Oligonucleotides containing each of eight mutations were cross-linked onto a nylon membrane by UV irradiation. A fragment of vWF exon 28 was amplified from peripheral blood leukocyte DNA using biotinylated primers and hybridized to the immobilized oligonucleotides. Positive signals were detected with an avidin-alkaline phosphatase conjugate and chemiluminescent substrate. Thus, in a single hybridization reaction, a patient sample could be analyzed for a large number of mutations simultaneously. Polymerase chain reaction (PCR) products from four patients did not contain any of the tested mutations and therefore were sequenced. Three additional candidate missense mutations, two of them novel, were identified: Arg(834)-->Gln in one patient, Gly(846)-->Arg in one patient, and Val(902)-->Glu in three ostensibly unrelated patients. By ASO hybridization, the mutations were confirmed in the affected patients and excluded in unaffected relatives and 50 normal controls. In one family, the Val(902)-->Glu mutation was shown to be a de novo mutation. This rapid screening method is applicable to other subtypes of vWD for which mutations have been identified.     

Quantitative accuracy of dopaminergic neurotransmission imaging with (123)I SPECT.

123I-Labeled radiotracers are suitable for in vivo imaging of the dopaminergic system by SPECT. However, precise measurement of striatal uptake is limited by scatter, attenuation, and the finite spatial resolution of the camera. We studied the quantitative accuracy that can be achieved with (123)I SPECT of the dopaminergic neurotransmission system. METHODS: Using a Monte Carlo simulation and brain phantom experiments, we studied the biases in brain and striatal absolute uptake estimates and in binding potential (BP) values for different processing schemes with corrections for attenuation, scatter, and the partial-volume effect. RESULTS: Without any correction, brain activity was underestimated by at least 65%, and absolute striatal activity measured in regions corresponding to the anatomic contours of the striata was underestimated by about 90%. With scatter and attenuation corrections only, estimated brain activity was accurate within 10%; however, striatal activity remained underestimated by about 50%, and BP values were underestimated by more than 50%. When combined with attenuation and scatter corrections, anatomically guided partial-volume effect correction (PVC) reduced the biases in striatal activity estimates and in BP values to about 10%. PVC reliability was affected by errors in registering SPECT with anatomic images, in segmenting anatomic images, and in estimating the spatial resolution. With registration errors of 1 voxel (2.1 x 2.1 x 3.6 mm(3)) in all directions and of 15 degrees around the axial direction, PVC still improved the accuracy of striatal activity and BP estimates compared with scatter and attenuation corrections alone, the errors being within 25%. A 50% overestimation of the striatal volume yielded an approximate 30% change in striatal activity estimates with respect to no overestimation but still provided striatal activity estimates that were more accurate than those obtained without PVC (average errors +/- 1 SD were -22.5% +/- 1.0% with PVC and -49.0% +/- 5.5% without PVC). A 2-mm error in the spatial resolution estimate changed the striatal activity and BP estimates by no more than 10%. CONCLUSION: Accurate estimates of striatal uptake and BP in (123)I brain SPECT are feasible with PVC, even with small errors in registering SPECT with anatomic data or in segmenting the striata.