A 38-Year-Old Man With Well Treated OSA on CPAP With Persistent Nocturnal Hypoxemia.

CASE PRESENTATION: A 38-year-old male with a prior diagnosis of severe OSA (apnea-hypopnea index [AHI] 99/h) presented for transfer of care. He was successfully titrated to CPAP of 10 cm H2O at an outside laboratory and was compliant with therapy with residual AHI 1.9/h. On presentation, he was polycythemic, with negative evaluation for primary polycythemia, and evaluation for hypoxemia was initiated.

Detection of uric acid stones in the ureter using low- and conventional-dose computed tomography.

OBJECTIVE: To determine the ability of low- and conventional-dose computed tomography (CT) in identification of uric acid stones, which are of lower density than calcium oxalate stones. MATERIALS AND METHODS: Uric acid stones (3, 5, and 7 mm) were randomly placed in human cadaveric ureters and scanned using conventional 140-mAs and low-dose 70-, 50-, 30-, 15-, 7.5-, and 5-mAs settings. A single-blinded radiologist reviewed a total of 523 scanned stone images. Sensitivity and specificity were compared among different settings and stone sizes. RESULTS: Imaging using 140-, 70-, 50-, 30-, 15-, 7.5-, and 5-mAs settings resulted in 97%, 97%, 96%, 93%, 83%, 83%, and 69% sensitivity and 92%, 92%, 91%, 89%, 88%, 91%, and 94% specificity, respectively. There was a significant difference in sensitivity between 140 mAs and 15, 7.5, and 5 mAs (P = .011, P = .011, and P <.001, respectively). Sensitivity for 3-, 5-, and 7-mm stones was 83%, 90%, and 93%, respectively. At ≤ 15 mAs, 3-mm stones had a higher rate of false negatives (P <.001). CONCLUSION: Both low- and conventional-dose CTs demonstrate excellent sensitivity and specificity for the detection of ureteral uric acid stones. However, low-dose CT at ≤ 15 mAs resulted in reduced detection of uric acid stones.

A prospective, randomized, controlled trial assessing diazepam to reduce perception and recall of pain during transrectal ultrasonography-guided biopsy of the prostate.

BACKGROUND AND PURPOSE: The effect of oral anxiolytics in diminishing patient discomfort and pain perception has been demonstrated in GI endoscopy, percutaneous coronary interventions, and various procedures in the emergency department setting, but has not been prospectively studied in the setting of prostate biopsy. The purpose of this study was to investigate the effect of diazepam on pain perception during and after prostate biopsy. PATIENTS AND METHODS: Sixty patients undergoing prostate biopsy at a single academic institution were enrolled into a prospective, randomized, placebo-controlled study. A questionnaire was administered prebiopsy to determine baseline discomfort and pain history. A visual analog pain scale was used to determine pain associated with each step of the transrectal Ultrasonography-guided prostate biopsy and was administered 20 minutes after biopsy and 1 week later. Responses were compared between groups using the Mann-Whitney U test, Fisher exact test, and Wilcoxon signed rank test as appropriate. RESULTS: A total of 60 patients (29 diazepam, 31 placebo) completed pre- and postbiopsy surveys for analysis. The number of cores sampled during biopsy was controlled during analysis and was found to have no correlation with total pain measured. There were no differences between diazepam and placebo groups in age, prebiopsy survey results, immediate and 1 week postbiopsy survey results. There was no difference in the patients' willingness to undergo a repeated procedure in the control and treatment groups. Complications of taking diazepam prebiopsy included drowsiness, chills, and ankle injury. CONCLUSIONS: Diazepam does not improve patient pain perception immediately after or at 1-week recall after prostate biopsy. Omitting diazepam simplifies the biopsy regimen and allows the patient to drive himself home. Based on these results, routine use of diazepam in prostate biopsy is not recommended.

Combining different design strategies for rational affinity maturation of the MICA-NKG2D interface.

We redesigned residues on the surface of MICA, a protein that binds the homodimeric immunoreceptor NKG2D, to increase binding affinity with a series of rational, incremental changes. A fixed-backbone RosettaDesign protocol scored a set of initial mutations, which we tested by surface plasmon resonance for thermodynamics and kinetics of NKG2D binding, both singly and in combination. We combined the best four mutations at the surface with three affinity-enhancing mutations below the binding interface found with a previous design strategy. After curating design scores with three cross-validated tests, we found a linear relationship between free energy of binding and design score, and to a lesser extent, enthalpy and design score. Multiple mutants bound with substantial subadditivity, but in at least one case full additivity was observed when combining distant mutations. Altogether, combining the best mutations from the two strategies into a septuple mutant enhanced affinity by 50-fold, to 50 nM, demonstrating a simple, effective protocol for affinity enhancement.

Systematic mutation and thermodynamic analysis of central tyrosine pairs in polyspecific NKG2D receptor interactions.

The homodimeric, activating natural killer cell receptor NKG2D interacts with multiple monomeric ligands polyspecifically, yet without central conformational flexibility. Crystal structures of multiple NKG2D-ligand interactions have identified the NKG2D tyrosine pair Tyr 152 and Tyr 199 as forming multiple specific but diverse interactions with MICA and related proteins. Here we systematically altered each tyrosine to tryptophan, phenylalanine, isoleucine, leucine, valine, serine, and alanine to measure the effect of mutation on affinity and thermodynamics for binding a range of similar ligands: MICA, the higher-affinity ligand MICB, and MICdesign, a high-affinity version of MICA that shares all NKG2D contact residues with MICA. Affinity and residue size were related: tryptophan could often substitute for tyrosine without loss of affinity; loss of the tyrosine hydroxyl through mutation to phenylalanine was tolerated more at position 152 than 199; and the smallest residues coincide with lowest affinities in general. NKG2D mutant van't Hoff binding thermodynamics generally show that substitution of other residues for tyrosine causes a moderate positive or flat van't Hoff slope consistent with moderate loss of binding enthalpy. One set of NKG2D mutations caused MICA to adopt a positive van't Hoff slope corresponding to absorption of heat, and another set caused MICB to adopt a negative slope of greater heat release than wild-type. MICdesign shared one example of the first set with MICA and one of the second set with MICB. When the NKG2D mutation affinities were arranged according to change in nonpolar surface area and compared to results from specific antibody-antigen and protein-peptide interactions, it was found that hydrophobic surface loss in NKG2D reduced binding affinity less than reported in the other contexts. The hydrophobic effect at the center of the NKG2D binding appears more similar to that at the periphery of an antibody-antigen binding site than at its center. Therefore the polyspecific NKG2D binding site is more tolerant of structural alteration in general than either an antibody-antigen or protein-peptide binding site, and this tolerance may adapt NKG2D to a broad range of protein surfaces with micromolar affinity.