Myocardial perfusion SPECT reconstruction: Receiver operating characteristic comparison of CAD detection accuracy of filtered backprojection reconstruction with all of the clinical imaging information available to readers and solely stress slices iteratively reconstructed with combined compensation

BACKGROUND: Past receiver operating characteristic (ROC) studies have demonstrated that single photon emission computed tomography (SPECT) perfusion imaging by use of iterative reconstruction with combined compensation for attenuation, scatter, and detector response leads to higher area under the ROC curve (A(z)) values for detection of coronary artery disease (CAD) in comparison to the use of filtered backprojection (FBP) with no compensations. A new ROC study was conducted to investigate whether this improvement still holds for iterative reconstruction when observers have available all of the imaging information normally presented to clinical interpreters when reading FBP SPECT perfusion slices. METHODS AND RESULTS: A total of 87 patient studies including 50 patients referred for angiography and 37 patients with a lower than 5% likelihood for CAD were included in the ROC study. The images from the two methods were read by 4 cardiology fellows and 3 attending nuclear cardiologists. Presented for the FBP readings were the short-axis, horizontal long-axis, and vertical long-axis slices for both the stress and rest images; cine images of both the stress and rest projection data; cine images of selected cardiac-gated slices; the CEQUAL-generated stress and rest polar maps; and an indication of patient gender. This was compared with reading solely the iterative reconstructed stress slices with combined compensation for attenuation, scatter, and resolution. With A(z) as the criterion, a 2-way analysis of variance showed a significant improvement in detection accuracy for CAD for the 7 observers (P = .018) for iterative reconstruction with combined compensation (A(z) of 0.895 +/- 0.016) over FBP even with the additional imaging information provided to the observers when scoring the FBP slices (A(z) of 0.869 +/- 0.030). When the groups of 3 attending physicians or 4 cardiology fellows were compared separately, the iterative technique was not statistically significantly better; however, the A(z) for each of the 7 observers individually was larger for iterative reconstruction than for FBP. Compared with results from our previous studies, the additional imaging information did increase the diagnostic accuracy of FBP for CAD but not enough to undo the statistically significantly higher diagnostic accuracy of iterative reconstruction with combined compensation. CONCLUSIONS: We have determined through an ROC investigation that included two classes of observers (experienced attending physicians and cardiology fellows in training) that iterative reconstruction with combined compensation provides statistically significantly better detection accuracy (larger A(z)) for CAD than FBP reconstructions even when the FBP studies were read with all of the extra clinical nuclear imaging information normally available.     

Notochordal cells stimulate migration of cartilage end plate chondrocytes of the intervertebral disc in in vitro cell migration assays

Background contextIt was recently demonstrated that the postnatal transition from a notochordal to a fibrocartilaginous nucleus pulposus (NP) is accomplished exogenously by chondrocytes migrating from hyaline cartilage end plates (CEs) into the ectopic notochordal NP region. Although our previous in vivo studies showed evidences for the migration of CE chondrocyte from hyaline CEs into the notochordal NP, it is unknown whether CE chondrocytes of the intervertebral disc (IVD) really have a motile property. In addition, the effect of notochordal cells on this property has not been elucidated.PurposeThe purpose of this in vitro study was to demonstrate whether CE chondrocytes of the IVD are capable of migration, and whether there is any biological link between notochordal cells and CE chondrocytes that may regulate the CE chondrocyte migration.Study design/settingIn vitro cell migration assays were performed using rat IVDs.MethodsNotochordal cells and chondrocytes were obtained from the NP and CE tissues, respectively, and were cultured separately. The different numbers of notochordal cells and the supernatant (conditioned medium) that contained soluble factors produced by notochordal cells were used to demonstrate their effects on the migration of CE chondrocytes. Bovine serum albumin (BSA) and lysophosphatidic acid (LPA) were used as negative and positive controls, respectively.ResultsCompared with BSA, LPA, notochordal cells (N=4×, 2×, 1×, and 0.5×10⁵), and its conditioned media (unconcentrated and fivefold concentrated) significantly increased migration of CE chondrocytes (p<.05 in all comparisons). Particularly, notochordal cells and its conditioned media increased migration in a number- and concentration-dependent manner, respectively.ConclusionsThis study demonstrates that CE chondrocytes of the IVD are capable of migration and that soluble factors produced by notochordal cells stimulate the migration. These results provide a plausible explanation to the question of why CE chondrocytes of the IVD migrate into the ectopic NP region during the natural transition from the notochordal to fibrocartilaginous NP.     

Nucleotide Sequence of the ADH23 Gene Encoding the Human Alcohol Dehydrogenase β3 Subunit

All nine exons of the ADH2(3) allele, which encodes the human alcohol dehydrogenase beta 3 subunit, have been cloned and sequenced. Comparison of this sequence to the ADH2(1) nucleotide sequence revealed only a single difference that results in an amino acid change, thus proving that the significant kinetic differences between these two isozymes is due to the Cys for Arg substitution at position 369. There are also two silent polymorphisms, and two changes in noncoding regions.     

Comparative genomic hybridization (CGH) of augmentation cystoplasties

OBJECTIVE: Tumors arising within augmentation cystoplasties are aggressive, have poor prognosis and the majority are not detected at follow-up cystoscopy. Genetic changes in tumors precede morphological abnormalities. Therefore, the aim of this study was to investigate whether genetic abnormalities detected by comparative genomic hybridization (CGH) could be used to identify those patients with augmentation cystoplasties at increased risk of tumorigenesis. METHODS: Bladder biopsy samples were obtained from 16 augmentation cystoplasty patients both distant from and near to the enterovesical anastomosis. CGH was used to detect genetic abnormalities in DNA extracted from the biopsies, archival specimens of two augmentation cystoplasties and two de novo bladder adenocarcinomas. RESULTS: A greater number of amplifications on 2p, 3q, 8q, 9p, 17p, 18pq and 20pq, were observed in bladder biopsies obtained near to the enterovesical anastomosis compared to those taken distant to the suture line. CGH of archival augmentation cystoplasty tumor DNA indicated abnormalities at several loci with amplifications at 2q, 5q, 10p and 21pq, while deletions occurred at 5p and 16p. CONCLUSIONS: The results of this study suggest that the urothelium adjacent to the bladder and/or bowel anastomosis in augmentation cystoplasties is genetically unstable. Furthermore, longitudinal studies are required to establish whether or not patients exhibiting genetic instability following augmentation cystoplasty are at greater risk of developing tumors than those with genetically stable epithelia.     

COMPARISON OF REFLEX MODIFICATION PROCEDURES AND AUDITORY BRAINSTEM RESPONSE IN HIGH-RISK NEONATES

This study compared the results of reflex modification (RM)--an objective technique for assessing brainstem sensorineural processing--with those of auditory brainstem response (ABR) for a group of high-risk infants at comparable postconceptional ages. For the RM procedure, an eyeblink-eliciting tap to the glabella was presented either alone or accompanied by a brief 90dB SPL tone. 37 high-risk infants were tested with both RM and ABR at a mean postconceptional age of 37.3 weeks. Seven had an increased brainstem conduction time ('failed ABR') and eight did not exhibit significant reflex augmentation ('failed RM'), seven of whom also failed the ABR. These data provide evidence that sensory stimuli which affect the neural mechanisms responsible for the organization of the startle response and auditory processing share essential neural components.     

In-vitro/in-vivo correlation of pulsatile drug release from press-coated tablet formulations: a pharmacoscintigraphic study in the beagle dog.

The aim of the current study was to investigate the in-vitro and in-vivo performance of a press-coated tablet (PCT) intended for time delayed drug release, consisting of a rapidly disintegrating theophylline core tablet, press-coated with barrier granules containing glyceryl behenate (GB) and low-substituted hydroxypropylcellulose (L-HPC). The PCTs showed pulsatile release with a lag time dependent upon the GB and L-HPC composition of the barrier layer. In-vivo gamma-scintigraphic studies were carried out for PCTs containing GB:L-HPC at 65:35 w/w and 75:25 w/w in the barrier layer in four beagle dogs, in either the fed or fasted state. The in-vivo lag time in both the fed and fasted states did not differ significantly (p>0.05) from the in-vitro lag time. Additionally, no significant difference (p<0.05) between in-vivo fed and fasted disintegration times was observed, demonstrating that in-vivo performance of the PCT was not influenced by the presence or absence of food in the gastrointestinal tract. A distinct lag time was obtained prior to the appearance of drug in plasma and correlated (R2=0.98) with disintegration time observed from scintigraphic images. However, following disintegration, no difference in pharmacokinetic parameters (AUC(0-6 dis), K(el), Cmax) was observed. The current study highlighted the potential use of these formulations for chronopharmaceutical drug delivery.