Effect of the number of projections collected on quantitative perfusion and left ventricular ejection fraction measurements from gated myocardial perfusion single-photon emission computed tomographic images

Background

Gated myocardial perfusion single-photon emission computed tomographic (SPECT) imaging is currently performed by step-and-shoot detector rotation, resulting in acquisition dead time and lengthened study duration compared with nongated SPECT imaging with continuous or pseudocontinuous rotation. Dead time is particularly undesirable in new fast-gated SPECT imaging protocols with inotropic pharmacologic stress.

Methods and Results

This article evaluated the influence of projections’ angular spacing on quantitative measurements of left ventricular ejection fraction (LVEF) and perfusion from postexercise ^99mTc-labeled sestamibi images. Gated 60-projection data sets from 30 patients were compacted into 30- and 15-projection sets. The three sets (corresponding to 3-, 6-, and 12-degree spacing over 180 degrees) were reconstructed into gated and ungated short-axis image sets. LVEFs were measured from the gated images according to a previously described automatic algorithm, whereas perfusion was assessed from the ungated images by a 20-segment division of their maximal pixel polar maps. LVEF values were essentially unchanged between 60- and 30-projection images (y=0.37+0.996x; r=0.999; standard error of the estimate=0.56) and 60- and 15-projection images (y=1.35+0.987x; r=0.999; standard error of the estimate=0.77) in the 30 patients. Overall, 30- and 15-projection polar maps differed by 1.87%±1.24% and 4.38%±2.25% from the 60-projection polar maps, respectively. Segmental perfusion score agreement between 60- and 30-projection images and between 60- and 15-projection images was 93% (κ=0.92; p<0.001) and 83% (κ=0.81; p<0.001), respectively. Sixty- and 30-projection images were visually undistinguishable, whereas loss of image resolution was noticed in many 15-projection gated and ungated images.

Conclusions

Thirty-projection gated SPECT imaging is a practical, accurate, and time-saving approach in standard gated protocols and, potentially, fast-gated protocols. Fifteen-projection gated SPECT imaging is not generally recommended and should be considered only for LVEF assessment in conjunction with fast-gated protocols.     

Molecular basis of defective anion transport in L cells expressing recombinant forms of CFTR

Cystic fibrosis (CF) is caused by mutations in the gene encodinga chloride channel called the CF transmembrane conductance regulator(CFTR). A single mutation in this gene, deletion of three nucleotidesthat leads to the absence of phenylalanine 508 (i.e., F508),is found on 70% of all CF chromosomes. To explore the molecularmechanism(s) responsible for defective chloride transport inpatients with CF, we have studied the processing, localization,and function of wild type (W.T.), F508 and G551D CFTR (a GDmissense mutation at position 551) in retrovirus transducedL cells. Cell transduced with W.T. CFTR expressed a 170 kd CFTRprotein that was endoglycosidase H (Endo H) resistant, localizedto the plasma membrane, and generated a cAMP-mediated anionconductance (G_Cl) when stimulated with standard concentrationsof forskolin (5 µM), cpt cAMP (400 µM) and IBMX(100 µM). The G551D CFTR was indistinguishable from W.T.CFTR with respect to post-translational processing and localization,but it did not produce a cAMP-activated G_CI in response to thestandard stimulation cocktail. However, raising the IBMX concentrationto 4 mM produced Gc, in G551D expressing cells. Cells transducedwith F508 CFTR expressed an Endo H sensitive CFTR protein (140kd) that was found in a cytosolic, perinuclear location. Thesecells did not respond to the standard cocktail, but 20% of cellsincreased G_CI when the cocktail contained 4 mM IBMX. Incubationof cells at 26°C for 48 hours prior to analysis elicitedresponses in F508 expressing cells at low IBMX concentrations,but had no effect on the responses of cells expressing W.T.or G551D CFTR. The response of F508 to 26°C was associatedwith plasma membrane localization of CFTR protein. These resultssuggest that there are two mechanisms whereby CFTR mutationslead to loss of cAMP-responsive GCI. First, shown by G551D CFTR,the protein can be processed and targeted to the plasma membranecorrectly, but lack full responsiveness to stimulation by cAMP.Second, as examplified by F508 CFTR, a partially functionalprotein which is not targeted to its correct cellular locationcan also lead to loss of the cAMP, responsive G_CI.     

Noninvasive imaging of the lower extremity for deep venous thrombosis

Noninvasive imaging for LE DVT has advanced remarkably in the past decade. Currently, IPG and ultrasound techniques (RTU and DS) have been proven to be quick, accurate, relatively inexpensive, and widely available methods for detecting proximal LE DVT and can be used as the initial diagnostic studies in many settings. Color-flow Doppler ultrasound studies may be more accurate than other ultrasound techniques in diagnosing calf DVT and in differentiating acute from chronic LE DVTs, though this bears further review. Many concerns remain regarding noninvasive LE DVT imaging, including:

Kraepelin-oriented research-diagnosable schizophrenia,mania, and depression in schneider-negative schizophrenics

Summary The rigorous neo-Kraepelinean research criteria of the St. Louis/ Iowa and Taylor groups were applied to case record data of 116 first admissions of Schneider-negative schizophrenics—that is, those without first-rank symptoms (FRSs)—hospitalized in a strongly Schneider-oriented German University Psychiatric Clinic from 1962 to 1971. This sample had a total of 45.7% (53 cases) of psychiatric illness diagnosable by research methods. Indeed, only 31% (36 cases) of Schneider-negative schizophrenics turned out to have research-positive Kraepelin-oriented schizophrenia; and of these, 21 fulfilled both sets of research criteria for schizophrenia. It is important that 14.6% (17 cases) of Schneider-negative schizophrenia consisted of research-diagnosable affective disorder, with mania making up 5.2% and depression 9.4% of this figure. The findings suggest that a sample of Schneider-oriented schizophrenia without FRSs as routinely diagnosed in Germany does not seem to represent a clear-cut homogeneous and uncontaminated group of schizophrenics.     

Pharmacokinetics of hydralazine and its acid-labile hydrazone metabolites in relation to acetylator phenotype

The pharmacokinetics of hydralazine (H) and its acid-labile hydrazone metabolites were compared in rapid and slow acetylators. Following a 20-mg intravenous infusion, the elimination half-life (t_1/2) and the apparent volume of distribution of H did not differ between the two groups. Plasma clearance estimates approached hepatic blood flow. When a single 100-mg dose of H was given-orally, the area under the plasma concentration-time curve (AUC) and systemic availability () in slow acetylators were, on the average, twice as high as in the rapid acetylators, indicating a difference in the extent of first-pass metabolism of the drug. Furthermore, the observed in the slow individuals exceeded theoretical predictions. Hence saturation of first-pass metabolism of H is suggested, and a nonlinear relationship between AUC and oral dose of H was indeed observed in the three subjects studied with two doses. The half-life of decline of the acidlabile metabolites was similar to the t_1/2 of H. The AUCs for metabolites were 4–12 times larger than for the parentdrug. However, the ratio between the metabolite AUC and drug AUC did not differ irrespective ofroutes of administration or the acetylator status.This study was supported in part by Grant RR 828 from United States Public Health Service and a Research Starter grant from the Pharmaceutical Manufacturers Association Foundation, Inc. (D. D. S.).     

Factors affecting the performance of the styles cell transformation test

The effects of certain factors on the performance of the cell transformation test of Styles were examined by testing the demonstrability of transformation of cells of a subclone of BHK21 C13 in response to treatment with 4-nitroquinoline-1-oxide, N-methyl-N'-nitro-N-nitrosoguanidine, benzo[a]pyrene and 2-acetamidofluorene. An important requirement for success was supplementation of the soft agar medium with a serum which supported microcolony formation by a high proportion of the cells. Increasing the concentration of an unsuitable serum improved the results obtained; this suggests that the serum was inadequate rather than inhibitory. Alteration of the concentration of S-9 fraction used to activate the precarcinogens benzo[a]pyrene and 2-acetamidofluorene had little effect on the induction of transformation by either. A clearer distinction between the transformation frequencies for control and treated cells was usually obtained when 500 microm rather than 200 microm was the minimum diameter set for definition of transformation. It is suggested that, to assess the validity of results obtained with compounds which appear to induce transformation only at highly toxic levels, transformation frequencies for treated cells should be compared with those for control cells seeded at comparable densities.     

Pharmacokinetics and protein binding of cis-dichlorodiammine platinum (II) administered as a one hour or as a twenty hour infusion

Summary The pharmacokinetics of cis-dichlorodiamminoplatinum (II) (cisplatin) have been studied in seven patients, of whom four received the drug as a one hour infusion and three received it as a 20 h infusion. The patients receiving the drug over one hour exhibited biphasic clearance of total platinum with a rapid initial phase (8.7–22.5 min) and a prolonged second phase (30.5–106 h). Free (ultrafilterable) cisplatin was readily detectable in this group and was rapidly cleared (half-life about 22 min). The volume of distribution of the drug was 50.3–65.6 liters and it was 26.6–50% excreted in the urine in 48h. In the patients receiving the 20 h infusion, a more complex plasma elimination curve was seen, with the appearance of a secondary peak. Free drug was not detectable in these patients and they showed less urinary excretion (21.4–25.9% at 48 h) than the one hour group. Cisplatin was bound to several plasma proteins, including albumin, transferrin, and -globulin. The data indicate that cisplatin is retained in the body more extensively after a 20 h infusion than after a one hour infusion.