Search PubMed⌕ Search

Biomedical subjects

K Nichols

Publications and source records attributed to K Nichols.

At least 55 records · Page 3Linked to original sources
PubMed1986

Relationship between HLA-DR expression by normal myeloid progenitor cells and inhibition of colony growth by prostaglandin E. Implications for prostaglandin E resistance in chronic myeloid leukemia.

The expression of HLA-DR antigens by normal myeloid progenitor cells (CFU-GM) has been linked to inhibition of colony growth by prostaglandin E (PGE), while resistance to the inhibitory effects of PGE in chronic myeloid leukemia (CML) has been attributed to a lower fraction of HLA-DR+ CFU-GM in this disease. However, we have previously shown that virtually all CFU-GM in normal bone marrow (NBM) as well as CML peripheral blood express HLA-DR antigens, which raises the possibility that these surface molecules may not be the sole determinants of a progenitor cell's sensitivity to PGE. In order to evaluate the relationship between HLA-DR expression and prostaglandin inhibition, we partially purified NBM progenitor cells using fluorescence-activated cell sorting to prepare cell fractions with high and low HLA-DR antigen density. Normal progenitor cells with high DR density tended to form monocyte colonies in agar culture, whereas the low DR density fraction was enriched for granulocyte colony-forming cells. Inhibition by PGE was greatest in the high DR+ fraction and was largely restricted to monocyte progenitor cells. Inhibition of CFU-GM by PGE was less in CML than in NBM, but this decreased inhibition correlated with a significantly lower number of monocyte-CFU in CML. These data suggest that high HLA-DR antigen density may select for normal progenitor cells that are committed to monocyte differentiation and are, therefore, more likely to be inhibited by PGE. The relative deficit of monocyte progenitor cells in CML may partially explain the phenomenon of PGE resistance in this disease.

Alprostadil↗
PubMed1986

Hematogenous pyogenic vertebral osteomyelitis: diagnostic value of radionuclide bone imaging.

Hematogenous pyogenic vertebral osteomyelitis (HPVO) continues to be a diagnostic problem for clinicians due to nonspecific presentation of the disease (1,2). We reviewed our experience of the last 10 years to determine the diagnostic usefulness of radionuclide bone studies in this disease. We found 15 patients whose primary diagnosis was HPVO. Of the 15 patients, 12 had [99mTc]MDP bone scans which were all positive. Five of the 12 patients had positive [67Ga]citrate scans and one patient with chronic active HPVO had negative 67Ga and [111In]WBC bone images. At the same time, three patients' spine x-rays and one patient's CT scan of the vertebra were normal. Additionally, in three patients spine x-rays were interpreted as consistent with degenerative joint disease that contributed to the delay of the diagnosis. We conclude that when HPVO is suspected an abnormal [99mTc]MDP bone image increases the probability of the disease, even if the x-rays and CT scans of the spine are normal. An abnormal 67Ga image following an abnormal 99mTc bone image increases the specificity of the diagnosis. Normal [99mTc]MDP and [67Ga]citrate bone images of the vertebra virtually exclude the diagnosis of HPVO.

Adolescent↗
PubMed1985

Differential expression of HLA-DR antigens in subsets of human CFU-GM.

Expression of HLA-DR surface antigens by granulocyte/monocyte colony-forming cells (CFU-GM) may be important in the regulation of proliferation of these cells. Using immunological techniques to enrich for progenitor cells, we investigated the expression of HLA-DR in subsets of CFU-GM. "Early" (day 14) CFU-GM express higher levels of HLA-DR than do "late" (day 7) CFU-GM. Among late CFU-GM, cells destined to form monocyte (alpha-naphthyl acetate esterase-positive) colonies express higher levels of HLA-DR than do CFU-GM destined to form granulocyte (chloroacetate esterase-positive) colonies. Because high-level expression of DR antigen was a marker for monocyte differentiation, we examined several lymphokines for their effects on both DR expression and in vitro commitment to monocyte differentiation by myeloid precursor cells. DR antigen density could be increased by more than twofold over 48 hours upon exposure to gamma-interferon (gamma-IFN), whereas colony-stimulating factors had no effect. This was associated with a dose-dependent inhibition of total CFU-GM number, and a relative, but not absolute, increase in the ratio of monocyte colonies to granulocyte colonies. Similarly, in day 7 suspension cultures of purified myeloid precursor cells, gamma-IFN inhibited cell proliferation and increased the ratio of monocytes to granulocytes. Thus, despite the induction of high levels of HLA-DR antigen on precursor cells (a marker of monocyte commitment), the dominant in vitro effect of gamma-IFN was inhibition of granulocyte differentiation.

Antibodies, Monoclonal↗
PubMed1985

Effect of narcotic premedication on scintigraphic evaluation of gallbladder perforation.

A case of gallbladder perforation is presented in which a small bile leak was demonstrated by cholescintigraphy while the patient was receiving meperidine, but not after meperidine was discontinued. The scintigrams obtained during meperidine therapy also showed a pattern of bile-duct obstruction. It is suggested that increased biliary pressure secondary to meperidine administration permitted visualization of the leak. Use of narcotic drugs may be a useful pharmacologic intervention in cases of peritonitis due to small or obscure bile leaks.

Adult↗
PubMed1984

A new scintigraphic method for determining left ventricular volumes.

A new scintigraphic count-based method for measuring absolute left ventricular volumes is presented. It is a fast and simple technique that allows geometrical assumptions to be avoided and is free of radiation attenuation corrections. This method requires the acquisition of an image of the left ventricle in the right anterior oblique projection and the collection of gated blood pool images in the left anterior oblique projection. To assess the accuracy of the method scintigraphic stroke volumes were compared with those derived from thermodilution measurements during cardiac catheterization in 20 subjects, and to assess its precision the technique was applied to phantom data of known radionuclide volumes. Excellent correlations were found between the scintigraphic and both the thermodilution (r = .98) and phantom data (r = .99). The reproducibility (r = .97) of results was investigated by repeating data acquisition and analysis for 15 subjects on two different days, and the interobserver variability (r = .97) of the method was studied by having two computer operators calculate volumes for the same patient data for 20 randomly selected studies.

Adult↗
PubMed1977

Extraocular muscle fibers: ultrastructural identification of iontophoretically labeled fibers contracting in response to succinylcholine.

Cat extraocular muscle fibers (from the superior rectus or inferior oblique) were penetrated in vivo with Procion red-filled glass microelectrodes. When stable penetrations were obtained, succinylcholine (Sch), 8 to 20 microng, was injected into the femoral vein. In some fibers, a depolarization-repolarization response was obtained with the same time course (2 min.) as the total muscle contraction. The depolarizing fibers were labeled iontophoretically. The ultrastructural characteristics of five depolarizing fibers and three control (nondepolarizing) fibers were then studied. The fibers that did not depolarize to Sch had the characteristics of singly innervated cells, whereas those sensitive to Sch had morphological characteristics of multi-innervated fibers.

Animals↗
PubMedDate not supplied

Automation of gated tomographic left ventricular ejection fraction.

BACKGROUND: The feasibility of determining left ventricular (LV) ejection fraction (EF) from 99mTc-labeled sestamibi gated tomography (GSPECT) is well established. To improve precision of measurement, rules used by observers in processing tomograms were encoded for automation. METHODS AND RESULTS: LV centers were estimated from activity centroids of time-difference images exceeding 50% of maximum counts. End diastole and end systole were defined by time-varying maximum count extremes. Endocardial borders were generated by fitting maximum locations with fifth-order two-dimensional harmonics, searching inward to predetermined thresholds, and reconciling endocardial with valve plane points. Regression analysis of GSPECT EF yielded r = 0.87 versus equilibrium gated blood pool in 75 patients and r = 0.87 versus gated first pass in 65 patients. GSPECT EF interobserver variability was r = 0.92 and intraobserver automatic versus manual linear correlation was r = 0.94. A subgroup of 25 studies was analyzed by six independent observers, for whom EF agreement with the core laboratory ranged from r = 0.93 to r = 0.96. Experienced observers judged it necessary to alter end-diastolic or end-systolic frames in 7% of patients, endocardial borders in 14%, and LV centers in 28%. CONCLUSION: Results of automated GSPECT LV EF correlated well with those of manual GSPECT and gated first-pass and equilibrium blood pool values and were highly reproducible.

Algorithms↗
PubMedDate not supplied

First-pass radionuclide angiocardiography with single-crystal gamma cameras.

Both multicrystal and single-crystal detectors have been in use for more than 25 years for measurement of ejection fraction by analysis of images collected during the first-pass transit of radionuclides through the heart. Originally, multicrystal cameras were preferred, because they provided higher count rates than Anger cameras; however, over the years improvements in count rate capability and collimator design have enabled Anger cameras to perform equally well. This has become an important issue now that readily available 99mTc agents, such as sestamibi, enable evaluation of both myocardial function and perfusion from a single injection. The technical abilities of a particular camera determine which acquisition protocols are most likely to provide clinically useable images for the widest spectrum of patients. Electrocardiographic-gated list mode collection is highly desirable for first-pass imaging, providing the greatest flexibility of data review, rebinning, and analysis. Attention to quality control issues of data characterization and processing is important to ensure accuracy and precision of all measurements. Accurate determinations of ejection fraction of the left ventricle are possible routinely and, under favorable circumstances, of the right ventricle as well.

Coronary Circulation↗
PubMedDate not supplied

Relationship of gated SPECT ventricular function parameters to angiographic measurements.

OBJECTIVES: Left ventricular volumes and ejection fractions constitute important information in the diagnosis of cardiac disease. This investigation examined the relations of functional parameters computed with a recently published scintigraphic gated tomographic method with those from angiography, analyzing discrepancies arising from differences involved in modeling the left ventricle. BACKGROUND: While left ventricular ejection fractions obtained from myocardial perfusion gated single-photon emission computed tomography (SPECT) have demonstrated accurate comparisons with other imaging modalities, validations of volumes have not been examined as extensively, and some recent studies have reported a wide range of angiographic correlation. It is important to know how volumes obtained by a new class of methods compare with those from older, well-established techniques in order to interpret individual patients' results, particularly when scintigraphic images are severely hypoperfused. METHODS AND RESULTS: Tc-99m sestamibi myocardial perfusion gated SPECT data were processed retrospectively for 58 patients studied by single-plane angiography. Endocardial borders were generated automatically on paired vertical and horizontal long-axis Tc-99m sestamibi gated tomograms for computing ventricular volume using a Simpson's rule summation of elliptical slices. Linear regression and paired t tests were used to compare SPECT with angiographic parameters for all patients and for groups identified on the basis of tomogram visual examination as hypoperfused, ischemic or nonischemic, with the latter category further subgrouped as to fixed defects or normal perfusion. Linear regression analysis demonstrated Pearson correlation coefficients of 0.87 for end-diastolic volumes, 0.91 for end-systolic volumes, and 0.86 for ejection fraction; paired t test analysis showed end-systolic volumes to be nearly identical (p > 0.99) to angiographic values. However, paired t tests also revealed gated SPECT end-diastolic volumes and ejection fractions were significantly lower (p < 10(-4)) than angiography. Correlations and trends were essentially the same for all subgroups except for the small sample (n = 10) of patients with normal perfusion. CONCLUSIONS: Gated SPECT provides ventricular volumes and ejection fractions that correlate well with angiography, even in hypoperfused and ischemic populations. However, gated SPECT end-diastolic volumes and ejection fractions are significantly lower than angiographic measurements, partly because of inclusion of greater outflow tract amounts in standard angiographic models. Because myocyte concentration decreases rapidly at the ventricular base, it is likely that most gated SPECT methods will produce endocardial borders encompassing less of the outflow tract than do angiographic outlines.

Coronary Angiography↗
PubMedDate not supplied

Reliability of enhanced gated SPECT in assessing wall motion of severely hypoperfused myocardium: echocardiographic validation.

BACKGROUND: A method has been described for improving myocardial visibility on 99mTc-labeled sestamibi gated tomograms, even in the presence of severe hypoperfusion. It is essential to verify that images transformed in this manner truly depict the myocardium and do not contain image artifacts. This is especially important if transformed images are to be used to aid in the discernment of regional wall-motion abnormalities. METHODS AND RESULTS: All radially detected maximum counts were mapped automatically to the same brightness level for each cinematic frame. This produced tomographic cine images strongly suggestive of myocardium that appeared to translate but not to brighten from diastole to systole. Transformed scintigrams were compared with echocardiographic cine images of horizontal long axis and short axis views for 40 patients. Echocardiograms were of sufficient quality to allow comparison of radial distances from left ventricular center to midmyocardium for 15 short axis images and 25 horizontal long axis images. Readings were graded independently for 10 territories on a five-point scale (normal, mild-to-moderate hypokinesis, severe hypokinesis, akinesis, dyskinesis) of regional wall motion of original and enhanced scintigrams and echocardiograms. Comparison of echocardiographic and single photon emission computed tomographic (SPECT) locations of midmyocardial horizontal long axis points yielded a root-mean-square error value of 1.5+/-0.6 pixels (average absolute error, 11%+/-5%). SPECT versus echocardiographic wall-motion readings were compared by means of contingency table analysis. The log-likelihood ratio (G2) was 109.3 (n = 364; df = 16) with probability of no association <10(-6). Although readings of unenhanced SPECT cine images agreed well with those of echocardiograms (G2 = 94.3; n = 350; df = 16; P < 10(-6), Pearson-corrected contingency coefficients indicated stronger association with echocardiograms of transformed tomograms than with readings of original scintigrams (0.57 versus 0.51). The McNemar chi2 test indicated this improvement to be significant. The strongest associations were found between readings of unenhanced and enhanced scintigrams. Overall, similar results were obtained for horizontal long axis and short axis territories when analyzed separately. Linear regression analysis indicated strong correlations (r = .80 to r = .92) of ejection fractions from unenhanced gated SPECT images, enhanced gated SPECT images, echocardiograms, and first-pass radionuclide angiograms with no significant differences among correlations. CONCLUSIONS: Regional image enhancement succeeded in revealing shapes that genuinely represented myocardium in this population with hypoperfusion. Wall-motion conclusions were similar whether drawn from original or enhanced scintigrams, although enhancement significantly improved agreement with echocardiographic readings. Enhanced SPECT cine images allowed sensitive discrimination of regional wall-motion abnormalities, even in areas of severely hypoperfused myocardium, in excellent agreement with visual echocardiographic assessment for which myocardial visualization is independent of perfusion.

Aged↗
PubMedDate not supplied

Do patient data ever exceed the partial volume limit in gated SPECT studies?

BACKGROUND: Some single photon emission computed tomography (SPECT) methods to detect percent myocardial wall thickening (%WT) assume a linear relationship to changes in maximum myocardial counts, predicated on myocardial walls never exceeding the SPECT camera's partial volume limit. Recent studies have challenged such assumptions, reporting that systolic count changes underestimate wall thickening as measured by echocardiography and magnetic resonance imaging. METHODS AND RESULTS: To test whether clinical data ever are observed to exceed the partial volume limit, we examined gated tomograms of 75 patients selected at random and of an additional 25 patients known to have hypertension with electrocardiographic evidence of left ventricular hypertrophy. Image transformations were performed such that for every cinematic frame, radial counts at every angle were automatically normalized to the same maximum count. If no patient's myocardium ever exceeded the partial volume limit, thickness quantified from transformed images would always be the same throughout the cardiac cycle and would just correspond to the camera's line spread function. Thickness was measured by Gaussian fitting of transformed myocardial counts in the epicardial direction only to exclude cavitary count contamination. % WT was computed from thickness differences from diastole to systole. % WT values were assessed from clinical data at lateral, inferior, septal, anterior, and apical territories. Resulting %WT distributions were tested against the null hypothesis of %WT = 0 by the Z-test. Although some distributions were not actually Gaussian, the maximum mean %WT was only +3% +/-5% for the septal wall, in agreement with an observer's impressions of no detectable wall thickening. Thus mean %WT values were trivial compared with expected physiologic normal values of 30% to 50%. CONCLUSION: No convincing evidence was found of thickness above the partial volume limit in this large sample of 75 normotensive and 25 hypertensive patients. Therefore it is likely that relations between myocardial count increases and wall thickening are similar throughout the cardiac cycle, even in patients with left ventricular hypertrophy.

Adult↗
PubMedDate not supplied

Comparative performance of gated perfusion SPECT wall thickening, delayed thallium uptake, and F-18 fluorodeoxyglucose SPECT in detecting myocardial viability.

To evaluate the comparative abilities of gated single photon emission computed tomography (SPECT) wall thickening, delayed thallium-201 (Tl-201) SPECT, and F-18 fluorodeoxyglucose (FDG) SPECT in detecting myocardial viability, 23 patients with previous myocardial infarction and clinically suspected viability were studied. Each patient had at least 1 extensive fixed perfusion defect on rest/stress technetium-99m sestamibi SPECT. A total of 41 major vascular territories had fixed defects. The mean (+/- 1 SD) left ventricular ejection fraction determined from gated perfusion SPECT was 26% +/- 11%. Wall thickening was assessed in a semiquantitative fashion by the regional increase in myocardial intensity during systole and was considered normal when a > or = 20% increase was observed. Tl-201 SPECT was acquired 4 hours after resting tracer injection was administered. Viability was considered present when regional defect Tl-201 count density, determined by quantitative analysis, was > 20% greater than that on the resting sestamibi scan. FDG SPECT was performed independently with a 10 mCi F-18 FDG dose after oral glucose loading was performed. A camera equipped with ultrahigh energy collimation was used. Quantitative criteria for viability were the same as for Tl-201. In the 23 patients viability within the fixed sestamibi defects was manifest by preserved wall thickening in 8 patients, delayed Tl-201 uptake in 10 patients, and FDG uptake in 18 patients. Nine major vascular territories with fixed defects were judged viable by wall thickening, 11 by Tl-201 SPECT, and 24 by FDG SPECT (P = .0009). We conclude that FDG SPECT demonstrates more evidence of myocardial viability than either gated sestamibi wall thickening or delayed Tl-201 SPECT.

Female↗
PubMedDate not supplied

Comparison of Tc-99m sestamibi and Tl-201 gated perfusion SPECT.

BACKGROUND: To determine the interpretability of gated thallium-201 perfusion SPECT compared with that performed by use of technetium-99m sestamibi (MIBI), 33 patients with prior myocardial infarction were studied. Patients received 22 to 30 mCi (814 to 1110 MBq) MIBI at peak stress, and a 15-minute gated SPECT acquisition was begun 30 to 40 minutes thereafter. On a subsequent day gated Tl-201 SPECT was acquired for 15 minutes, 4 hours after a resting 3.5 mCi (130 MBq) injection. SPECT was performed over a 180-degree arc by use of a 90-degree angled 2-detector camera. RESULTS: Gated studies were interpreted independently by 4 experienced physicians. Study quality was graded (0 = uninterpretable to 4 = excellent). Wall motion (0 = normal to 2 = akinetic/dyskinetic) and wall thickening (0 = normal to 2 = absent) were graded for each of 10 segments viewed in orthogonal planes. Left ventricular ejection fraction (LVEF) was calculated by use of software thus far validated only for MIBI. The average count density of mid-ventricular end-diastolic short axis tomograms with sestamibi was 3.47 times greater than with thallium. Mean study quality was 3.4 for MIBI and 1.8 for thallium (P < 10(-6)). No gated MIBI SPECTs, but 2 gated thallium studies (6%) were judged uninterpretable. Among interpretable scans, interobserver agreement (Kendall statistic) in assessing wall motion was 0.73 for MIBI and 0.66 for thallium (P = .01). For assessing wall thickening, the Kendall statistic was 0.73 for MIBI and 0.69 for thallium (P = .05). Correlation (r) of LVEFs was 0.91, SEE = 6.4. CONCLUSIONS: We conclude that gated thallium SPECT is inferior to MIBI because of much poorer image quality and somewhat poorer interobserver agreement among experienced physicians. However, LVEF can be determined reliably from gated thallium SPECT.

Female↗
PubMedDate not supplied

Clinical impact of arrhythmias on gated SPECT cardiac myocardial perfusion and function assessment.

BACKGROUND: We reported previously that mean quantified cardiac functional parameters computed by one gated single photon emission computed tomography (SPECT) technique were not significantly altered by common gating errors. However, it is not known to what extent other gated SPECT approaches that are based on different ventricular modeling assumptions are influenced by arrhythmias, nor are the effects of gating errors on visual analyses and their subsequent clinical implications known. METHODS: Projection data for 50 patients (aged 64 +/- 12 years; 68% men; 76% with myocardial perfusion defects) undergoing technetium-99m sestamibi gated SPECT who were in sinus rhythm during data acquisition were altered to simulate common arrhythmias. To determine quantitative effects, we performed calculations for original control and altered images by Gaussian myocardial detection (Quantitative Gated SPECT [QGS] program) and by wall thickening derived from gated perfusion polar maps (Emory Cardiac Toolbox program). To evaluate visual assessment in control and simulated-arrhythmia tomograms, 2 experienced blinded observers independently interpreted perfusion from polar maps and wall motion and thickening from tomographic cines, using a 4-point scale. RESULTS: Although mean functional parameters were scarcely altered, paired t tests showed ejection fraction fluctuations to be significantly different from control values, causing patients to change between abnormal and normal ejection fraction categories (2% of patients by QGS and 14% by Emory Cardiac Toolbox). Visual examination of QGS polar perfusion and function maps showed changes for 72% of cases, although in only 4% were these considered to have potential clinical consequences. The kappa statistic for visual analysis of concordance between control and arrhythmia readings showed that agreement was "excellent" for perfusion, "good" for motion, and "marginal" for thickening. CONCLUSIONS: As with quantitative measurements, thickening is the parameter most prone to error in the presence of arrhythmias. It is important to test data for gating errors to avoid potentially erroneous measurements and visual readings.

Arrhythmias, Cardiac↗