Usefulness of Telfa pads in the histologic assessment of stereotactic-guided breast biopsy specimens.

Stereotactic core-needle biopsies (SCNBs) are being increasingly used for the diagnosis of breast lesions. Focal mammographic calcifications are often considered significant and sampled by SCNB. We compared diagnostic outcomes in breast tissue cut from 59 core biopsy blocks using Telfa pad embedding with those of 48 routinely embedded blocks. Specifically, we addressed the total length of core tissue in the first histologic section, the continuity and average core length in the first section, the frequency with which mammographic calcifications were confirmed histologically, and the number of sections per case needed to assure histologic-mammographic correlation. The first level of Telfa pad-embedded material showed significantly greater aggregate tissue length, more core continuity, and greater average core length. With routine embedding, we missed 3 of 17 radiologic calcific foci. With Telfa pad embedding, we detected all of the 24 calcific foci and consumed 50% fewer slides in doing so. We conclude that Telfa pad embedding of SCNBs of the breast provides an improved, cost-effective approach to diagnosis and histologic-radiologic correlation.

Diagnostic accuracy of salivary scintigraphic indices in xerostomic populations.

PURPOSE: Three decades of work to enhance the diagnostic accuracy of salivary scintigraphy have generated various plausible decision criteria. This study evaluates four commonly cited numeric indices in studies of xerostomic populations and how accurately they identify Sjögren's syndrome, chronic sialadenitis, radiation sialadenitis, and drug effects and distinguish each from the other. METHODS: Stimulated dynamic salivary scintigraphy was performed on 295 xerostomic patients and on 31 controls. The nonparametric area under the receiver operating characteristic curves expressed the diagnostic accuracy of the following scintigraphic indices: the parotid:submandibular ratio of unstimulated glandular activity, the peak:baseline uptake ratio, its time of occurrence, and the stimulated excretion fraction. RESULTS: The stimulated excretion fraction distinguished Sjögren's syndrome and radiation sialadenitis from healthy states with respective accuracies of 0.78 and 0.90. The maximum diagnostic payoff in Sjögren's syndrome occurred at a cutoff of 73%, yielding a 73% rate of test sensitivity and a 73% rate of specificity. The other three indices were not useful. Even the stimulated excretion fraction performed indifferently or poorly in most other diagnostic tasks. CONCLUSIONS: In the scintigraphic examination of xerostomic and healthy populations, an acceptable diagnostic utility of the stimulated excretion fraction was evident only in Sjögren's syndrome and radiation sialadenitis. When presented with differential diagnostic alternatives not involving radiation sialadenitis, none of the four numeric indices performed acceptably.

Scintigraphic features of chronic sialadenitis and Sjögren's syndrome: a comparison.

An abnormal salivary scintigram is an accepted objective criterion in the diagnosis of primary and secondary Sjögren's syndrome, an immune-mediated disorder characterized by xerostomia and kerato-conjunctivitis sicca. However, chronic sialadenitis constitutes a major differential diagnostic consideration in the xerostomic population. We investigated 39 cases of biopsy-confirmed chronic sialadenitis and 152 individuals with first- or second-degree Sjögren's syndrome, according to international classification criteria. We analysed scintigraphic defects in terms of glands per patient, distribution patterns, kinetics and severity. Relative to Sjögren's syndrome, chronic sialadenitis showed significantly fewer defective glands per patient, less frequent dual parotid-submandibular defects, fewer combined deficits of uptake and discharge, and milder uptake failure. No statistically significant differences were found in the frequency of single gland abnormality, predilection for submandibular involvement, and respective proportions of uptake-only and discharge-only defects. Unevaluable discharge due to low uptake, although comprising only 34% of test-positive cases, appeared to be a highly specific but insensitive scintigraphic marker for Sjögren's syndrome. In non-irradiated xerostomic populations, scintigraphy provides specific, albeit limited, diagnostic information. The procedure's ability to distinguish uptake failure from secretory failure may be a useful asset in guiding clinical management strategies and estimating outcomes.

Variability of quantitative scintigraphic salivary indices in normal subjects.

UNLABELLED: Several quantitative measures of salivary uptake and discharge have been proposed recently in the scintigraphic evaluation of xerostomia. We investigated the scatter of four time-activity curve C(TAC)-derived indices in a group of volunteer subjects who met extensive inclusionary and exclusionary criteria of salivary normalcy. METHODS: Thirty-one adult volunteers underwent dynamic salivary scintigraphy with gustatory stimulation. Any candidates with subjective xerostomia, conditions or medications associated with dry mouth, salivary gland enlargement or pregnancy were excluded from study. All subjects had normal oral exams, xerostomia scores and unstimulated whole-mouth salivary flow rates. After the intravenous administration of 99mTcO-4, scintigraphy was performed with generation of TACs derived from regions of interest centered about the four major salivary glands and the oral cavity. At 45 min postinjection, hard lemon candy was given for 15 min as a gustatory stimulus. The following functional indices were calculated for each gland: partitioned percentage (PP) of total prestimulated activity, maximum net uptake ratio (NUR) and its time of occurrence (TNUR) and percentage stimulated discharge fraction (DF). RESULTS: The following ranges were observed: parotid PP, 22%-49%; submandibular PP, 4%-31%; parotid NUR, 2.2-16.0; submandibular NUR, 1.4-16.2; parotid TNUR, 8-45 min; submandibular TNUR, 2-45 min; parotid DF, 20%-99%; and submandibular DF, 27%-98%. Every subject except one 91-yr-old man showed frequent periodic unstimulated oral transfer of salivary activity with a rising oral TAC and responded to gustatory stimulation. CONCLUSION: So-called quantitative indices may perform poorly in the scintigraphic evaluation of xerostomic patients because the effects of normal simultaneous glandular trapping, uptake, oral discharge and possible vascular washout combine to widen reference limits. Coordinated analysis of oral cavity and glandular activities, glandular index averaging and better temporal resolution may help improve diagnostic performance.

Gastrointestinal blood loss with low dose (325 mg) plain and enteric-coated aspirin administration.

OBJECTIVES: The purpose of this study was to assess gastrointestinal blood loss with low dose (325 mg) plain and enteric-coated aspirin. METHODS: A total of 47 healthy volunteers participated in randomized, controlled acute and chronic trials. Seventeen participated in a repeated measures acute trial, and 30 participated in an independent sample chronic trial. Gastrointestinal blood loss was determined by obtaining 72-hour stool collections and quantitating Chromium-51 labeled erythrocytes. RESULTS: Acute phase trials: gastrointestinal blood loss during base line was 0.47 (+/- 0.11) mL/day, 0.96 (+/- 0.12) mL/day with enteric-coated aspirin (p < 0.0006), and 1.82 (+/- 0.35) mL/day with plain aspirin (p < 0.0001 vs. base line, p = 0.0476 vs. enteric-coated aspirin). Chronic phase trials: gastrointestinal blood loss was 1.12 (+/- 0.31) mL/day with enteric-coated aspirin (p = 0.0024 vs. control) and 2.60 (+/- 0.68) with plain aspirin (p < 0.0001 vs. control, p = 0.0364 vs. enteric-coated aspirin). CONCLUSIONS: During acute and chronic ingestion, plain aspirin at a dose of 325 mg/day significantly increased gastrointestinal blood loss when compared to control or enteric-coated aspirin values, although enteric-coated aspirin values were also significantly increased compared to control. Gastric adaptation does not decrease blood loss with low dose aspirin consumption.

Hepatitis C infection, cryoglobulinemia, and vasculitic neuropathy. Treatment with interferon alfa: case report and literature review.

A patient with mononeuropathy multiplex, hepatitis C viral infection, and mixed cryoglobulinemia had axonal degeneration by EMG and vasculitis of the epineurial vessels on sural nerve biopsy. There was no evidence of viral particles in the nerve by immunofluorescence. Treatment with interferon alfa improved the patient's symptoms and cleared the hepatitis C viral RNA and cryoglobulins from the serum.

Fine-needle aspiration cytology of idiopathic pancreatic islet cell adenosis.

A 68-yr-old woman was hospitalized because of abdominal pain, an enlarged pancreatic head by CT, and a questionable 4-cm mass in the liver. Fine-needle aspiration (FNA) of the pancreatic head disclosed a highly cellular specimen consisting of clusters of cytologically bland, monotonous, small nuclei and variable but generally sparse cytoplasm. Because of the differentiated monomorphic character of the cell clusters, the postaspiration differential cytopathologic diagnosis included islet cell tumor, acinic cell tumor, carcinoid, lymphoma, and well differentiated ductal adenocarcinoma. Pancreaticoduodenectomy and hepatic biopsy yielded a grossly normal pancreas and a cirrhotic liver. Histologic examination of the pancreas revealed a spotty but extensive spectrum of islet changes ranging from normal to bland hyperplasia, nesidioblastosis, microadenosis, and neuroendocrine microadenomas, all appearing in a light and electron microscopic context of an otherwise normal pancreas. This case highlights the differential diagnostic ambiguities presented by a continuum of pancreatic islet cell proliferations, especially among patients in whom there are no known predisposing factors for such diffuse preneoplastic or neoplastic changes.

Quantification of absolute luminal diameter by computer-analyzed digital subtraction angiography: an assessment in human coronary arteries.

Determination of absolute lumen diameters has been shown to be useful in predicting the functional importance of a coronary stenosis. In this study, both single-plane and orthogonal biplane digital subtraction angiograms were obtained in human cadaver coronary arteries. A single absolute diameter was calculated at the site of greatest narrowing in 20 segments by two automated computerized algorithms. Minimum and maximum diameters at the site of the stenosis were measured from pathologic sections prepared after pressure fixation. Method 1, which determines the edges by means of the first derivative of the videodensity curve, derived absolute diameters that fell between the pathologic minimum and maximum in 10 of 20 segments. Method 2, which determines the edges by an average of the first and second derivatives of the videodensity change, derived absolute diameters that fell between the pathologic minimum and maximum diameters in 15 of 20 segments. Method 1 correlated well with the maximum pathologic diameter (r = .76) and less well with the minrmum pathologic diameter (r = .67). Method 2 correlated very well with the maximum pathologic diameter (r = .79) and also correlated well with the minimum pathologic diameter (r = .74). As would be expected, the computerized algorithms tended to overestimate the minimum pathologic diameter and to underestimate the maximum pathologic diameter. In six segments, two orthogonal views were analyzed; no further accuracy was discernible over single-plane determinations. Thus quantitative coronary angiography by digital subtraction angiography is sufficiently accurate to be of use in the measurement of the severity of a coronary stenosis.

Comparison of thyrotropin assays by relative operating characteristic analysis.

We compared two versions of a commercial double-site immunoradiometric assay for human thyrotropin, one of them claimed to show superior ability in apportioning euthyroid and hyperthyroid populations. Relative operating characteristic (ROC) analysis permits the calculation of the area under the ROC curve as an unbiased unit measure of diagnostic validity, and also yields an optimal decision point for separating the two populations, based on relative prevalences and locally perceived utilities of test outcomes. We examined 48 hyperthyroid and 50 euthyroid subjects with the original assay and with a later version from the same manufacturer and conclude that the latter demonstrates a small but significant superiority in diagnostic performance throughout the clinical range of interest. Furthermore, peak diagnostic efficacy is attained when the boundary between the two populations is set at 0.3 mIU/L. At this decision point, sensitivity is 58%, specificity is 96%, and the predictive value of a positive test is 75%.

The relationship of instrument parameters to performance within a survey peer group.

Using simulators of transmission imaging, an interlaboratory survey assessed the discriminatory performance of 86 subscribers, each of whom imaged a liver phantom in anterior and right lateral projections. Analysis was by receiver operating characteristic (ROC) with Az, the area under the ROC curve, used as a measure of accuracy unconfounded by decision bias. Az values were then defined as the dependent variable in a statistical model that related performance to several instrument design and operating parameters. Six of 14 postulated parameters explained approximately half of observed subscriber variability. These were: year of camera manufacture or upgrade, number of photomultiplier tubes, collimator type, total counts collected, use of a Co-57 disk source for imaging the phantom, and computer processing of the image. The findings confirm previous inferences drawn from controlled intralaboratory experimentation, but hitherto unsubstantiated by clinical imaging data.

Comparison of interlaboratory survey date in terms of receiver operating characteristic (ROC) indices.

Receiver Operating Characteristic (ROC) analysis in the field of visual imaging has hitherto dealt with the performance of imaging modalities, system displays, or individual readers. This study combines previously established interlaboratory survey techniques with ROC concepts to evaluate selected indices of group discrimination and of group decision criteria in a quantitative and comparative manner. One hundred forty-two subscribers to the College of American Pathologists Phantom-Imaging Series performed a series of visual detection tasks on a fabricated radioactive phantom image. Results suggest that group performance may be legitimately assessed by ROC analysis if the variables of system modality, image display, and cases are controlled, and the number of trials is sufficiently large. The latter condition may be fully satisfied through interlaboratory survey techniques that utilize currently existing peer groups.

The College of American Pathologists Phantom Series--an assessment of current nuclear imaging capabilities.

Twelve sets of emission phantoms were distributed semiannually to laboratories of nuclear medicine from 1973 through 1978. This survey aimed to create a national peer group within which it might become possible to compare and standardize nuclear imaging technics, and to evaluate and define the current state of the art in a clinical setting. Results were analyzed in terms of sensitivity (percentage of true-positives), nonspecificity (percentage of false-positives), and performance indices (true-positive/false-negative ratios) for conventional gamma cameras and for rectilinear scanners. The chief determinants of target detectability proved to be target-to-surface depth, target diameter, and intrinsic target contrast. Operational variables and instrument type produced relatively minor effect upon subscriber performance. Gamma cameras tended to show slightly more sensitivity than rectilinear scanners, but were somewhat troubled by nonspecificity. Improvements in the intrinsic resolution of second- and third-generation gamma cameras increasingly employed since 1975 showed negligible impact on performance indices. A consideration of the overall survey performance indices. A consideration of the overall survey performance permits the beginning of a quantitative estimate of current detection capability in day-to-day nuclear imaging.

Comparison of wall motion and regional ejection fraction at rest and during isometric exercise: concise communication.

The detection of regional abnormalities of left-ventricular wall motion provides strong evidence for the presence of coronary heart disease. In 129 patients undergoing coronary arteriography, the relative value of radionuclide angiographic assessment of wall motion was compared with computer-generated regional ejection fraction, at rest and during handgrip exercise. Wall motion was determined by superposition of computer-derived end-diastolic and end-systolic perimeters. Relative regional ejection fraction was determined using a computer-generated 16-color isocount image that permitted a quantitative assessment of zonal contribution to ejection fraction. Of the 129 patients, coronary arteries were normal in 31 and diseased in 98. Of 24 patients with single-vessel disease, wall-motion abnormalities were present, at rest or during exercise in 15, whereas regional ejection fraction detected 20 patients. Seventy-four patients had multivessel disease. Of these, wall-motion abnormalities occurred in 52 but regional ejection fraction was abnormal in 69 (p less than .01). Overall, sensitivity was 67% by wall motion and 91% by relative regional ejection fraction (p less than .001). Specificity was 94% by wall motion and 87% by regional ejection fraction (not significant). Thus, radionuclide angiographic assessment of regional ejection fraction during handgrip exercise is both highly sensitive and specific for coronary heart disease and significantly enhances detection of coronary heart disease compared with wall-motion assessment, with little loss in specificity.

Progressive transmural electrographic, myocardial potassium ion/sodium ion ratio and ultrastructural changes as a function of time after acute coronary occlusion.

The progressive transmural electrographic, biochemical and ultrastructural changes as a function of time after acute coronary occlusion were systematically assessed in eight dogs. Transmural plunge electrodes with poles 1 mm apart were placed in the ischemic and nonischemic zones, and coronary occlusion was maintained for 4 hours. Transmural full thickness biopsy specimens were obtained from each zone for electron microscopy before, and 1 and 4 hours after occlusion. Endocardial and epicardial layers were also obtained for assessment of myocardial potassium ion (K+) and sodium ion (Na+) concentrations. Before coronary occlusion, local Q waves were recorded an average depth of 1.0 +/- 0.34 mm from the endocardial surface. After 1 hour of occlusion, Q waves appeared at an average depth of 3.8 +/- 0.67 mm and progressed to a depth of 5.2 +/- 0.7 mm at 2 hours, 6.2 +/- 0.5 mm at 3 hours and 7.0 +/- 0.5 mm at 4 hours. After 1 hour, ultrastructural changes of early ischemia, including a decrease in glycogen and mild mitochondrial swelling, were seen in the endocardial layer; the epicardial layer showed normal morphologic features. After 4 hours, the endocardial layer showed well developed ischemic changes marked by the loss of mitochondrial cristae, vacuolization, the appearance of amorhopous mitochondrial cristae, vacuolization, the appearance of amorphous mitochondrial densities, an increase in interfibrillary space and the appearance of I bands. In contrast, the epicardial layer at this time showed only early ischemic changes. At the end of 4 hours, the endocardial layer showed a marked decrease in myocardial K+ concentration and an increase in Na+ concentration leading to complete reversal of K+/Na+ ratio (0.7 +/- 1.0; P less than 0.001). In the epicardial layer, a smaller decrease in K+ concentration and an increase in Na+ concentration occurred, resulting in a diminution but not a reversal of K+/Na+ ratio (1.4 +/- 0.2; P less than 0.005). Thus, the dynamic evolution of an acute myocardal infarction involves a sequential progression from endocardium to epicardium as a function of time, resulting in an epicardial "border zone" in the early stages after acute coronary occlusion.