Cytopathogenic mechanisms of Entamoeba histolytica.

Cinemicrography of Entamoeba histolytica destruction of Chinese hamster ovary (CHO) cells shows that ameba cytopathogenicity consists of separate components: a contact-dependent cytolethal effect, and phagocytosis. Cells not in contact with amebae remain intact. Quantitation of ameba destruction of CHO cells by applying the one-hit hypothesis confirms that the cytoethal effect of amebae is contact dependent. Studies with 111Indium oxine-labeled cells provide further evidence of extracellular killing by E. histolytica and indicate that > 94% of the target cells are killed before phagocytosis. When we examined for a cytotoxin release by E. histolytica, we found no effect on CHO cells with filtrates of amebae, and a nonspecific effect of cell rounding and release with sonicates of amebae. The ameba sonicate effect was time-dose dependent, was not cytolethal, was reversible, and was inhibited by alpha II macroglobulin. Cytochalasin B altered ameba motility and morphology, and monolayer experiments confirmed that cytochalasins A, B, or D inhibited CHO cell destruction by E. histolytica. Cytochalasin D also inhibited extracellular killing of CHO cells by amebae in pellets, apparently independent of effects on ameba motility or phagocytosis. Colchicine and vinblastine, alone or in combination with cytochalasin D, did not inhibit E. histolytica cytopathogenicity, which indicates that microtubule function is not required for target cell killing by amebae.

The Reference Image Database to Evaluate Response to therapy in lung cancer (RIDER) project: a resource for the development of change-analysis software.

Critical to the clinical evaluation of effective novel therapies for lung cancer is the early and accurate determination of tumor response, which requires an understanding of the sources of uncertainty in tumor measurement and subsequent attempts to minimize their effects on the assessment of the therapeutic agent. The Reference Image Database to Evaluate Response (RIDER) project seeks to develop a consensus approach to the optimization and benchmarking of software tools for the assessment of tumor response to therapy and to provide a publicly available database of serial images acquired during lung cancer drug and radiation therapy trials. Images of phantoms and patient images acquired under situations in which tumor size or biology is known to be unchanged also will be provided. The RIDER project will create standardized methods for benchmarking software tools to reduce sources of uncertainty in vital clinical assessments such as whether a specific tumor is responding to therapy.

Plasma renin activity and albumin excretion in teenage type I diabetic subjects. A prospective study.

Plasma renin activity (PRA) may be high among teenage and young adult insulin-dependent diabetic subjects. Supine PRA and stimulated PRA were therefore measured in 50 female and 50 male diabetic subjects, 13-20 years old, diagnosed before the age of 16. Fifty percent have been restudied after 4.6 +/- 0.2 (mean +/- SEM) years. Initially, 43% had high PRA (supine 4.0 +/- 0.37, stimulated 12.02 +/- 0.8 ng/ml/hr angiotensin I), 45% had normal activity (supine 2.89 +/- 0.26, stimulated 6.47 +/- 0.34 ng/ml/hr/angiotensin I), and 12% had low activity (supine 1.57 +/- 0.05, stimulated 3.09 +/- 0.08 ng/ml/hr/angiotensin I). Levels were directly associated with prepubertal duration of diabetes and were inversely associated with duration of diabetes after onset of puberty but not with total duration or patient age. Within 4.6 +/- 0.2 years the percentage of subjects with high PRA fell to 13%, and the percentage of those with low PRA rose to 35%. Initially 51% of the cohort had normal albumin excretion rates (AER) at rest and during exercise equal to or less than 10 micrograms/min/m2; 32% had elevated rates only during exercise of 39 +/- 5 micrograms/min/m2; 13% had elevated rates at rest of 41 +/- 8 micrograms/min/m2 and during exercise of 116 +/- 21 micrograms/min/m2; and 4% had clinical proteinuria at rest and during each exercise period equal to or greater than 150 micrograms/min/m2. After 5 years, 58% continued to have normal AER, or their AER improved.(ABSTRACT TRUNCATED AT 250 WORDS)

Lymphoscintigraphy and lymphedema of the lower extremities.

Lymphoscintigraphy, using technetium-99m-labeled sulphur microcolloid, was employed to study the flow and transport of lymph in the lower extremities of 39 consecutive patients in whom lymphedema of one or both legs was suspected clinically. Time-activity curves of four segments of each leg were evaluated for lymph capacity, flow and soft-tissue uptake, and compared with the results from film scintigraphy. Curve analysis provided quantitative evaluation of the extent of hypoplasia or aplasia in primary lymphedema and of lymphatic obstruction in secondary lymphedema, and is particularly suited to assess the involvement of lymphatics in chronic venous disease. Film scintigraphy, on the other hand, is preferable in cases in which the pattern of activity distribution in the affected extremity is diagnostic, such as in dermal back flow, traumatic lymphocele, or megalymphatics. Venography is most informative in cases of suspected underlying venous disease, but the role of lymphangiography, which shows only part of the lymphatic system and requires incision of the edematous tissues, is considered questionable.

A noninvasive scintigraphic assessment of the colonic transit of nondigestible solids in man.

A noninvasive, scintigraphic technique for quantifying large intestinal transit time that provides low radiation doses was developed. The scintigraphic large intestinal transit (SLIT) method uses a total of 100 microCi of 111In encapsulated in ten 2-cm nondigestible capsules, which are ingested after a 6-hr fast. Two hundred fifty microcuries of 99mTc-sulfur colloid were given to outline the gastrointestinal tract. Images were acquired at 4-hr intervals until all capsules were excreted. Normal volunteers (n = 10) consumed a standardized diet 2 days prior and during imaging. Segmental transit times were measured in the following: ascending, transverse, descending, recto-sigmoid colons; hepatic and splenic flexures. The radiation absorbed dose to the large intestine for the SLIT technique is less than half of that associated with other radiographic methods of colonic transit time measurement.

Considerations in the purchase of a nuclear medicine computer system.

Selection of a nuclear medicine computer system is a process that should be approached with care and forethought. The general scheme should be to define your needs and constraints, determine what is available, investigate the leading candidates, make a site visit, and, finally, submit an order. Through a series of discussions between members of the Computer Council of the Society of Nuclear Medicine and representatives from the manufacturers of computer systems, a set of important considerations emerged, which are reported in this paper. This paper is not intended to be a step-by-step guideline to the purchase of a computer system. Rather, it is a set of concepts and considerations with which the prospective purchaser should be familiar before undertaking such a purchase.

Instrumentation and computers for brain single photon emission computed tomography.

Cerebral single-photon emission computed tomography (SPECT) requires attention to the instrumentation because of the anatomical location of the head at one end of the body, with a generally narrower diameter than the rest of the body. For a number of years, there have been SPECT units designed especially for head work, as well as general-purpose units that have performed well in imaging the head. The current emphasis on cerebral perfusion, using either agents that wash in and out with blood flow or agents that reflect blood flow in their static distribution, has allowed a concentration on imaging hardware and computer hardware and software for this purpose.

Effects of percutaneous transluminal angioplasty on renal plasma flow.

Percutaneous transluminal angioplasty is being used with increasing frequency for the treatment of renal artery stenosis. Several noninvasive techniques that utilize radioactive tracers have been used for monitoring the effects of angioplasty and progression of disease. Forty-one patients were studied before and after renal angioplasty by using renograms and fractionated measurements of effect renal plasma flow. Although there were striking examples of improvement in effective renal plasma flow following angioplasty, this was not a consistent finding. There was a tendency for effective renal plasma flow to revert to the baseline level on follow-up studies. Cure of hypertension was more likely in patients without renal insufficiency and in patients with shorter periods of sustained hypertension. Fractionated effective renal plasma flow studies did not reliably differentiate patients who were cured from those who were improved nor were we able to delineate clearly those requiring repeat dilatation. Nevertheless, this technique is useful for noninvasively measuring fractionated renal function in the immediate postoperative or postdilatation recovery period and for detecting the difference between occlusion of the renal artery and transient renal insufficiency due to contrast material. Also, long-term measurement of fractionated function has value in following potential progression of the basic disease process.

Preparation, biodistribution, and dosimetry of 188Re-labeled MoAb ior cea1 and its F(ab')2 fragments by avidin-biotin strategy.

The biotinylated monoclonal antibody (MoAb) ior cea1 and its F(ab')2 fragments were labeled with Re-188 by combination of avidin-biotin strategy. 188Re-MoAb, 188Re-MoAb-biotin, 188Re-F(ab')2, and 188Re-F(ab')2-biotin preparations were produced for these studies with specific activities of 1.30+/-0.18 GBq/mg and from instant freeze-dried kit formulations using ethane-1-hydroxy-1,1-diphosphonic acid (EHDP) as a weak competing ligand. There were no significant differences (p > 0.05) between the biodistribution in mice of biotinylated and unbiotinylated 188Re-labeled immunoconjugates. When avidin was injected as a chase after injection of 188Re-MoAb-biotin or 188Re-F(ab')2-biotin, the blood radioactivity level decreased approximately 75% (cumulated activity) and the effective dose decreased almost 25% with respect to that of the radioimmunoconjugates in which the chase effect was not used. Our results suggest that 188Re-labeled biotinylated MoAb ior ceal and its F(ab')2 fragments prepared by this method are stable complexes in vivo.

Evaluation of digital image enhancement techniques for liver scintigrams.

Digital image enhancement techniques were employed in an effort to improve the resolution of Anger camera liver images. The premise employed was that methods which improve lesion detectability in liver phantoms should also do so in actual liver scintigrams. The types of image processing evaluated were: contrast enhancement, finite and infinite impulse response, modulation transfer function correction, homomorphic and median filtering. Observers were used to evaluate each method for its ability to improve lesion detectability using a five category rating system. The Localization Receiver Operating Characteristic (LROC) curve was used as the primary rank ordering method. A point system and analysis of variance were used as corroborative methods, incorporating measures of accuracy and consistency of the observers' answers.

National Cancer Institute initiative: Lung image database resource for imaging research.

Preliminary clinical studies suggest that spiral computed tomography (CT) of the lungs can improve early detection of lung cancer in high-risk individuals. More clinical studies are needed, however, before public health recommendations can be proposed for population-based screening. Spiral CT generates large-volume data sets and thus poses problems in terms of implementation of efficient and cost-effective screening methods. Image processing algorithms such as computer assisted diagnostic (CAD) methods have the potential to assist in lesion (eg, nodule) detection on spiral CT studies. CAD methods may also be used to characterize nodules by either assessing the stability or change in size of lesions based on evaluation of serial CT studies, or quantitatively measuring the temporal parameters related to contrast dynamics when using contrast material-enhanced CT studies. CAD methods therefore have the potential to enhance the sensitivity and specificity of spiral CT lung screening studies. Lung cancer screening studies now under investigation create an opportunity to develop an image database that will allow comparison and optimization of CAD algorithms. This database could serve as an important national resource for the academic and industrial research community that is currently involved in the development of CAD methods. The National Cancer Institute request for applications (RFA) (CA-01-001) has already been announced (April 2000) to establish and support a consortium of academic centers to develop this database, the consortium to be referred to as the Lung Image Database Consortium (LIDC). This RFA is now closed. Five academic sites have been selected to be members of the LIDC, the first meeting of this consortium is planned for spring of 2001, and a public meeting is to be held in 2002. This report is abstracted from the previously published RFA to serve as an example of how an initiative is developed by the National Cancer Institute to support a research resource. For specific details of the RFA, please access the following Internet site: http://www. nci.nih.gov/bip/NCI-DIPinisumm.htm#a11.

Study design in the evaluation of breast cancer imaging technologies.

RATIONALE AND OBJECTIVES: Bringing a new imaging technology to market is a complex process. Beyond conceptualization and proof of concept, obtaining U.S. Food and Drug Administration (FDA) approval for clinical use depends on the documented experimental establishment of safety and efficacy. In turn, safety and efficacy are evaluated in the context of the intended use of the technology. The purpose of this study was to examine a conceptual framework for technology development and evaluation, focusing on new breast imaging technologies as a highly visible and current case in point. MATERIALS AND METHODS: The FDA views technology development in terms of a preclinical and four clinical phases of assessment. With a concept of research and development as a learning model, this phased-assessment concept of regulatory review against intended use was integrated with a five-level version of a hierarchy-of-efficacy framework for evaluating imaging technologies. Study design and analysis issues are presented in this context, as are approaches to supporting expanded clinical indications and new intended uses after a new technology is marketed. CONCLUSION: Breast imaging technologies may be intended for use as replacements for standard-of-care technologies, as adjuncts, or as complementary technologies. Study designs must be appropriate to establish claims of superiority or equivalence to the standard for the intended use. Screening technologies are ultimately judged on their demonstrated effectiveness in decreasing cause-specific mortality through early detection, but they may be brought to market for other uses on the basis of lesser standards of efficacy (eg, sensitivity, specificity, positive and negative predictive value, and stage of disease detected).

Radiographic examination of the stomach and duodenum: comparison of single-, double- and biphasic-contrast methods.

We compared retrospectively three groups of 150 patients who had undergone radiologic examinations of the stomach and duodenum. Each group was examined with a different barium suspension and radiographic technique: single-contrast (SC), double-contrast (DC), or biphasic-contrast (BC). The radiographs of each study were evaluated for technical quality and visualization of lesions. The number of X-ray exposures, films, and the amount of fluoroscopic time for each study were tabulated. The total radiation dose and cost for each technique were calculated. The BC examinations required the greatest number of radiographic exposures and X-ray films; however, cost was highest for the DC method. Fluoroscopy was significantly longer during the DC procedures, and the total radiation dose was also highest with this technique. Gaseous distention and barium coating of the stomach were equally good for the BC and DC groups, but X-ray penetration of the barium suspension during compression filming was significantly better in the BC and SC groups. Areae gastricae were most frequently seen during the BC studies and artifacts from excess secretions, barium flocculation or gas bubbles were least commonly present using this technique. Significantly more lesions were demonstrated in the stomach with the BC technique than with the other methods; however, the number of lesions found in the duodenum was the same for each technique.

Computed tomography as a diagnostic aid in diabetic and other problem feet.

Determining whether osteomyelitis is present in patients with foot infections represents a significant diagnostic challenge. As bone uptake with nuclide scans can be affected by soft tissue infection, we performed computed tomography (CT) on seven patients to see if marrow or bone abnormalities could be seen and used to predict the presence or absence of osteomyelitis. The CT scans correctly predicted the presence or absence of osteomyelitis in all seven patients. Four patients had osteomyelitis and three patients did not. Nuclide bone scans had one false-positive and one false-negative result. In this small series, CT proved helpful in evaluating foot problems.

"Lunch syndrome," a bone-scanning artifact: case report.

After a photon-deficient area in the region of the stomach under the ribs on the left side was noted in some bone-scanning patients, a successful attempt was made to produce the artifact by having a cooperative patient eat a large lunch. The comparison of the scans before and after lunch showed the presence of a postprandial artifact in the area in question. It is important not to confuse this artifact with a space-occupying avascular mass in that part of the abdomen.

Estimation of 24-hour thyroid uptake of I-131 sodium iodide using a 5-minute uptake of technetium-99m pertechnetate.

The authors have developed a method to estimate the 24-hour sodium iodide thyroid uptake based on a 5-minute Tc-99m pertechnetate thyroid uptake using the equation: Estimated Iodide Uptake = 17.72*In(Pertechnetate Uptake) + 30.40. This estimation has a correlation coefficient of 0.90. It is based on a data pool of 44 patients who underwent I-131 and Tc-99m studies within 2 weeks of each other from 1978-1988, with established diagnoses as follows: 12 euthyroid, 6 hyperthyroid with multinodular goiters, 15 hyperthyroid with diffuse goiters, 4 with subacute thyroiditis, and 7 unknown. The population consisted of 30 women and 14 men with a mean age of 52.0 +/- 17.5 years; this sample was screened for use of thyroid hormone, propylthiouracil, and radiographic contrast. The authors believe this estimation method is of value whenever a 24-hour iodide uptake is desired, and where speed and minimizing radiation dose are factors. This method is strongly recommended for thyroid uptake evaluation before I-131 therapy.

Labelling of Re-ABP with 188Re for bone pain palliation.

Etidronate and medronate have been labelled with technetium-99m (99mTc-HEDP, 99mTc-MDP) for bone scanning and, with rhenium-188 (188Re-HEDP) to palliate the pain resulting from bone metastases. The objective of this study was to label alendronate, ABP, a new bisphosphonate, with SnF2-reduced-188Re. The reagents for the 5 mg ABP kit were SnF2, KReO4 and gentisic acid at acid pH. The chemical, spectroscopic and microscopic characteristics, quality control, rat bone uptake of [188Re]Re-ABP and similarities with 99mTc-ABP are presented. We conclude that this is a promising new radiopharmaceutical for bone metastases pain palliation.

Future directions in small animal imaging.

The adaptation and development of imaging technologies for use in small animals has the potential to be a refinement with profound effects on how basic cancer research using animals is conducted. The authors describe how NCI funding is helping to advance research in this area.