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Biomedical subjects

W B Nelp

Publications and source records attributed to W B Nelp.

At least 37 records · Page 2Linked to original sources
PubMed1987

Use of iodine-131-labeled anti-immune response-associated monoclonal antibody as preparative regimen prior to bone marrow transplantation: initial dosimetry.

Despite the use of near maximal doses of external beam total-body irradiation, many patients who received transplants for relapsed hematologic cancers will fail because of tumor recurrence following therapy. With the use of radioisotope-labeled monoclonal antibodies, a more directed delivery of systemic radiotherapy may be achieved; tumor cell kill is increased without increased toxicity. On the basis of this hypothesis, we have begun dosimetry studies in normal dogs using an anti-immune response-associated antibody (7.2) labeled with 131I. Compared with an irrelevant isotype-matched antibody, the blood concentration of 131I-labeled 7.2 fell rapidly over the first 3 hours and then cleared more slowly. During this time, there was specific localization of 131I-7.2 in lymph nodes, spleen, and marrow. On the basis of the concentration curves generated over 48 hours, administration of enough 131I-7.2 to deliver 10 Grays to the blood would result in radiation doses of 9.8, 16.3, and 32.3 Grays to liver, marrow, and spleen, respectively. The liver uptake of labeled 7.2 appeared to be the result of its direct antigen-specific binding to hepatic Kupffer cells rather than to the clearance by the liver of either antigen-antibody complexes or antibody-coated cells. Gastric or intestinal radiation toxicity may be a problem due to gastric excretion of free I following binding of 131I-7.2 and subsequent deiodination.

Animals↗
PubMed1987

Preliminary studies of monoclonal antibody lymphoscintigraphy in malignant melanoma.

Lymphoscintigraphy was performed at 3 and 20 hr following subcutaneous injection of 131I anti-melanoma antibody (Fab) in 11 patients who had surgical resection of lymph nodes (neck, axilla, groin) at 24 hr for suspected metastatic melanoma. Comparable amounts of 125I nonspecific control antibody (Fab) were co-administered. Six patients had nodal metastases and three showed positive images at both time periods. Five patients had no metastases though one was image positive. Four other nondiseased inguinal node groups were image negative. A total of 28 tumored nodes and 110 normal nodes were removed, counted and histologically examined. All metastatic tumors expressed antigen against which the specific Fab was directed. The concentrations of both specific and nonspecific Fab were similar in tumored nodes and both were significantly greater than in normal nodes showed essentially identical intranodal spatial distribution of the specific and control Fab in areas containing tumor. These preliminary results suggest the increased concentration of murine immunoglobulin (Fab) retained in diseased nodes was a nonspecific phenomenon.

Adult↗
PubMed1986

Autoradiolysis of iodinated monoclonal antibody preparations.

We investigated the effects of ionizing radiation on the immunointegrity of antibody fragments (Fab) because large amounts of high specific activity 131I may damage the proteins. We found that 1000 Gy of external 137Cs gamma radiation was sufficient to destroy 80-90% of the immunointegrity of the initial preparation. This effect was also produced by internally added [131I]NaI in a quantity sufficient to provide the same radiation absorbed dose. Since radioiodinated monoclonal antibodies labeled to high specific activity are being evaluated for radioimmunotherapy, the above observation is significant since high levels of internal radiation occur with therapeutic doses of 131I-labeled antibody. Human serum albumin in low concentration (2%) added to the iodinated antibody solutions was successful in preventing loss of immunoreactivity and can be used to protect and stabilize therapeutic quantities of radiolabeled monoclonal antibody preparations.

Antibodies, Monoclonal↗
PubMed1986

Indium-111 labeled leukocyte uptake: false-positive results in noninfected pseudoaneurysms.

Indium-111 (In-111) leukocyte scintigraphy was performed in two patients with postsurgical pseudoaneurysms as part of preoperative evaluation for evidence of graft infection. Despite positive In-111 uptake by the pseudoaneurysms, surgical and pathologic examinations failed to reveal any evidence of infection. The most likely explanation for the false-positive results is the labeling of "contaminating" platelets and erythrocytes in the leukocyte mixture. Caution must be exercised in interpretation of In-111 leukocyte scans in patients with postsurgical pseudoaneurysms.

Aneurysm↗
PubMed1986

Immunoreactivity assay for labeled anti-melanoma monoclonal antibodies.

A convenient, rapid, and reproducible assay was developed to evaluate the immunoreactivity of radiolabeled monoclonal antibodies against three different human melanoma-associated antigens, p97, a proteoglycan and a GD3 ganglioside. A cloned melanoma cell line (M 2669 CL 13) was selected as the target and, when fixed with paraformaldehyde, showed binding as good as or better than that obtained with live cells for the three antigens. Fixed cells retained good binding properties stored at 4 degrees C for over 6 mo. This assay has general applicability to other antigen-antibody systems for testing chemically modified monoclonal antibodies or fragments during the development of a radiopharmaceutical or as a routine quality control measure for clinical agents.

Antibodies, Monoclonal↗
PubMed1985

Measurement of left ventricular volume using single-photon emission computed tomography.

A count-based method for measuring left ventricular (LV) volume using technetium-99m-labeled red cells and ungated single-photon emission computed tomography is described. The tomographic slices were used to determine the counts per milliliter in the center of the left ventricle and total LV counts, which were used to derive mean LV volume. End-diastolic and end-systolic volumes were calculated from the mean volume using the LV time-activity curve from planar gated blood pool images. Phantom evaluation with simulated LV volumes (50 to 400 ml) in air, in a phantom filled with water, with 10% background, and with a simulated right ventricle, showed excellent accuracy. For clinical validation, 30 patients underwent electrocardiographically gated planar and nongated tomographic acquisition of the cardiac blood pool followed by single-plane cineangiography. For end-diastolic and end-systolic volumes combined, the correlation with cineangiography showed a standard error of the estimate (SEE) of 24 ml and 14 ml, respectively. Mean intra- and interobserver deviation was 12 ml and 14 ml (SEE 13 ml and 16 ml), respectively. It is concluded that this noninvasive count-based technique, requiring no assumptions regarding LV geometry, is an accurate and reproducible way to measure LV volume.

Adult↗
PubMed1985

Intraarticular volume and clearance in human synovial effusions.

Intraarticular volumes were measured by radiolabeled albumin (RISA) distribution in chronic knee effusions from 11 rheumatoid arthritis patients and 9 osteoarthritis patients. Volumes of synovial fluid obtained at joint aspiration were substantially less than those found by RISA dilution. Up to 24 hours was needed for full distribution of RISA throughout the intraarticular compartment. Measured 123I and RISA radioactivity over the knee described monoexponential rate constants, lambda (minute-1). The clearance of 123I and RISA from synovial effusions was derived by the formulation volume (ml) X lambda (minute-1) = clearance (ml/minute). RISA clearance in rheumatoid effusions was significantly greater than that found in osteoarthritis effusions. Intraarticular volume and isotope clearance were easily quantified and provide measures for further evaluating the microvascular physiology of synovial effusions.

Adult↗
PubMed1985

Low synovial clearance of iodide provides evidence of hypoperfusion in chronic rheumatoid synovitis.

Iodide clearance was measured in the chronic knee effusions of 11 patients with rheumatoid arthritis and 9 patients with osteoarthritis. The mean (+/- SE) iodide clearance of 1.92 +/- 0.30 ml/minute in rheumatoid arthritis effusions did not differ significantly from the 2.19 +/- 0.52 ml/minute found in osteoarthritis effusions. Clearance values in rheumatoid arthritis patients ranged widely (0.79-3.22 ml/minute). Iodide clearance in these patients correlated directly with synovial fluid (SF) pH (r = 0.731, P = 0.005), SF glucose:serum glucose ratio (r = 0.746, P = 0.004), and SF temperature (r = 0.878, P = 0.001), and directly with SF lactate (r = -0.782, P = 0.002) and percentage of SF neutrophils (r = -0.581, P = 0.03). These relationships support the hypothesis that rheumatoid synovitis is often marked by tissue hypoperfusion, and that the "sickest" rheumatoid joints (as defined by physiologic indices) are the most ischemic.

Arthritis, Rheumatoid↗
PubMed1985

Ventilation-perfusion scanning for pulmonary embolism: refinement of predictive value through Bayesian analysis.

The diagnosis of pulmonary embolism (PE) by pulmonary perfusion and ventilation scintigraphy presents problems common to all imperfect diagnostic tests. Bayesian analysis indicates that the posttest probability of PE is a function of the prevalence (or pretest probability) of PE as well as the scintigraphic findings. The authors propose that Bayesian analysis allows an explicit refinement in communicating the implications of scintigraphic findings to referring clinicians. Recent data reported from a prospective study of ventilation-perfusion scanning compared with pulmonary angiography in patients suspected of PE were reviewed. Using the reported scintigraphic and chest radiographic findings, the sensitivity and specificity of each of the various test result combinations for angiographically proven PE were derived. The overall prevalence of PE was estimated to be 20% in patients suspected of PE who were referred for nuclear imaging. A Bayesian analysis was then performed for each category of test result to estimate the posttest probability of PE for different prevalence estimates. If a perfusion study alone is done which shows segmental or larger defects without corresponding chest radiographic changes, the sensitivity for PE is 80%, and the specificity is 86%. With a 20% prevalence of PE, the posttest probability of PE is 58%. The use of ventilation imaging improves the predictive power of the test by its effect on specificity. When a ventilation image shows preserved (mismatched) ventilation in concert with the above findings, the sensitivity for PE is 75%, and the specificity increases to 95%. For these findings the posttest probability increases to 79%, and for a prevalence of 50%, the posttest probability of PE is 94%.

Bayes Theorem↗
PubMed1985

Melanoma localization in nude mice with monoclonal Fab against p97.

The tumor targeting capacity of monoclonal antibody Fab fragments was explored in nude mice bearing human melanoma xenografts. Radioiodinated Fab 8.2 and 96.5, specific for melanoma-associated antigen p97, were tested in vitro for immunoreactivity and in vivo for tumor localization relative to a co-administered control, Fab 1.4. Fab was cleared rapidly from the blood with a T1/2 of 3-3.5 hr and greater than 90% of the injected radioactivity was excreted by 16 hr. The mean specific Fab in tumor reached a maximum of 3.5% injected dose/g at 4 hr and decreased to 1.5% at 16 hr. Over the same period, the ratio of specific/control Fab in tumor normalized to blood, the localization index, rose from 3 to 25 compared with ratios near unity for all other tissues. The concentration of specific Fab in tumor could be correlated to the amount of Fab protein administered as well as its immunoreactivity.

Animals↗
PubMed1985

Indium-111 white blood cell scan for infectious complications of polycystic renal disease.

This case report describes the localization of a unilateral renal abscess with [111In]oxine-labeled autologous leukocyte scanning in a febrile patient with polycystic renal disease, after other noninvasive imaging procedures failed to identify a source of infection. In polycystic renal disease, leukocyte scans have advantages over standard diagnostic modalities and are very helpful in planning appropriate therapy.

Abscess↗
PubMed1984

The design of a computer-assisted education system using a CT scanner computer.

The minicomputer that is part of a commercial CT scanner has been used to develop a general purpose computer-assisted education system. This allows instruction in radiology using the CT computer already installed in the radiology department. The computer software was designed as a course interpreter, allowing the courses themselves to be written in English. Images and educational text are stored on separate disk files and displayed by the interpreter.

Computer-Assisted Instruction↗
PubMed1984

Long-term calcitonin therapy in postmenopausal osteoporosis.

Results are presented from a 2-year controlled study evaluating the efficacy of 100 units synthetic salmon calcitonin/d in the treatment of postmenopausal osteoporosis. All patients received 400 units D2 po qd and 1200 mg CaCO3 po qd. The 21 control and 24 treated patients (mean age 65) were not statistically different at baseline. Although mean total body calcium (TBCa) was not significantly different between treated and control patients throughout the study, mean differences in the change in TBCa from baseline (treated minus control) were significant at 12, 18, and 26 months. The mean slope of TBCa for treated patients, but not for controls, was significantly positive through 18 months. Iliac crest bone biopsies showed (1) a significantly greater percent total bone area in treated compared to control patients at 2 years, and (2) a significantly decreased percent resorbing surface in treated patients when evaluated by paired difference from baseline. At 4 months, serum calcium values were significantly lower in treated patients than in controls (mean difference, treated minus controls), but were not statistically different from controls at study completion. Urine calcium increased significantly for the first 4 months in treated subjects and then declined to baseline levels. Since urinary calcium increased, the increase in TBCa was probably associated with an increase in net intestinal calcium absorption.

Age Factors↗
PubMed1984

The need for routine delayed radionuclide hepatobiliary imaging in patients with intercurrent disease.

A retrospective review was made of all radionuclide hepatobiliary studies performed in a major trauma center over a 27-month period and correlated with the patients' clinical course. In a population of 42 patients (27 of whom were on total parenteral nutrition [TPN]) who had severe intercurrent illness (primarily trauma), and an additional 18 patients who had hepatocellular dysfunction, hepatobiliary imaging confirmed a patent cystic duct in 43 of 60 patients (72%). Fourteen of these 43 patients (33%) had gallbladder visualization at later than one hour after radiotracer administration, and seven of these 14 required imaging from four to 24 hours. Of 17 patients who had nonvisualization of the gallbladder, four had surgically proved acute cholecystitis. Images of nine of the remaining 13 patients with gallbladder nonvisualization were not obtained for 24 hours. The presence of gallstones, wall thickening, or sludge on sonograms did not correlate with cystic duct patency, and was not specific for acute cholecystitis. Though gallbladder function is compromised in the population with severe intercurrent disease, radionuclide hepatobiliary imaging is still valuable; it can confirm a patent cystic duct in at least 72% of patients if routine imaging is continued for up to 24 hours.

Acute Disease↗
PubMed1984

Should single-phase radionuclide bone imaging be used in suspected osteomyelitis?

The records of 69 patients who had 86 delayed, static radionuclide bone images for suspected osteomyelitis were studied to determine the effects of this procedure on diagnosis and treatment. Sensitivity, specificity, and positive predictive value were lower than reported in several other studies. When osteomyelitis was unlikely, imaging was either negative or falsely positive and rarely affected treatment. In 46 cases where osteomyelitis was more likely, imaging potentially changed therapy in 19 but was unhelpful or misleading in 15. One third of the interpretations were "equivocal" and these were incorrect four times more often than "definite" readings. Two false-positive images led to unnecessary surgeries, and one patient with negative images died with unrecognized osteomyelitis. Static-phase images with "definite" interpretations, particularly when negative, are specific, but "equivocal" studies may lead to diagnostic and therapeutic errors. When osteomyelitis is improbable, imaging rarely changes diagnosis or therapy.

Adolescent↗
PubMed1984

Heterotopic bone formation (myositis ossificans) and lower-extremity swelling mimicking deep-venous disease.

A quadriplegic patient with a swollen leg was suspected of having deep-venous thrombosis, and was studied with radionuclide venography (RNV) and contrast venography. Focal narrowing of the femoral vein, seen on RNV, was due to extrinsic compression. Although soft-tissue radiographs were normal, Tc-99m diphosphonate imaging established the diagnosis of early heterotopic bone formation (myositis ossificans), which was responsible for the venous compression. Clinically this inflammatory process can mimic deep-venous thrombosis, and should be considered in evaluating patients at risk for both heterotopic bone formation and deep-venous thrombosis.

Adult↗
PubMed1984

Local muscle blood flow and temperature responses to 915MHz diathermy as simultaneously measured and numerically predicted.

The therapeutic benefits of diathermy are tied to the relationship thought to exist between tissue temperature and augmented blood flow (BF). To further define this relationship, simultaneous measurements of thigh muscle blood flow (MBF) and temperature have been made in 15 human subjects during 915MHz, direct-contact microwave diathermy (MWD) with simultaneous skin cooling. Tissue temperatures were measured invasively by special thermistor probes designed to minimize MW-induced artifacts, and the local rates of MBF were measured by monitoring the radioactive washout of injected Xenon133 (Xe133). The experimental results have shown that the initial MBF response is characterized by a "critical temperature" behavior such that rapid increases in MBF occur for tissues above approximately 42C when diathermy power is sufficient. A proportionality between tissue temperature and MBF has not been found. To provide more useful descriptions of the temperature fields and diathermic BF responses, two-dimensional numerical thermal simulations of six of the subjects' treatments were constructed and recorded. An average peak simulated MBF of 48ml/min-100g was found for these subjects, a level in excess of previous estimates for maximum perfusion during diathermy.

Body Temperature↗