Humanized anti-CD20 monoclonal antibody in the treatment of severe resistant systemic lupus erythematosus in a patient with antibodies against rituximab.
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Biomedical subjects
Publications and source records attributed to W A Wegener.
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BACKGROUND: An adjunctive noninvasive test that is predictable and highly specific for breast carcinoma would complement the high false-positive rate of mammography in certain patients. METHODS: This prospective, multicenter study evaluated the accuracy, safety, and immunogenicity of carcinoembryonic antigen (CEA) antibody imaging in women with known or suspected breast carcinoma. Scintigraphic breast images were obtained approximately 3-8 hours after the administration of technetium 99m ((99)Tc) labeled anti-CEA Fab' and correlated with histopathology. RESULTS: The (99)Tc labeled anti-CEA Fab' detected tumor CEA expression in 46 of 49 women (94%) initially entered with known primary breast carcinoma regardless of histology or serum CEA levels. In women scheduled for biopsy confirmation of mammographic and physical examination findings, 104 (99)Tc labeled anti-CEA Fab' studies had a sensitivity of 61% (17 of 28 cases) and a specificity of 91% (69 of 76 cases). In total, (99)Tc labeled anti-CEA Fab' detected 52 of 62 invasive ductal carcinomas, 5 of 5 invasive lobular carcinomas, and 3 of 6 noninvasive tumors (2 ductal carcinomas in situ and 1 intracystic papillary carcinoma). Tumor size significantly affected sensitivity (P = 0.041), with 11 of 14 missed lesions </= T1, and proliferative histology significantly affected specificity (P = 0.012), with 5 of 7 false-positive tumors being premalignant. In 50 breast carcinoma patients, (99)Tc labeled anti-CEA Fab' also demonstrated axillary lymph node involvement regardless of serum CEA levels, with a sensitivity of 80% when more than three lymph nodes were positive. No immune response or other meaningful side effects occurred. CONCLUSIONS: (99)Tc labeled anti-CEA Fab' had high specificity and positive predictive values for breast carcinoma and the majority of false-positive studies were associated with an increased risk of malignancy. Improved imaging techniques, including dedicated gamma cameras for breast and axillary lymph node imaging, will likely improve the test's sensitivity for smaller lesions.
UNLABELLED: In pivotal phase III clinical trials for detecting recurrent or metastatic colorectal cancer, most patients received a single arcitumomab injection. However, the early detection of postsurgical recurrence or metastases with arcitumomab will necessitate serial studies for surveillance. We present immunogenicity, safety, and imaging data supporting the use of multiple administrations of arcitumomab. METHODS: Human antimouse antibody (HAMA) response, adverse events, clinical laboratory values, and diagnostic imaging results were evaluated in 44 patients (24 men, 20 women; age range, 2878 y) after repeated arcitumomab administration (44 second and 3 third injections). Most patients initially had Dukes' class B or C colorectal cancer and had known or occult disease recurrence and elevated serum carcinoembryonic antigen levels at the time of the repeated injection. RESULTS: At the repeated injection, in no patient did elevated HAMA titers develop, hematology and serum chemistry changes were clinically insignificant, and only 1 adverse event (eosinophilia) was judged at least possibly related to arcitumomab. Arcitumomab imaging results at the second injection were comparable with those obtained in phase III trials after a single injection of arcitumomab, having a 78% per-lesion concordance with CT in the abdomen and pelvis and a 73% sensitivity and 94% specificity based on 9 patients with cancer confirmed surgically at 11 anatomic sites and excluded at 16 sites. CONCLUSION: These data indicate that at least 2 injections of arcitumomab can be given safely to patients with colorectal cancer, without increased immunogenicity and with imaging efficacy equivalent to the first administration.
BACKGROUND: The purpose of this study was to evaluate the safety and efficacy of a technetium 99m-labeled antigranulocyte antibody Fab' fragment (sulesomab) as a diagnostic imaging agent in patients with suspected acute, nonclassic appendicitis. METHODS: This prospective multicenter trial involved 141 children and adults with suspected acute, nonclassic appendicitis. The investigators interpreted planar images acquired 15 to 30 minutes and 1, 2, and 4 hours after injection and also by single-photon emission computed tomography (SPECT). The imaging results were confirmed surgically, whereas nonsurgical patients were considered as not having appendicitis (intent to treat). RESULTS: Sulesomab had a sensitivity of 91% (29/32 patients) and a negative predictive rate of 97% for acute appendicitis. It detected additional abnormalities in 7 of 9 patients with other inflammatory abdominal disease and had a specificity of 92% (91/99 patients) and a positive predictive value of 80% for surgically confirmed right-lower-quadrant disease. In positive studies, 26% were identified by planar imaging at 15 to 30 minutes, 46% by 1 hour, 63% by 2 hours, and 71% by 4 hours; 29% required SPECT to detect the abnormality. Scanning time was 5 to 10 minutes per planar image and about 45 minutes for a SPECT study. Investigators found that sulesomab would have changed clinical management or reduced additional diagnostic studies in 64% of the patients. Adverse events were infrequent, minor, and self-limiting (9/141 patients, 6%). No human antimurine antibody response occurred in 48 evaluable patients. CONCLUSIONS: Sulesomab is safe, well-tolerated, and with no apparent immunogenicity. Focal inflammation or infection in the setting of suspected atypical appendicitis is rapidly and accurately detected. Management decisions incorporating sulesomab imaging potentially provide clear patient benefits, especially by correctly predicting surgery to be unnecessary in 97% of patients without acute appendicitis.
In many neuropsychiatric disorders, PET imaging offers functional insights unavailable from anatomic imaging alone. Functional deficits may be more extensive than structural findings would indicate, may occur before the detection of anatomic changes, or may even occur in the absence of any structural lesions. We contrast the current role of PET with that of MRI and CT in the investigation of neuropsychiatric disorders including stroke, tumor, head trauma, epilepsy, schizophrenia, movement disorders, normal aging and dementia.
A great deal of effort has been made to evaluate and define the role of various diagnostic imaging techniques in various clinical settings that complicate the diagnosis of osteomyelitis. Except possibly in neonates, bone scintigraphy remains generally recommended when there has been no previous osseous involvement. In other cases of chronic disease, previous fracture or trauma, prosthesis, and diabetic foot, In-WBC scintigraphy is generally accepted as an appropriate imaging technique. MRI will play an increasingly important role in diagnosing osteomyelitis and may prove to be an important adjunct in these cases. Research continues to improve our current diagnostic armamentarium. In-IgG appears to avoid practical deficiencies encountered with 67Ga and In-WBC; it remains to be seen what role this agent will play in routine clinical practice. All agents to date image inflammation, not infection, and most require delayed imaging sessions, usually at 24 hours. These shortcomings necessitate further research to develop new radiotracers that can provide useful images within several hours and that are specific for infection, perhaps ultimately delineating the particular microorganism involved.
Nonspecific polyclonal immunoglobulin (IgG), prepared from pooled human serum gamma globulin and labeled with 111In has been reported to be equivalent to antigen-specific antibody in the detection of focal infection or inflammation during the first 24 hr after injection. We describe our experience in a Phase II clinical study using 111In-IgG in 15 patients (8 males, 7 females) ranging from 26 to 80 (mean = 50) yr of age with suspected focal infection/inflammation. Pathologic confirmation was obtained in 5/15 cases. A combination of clinical course, laboratory results, and other imaging procedures were used to categorize the other 10 patients. One possible false-negative involved a presumed aspiration pneumonia in a patient with a history of aspiration, bibasilar infiltrates on chest film, and no other identified source of infection. Otherwise, there were 10 confirmed positives, 4 confirmed negatives, and no false-positives. Our findings confirm earlier reports that 111In-IgG may be a superior imaging agent for infection/inflammation with practical advantages over 67Ga-citrate and 111In-labeled leukocytes.
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Patients with primary hypercoagulopathies often present with recurrent, spontaneous deep venous thrombosis and pulmonary embolism. An adolescent eventually diagnosed with protein S deficiency presented with unilateral deep venous thrombosis documented ultrasonographically. Scintigraphic studies showed no evidence of pulmonary embolism but revealed a complete absence of deep venous flow in both lower extremities, the pelvis, and the abdomen. Subsequent ultrasonography and CT scanning documented this marked thrombotic extension. Radionuclide scintigraphy may play an important role in the serial evaluation of primary hypercoagulable states, particularly when pulmonary scintigraphy is combined with bilateral, lower extremity venography.
A variety of congenital and acquired etiologies can give rise to the radiographic finding of a unilateral hyperlucent lung. An unusual case of congenital lobar emphysema diagnosed in a young adult following the initial discovery of a hyperexpanded, hyperlucent lung is reported. Although subsequent bronchoscopy and radiologic studies detailed extensive anatomic abnormalities, functional imaging also played an important role in arriving at this rare diagnosis. In particular, ventilation-perfusion scintigraphy identified the small contralateral lung as the functional lung and helped narrow the differential diagnosis to etiologies involving obstructive airway disorders.
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Although fluorescence photobleaching recovery (FPR) experiments are usually interpreted in terms of the translational motions of a fluorescently labeled species, rotational motions can also modulate recovery through the cosine-squared laws for dipolar absorption and emission processes. In a complex interacting system, translational and rotational contributions may both be simultaneously present. We show how these contributions can be separated in solution studies using an FPR setup in which (a) the linear polarization of the low-intensity observation beam and the high-intensity photobleaching pulse can be varied independently, and (b) all emitted fluorescent photons are counted equally. The fluorescence recovery signal obtained with the observation beam polarized at the magic angle, 54.7 degrees, from the bleach polarization direction is independent of label orientation, whereas the anisotropy function formed from a combination of parallel and perpendicular polarizations isolates the orientational recovery. The anisotropy function is identical to that in fluorescence correlation spectroscopy and, for rigid-body rotational diffusion, can be expressed as a sum of five exponential terms.
Pump-and-probe techniques can be used to follow the slow rotational motions of fluorescent labels bound to macromolecules in solution. A strong pulse of polarized light initially anisotropically depletes the ground-state population. A continuous low-intensity beam of variable polarization then probes the anisotropic ground-state distribution. Using an additional emission polarizer, the generated fluorescence can be recorded as it rises towards its prepump value. A general theory of fluorescence recovery spectroscopy (FRS) is presented that allows for irreversible depletion processes like photobleaching as well as slowly reversible processes like triplet formation. In either case, rotational motions modulate recovery through cosine-squared laws for dipolar absorption and emission processes. Certain pump, probe, and emission polarization directions eliminate the directional dependence of either dipole and simplify the resulting expressions. Two anisotropy functions can then be constructed to independently monitor the rotations of either dipole. These functions are identical in form to the anisotropy used in fluorescence depolarization measurements and all rotational models developed there apply here with minor modifications. Several setups are discussed that achieve the necessary polarization alignments. These include right-angle detection equipment that is commonly available in laboratories using fluorescence methods.