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Biomedical subjects

J L Werner

Publications and source records attributed to J L Werner.

At least 19 recordsLinked to original sources

Successful imaging of human cancer with indium-111-labeled phospholipid vesicles.

Twenty-four patients with proven primary and/or metastatic cancer received single intravenous injections of phospholipid vesicles containing 0.5 mCi of Indium-111. Gamma camera scintigraphy 1 to 72 hours later visualized tumors in 22 patients (92%), including carcinomas of breast, lung, colon, prostate, kidney, cervix, thyroid, and soft tissue sarcoma, lymphoma, and melanoma. Tumor sites that were identified included soft tissues, bone, lung, liver, lymph node, and spinal cord. There were only two false-positive images in metastatic sites and four false-negative images in metastatic sites. Overall sensitivity for tumors in 97 individual sites was 85%, whereas specificity was 96%. Unsuspected areas of malignancy were seen in the lumbar subdural space, pleura, liver, thyroid, and lung. Besides tumor accumulations, homogeneous uptake was observed in normal liver and spleen. Radiation doses to these two organs were 2.2 and 2.9 cGy/0.5 mCi In-111, respectively. Whole body radiation dose was 0.3 cGy/0.5 mCi. The use of Indium-111-labeled vesicles permits a wide variety of human tumors in primary and metastatic sites to be imaged without toxicity and with radiation doses comparable to other radionuclide scanning techniques.

Humans↗

In-111-labeled liposomes: dosimetry and tumor depiction.

Neutral phospholipid vesicles (liposomes) were loaded with 0.5 mCi (18.5 MBq) indium-111 and administered to 24 patients with various types of cancer. The median diameter of the liposomes was 77 nm, and lipid dose was 0.78-6.25 mg/kg. Scans obtained 24 and 48 hours after injection of In-111 liposomes showed gradual blood clearance with homogeneous uptake in the normal liver and spleen. Dosimetric estimates for these organs were 2.3 +/- 1.1 and 2.3 +/- 1.4 rad (.02 +/- .01 Gy), respectively, with a whole-body estimate of 0.28 rad (.003 Gy). Radiation dose did not correlate with lipid dose. Total renal excretion of In-111 was less than 2% of the injected dose in all but two patients. Transient eosinophilia occurred in two patients. Tumor was seen in the scans of 22 of 24 patients (unbinded readings). In-111-labeled liposomes may enable the demonstration of suspected or unsuspected sites of tumor.

Breast Neoplasms↗

Imaging of colon carcinoma with 111-indium-labeled anti-CEA monoclonal antibodies (Indacea) prior to surgery.

Patients with primary and/or metastatic colorectal cancer who had been scheduled for operative intervention were injected intravenously with 200 micrograms of a high-affinity anti-carcinoembryonic antigen (CEA) monoclonal antibody labeled with 2 mCi of 111-indium (Indacea). Patients were imaged by gamma camera at 24 and 48 hours. Primary tumors were identified in 3/10 cases and were not visualized in 3/10 cases. Four scans were considered equivocal. Hepatic metastases were identified as image defects in 5/13 cases and were not visualized in 8/13 cases. All tumors contained CEA by immunoperoxidase staining. In all cases, the primary tumor uptake (5.44 +/- 1.07% ID/kg) was much higher than the uptake of the adjacent fat (0.18 +/- 0.04% ID/kg). There was a direct correlation between tumor CEA content, tumor radioactivity, and the imaging of primary tumor by Indacea. High liver uptake (30.3 +/- 3.0% ID/kg), seen when scanning all patients, was the main limitation of imaging and led to photopenic visualization of hepatic metastases. These results suggest that selection of patients with colorectal carcinoma on the basis of tumor CEA content will lead to improved rates of tumor imaging by Indacea in post-surgical scanning.

Antibodies, Monoclonal↗

Imaging of human colorectal adenocarcinoma with indium-labeled anticarcinoembryonic antigen monoclonal antibody.

Twenty patients with 21 primary colorectal adenocarcinomas were studied with 2 mCl (7.6 X 10(7) becquerels) of indium-labeled monoclonal antibody (200 micrograms) specific for carcinoembryonic antigen (CEA). Fifteen lesions (71%) were visualized by gamma camera scintigraphy at 48 hours postinjection. Tumors that were identified by immunoscintigraphy were large (38.10 +/- 17.76 cm3 vs 6.00 +/- 1.65 cm3), had a grossly fungating component, had a high content of CEA by enzyme immunoassay (12.9 +/- 3.6 micrograms/g vs 3.3 +/- 1.7 micrograms/g), and had an apical and/or intraluminal staining pattern on immunohistologic section. Patients whose tumors were visualized had a low serum CEA level (1.9 +/- 0.4 ng/mL vs 14.6 +/- 8.0 ng/mL). Prospective selection of patients for follow-up imaging or therapy with radiolabeled monoclonal antibodies may be feasible using these measurements.

Antibodies, Monoclonal↗

Preoperative imaging of colorectal carcinoma with 111In-labeled anticarcinoembryonic antigen monoclonal antibody.

Patients with primary, recurrent, or metastatic colorectal adenocarcinoma were given injections of 200 micrograms of anticarcinoembryonic antigen (CEA) monoclonal antibody labeled with 2 mCi of 111In (Indacea). Patients were imaged at 24 and 48 h. Celiotomy was performed on 40 patients between 3 and 17 days post-Indacea injection. Of 16 primary tumors, 11 (69%) were imaged. Of six extrahepatic recurrences, none was imaged. Intrahepatic metastases were visualized as negative images in 10 of 24 (42%) patients. On the basis of the activity in tissue expressed as a percentage of the total radioactive dose per kg injected into the patient (% ID/kg), extrahepatic tumors that were imaged using Indacea had a significant uptake of radiolabel in the tumor [5.99 +/- 0.91% ID/kg (SE)] and in the associated normal mesenteric lymph nodes (12.0 +/- 2.4% ID/kg). The CEA content of these tumors was high (13.3 +/- 4.7 micrograms/g), and, histologically, the CEA was located primarily apically or intraluminally. Intrahepatic tumor imaging correlated only with tumor size. The greatest Indacea uptake was seen in normal liver (22.1 +/- 3.2% ID/kg). Low Indacea uptake was seen in fat (0.21 +/- 0.05% ID/kg) and bowel wall (1.11 +/- 0.17% ID/kg). In conclusion, Indacea imaging of colorectal carcinoma is specific for high concentrations of accessible CEA in CEA-bearing tumors or in lymph nodes draining these tumors. The successful clinical use of monoclonal antibodies for tumor imaging and therapy will require careful selection of patients for a number of antigen-related parameters including antigen content and distribution in tumors. This information will only come from careful correlation between image results and tissue analysis. High uptake by normal liver tissue is the major unresolved problem with labeled antibody imaging.

Antibodies, Monoclonal↗

Professional liability environment and physicians' responses: a regional examination.

This article examines the relationship between measures of severity of the professional liability "crisis" and physicians' responses, which may affect both costs of medical care and availability of care. Data from the American Medical Association's Periodic Surveys of Physicians are stratified by Census Region and specialty category. Claim frequencies, premiums and increases in premiums are calculated as indicators of the professional liability environment. Responses of physicians in each Region to questions on refusal cases, additional testing and fee increases due to liability considerations are then examined and compared with the liability environment to determine if there appears to be an association between liability environment severity factors and physicians' responses.

Economics, Medical↗

Economic incentives in health manpower policy.

Policymakers have evidenced continued concern with the issue of maldistribution of physicians among specialties and locations. Many of the recent policy proposals in this area have involved increasing the financial rewards to primary care specialization and to location of practice in underserved areas. This article examines the evidence on current economic incentives to specialize and to locate, including income and the hours of work needed to produce income. Findings suggest that current distributions of physicians among locations and specialties are more consistent with a decision to minimize hours worked, rather than an income maximization rule. Policy implications are discussed with respect to potentially perverse results which may occur if consideration is not given to this aspect of career decisions.

Health Policy↗

Regional variations in the determinants of professional liability claims.

The problem of professional liability claims and impact on the medical care market has become increasingly important in recent years. Professional liability insurance premiums, and the practice of defensive medicine by physicians in response to potential professional liability claims, have been cited as partly responsible for the increasing costs of medical care. This study is an analysis of factors which influence the probability of a professional liability claim occurring for physicians in each of the four Census Regions. The data analyzed are from the Eleventh Periodic Survey of Physicians conducted by the American Medical Association in 1977, in which respondents indicated whether they had a professional liability claim filed against them. A logit analysis suggests that variations across Census Regions in population characteristics, availability of medical resources and supply of legal services are determinants of the occurrence of claims.

Catchment Area, Health↗

Adaptive communication systems for patients with mobility disorders.

An adaptive communication system has been developed for individuals with mobility disorders. It uses specialized computer software and hardware that compensate for this disability. For an individual with a motor-control impairment who is not able to use a keyboard effectively, a computer voice-recognition technology now removes this communication barrier. Speech-recognition systems consist of three basic components: speech processing, speech recognition, and speech understanding. The new Dragon Dictate (Dragon Systems, Inc., Newton, Mass.) is the first large-vocabulary speech recognition system in the personal computer industry that interactively learns a user's vocabulary and mode of speaking and responds to natural language rather than to limited sets of words. This speech-recognition system requires a microprocessor, a display monitor, a printer, and specific software packages, including word-processing and enhanced memory-management software. Important considerations in the use of this speech-recognition system include microphone positioning and training of the system. With the advent of this new voice-recognition computer system, another communication barrier between the disabled and society has been overcome.

Communication Devices for People with Disabilities↗