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Biomedical subjects

G Levine

Publications and source records attributed to G Levine.

At least 37 records · Page 2Linked to original sources

Stereotactic options in the management of craniopharyngioma.

Multimodality stereotactic techniques were used in the management of 39 patients with craniopharyngiomas in a 12-year interval. Monocystic craniopharyngiomas were treated successfully by intracavitary beta-irradiation using 32P (96% cyst control rate). Solid tumor progression or secondary cyst formation required repeat irradiation, radiosurgery or microsurgery in selected patients. In the future, wider and earlier application of stereotactic techniques may further reduce the still unacceptable morbidity currently associated with initial radical microsurgical resection of craniopharyngiomas.

Adolescent↗

Fecal occult blood testing: a false sense of security?

BACKGROUND: Recent screening studies with fecal occult blood testing (FOBT) report that one of three patients with colorectal cancer (CRC) can be cured of the disease; minimal attention has been given to the two of three patients who despite repeated screening go on to die of silent CRC. We report the known "miss rate" (known false negatives) of our 14-year ongoing program of FOBT that was organized in 1979 to detect early CRC. METHODS: From October 1979 through December 1993, 36,034 FOBT kits were distributed to patients who were without gastrointestinal complaints at Hines Veterans Affairs Hospital. The test was considered positive if at least one result of the six tests was positive and negative if the test result was equivocal. Patients with negative FOBT received a new test kit each year by mail. A positive test was followed by full colonoscopy or an air contrast barium enema if a full colonoscopy was not possible. RESULTS: The overall return rate was 47.8%. CRC was detected in 115 patients: 94 had a favorable and 21 had an unfavorable Duke's C or D or lymphoma prognosis. Of 21 patients 13 (62%) had initially tested FOBT negative (missed lesion). Of the 21 cases of advanced CRC 15 (71.43%) were in the descending, sigmoid, or rectosigmoid colon or rectum. CONCLUSIONS: (1) The majority (82%) of all CRC detected by FOBT screening are diagnosed at a favorable stage. (2) The majority of known advanced CRC (62%) escape early detection with FOBT. (3) Five (62.5%) of eight of the advanced CRC cases discovered on initial FOBT and 10 (76.9%) of 13 of advanced CRC cases missed on initial FOBT but detected in subsequent years were in the left colon and most likely in the range of the flexible sigmoidoscope. (4) FOBT as a sole screening test may provide a false sense of security, especially in patients with advanced left-side CRC.

Aged↗

A phase 1 study of adoptive transfer of autologous CD8+ T lymphocytes in patients with acquired immunodeficiency syndrome (AIDS)-related complex or AIDS.

Based on preclinical studies showing that CD8+ T lymphocytes of human immunodeficiency syndrome (HIV)-infected subjects have anti-HIV activities, a phase 1 study was undertaken to determine the safety and feasibility of infusing in vitro purified, activated, and expanded CD8+ cells as a therapeutic measure in seven patients with acquired immunodeficiency syndrome (AIDS)-related complex (ARC) or AIDS. Autologous CD8+ cells were first selectively isolated in monoclonal antibody-coated flasks from peripheral blood mononuclear cells recovered by leukapheresis. They were then cultured and expanded with phytohemagglutinin and recombinant interleukin-2 (rIL-2) before infusion. Five cycles of isolations and infusions of increasing numbers of CD8+ T cells were achieved in five of seven subjects. Five cycles could not be completed in two subjects with AIDS whose CD4+ cell counts were < or = 48/microliters. Infusions of CD8+ cells alone were well tolerated. Four patients received rIL-2 by continuous infusion for 5 days with their final cycle of CD8+ cells. All developed reversible adverse effects attributable to rIL-2. After infusion, 111In-labeled CD8+ cells quickly accumulated in the lungs, with less than 10% of the labeled cells remaining in the circulation. After 24 hours, labeled CD8+ cells were reduced in the lungs, but increased and persisted in liver, spleen, and bone marrow. Four of five patients who were treated with multiple infusions of CD8+ cells have improved or remained clinically stable, and the fifth developed Pneumocystis carinii pneumonia but recovered. This study demonstrated that infusion of autologous, in vitro expanded and activated CD8+ cells was feasible and clinically well tolerated in five of seven subjects with advanced HIV infections.

AIDS-Related Complex↗

Occult traumatic pneumothorax: immediate tube thoracostomy versus expectant management.

Occult pneumothorax is pneumothorax identified by computed tomography but not seen on conventional chest radiographs. Twenty-seven occult traumatic pneumothoraces in 26 patients were identified retrospectively at the authors' level I trauma center. Of these, 24 patients survived to discharge or transfer; 2 died of brain injury. Eleven patients were treated immediately with tube thoracostomy (TT) and 13 were observed with interval chest radiography. The authors' data support the conclusion that it is safe to withhold immediate TT in patients who are hemodynamically stable. Close clinical observation and interval chest radiography can identify those patients who require subsequent TT. Prospective study of larger numbers of patients is needed to confirm the safety and cost efficacy of this approach.

Adolescent↗

A survey of community (out-of-hospital) sites used in pediatric training.

A survey was completed of US pediatric residency programs about the use of community sites in training. A total of 85% of program directors responded and reported a wide use of the 21 identified survey sites. Further study is needed to determine the appropriate contribution that community sites can make to pediatric training.

Internship and Residency↗

Colorectal carcinoma metastases: detection with In-111-labeled monoclonal antibody CCR 086.

A phase I/II clinical trial with indium-111-labeled antimucin murine monoclonal antibody (MoAb) CCR 086 was conducted. Seventeen patients with histologically proved colorectal carcinoma and known metastatic disease underwent external scintigraphy after administration of 5.5 mCi (203.5 MBq) of In-111 CCR 086 at doses of 5 and 20 mg. Of 25 known lesions, 17 were detected (sensitivity, 68%). The smallest detected lesion in the lung was 1 cm and in the liver was 1.5 cm. The serum half-life of In-111-labeled CCR 086 MoAb was approximately 64 hours. The formation of human antimouse antibody (HAMA) was detected in the serum of four of five patients who received 20 mg of MoAb. No HAMAs were detected in four patients receiving 5 mg of MoAb. No side effects were encountered. Because of effective detection of liver and lung metastases with lower doses (5-20 mg) of CCR 086 conjugated with In-111, further investigations are warranted to assess clinical and therapeutic potentials of CCR 086 in the management of colorectal cancer.

Adult↗

New monkey model of severe-volume controlled hemorrhagic shock.

Three series of experiments were conducted to develop a model of volume-controlled severe hemorrhagic shock in the unanesthetized analgesic cynomolgus monkey. This report concerns the insult without resuscitation. In Series I, seven monkeys were sedated with 75% N2O/25% O2, bled 40% of their measured blood volume over 20 min and observed until death. Mean arterial pressure (MAP) decreased to 21 +/- 6 mmHg, spontaneously increased to 46 +/- 5 mmHg, then gradually decreased to pulselessness at 146 +/- 42 min (range 101-213). Hemodynamic variables, lactate, base excess, electroencephalogram and sagittal sinus PO2 followed the same biphasic pattern. In Series II, eight monkeys were bled 27 ml/kg (43% of estimated blood volume) over 20 min under the same N2O analgesia and with similar responses as in Series I. In Series III 26 monkeys were bled 27 ml/kg over 20 min (time zero) as in Series II. Three developed apnea and pulselessness at end of hemorrhage. In 23 the shock period was prolonged for testing resuscitation therapies. Starting at 0 + 30 min, MAP was controlled with minute blood volume adjustments at 30 mmHg until 0 + 2 h. Three died due to inaccurate (preventable) MAP adjustments. At MAP 30 mmHg, all animals lost consciousness, EEG activity decreased, and brain stem reflexes disappeared. The "volume-pressure controlled" hemorrhagic shock model of Series III retains the initial natural response to bleeding, simulates the clinical picture of severe prolonged shock without anesthesia, and represents a more controllable insult than volume controlled hemorrhage alone.

Animals↗

Stereotaxic intracavitary irradiation for cystic craniopharyngiomas.

Stereotaxic intracavitary irradiation with instillation of phosphorus-32 (32P) colloidal chromic phosphate was performed in nine patients with cystic craniopharyngiomas. Serial neurological, ophthalmological, neuroendocrinological, and radiological examinations were performed before and after treatment. Dosimetry was determined based on a computerized tomography (CT) estimation of tumor volume, and was calculated to provide a tumoricidal dose (200 to 300 Gy) to the cyst wall. The follow-up period ranged from 14 to 45 months (mean 27 months). After treatment, all nine patients showed improvement of symptoms and radiological evidence of cyst regression. Because of an expanding solid component producing recurrent symptoms, one patient required a craniotomy 14 months after isotope instillation. Three of five patients with impaired visual acuity before surgery had significant improvement in acuity after treatment. Preoperative visual field defects in eight patients improved in four after 32P therapy. Of seven patients with preoperative endocrine abnormalities, one individual showed almost complete normalization and another had improvement in endocrine function. Patients who exhibited residual neuroendocrine function before isotope instillation developed no significant deterioration in endocrine status during the follow-up period. The findings suggest that stereotaxic intracavitary irradiation is a safe and effective treatment which should be considered as the initial surgery for cystic craniopharyngiomas.

Adolescent↗

Radioimmunoimaging of metastatic medullary carcinoma of the thyroid gland using an indium-111-labeled monoclonal antibody to CEA.

Elevated levels of carcinoembryonic antigen (CEA) or calcitonin after surgical therapy for medullary carcinoma of the thyroid gland (MCT) indicate the presence of residual or metastatic disease. CEA elevations appear to be prognostically more reliable in patients with metastatic disease and suggest a more virulent tumor. Attempts to stage the disease with use of conventional imaging techniques are usually inadequate, as is the therapy for disseminated or recurrent MCT. An indium-111-labeled anti-CEA monoclonal antibody (ZCE-025) was used to image metastases in a patient with MCT. Potential applications of monoclonal antibody technology in the management of MCT would include (1) preoperative differentiation of unicentric from multicentric thyroid gland involvement, (2) detection of regional or distant metastases or both, (3) measurement of response to systemic therapy, and (4) the facilitation of radionuclide immunoconjugate therapy.

Antibodies, Monoclonal↗

Radioimmunolocation of a heterotransplanted human choriocarcinoma (BeWo) using monoclonal anti-SSEA-1: pharmacokinetics.

Stage-Specific Embryonic Antigen-1 (SSEA-1), originally discovered on mouse teratocarcinomas, has since been found on some human non-seminomatous germ-cell tumors and adenocarcinomas, as well as on some adult mouse and human tissues. A monoclonal antibody to this antigen (anti-SSEA-1; IgM, kappa) was used for radioimmunolocation. Nude mice bearing the human choriocarcinoma BeWo, which is SSEA-1 positive, were injected using a mixture of [131I]anti-SSEA-1 and [125I]MOPC 104E, an unselected myeloma protein of the same heavy-chain isotype. Animals were sacrificed at 24 hour intervals; the radioactive deposition due to both antibodies was determined for both tumors and normal organs. Accumulation of anti-SSEA-1 in the tumor was consistantly rapid and specific, while little accumulation of the unselected myeloma protein occurred. At five days after injection, an average of 3% of the initial dose of specific antibody was retained per gram of tumor; the tumor/blood ratio was 11, tumor/muscle was 80. Gamma-camera imaging allowed ready location of the tumors. Tumors could also be imaged using F(ab')2 antibody fragments.

Animals↗