Retroviral particles produced from a stable human-derived packaging cell line transduce target cells with very high efficiencies.

The goal of this work was to determine whether a stable 293 amphotropic packaging line, which we have designated 293-SPA, is useful for the production of high-titer stable virus by comparison to the murine psiCRIP line. Here, we report our unexpected findings that particles derived from the 293-SPA line transduce target cells (both NIH-3T3 cells and primary melanoma cells) with greatly enhanced efficiencies (at least 10-fold) compared to particles derived from the psiCRIP packaging line. We show that the presence of a transferable inhibitor in the psiCRIP line at least partially accounts for this dramatic difference in transduction efficiency. This work has important implications for improving the efficiency of retrovirus-mediated gene transfer in general as well as in the design of new packaging cell lines.

Direct comparison of fluorine-18-FDG SPECT, fluorine-18-FDG PET and rest thallium-201 SPECT for detection of myocardial viability.

UNLABELLED: Twenty consecutive patients were evaluated for presumptive myocardial viability using rest TI-SPECT, FDG-PET and FDG-SPECT. The FDG studies were performed after rest TI-SPECT to guide intervention or medical management. METHODS: Twenty patients with proven coronary artery disease, either known or suspected to have previous myocardial infarction and persistent perfusion defects shown by rest reinjection TI-SPECT, underwent FDG-PET and subsequent FDG-SPECT with a three-detector SPECT camera. FDG-PET and SPECT images were compared by five observers to determine if any fixed thallium segments were visualized by either FDG imaging method. RESULTS: Thirteen of 60 fixed segments were shown probably viable by FDG-SPECT (8 of 20 patients) and 14 of 60 by FDG PET (7 of 20 patients). Two patients had fixed thallium segments found probably viable with FDG by SPECT alone and one by PET alone. CONCLUSION: FDG is shown to provide additional information about myocardial viability. Both SPECT, using a three-detector camera, and PET with a specialized instrument are equally effective for imaging FDG in this application.

Acetazolamide enhanced single photon emission computed tomography (SPECT) evaluation of cerebral perfusion before and after carotid endarterectomy.

Twenty-five patients were tested before and after carotid endarterectomy with resting and acetazolamide enhanced single photon emission computed tomography (SPECT) scans with hexamethyl propyleneamine oxine (HMPAO) or iofetamine hydrochloride I123 (123I labeled IMP), both widely available radiopharmaceuticals. Twenty preoperative SPECT studies were asymmetric, revealing focal or diffuse decreased perfusion reserve, and 13 also demonstrated infarcts. Five patients had symmetric (normal) studies. After carotid endarterectomy, 22 cases had changed flow distribution patterns. Usually improvement of reactivity ipsilateral occurred to the area operated on. In four, contralateral improvement was also found. Three of the patients who had preoperative symmetrical scans had increased ipsilateral reactivity after surgery indicating previous global loss of reactivity. Acetazolamide SPECT scans demonstrate a decreased perfusion reserve in 20 patients with carotid artery stenosis, indicating reduced perfusion and poor collateral circulation. Postoperative studies confirm improvement by demonstrating recovery of vascular reactivity in 84% of the patients. Acetazolamide enhanced SPECT scans may be helpful in providing objective evidence for selection of patients for carotid endarterectomy, especially in those who have an 80% carotid artery stenosis, but are asymptomatic.

Carotid artery disease: evaluation with acetazolamide-enhanced Tc-99m HMPAO SPECT.

Sixty patients were studied for carotid artery disease and were further evaluated with hexamethyl-propyleneamine oxime (HMPAO) single photon emission computed tomography (SPECT) both at baseline (with the patient resting) and after administration of acetazolamide (ACZ). Of these 60 patients, 58 (97%) had symptoms and 49 (82%) had stenoses greater than 70% in at least one internal carotid vessel. Nine patients (15%) had symmetric findings on baseline examinations and at SPECT with ACZ. Thirty-two patients (53%) had asymmetric findings on baseline, but in 24 of these patients (75%) additional lesions were observed after ACZ administration. Nineteen patients (32%) had asymmetric findings only after ACZ was administered. HMPAO SPECT with ACZ allows detection of diminished cerebral perfusion reserve that is not found when HMPAO SPECT is performed with the patient at rest. This procedure helps provide an objective evaluation of the hemodynamic effects of carotid stenosis.

Increased brain retention of Tc-99m HMPAO following acetazolamide administration.

Sixty-five patients referred for Tc-99m HMPAO SPECT brain perfusion studies had measurements of global Tc-99m HMPAO retention after injection at rest and after acetazolamide pretreatment. Acetazolamide produced relative changes in Tc-99m HMPAO retention similar to those previously reported with Xe-133 regional cerebral blood flow (rCBF) measurements. This addition to imaging protocols allows another objective evaluation of the cerebral vascular reserve.

Initial experience with a radiology imaging network to newborn and intensive care units.

A digital image network has been installed in the James Whitcomb Riley Hospital for Children on the Indiana University Medical Center to create a limited all digital imaging system. The system is composed of commercial components, Philips/AT&T CommView system, (Philips Medical Systems, Shelton, CT; AT&T Bell Laboratories, West Long Beach, NJ) and connects an existing Philips Computed Radiology (PCR) system to two remote workstations that reside in the intensive care unit and the newborn nursery. The purpose of the system is to display images obtained from the PCR system on the remote workstations for direct viewing by referring clinicians, and to reduce many of their visits to the radiology reading room three floors away. The design criteria includes the ability to centrally control all image management functions on the remote workstations to relieve the clinicians from any image management tasks except for recalling patient images. The principal components of the system are the Philips PCR system, the acquisition module (AM), and the PCR interface to the Data Management Module (DMM). Connected to the DMM are an Enhanced Graphics Display Workstation (EGDW), an optical disk drive, and a network gateway to an ethernet link. The ethernet network is the connection to the two Results Viewing Stations (RVS) and both RVSs are approximately 100 m from the gateway. The DMM acts as an image file server and an image archive device. The DMM manages the image data base and can load images to the EGDW and the two RVSs. The system has met the initial design specifications and can successfully capture images from the PCR and direct them to the RVSs.(ABSTRACT TRUNCATED AT 250 WORDS)

Clinical comparison of indium-111 acetylacetone and indium-111 tropolone granulocytes.

This clinical study compares the efficacy of two 111In white blood cells preparations. Seventy-six patients were imaged after an injection of granulocytes (GRAN) isolated on a Ficoll-Hypaque gradient and labeled with [111In]acetylacetone (ACAC) in saline; 105 patients were imaged after an injection of GRAN isolated on a metrizamide-plasma gradient and labeled with [111In]tropolone (TROP) in plasma. Early (2-4 hr), intermediate (4-6 hr), and delayed (24 hr) images were obtained. The specificity was quite high (94-100%) in both preparations and no statistical differences could be found. The sensitivity for ACAC-GRAN for the early, intermediate, and delayed images were 39%, 63%, and 64%, respectively; for TROP-GRAN it was 80%, 89%, and 92%, respectively. In all cases the TROP-GRAN images were significantly more sensitive than the ACAC-GRAN images obtained at the same time after injection (p less than 0.001 for early and delayed images, 0.01 less than p less than 0.025 for intermediate images). For ACAC-GRAN the intermediate and delayed images were significantly more sensitive than the early images, while no significant difference could be found for TROP-GRAN. In a blinded experiment, the ability of TROP-GRAN to demonstrate a lesion was compared to that of ACAC-GRAN. TROP-GRAN demonstrated the lesions better than ACAC-GRAN, both in the early and late images (p less than 0.001). TROP-GRAN visualization scores at 4-6 hr equaled those obtained 24 hr after injection. In conclusion, GRAN separated and labeled in plasma with TROP are superior to those separated and labeled in saline with ACAC in three ways: higher visualization scores, earlier visualization of the lesion, and greater sensitivity.

Early menopausal changes in bone mass and sex steroids.

Eighty-four healthy perimenopausal and early postmenopausal women were divided into four groups: group A, those with slightly irregular menstrual periods and plasma FSH below 40 mIU/ml; group B, those with irregular periods and FSH above 40 mIU/ml; group C, those whose last menstrual period was within 1 yr of study; and, group D, those whose last menstrual period was between 12 and 55 months before the study. Plasma concentrations of estrone and estradiol progressively decreased in groups B, C and D compared to those in A in parallel with a decrease in the production rates, and FSH and LH were significantly increased. There was little change in the concentration of androstenedione or testosterone. Vertebral bone mass was significantly decreased in groups B, C, and D compared to that in A, and radial bone mass was decreased in group D. There was a significantly positive correlation between plasma estrone and estradiol and bone mass at both the radius and vertebra. Increased bone remodeling was suggested by increases in serum calcium and bone gla protein. These data suggest that bone loss, at least from the spine, may begin before menses cease and is correlated with decreases in estrogen production and increases in bone remodeling.

Photon absorptiometry of soft tissue and fluid content: the method and its precision and accuracy.

Dichromatic absorptiometry (DA) is a new, non-invasive method for determining soft tissue (STC) and fluid content (FC), and their changes. The technique uses linear transmission scans made across the limbs with a congruent 125I and 241Am dual-photon source and a NaI(TI)--PMT detector. Patient measurements could be made at the bedside with the mobile system. Factors affecting the precision and accuracy were evaluated theoretically and experimentally. Repositioning and subject motion were the greatest sources of variation and limited the precision to 2--3% in normals and 3--7% in patients; instrumental variation was 0.5%. The accuracy was 4% for typical (p10%) fluid changes observed in vivo. The ease, simplicity and small errors of the technique suggest its utility in monitoring the time course and degree of fluid changes in patients.

The study of burn wound edema using dichromatic absorptiometry.

Burn wound edema is a source of major morbidity and mortality. To quantitatively study this edema, we have devised a noninvasive method called Dichromatic Absorptiometry (DA) which is precise (2-3%) and accurate (r equal to 0.99) in measuring changes in tissue fluid. A scanning technique using a dual photon source, 125I and 241Am, is used. The variable attenuation of the two photon energies allows for selective mass measurements of fluid, protein, lipid, and bone. In limbs with thermal injury the correlation of DA changes in fluid mass with circumference was (r equal to 0.97), but DA was more sensitive. In deep second- and third-degree burns, edema formation was maximum between 12 and 18 hours postburn with 80% of maximum already present at 4 hours. Resorption was complete by 1 week in second-degree burns, but significantly delayed in third-degree burns. Superimposed infection produced persistent edema.

Soft-tissue fluid determination by dichromatic absorptiometry.

Dichromatic absorptiometry (DA) in a noninvasive method for individually determining the amount of lipid, bone mineral, and protein and water present in a mixture by differential attenuation of radiation beams emitted from a dual photon source. The physics involved permit these components to be determined extremely accurately and precisely. The present study investigated the ability of DA limb scans to measure changes in total body water produced in dogs and in patients. Dichromatic absorptiometry was determined to be a valid method of measuring changes in total body water content as reflected by limb fluid content changes. Precision was limited by the accuracy in positioning the limb for repeated scanning. Dichromatic absorptiometry has the potential of becoming a clinically useful instrument for measuring fluid content changes in limbs produced either by changes in total body water content or by conditions causing limb edema.