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Biomedical subjects

S J Goldsmith

Publications and source records attributed to S J Goldsmith.

At least 19 recordsLinked to original sources

Biologic bypass with the use of adenovirus-mediated gene transfer of the complementary deoxyribonucleic acid for vascular endothelial growth factor 121 improves myocardial perfusion and function in the ischemic porcine heart.

OBJECTIVES: Vascular endothelial growth factor (VEGF), a potent angiogenic mediator, can be delivered to targeted tissues by means of a replication-deficient adenovirus (Ad) vector. We hypothesized that direct administration of Ad vector expressing the VEGF121 complementary deoxyribonucleic acid (AdGVVEGF121.10) into regions of ischemic myocardium would enhance collateral vessel formation and improve regional perfusion and function. METHODS: Yorkshire swine underwent thoracotomy and placement of an Ameroid constrictor (Research Instruments & MFG, Corvallis, Ore.) on the circumflex coronary artery. Three weeks later, myocardial perfusion and function were assessed by single photon emission computed tomography imaging (SPECT) with 99mTc-labeled sestamibi and by echocardiography during rest and stress. AdGVVEGF121.10 (n = 7) or the control vector, AdNull (n = 8), was administered directly into the myocardium at 10 sites in the circumflex distribution (10(8) pfu/site). Four weeks later, these studies were repeated and ex vivo angiography was performed. RESULTS: SPECT imaging 4 weeks after vector administration demonstrated significant reduction in the ischemic area at stress in AdGVVEFG121.10-treated animals compared with AdNull control animals (p = 0.005). Stress echocardiography at the same time demonstrated improved segmental wall thickening in AdGVVEGF121.10 animals compared with AdNull control animals (p = 0.03), with AdGVVEGF121.10 animals showing nearly normalized function in the circumflex distribution. Collateral vessel development assessed by angiography was also significantly greater in AdGVVEGF121.10 animals than in AdNull control animals (p = 0.04), with almost complete reconstitution of circumflex filling in AdGVVEGF121.10 animals. CONCLUSIONS: An Ad vector expressing the VEGF121 cDNA induces collateral vessel development in ischemic myocardium and results in significant improvement in both myocardial perfusion and function. Such a strategy may be useful in patients with ischemic heart disease in whom complete revascularization is not possible.

Adenoviridae

SPECT and lumbar MRI in back pain with emphasis on changes in end plates in association with disc degeneration.

Over a two-year period, 48 sequential patients were selected because they showed type I or II end plate changes on magnetic resonance imaging (MRI) and/or had positive single-photon emission computerized tomography (SPECT) scan in the area of disc degeneration. They were selected out of a large group of patients who were being evaluated by MRI and SPECT scan for low back pain. In this group of 48 patients, 47 had positive SPECT scans at the disc space, which on MRI indicates degenerative disc disease. Of these, 38 had end plate changes on the MRI, but 10 did not have end plate changes on the MRI even though their SPECT was positive. None of the 48 patients had evidence of other pathology such as fracture, metastatic disease or spondylolysis. The MRI changes were both of type I and type II and thought to represent increased vascularization of the fibrous tissue or fatty replacement of marrow in the area of the end plate. Based on this study, we are proposing that a positive end plate SPECT in degenerative disc disease is related to marrow changes in the region of the end plate of the disc. Also, we are proposing that SPECT may be of value in delineating early end plate changes prior to the MRI showing type I or type II change in the same area.

Adult

Receptor imaging: competitive or complementary to antibody imaging?

Both radiolabeled ligands to specific receptors on cell surfaces and radiolabeled antibodies to specific cell surface epitopes provide new opportunities to scintigraphically identify tumors. Both radiolabeled ligands and antibodies are characterized by high orders of affinity for their respective binding sites and offer greater specificity over the agents previously used for tumor imaging including gallium 67, thallium 201, technetium 99m MIBI, and flourine-18-labeled deoxyglucose. The two classes of tumor-binding tracers differ primarily based on molecular weight although the nonspecific portion of the immunoglobulins are also antigenic. Increased molecular weight results in prolonged plasma survival, which increases the interval available for tumor permeation but also produces increased nonspecific background activity, which impairs image contrast. At the present time, encouraging clinical results have been obtained with both agent types, but further development is necessary. Receptor-ligand tracers provide better contrast than antibodies or antibody fragments. Receptor-ligand imaging technology awaits further developments in an understanding of the biology of receptor expression in normal tissue and tumors and improved radio-chemical techniques and pharmacology to define the radioligands of choice. Radiolabeled antibodies will probably evolve in the direction of increased use of antibody fragments and possibly the identification and polymerization of epitope-recognition units in order to provide high-affinity, nonantigenic, small molecular weight tracers that will be more permeable in tumors and clear more rapidly from background tissue. Rather than compete or complement each other, the techniques will likely produce a hybrid technology, radiolabeled molecular recognition units, with the better features of both technologies including high binding affinity (low dissociation constant) for surface membrane epitopes, including receptor sites.

Animals

Psychiatric symptoms in clients presenting for commercial weight reduction treatment.

OBJECTIVE: To study the prevalence and severity of psychiatric symptoms in a group of clients presenting to a commercial weight reduction program, compared with a group of patients seeking outpatient medical treatment. METHOD: Sixty-six clients presenting for commercial weight loss treatment and 52 patients presenting for general outpatient medical treatment were given self-report measures of anxiety (Spielberger State and Trait Inventory), depression (Beck Depression Inventory), body dissatisfaction (Body Shape Questionnaire), and overall impairment in functioning (Sheehan Disability Scale). RESULTS: Weight loss clients had significantly higher rates of depressive symptomatology and psychosocial disability than patients presenting for medical treatment. Weight loss clients were also more likely to demonstrate body dissatisfaction regardless of actual weight. Levels of anxiety were not significantly different, despite the medical group reporting themselves to be in poorer health as compared with the weight loss group. DISCUSSION: Regular screening for psychiatric symptoms in clients presenting for commercial weight reduction treatment may be valuable as this group may constitute an as yet unidentified cohort requiring psychiatric intervention.

Adult

Evaluation of four radiopharmaceuticals for imaging inflammation in a rabbit model of arthritis.

We compared the utility of four radiopharmaceuticals; 111In-chloride, 67Ga-citrate, 111In labeled leukocytes (WBCs) and 99mTc-MDP for assessing the inflammatory response in antigen induced arthritis in a rabbit model. A total of 20 rabbits, divided into four equal groups, were included in this study. Each group was studied twice with a single radiotracer; a baseline study and a follow-up study after induction of the arthritis. Knee to knee, knee to whole body, and knee to liver (except for the group studied with 99mTc-MDP) ratios were generated. Knee to knee ratios showed no significant change from baseline to arthritis studies in any of the four groups. Significantly increased knee to total body ratios were seen in all of the groups, except for the group studied with 99mTc-MDP. The greatest increase was seen in the group studied with 111In-chloride. Significantly increased knee to liver ratios were observed in all three groups for which these ratios were generated and again the greatest increase was observed in the group studied with 111In-chloride. In summary, based on the higher uptake observed in this group, of the four radiotracers evaluated, 111In-chloride is probably the most useful for monitoring the inflammatory response in antigen induced arthritis. The symmetry of the response suggests that it may also be useful in monitoring the response to therapy.

Animals

Detection of bony metastases of androgen-independent prostate cancer by PET-FDG.

Fourteen F-18 fluorodeoxyglucose (FDG) studies were carried out in 13 patients known to have bony metastases from carcinoma of the prostate. One patient was newly diagnosed. The remaining patients had various types of therapy and were considered hormonally resistant. The average age was 67. All patients had extensive bony metastases shown on the conventional Tc99m-MDP bone scans. Only about 18% of bony lesions apparent on the conventional bone scans showed corresponding increase of FDG uptake. Anatomical correlation was performed by using co-registered images of SPECT and PET in the same area. The positive FDG uptake was not related to the duration of illness, level of PSA, previous therapy, and magnitude of disease involvement. It appears that only a small percentage of bony metastases is associated with increased glycolysis. It is possible that other metabolic processes are more important than glycolysis for providing prostate cancer with a source of energy and nutrients.

Aged

Visualization of myocardial metastasis of carcinoid tumor by indium-111-pentetreotide.

We present a case of metastatic carcinoid tumor metastatic to the heart, presenting as ventricular arrhythmia and diagnosed by 111Inpentetreotide scintiscan despite negative endocardial biopsy. The incidence and diagnosis of carcinoid heart disease is discussed, as well as the complementary role of high-resolution anatomical images (CT, MRI) with functional images (SPECT, PET) to determine the correct diagnosis of this rare condition.

Carcinoid Heart Disease

Somatostatin-receptor imaging in lymphoma.

Patients with Hodgkin's or non-Hodgkin's lymphoma are staged for treatment based on the extent of known disease involvement and the histopathologic grading of the disease. Radiological techniques, including computed tomography, usually depend on estimates of lymph node enlargement and mass effects as the criterion for disease involvement. Lymphomatous tissue obtained at surgery has shown high-density somatostatin receptors. Several groups have evaluated the utility of 111In-DTPA-pentetreotide (Octreoscan, Mallinckrodt, St. Louis, MO) to detect lymphomatous tissue for more accurate staging of patients with lymphoma. The procedure is safe; both Hodgkin's and non-Hodgkins disease involvement is identified. The results, however, have not been uniformly predictive of disease involvement. Consequently, the routine use of this technique in place of currently used anatomic imaging methods is not recommended at this time. The significance of detecting somatostatin receptors in vivo in patients with malignant lymphoma requires further study.

Adult

The role of gallium and labeled leukocyte scintigraphy in the AIDS patient.

Because AIDS patients frequently present with minimal symptomatology, radionuclide imaging with its ability to survey the entire body, is especially valuable. Gallium-67 citrate, the most commonly performed radionuclide study for localizing infection in these patients, is most useful for detecting opportunistic infections, especially in the thorax. A negative gallium scan, particularly when the chest X-ray is unremarkable, rules strongly against pulmonary disease. A negative gallium scan in a patient with an abnormal chest X-ray and Kaposi's sarcoma, suggests that the patient's respiratory distress is related to the neoplasm. Diffuse pulmonary parenchymal uptake of gallium in the HIV (+) patient is most often associated with PCP. While there are other causes of diffuse pulmonary uptake, the more intense or heterogeneous the uptake, the more likely the patient is to have PCP. Focal pulmonary uptake is usually associated with bacterial pneumonia although PCP may occasionally present in this fashion. Lymph node uptake of gallium is usually associated with Mycobacterium avium complex, tuberculosis, or lymphoma. When corresponding abnormalities are present on thallium scintigraphy lymphoma is likely. Gallium positive, thallium negative, studies suggest mycobacterial disease. Labeled leukocyte imaging is not useful for detecting opportunistic infections probably because of the inflammatory response incited by these organisms. Leukocyte imaging is, however, more sensitive for detecting bacterial pneumonia. In the abdomen, gallium imaging is most useful for identifying lymphadenopathy, while labeled leukocyte imaging is superior for detecting AIDS-associated colitides. In summary, radionuclide studies are valuable diagnostic modalities in AIDS. Their success can be maximized by tailoring the study to the individual's needs.

AIDS-Related Opportunistic Infections

SPECT evaluation of lumbar spondylolysis and spondylolisthesis.

Fifty patients with back pain and radiologically diagnosed spondylolysis were evaluated by a single-photon emission computed tomography (SPECT bone scanning). These patients were separated into three groups according to the degree of spondylolisthesis accompanying the spondylolysis. The data obtained from the study indicate that in acute spondylolysis, the SPECT scan is positive at the pars interarticularis. As the spondylolysis becomes chronic, the SPECT scan tends to revert toward normal even though healing of the spondylolysis has not occurred. As spondylolisthesis develops and progresses, the SPECT scan again becomes positive. The positivity, however, is more anterior and more diffuse. The authors propose that SPECT scanning in spondylolysis is not a positive or negative process, but rather varies with the time and stability of the spondylolytic spine.

Adolescent

Gallium-67-citrate imaging in nuclear oncology.

Gallium-67-citrate is one of the most useful radiopharmaceuticals to detect tumors, stage extent of the disease, monitor response to treatment and distinguish recurrent disease from post-treatment changes. Gallium is likewise very sensitive to detect and locate infections and inflammatory foci. This application is extremely important in the management of immunocompromised cancer patients. Image interpretation should be tempered with full knowledge of the patients clinical condition, anatomic alterations due to prior surgery and correct timing of image acquisition. Early imaging at 4-6 h is useful to detect gastrointestinal infections, whereas 24 h imaging is used to evaluate chest infections. Although gallium-67 is a non-specific agent, the identification of the etiology of the inflammation may be improved by adequate clinical and laboratory information as well as correlation with other imaging modalities such as sonography and computerized x-ray tomography (CT). High dose (10 mCi) gallium-67 single photon emission computed tomography (SPECT) imaging with image co-registration is important for accurate uptake localization.

Citrates

Clinical applications of fusion imaging in oncology.

Recent developments in tumor imaging, made possible by advances in instrumentation and radiopharmaceuticals, has led to an increasing need for accurate anatomic correlation of single photon emission computed tomography (SPECT) and positron emission tomography (PET) images. Fusion imaging permits the functional strengths of SPECT and PET to be combined with the anatomic resolution of computed tomography (CT) and magnetic resonance imaging (MRI). Clinical applications of fusion imaging include the evaluation of brain tumors, lymphoma, hepatic lesions and monoclonal antibody studies. The continued development of these techniques will eventually allow fusion imaging to become a routine part of nuclear medicine practice.

Antibodies, Monoclonal

SPECT evaluation of unilateral spondylolysis.

Three patients with unilateral spondylolysis were evaluated with SPECT and Lumbar CT. All three cases had positive scans. However, the SPECT images were unique to each case. Therefore, the interpretation of the SPECT activity was undertaken in terms of the known natural history of both unilateral and bilateral spondylolysis.

Adolescent

Postoperative changes on brain SPECT imaging after aneurysmal subarachnoid hemorrhage. A potential pitfall in the evaluation of vasospasm.

Serial brain SPECT imaging was performed on patients after subarachnoid hemorrhage and surgical clipping of intracranial aneurysms. A total of 20 HMPAO scans were performed on 9 patients in whom clinical vasospasm did not develop. Areas of diminished regional cerebral blood flow (rCBF) were found near the operative site in 17 of 20 studies, which did not correlate with the patients' neurologic condition and were suggestive of postoperative edema. Brain SPECT imaging has a potentially valuable role to play in the evaluation of postoperative patients susceptible to vasospasm; however, it is important to be aware of postoperative changes in rCBF that are not related to vasospasm.

Brain

Flare on bone scintigraphy following Taxol chemotherapy for metastatic breast cancer.

UNLABELLED: Our goal was to determine if a healing flare response seen on bone scintigraphy occurs following chemotherapy with Taxol (paclitaxel; Bristol-Myers Squibb Co., Princeton, NJ), a novel antimicrotubule agent for metastatic breast cancer. METHODS: We performed 74 bone scans on 21 females with breast cancer and bone metastases entering a Phase II trial of Taxol chemotherapy with granulocyte colony stimulating factor (G-CSF). All patients had baseline scans within 6 wk prior to therapy, after the second cycle (4-6 wk) of Taxol, and then after 6-12 mo. All bone scans were reviewed by two nuclear medicine physicians, without knowledge of the patients' clinical history. Skeletal radiographs, CT and MRI scans, as well as clinical history were compared with scan findings. RESULTS: Seven of the 21 patients showed improvement in bone scan findings. Of these seven, three had a flare response following two cycles (4-6 wk) of Taxol, characterized by increased activity in baseline lesions and the appearance of new lesions, followed by improvement on follow-up scans. Evidence of clinical response (> or = 50% reduction in tumor mass) was seen in all of these patients. Seven patients showed no change in baseline findings on follow-up bone scans. Seven patients had post-Taxol scans showing new lesions, with no overall improvement on later follow-up. CONCLUSION: Flare on bone scintigraphy may be seen shortly after commencing Taxol chemotherapy. Bone scans done within the first 3 mo must be interpreted with caution and should be correlated with clinical and radiological findings to avoid inappropriate discontinuation of Taxol chemotherapy.

Adenocarcinoma

Radon update: facts concerning environmental radon: levels, mitigation strategies, dosimetry, effects and guidelines. SNM Committee on Radiobiological Effects of Ionizing Radiation.

The risk from environmental radon levels is not higher now than in the past, when residential exposures were not considered to be a significant health hazard. The majority of the radon dose is not from radon itself, but from short-lived alpha-emitting radon daughters, most notably 218Po(T1/2 3 min) and 214Po (T1/2 0.164 msec) along with beta particles from 214Bi (T1/2 19.7 min). Radon gas can penetrate homes from many sources and in various fashions. Measuring radon in homes is simple and relatively inexpensive and may be accomplished in a variety of ways. Although it is not possible to radon-proof a house, it is possible to reduce the level. In high radon areas, if the average level is higher than 4-8 pCi/liter (NCRP recommended level is 8 pCi/liter; EPA recommended level is 4 pCi/liter), appropriate action is advised. The shape of the dose response curves for miners exposed to alpha-emitting particles in the workplace is consistent with current biologic knowledge. It is linear in the low dose range and saturates in the high dose range. No detectable increase in lung cancer frequency is seen in the lowest exposed miners (those with exposures < 120 WLM, the relevant dose interval for most homes). Evidence for a health effect from radon exposure is based on data from animal studies and epidemiologic studies of mines. Extensive radiobiologic data predict a linear dose-response curve in the low dose region due to poor biological repair mechanisms for the high density of ionizing events that alpha particles create. However, no compelling evidence for increased cancer risks has yet been demonstrated from "acceptable" levels (< 4-8 pCi/liter).

Air Pollutants