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Biomedical subjects

P Zanzonico

Publications and source records attributed to P Zanzonico.

At least 19 recordsLinked to original sources
PubMed2003

A stereotactic method for the three-dimensional registration of multi-modality biologic images in animals: NMR, PET, histology, and autoradiography.

The objective of this work was to develop and then validate a stereotactic fiduciary marker system for tumor xenografts in rodents which could be used to co-register magnetic resonance imaging (MRI), PET, tissue histology, autoradiography, and measurements from physiologic probes. A Teflon fiduciary template has been designed which allows the precise insertion of small hollow Teflon rods (0.71 mm diameter) into a tumor. These rods can be visualized by MRI and PET as well as by histology and autoradiography on tissue sections. The methodology has been applied and tested on a rigid phantom, on tissue phantom material, and finally on tumor bearing mice. Image registration has been performed between the MRI and PET images for the rigid Teflon phantom and among MRI, digitized microscopy images of tissue histology, and autoradiograms for both tissue phantom and tumor-bearing mice. A registration accuracy, expressed as the average Euclidean distance between the centers of three fiduciary markers among the registered image sets, of 0.2 +/- 0.06 mm was achieved between MRI and microPET image sets of a rigid Teflon phantom. The fiduciary template allows digitized tissue sections to be co-registered with three-dimensional MRI images with an average accuracy of 0.21 and 0.25 mm for the tissue phantoms and tumor xenografts, respectively. Between histology and autoradiograms, it was 0.19 and 0.21 mm for tissue phantoms and tumor xenografts, respectively. The fiduciary marker system provides a coordinate system with which to correlate information from multiple image types, on a voxel-by-voxel basis, with sub-millimeter accuracy--even among imaging modalities with widely disparate spatial resolution and in the absence of identifiable anatomic landmarks.

Algorithms↗
PubMed2000

The intraoperative gamma probe: basic principles and choices available.

By taking advantage of the proximity to radioactive sentinel nodes and occult tumors achievable in an operative setting, intraoperative probes are becoming increasingly important in the surgical management of cancer. This article begins with a discussion of the statistical limitations of radiation detection and measurement and of the key performance parameters (sensitivity, energy resolution, and spatial resolution) that characterize detectors. The basic design and operating principle of radiation detectors used in intraoperative probes, scintillation and semiconductor detectors, are then reviewed. Scintillation detector-based intraoperative probes, generally using a NaI(T1) or a CsI(T1) crystal connected to a photomultiplier tube by a fiberoptic cable, have the advantages of reliability, relatively low cost, and high sensitivity, especially for medium- to high-energy photons. Disadvantages include poor energy resolution and scatter rejection, and bulkiness. Semiconductor (CdZn, CdZnTe, HgI2)-based probes are compact and have excellent energy resolution and scatter rejection, but with complex energy spectra reflecting charge-carrier trapping. Their main disadvantage is lower sensitivity. The performance parameters of various commercially available intraoperative probes are then compared. The article concludes with a discussion of the practical considerations in selecting and using intraoperative probes, including ergonomic and other design features, as well as performance parameters.

Gamma Cameras↗
PubMed2000

Focal angiogen therapy using intramyocardial delivery of an adenovirus vector coding for vascular endothelial growth factor 121.

BACKGROUND: Adenovirus (Ad) vector-mediated gene therapy strategies have emerged as promising modalities for the "biological revascularization" of tissues. We hypothesized that direct intramyocardial, as opposed to intracoronary, administration of an Ad vector coding for the vascular endothelial growth factor 121 cDNA (Ad(GV)VEGF121.10) would provide highly focal Ad genome levels, and increases in VEGF, ideal for inducing localized therapeutic angiogenesis. METHODS: Persistence and regional distribution of the vector were assessed by TaqMan real-time quantitative polymerase chain reaction technology and enzyme-linked immunosorbent assay, after intramyocardial Ad(GV)VEGF121.10 in the rat, and either intramyocardial or intracoronary (circumflex territory) vector in Yorkshire swine. Based on these results, we assessed the focal nature of the improved cardiac blood flow in a previously reported porcine myocardial ischemia model. RESULTS: Intramyocardial delivery of Ad(GV)VEGF121.10 in the rat resulted in local persistence of the Ad genome that decreased 1,000-fold over 3 weeks, with peak myocardial VEGF expression 24 to 72 h after vector delivery. After intramyocardial Ad(GV)VEGF121.10 in the circumflex distribution of pigs, Ad vector genome and VEGF protein levels were more than 1,000-fold and more than 90-fold higher, respectively, in this distribution than in other myocardial regions. In comparison, intracoronary injection yielded maximum myocardial Ad genome and VEGF levels 33-fold and 9-fold lower, respectively, than that after intramyocardial delivery. Angiograms obtained 28 days after intramyocardial Ad(GV)VEGF121.10 demonstrated rapid circumflex reconstitution via collaterals localized to the region of vector administration. CONCLUSIONS: These studies demonstrate that direct intramyocardial administration of Ad(GV)VEGF121.10 results in focal genome and VEGF levels, including focal angiogenesis, sufficient to normalize blood flow to the ischemic myocardium, findings that are relevant to designing human trials of gene therapy-mediated cardiac angiogenesis.

Adenoviridae↗
PubMed1999

Thyroid uptake of liquid versus capsule 131I tracers in hyperthyroid patients treated with liquid 131I.

The amount of 131I used to treat hyperthyroid patients is based in part on the 24-hour thyroid uptake of a diagnostic amount of radioiodine (tracer). We compared the 24-hour uptake of an 131I tracer administered in liquid or capsule form to the 24-hour uptake of 131I therapy administered as liquid. Sixty-five hyperthyroid patients with Graves' disease were evaluated and subsequently treated with radioiodine. The liquid group (45 patients) received a liquid 131I tracer (1.85 MBq [0.05 mCi]) and the capsule group (20 patients) received a capsule 131I tracer (1.63 MBq [0.044 mCi]). Probe calibration factors were the same for the liquid and capsule 131I standards. All patients received therapeutic amounts of 131I [114.7-1106.3 MBq [3.1-29.9 mCi]) in liquid form. Therapy uptakes were obtained using the same collimated uptake probe modified with a calibrated lead shield to attenuate the high photon flux. The mean therapeutic uptake was the same for both groups (58%). The mean diagnostic uptake for the capsule group, however, was less than the mean diagnostic uptake for the liquid group (44% vs. 63%). The mean diagnostic uptake for the capsule group was significantly lower than the mean therapeutic uptake for this group (44% vs. 58%), whereas the mean diagnostic and therapeutic uptakes were similar for the group receiving a liquid tracer (63% vs. 58%). In conclusion, diagnostic uptakes performed with a liquid tracer more accurately predicted liquid therapy uptakes than diagnostic uptakes performed with a capsule tracer. This raises concern about the bioavailability of 131I in capsule form and has implications for determining the amount of 131I to administer for therapy. Patients whose 131I therapy was based on the uptake of a capsule tracer received a higher than intended amount of radiation to the thyroid gland.

Administration, Oral↗
PubMed1998

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↗
PubMed1998

Salvage angiogenesis induced by adenovirus-mediated gene transfer of vascular endothelial growth factor protects against ischemic vascular occlusion.

PURPOSE: Vascular endothelial growth factor (VEGF) is a potent stimulator of angiogenesis, and transgene expression from adenovirus vectors can provide in vivo delivery of proteins. On the basis of this knowledge, we hypothesized that local administration of a replication-deficient adenovirus vector expressing complementary DNA for VEGF (AdVEGF) would induce collateral vessel formation in the setting of ischemia that could protect against subsequent acute vascular occlusion. METHODS: Hindlimb ischemia was induced in Sprague-Dawley rats by means of unilateral ligation of the common iliac artery immediately followed by administration of 4 x 10(9)-plaque-forming units VEGF, the control vector AdNull, or phosphate-buffered saline solution into the iliofemoral adipose tissue and thigh muscles. Untreated rats with common iliac ligation were used as an additional control group. RESULTS: Local VEGF expression was observed for 5 days in AdVEGF-treated rats but not in controls. Three weeks after ligation and vector administration, the ipsilateral femoral artery was ligated for a model of an acute vascular occlusion in the setting of preexisting ischemia. Blood flow to the ischemic hindlimb relative to the contralateral hindlimb evaluated with color microspheres demonstrated significantly increased blood flow in the AdVEGF-treated rats compared with each control group (p < 0.0001). Relative blood flow assessed by means of 99mTc-sestamibi radionuclide scans also demonstrated increased blood flow to the ligated hindlimb of AdVEGF-treated rats compared with each control group (p < 0.002). AdVEGF-treated rats also demonstrated increased vascularity in the ligated limb compared with each control group as assessed by means of angiography (p < 0.0001) and histologic quantification of blood vessels less than 80 microm diameter in local adipose tissue and capillaries per muscle fiber (p < 0.0002). AdVEGF treatment prevented a rise in femoral venous lactate femoral venous concentrations 1 hour after femoral artery ligation in control rats (p < 0.04). CONCLUSIONS: An adenovirus vector expressing VEGF complementary DNA is capable of stimulating an angiogenic response that protects against acute vascular occlusion in the setting of preexisting ischemia, suggesting that in vivo gene transfer of VEGF complementary DNA might be useful in prophylaxis of advancing arterial occlusive disease.

Adenoviridae↗
PubMed1998

Prospective study of simultaneous orthoiodohippurate and diethylenetriaminepentaacetic acid captopril renography. The Einstein/Cornell Collaborative Hypertension Group.

UNLABELLED: Captopril renography (CR) has been established in the past 10 yr as a useful diagnostic test for renovascular hypertension. However, direct comparison of tubular and glomerular tracers, quantitative criteria, comparison of quantitative and qualitative results and the reliability of the results in renal failure have not been described in a systematic, prospective fashion. METHODS: Same-day baseline and CR using 99mTc-labeled diethylenetriaminepentaacetic acid (DTPA) and [131I]orthoiodohippurate (OIH) were simultaneously performed in two groups of hypertensive subjects, one with demographically defined essential hypertension (n = 43) and the other (n = 60) with a high prevalence of renovascular disease, defined with angiograms. Quantitative criteria for abnormal CR were derived from results among the subjects with essential hypertension. Qualitative analysis was performed using widely established criteria. RESULTS: There were no statistically significant differences between quantitative and qualitative accuracy, between OIH and DTPA or among quantitative parameters. The best accuracies for quantitative CR were 56% with DTPA (n = 57) and 60% with OIH (n = 60), in both cases using the relative renal uptake parameter. Qualitative CR (n = 60) had accuracies of 43% (DTPA) and 50% (OIH), both hindered by 29 (DTPA) and 25 (OIH) abnormal but nondiagnostic studies. Two false-positive studies were detected. Twenty-seven of 29 nondiagnostic studies were associated with a glomerular filtration rate of <50 ml/min (n = 17), one small kidney (n = 17) and/or bilateral renal artery stenosis (n = 16). Supplemental measurement of in vitro stimulated plasma renin activity insignificantly (p > 0.10) and improved accuracies to 63% (DTPA) and 70% (OIH), without introducing additional false-positive tests. CONCLUSION: Orthoiodohippurate and DTPA have comparable accuracy in prospective simultaneous evaluation of CR. False-positive studies are fewer than 5%. The accuracies of quantitative and qualitative criteria do not differ significantly but may be improved by supplemental use of the in vitro stimulated plasma renin activity. In individuals with renal insufficiency, small kidneys and/or bilateral renal artery disease, up to 48% of CR studies are abnormal but nondiagnostic.

Antihypertensive Agents↗
PubMed1997

Potassium iodide for thyroid blockade in a reactor accident: administrative policies that govern its use.

A marked increase in thyroid cancer among young children who were in the vicinity of the Chernobyl nuclear power plant at the time of the 1986 accident strongly suggests a possible causal relationship to the large amounts of radioactive iodine isotopes in the resulting fallout. Although remaining indoors, restricting consumption of locally produced milk and foodstuffs, and evacuation are important strategies in a major breach-of-containment accident, stable potassium iodide (KI) prophylaxis given shortly before or immediately after exposure can reduce greatly the thyroidal accumulation of radioiodines and the resulting radiation dose. Concerns about possible side effects of large-scale, medically unsupervised KI consumption largely have been allayed in light of the favorable experience in Poland following the Chernobyl accident; 16 million persons received single administrations of KI with only rare occurrence of side effects and with a probable 40% reduction in projected thyroid radiation dose. Despite the universal acceptance of KI as an effective thyroid protective agent, supplies of KI in the US are not available for public distribution in the event of a reactor accident largely because government agencies have argued that stockpiling and distribution of KI to other than emergency workers cannot be recommended in light of difficult distribution logistics, problematic administrative issue, and a calculated low cost-effectiveness. However, KI in tablet form is expensive and has a long shelf life, and many countries have largely stockpiles and distribution programs. The World Health Organization recognizes the benefits of stable KI and urges its general availability. At present there are 110 operating nuclear power plants in the US and more than 300 in the rest of the world. These reactors product 17% of the world's electricity and in some countries up to 60-70% of the total electrical energy. Almost all US nuclear power plants have multistage containment structures with large steel and concrete shells and multiple redundancy of core cooling mechanisms. These successfully prevented the release of major amounts of radionuclides in the Three Mile Island partial loss-of-primary coolant accident in 1979. The Chernobyl accident, in a different type of reactor that is common in Eastern Europe, did not have effective outer shell containment and released almost 50 MCi of 131I compared to the 20 Ci of 131I released at Three Mile Island. Such accidents have precipitated extensive re-evaluation of the design and safety devices of all operating reactors. However, a major contributing factor to the accidents was human error and considerable efforts must be made to train plant operators so they have a better understanding of reactor operation and use of safety mechanisms.

Humans↗
PubMed1996

In vitro model to evaluate the relative efficacy of catheter-directed thrombolytic strategies.

RATIONALE AND OBJECTIVES: Catheter-directed thrombolytic therapy has become an accepted treatment for many vascular occlusions. However, the relative rates of lysis of the different methods of drug administration have not been quantified. We developed an in vitro model to simulate and quantify local lytic therapy of a thrombotic vascular occlusion and tested it by evaluating three catheter-directed lytic strategies. METHODS: Seven-centimeter-long segments of 125I-fibrinogen-labeled thrombus made from recently expired human blood from a blood bank were formed in plastic tubes and were placed in a flowing stream of saline. Using multisidehole catheters, the clots were "treated" with intrathrombic saline or urokinase administered by drip infusion or forced injection using identical total doses of drug and volumes of fluid. Using endhole catheters, saline or urokinase was drip infused into the leading edge of the thrombus using the same protocol. A collimated scintillation detector was used to quantify the amount of activity remaining in the thrombus during each experiment, and the resultant time-activity curves for the different trials were compared. RESULTS: Forced-injection administration of urokinase using a multisidehole catheter produced the fastest lysis, resulting in a half-life of 42 min. The other infusion methods were slower, with half-lives of 153 min for multisidehole urokinase drip infusion, 365 min for endhole urokinase drip infusion, and more than 1,000 min for multisidehole catheter forced injection of saline and multisidehole and endhole saline drip infusion. The differences among these groups were reproducible and statistically significant. CONCLUSION: Results suggest that a simple and inexpensive in vitro model simulating lysis of a vascular occlusion can produce reproducible quantitative data. The data demonstrate that forced injection of lytic agents with a multisidehole catheter enhances the rate of thrombolysis and that the enhancement is not primarily attributable to the mechanical effect of this mode of administration.

Catheterization, Peripheral↗
PubMed1996

Biodistribution and autoradiographic localization of I-125--labeled synthetic Peptide in aortic atherosclerosis in cholesterol-fed rabbits.

I-125 labeled SP4 is a synthetic oligopeptide derived from apolipoprotein B of low-density lipoprotein that has been shown to localized in atherosclerotic plaques in experimental animals. However, its biodistribution and mechanism of localization need to be further elucidated. Twenty-four cholesterol-fed (CF) and 20 normal (NL) New Zealand White rabbits were injected with I-125-SP4 and killed 15 to 30 min (6 NL; 6 CF) or 2 h (14 NL; 18 CF) later. We obtained aortic autoradiograms and activity concentrations (% injected dose/gm) in aortic segments and other tissues. The uptake of I-125-SP4 was higher in CF than in NL rabbits in all aortic segments (p < 0.05). I-125-SP4 was cleared rapidly in both CF and NL rabbits with 60 to 70% of the injected dose cleared from the blood by 1 h. No statistically significant differences in radiotracer biodistribution were observed between NL and CF rabbits although activity tended to be higher in the liver, gallbladder, and intestine in NL rabbits and in the kidney and spleen in CF rabbits. Silver grains were distributed mainly on foam cells of the fatty streaks in aortic microautoradiograms from two additional rabbits that had been injected with I-125-SP4. There were 23,518 plus minus 15,878 (SD) grains/mm(2) in fatty plaques but only 14,669 plus minus 11,035 grains/mm(2) in media muscle (p < 0.0001 [9 sections, 17 areas evaluated] in an atherosclerotic animal) in injected animals and 13,439 plus minus 5,565 grains/mm(2) in media muscle (two sections, four areas) in the normal control animals (NS versus media of atherosclerotic animal). I-125-SP4 specifically localizes in aortic atherosclerotic plaques in CF rabbits. There is no significant difference in tissue distribution between normal and CF rabbits except in the aorta. Preliminarily, it appears that the site of tracer uptake is on foam cells and this suggests the possibility of relative specificity for fatty plaque.

Journal Article↗
PubMed1996

Effect of prior radiopharmaceutical administration on Schilling test performance: analysis and recommendations.

UNLABELLED: Previously administered diagnostic and therapeutic radiopharmaceuticals may interfere with performance of the Schilling test for prolonged periods of time. Additionally, presence of confounding radionuclides in the urine may not be suspected if baseline urine measurements have not been performed before the examination. METHODS: We assumed that a spurious contribution of counts corresponding to 1% of the administered Schilling dose would begin to contribute clinically significant interference. Based on the typical amounts of radiopharmaceuticals administered, spectra of commonly used radionuclides and best available pharmacokinetic models of biodistribution and excretion, we estimated the interval required for 24-hr urinary excretion of diagnostic and therapeutic radiopharmaceuticals to drop below this threshold of significant interference. RESULTS: For previously administered 99mTc-based radiopharmaceuticals and 123I-Nal, the interval required for urinary levels of activity to fall below thresholds of allowable interference are between 2-5 days. For 67Ga-citrate, several 111In compounds, 131I-MIBG and 201Tl-thallous chloride, periods of 12-44 days are estimated. Estimates for 131I-Nal vary greatly between 4 and 115 days, depending on the amount administered, and the degree of thyroid uptake. CONCLUSION: Patients should be interviewed before performing the Schilling test to ensure that interfering radiopharmaceuticals have not been recently administered. The estimates developed in this paper can serve as guidelines for the necessary waiting time between prior radiopharmaceutical administration and the Schilling examination.

Aged↗
PubMed1993

Magnetic resonance imaging measurements and clinical changes accompanying transtentorial and foramen magnum brain herniation.

Current concepts of brain herniation have depended largely on correlating clinical signs and symptoms with indirect radiographic studies and the results of postmortem neuropathology. This article describes measurements on midsagittal magnetic resonance imaging (MRI) scans that distinctly define normal and abnormal rostral-caudal relationships between the diencephalic-mesencephalic junction and the plane of the tentorial incisura, herein termed the incisural line. We similarly provide quantitative MRI scan measurements relating the cerebellum and the plane of the foramen magnum, termed the foramen magnum line. Measurements from 156 midsagittal and 63 coronal MRI scans performed on 123 normal adults, placed the iter of the aqueduct 0.2 +/- 0.8 mm (mean +/- SD) below the incisural line and the cerebellar tonsils 0.1 +/- 2.1 mm below the foramen magnum line. Defining 2 SD from these norms as abnormal, 23 patients with intracranial mass or obstructive lesions showed 4 distinct patterns of brain herniation, i.e., upward or downward transtentorial shift with or without accompanying cerebellar tonsillar herniation. Five patients with posterior fossa masses demonstrated displacement of the iter above the incisura ranging from 1.6 to 6.3 mm. Eighteen patients with supratentorial masses demonstrated displacement of the iter ranging from 2.0 to 11.0 mm below the incisura. Two-thirds of patients with upward and one-half of those with downward transtentorial shift had concurrent tonsillar herniation. In acute illnesses, MRI scan changes anticipated or confirmed clinical signs of brain herniation. In chronic cases, clinical and MRI scans correlated less well, with MRI sometimes revealing major degrees of anatomical herniation well in advance of clinical abnormalities.

Adolescent↗
PubMed1993

External imaging of atherosclerosis in rabbits using an 123I-labeled synthetic peptide fragment.

The oligopeptide fragment of apolipoprotein B, SP-4, has demonstrated pronounced uptake in the healing edges of balloon-injured rabbit aortic endothelium. To assess 123I-labeled SP-4 for identification of atherosclerotic plaques by gamma camera imaging, 14 Watanabe heritable hyperlipidemic (WHHL) and 5 normal rabbits were imaged 5 minutes and 12 and 24 hours after intravenous injection of 123I-SP-4. In addition, two WHHL and two normal rabbits were injected with 125I-SP-4 for autoradiography. Twelve of the 14 WHHL, but none of the normal, rabbits had visually apparent focal radioiodine accumulation in the region of the aorta. Focus-to-lung and focus-to-heart count ratios were 2.4 +/- 1.3 and 1.0 +/- 0.4, respectively. Five of the visually positive WHHL rabbits were reimaged 4 and 8 weeks later with 123I-NaI and 123I-SP-2 (an apo E peptide), respectively, as negative controls. Perceptible, but faint, aortic localization of 123I-NaI and of 123I-SP-2 was seen in only one animal each. The distributions of atherosclerotic lesions on photographs of the opened WHHL aortas and of film blackening on 125I-SP-4 autoradiograms were identical. In contrast, the two normal rabbit aortas did not exhibit plaques on photographs or film blackening on autoradiograms. Thus, in an animal model closely simulating human atherosclerotic disease, SP-4 localizes specifically in aortic atherosclerotic lesions.

Amino Acid Sequence↗
PubMed1989

Torsion of the upper lobe in pneumothorax.

A rounded density is occasionally seen hanging down from the hilus in the presence of a large pneumothorax. To find an explanation for this appearance, the authors obtained a right-sided bronchogram on a baboon, after which they induced pneumothorax on the same side. This experiment demonstrated that the rounded density is formed by a twisted and atelectatic upper lobe.

Animals↗