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BACKGROUND: Hippocampal changes may be a useful biomarker for Alzheimer's disease if they are specific to dementia sub-type. We compare hippocampal volume and shape in population-based incident cases of Alzheimer's disease and vascular dementia (VaD). METHODS: Participants are Japanese-American men from the Honolulu Asia Aging Study. The following analysis is based on a sub-group of men with mild incident Alzheimer's disease (n=24: age=82.5 ± 4.6) or incident VaD (n=14: age=80.5 ± 4.5). To estimate hippocampal volume, one reader, blinded to dementia diagnosis, manually outlined the left and right formation of the hippocampus using published criteria. We used 3-D mapping methods developed at the Laboratory of Neuro Imaging (LONI) to compare regional variation in hippocampal width between dementia groups. RESULTS: Hippocampal volume was about 5% smaller in the Alzheimer's disease group compared to the VaD group, but the difference was not significant. Hippocampal shape differed between the two case groups for the left (p<0.04) but not right (p<0.21) hippocampus. The specific region of the hippocampus that most consistently differed between the Alzheimer's disease and VaD cases was in the lateral portion of the left hippocampus. Our interpretation of this region is that it intersects the CA1 sub-region to a great extent but also includes the dentate gyrus (and hilar region) and subiculum. CONCLUSION: As indicated by shape analysis, there are some differences in atrophy localisation between the Alzheimer's disease and VaD cases, despite the finding that volume of the hippocampi did not differ. These findings suggest hippocampal atrophy in Alzheimer's disease may be more focal than in VaD.

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Physics-based particle systems are an effective tool for shape modeling. Also, there has been much interest in the study of shape modeling using deformable contour approaches. In this paper, we describe a new deformable model with electric flows based upon computer simulations of a number of charged particles embedded in an electrostatic system. Making use of optimized numerical techniques, the electric potential associated with the electric field in the simulated system is rapidly calculated using the finite-size particle (FSP) method. The simulation of deformation evolves based upon the vector sum of two interacting forces: one from the electric fields and the other from the image gradients. Inspired by the concept of the signed distance function associated with the entropy condition in the level set framework, we efficiently handle topological changes at the interface. In addition to automatic splitting and merging, the evolving contours enable simultaneous detection of various objects with varying intensity gradients at both interior and exterior boundaries. This electric flows approach for shape modeling allows one to connect electric properties in electrostatic equilibrium and classical active contours based upon the theory of curve evolution. Our active contours can be applied to model arbitrarily complicated objects including shapes with sharp corners and cusps, and to situations where no a priori knowledge about the object's topology and geometry is made. We demonstrate the capabilities of this new algorithm in recovering a wide variety of structures on simulated and real images in both 2D and 3D.

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Characterizing the performance of segmentation algorithms in brain images has been a persistent challenge due to the complexity of neuroanatomical structures, the quality of imagery and the requirement of accurate segmentation. There has been much interest in using the Jaccard and Dice similarity coefficients associated with Sensitivity and Specificity for evaluating the performance of segmentation algorithms. This paper addresses the essential characteristics of the fundamental performance measure coefficients adopted in evaluation frameworks. While exploring the properties of the Jaccard, Dice and Specificity coefficients, we propose new measure coefficients Conformity and Sensibility for evaluating image segmentation techniques. It is indicated that Conformity is more sensitive and rigorous than Jaccard and Dice in that it has better discrimination capabilities in detecting small variations in segmented images. Comparing to Specificity, Sensibility provides consistent and reliable evaluation scores without the incorporation of image background properties. The merits of the proposed coefficients are illustrated by extracting neuroanatomical structures in a wide variety of brain images using various segmentation techniques.

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BACKGROUND: Data from our previous studies indicate that Taser X26 stun devices can acutely alter cardiac function in swine. We hypothesized that most transcardiac discharge vectors would capture ventricular rhythm, but that other vectors, not traversing the heart, would fail to capture the ventricular rhythm. METHODS: Using an Institutional Animal Care and Use Committee (IACUC) approved protocol, four Yorkshire pigs (25-36 kg) were anesthetized, paralyzed with succinylcholine (2 mg/kg), and then exposed to 10 second discharges from a police-issue Taser X26. For most discharges, the barbed darts were pushed manually into the skin to their full depth (12 mm) and were arranged in either transcardiac (such that a straight line connecting the darts would cross the region of the heart) or non-transcardiac vectors. A total of 11 different vectors and 22 discharge conditions were studied. For each vector, by simply rotating the cartridge 180-degrees in the gun, the primary current-emitting dart was changed and the direction of current flow during the discharge was reversed without physically moving the darts. Echocardiography and electrocardiograms (ECGs) were performed before, during, and after all discharges. p values < 0.05 were considered significant. RESULTS: ECGs were unreadable during the discharges because of electrical interference, but echocardiography images clearly demonstrated that ventricular rhythm was captured immediately in 52.5% (31 of 59) of the discharges on the ventral surface of the animal. In each of these cases, capture of the ventricular rhythm with rapid ventricular contractions consistent with ventricular tachycardia (VT) or flutter was seen throughout the discharge. A total of 27 discharges were administered with transcardiac vectors and ventricular capture occurred in 23 of these discharges (85.2% capture rate). A total of 32 non-transcardiac discharges were administered ventrally and capture was seen in only eight of these (25% capture rate). Ventricular fibrillation (VF) was seen with two vectors, both of which were transcardiac. In the remaining animals, VT occurred postdischarge until sinus rhythm was regained spontaneously. CONCLUSIONS: For most transcardiac vectors, Taser X26 caused immediate ventricular rhythm capture. This usually reverted spontaneously to sinus rhythm but potentially fatal VF was seen with two vectors. For some non-transcardiac vectors, capture was also seen but with a significantly (p < 0.0001) decreased incidence.

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OBJECTIVE: Electromuscular incapacitation (EMI) devices are being used and evaluated by both military and law enforcement agencies. Although the gross muscular response is obvious, physiological responses to these devices are poorly understood. We hypothesized that the intense, repetitive, muscle contractions evoked by EMI devices would cause dose-dependent metabolic acidosis, accompanied by neuromuscular or cardiac injury. METHODS: Using an approved protocol, 26 Yucatan mini-pigs (22 experimental animals and 4 control animals) were anesthetized with ketamine and xylazine. Experimental animals were exposed to MK63 (Aegis Industries, Bellevue, Idaho) discharges over the left anterior hind limb for 10, 20, 40, or 80 seconds. Electrocardiograms, electromyograms, troponin I levels, blood gas values, and electrolyte levels were recorded before and 5, 15, 30, and 60 minutes and 24, 48, and 72 hours after discharge. Skin, muscle, and nerve biopsies were taken from the shocked and contralateral sides. RESULTS: Core body temperature significantly decreased (1.0-1.5 degrees C) in all shocked animals but not in sham-treated control animals. No cardiac dysrhythmias or deaths were seen, and heart rate was unaffected. No clinically significant changes were seen in troponin I, myoglobin, or creatine kinase-MB levels. Central venous blood pH decreased, whereas carbon dioxide pressure and lactate levels increased for 60 minutes after discharge. All values returned to normal by 24 hours after discharge, and no significant histological or electromyographic changes were found. CONCLUSIONS: Changes in blood chemistry were observed but were of little clinical significance, and no neuromuscular damage was detected. Therefore, within the limitations of this model, it appears that EMI can safely be achieved by using this device, even for lengthy periods, without causing significant injury.

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Understanding the variability of the hippocampus in human brain research is essential. The effect of age on the hippocampus has been explored in several studies that have been focused on either normal aging or neural degeneration. Shape analysis of magnetic resonance imaging (MRI) provides morphological measures for brain structures. This study further investigates the age effects on hippocampal morphology in three groups (104 normal controls, 24 Alzheimer's disease (AD) and 14 vascular dementia (VaD) patients). By utilizing a parametric shape analysis of hippocampal MRI scans, each individual distance map is generated and analyzed statistically. Specifically, after eliminating similarity parameters (rotation, translation, and scaling) effects for each hippocampus, an individual distance map is generated from parametric hippocampal surfaces and medial axes. Then statistical methods, including regression, and permutation tests, are applied to detect the differences in hippocampal distance maps and volumes under the effect of age in each group. Statistical analyses reveal that the loss of hippocampal volume and changes in shape are more significantly related to aging in the control group than in AD/VaD. The results also show that the asymmetry of hippocampus in healthy subjects is greater than that in either of the disease groups. Our study shows that 3D statistical shape analysis could enhance the understanding of age effects on local areas of hippocampi. However, the sample sizes of disease groups are relatively low; further studies with more AD/VaD data are needed.

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OBJECTIVES: Data from the authors and others suggest that TASER X26 stun devices can acutely alter cardiac function in swine. The authors hypothesized that TASER discharges degrade cardiac performance through a mechanism not involving concurrent acidosis. METHODS: Using an Institutional Animal Care and Use Committee (IACUC)-approved protocol, Yorkshire pigs (25-71 kg) were anesthetized, paralyzed with succinylcholine (SCh; 2 mg/kg), and then exposed to two 40-second discharges from a TASER X26 with a transcardiac vector. Vital signs, blood chemistry, and electrolyte levels were obtained before exposure and periodically for 48 hours postdischarge. Electrocardiograms and echocardiography (echo) were performed before, during, and after the discharges. p-Values < 0.05 were considered significant. RESULTS: Electrocardiograms were unreadable during the discharges due to electrical interference, but echo images showed unmistakably that cardiac rhythm was captured immediately at a rate of 301 +/- 18 beats/min (n = 8) in all animals tested. Capture continued for the duration of the discharge and in one animal degenerated into fatal ventricular fibrillation (VF). In the remaining animals, ventricular tachycardia (VT) occurred postdischarge for 1-17 seconds, whereupon sinus rhythm was regained spontaneously. Blood chemistry values and vital signs were minimally altered postdischarge and no significant acidosis was seen. CONCLUSIONS: Extreme acid-base disturbances usually seen after lengthy TASER discharges were absent with SCh, but TASER X26 discharges immediately and invariably produced myocardial capture. This usually reverted spontaneously to sinus rhythm postdischarge, but fatal VF was seen in one animal. Thus, in the absence of systemic acidosis, lengthy transcardiac TASER X26 discharges (2 x 40 seconds) captured myocardial rhythm, potentially resulting in VT or VF in swine.

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A new deformable model, the charged fluid model (CFM), that uses the simulation of charged elements was used to segment medical images. Poisson's equation was used to guide the evolution of the CFM in two steps. In the first step, the elements of the charged fluid were distributed along the propagating interface until electrostatic equilibrium was achieved. In the second step, the propagating front of the charged fluid was deformed in response to the image gradient. The CFM provided sub-pixel precision, required only one parameter setting, and required no prior knowledge of the anatomy of the segmented object. The characteristics of the CFM were compared to existing deformable models using CT and MR images. The results indicate that the CFM is a promising approach for the segmentation of anatomic structures in a wide variety of medical images across different modalities.

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BACKGROUND: Very little objective laboratory data are available describing the physiologic effects of stun guns or electromuscular incapacitation devices (EIDs). Unfortunately, there have been several hundred in-custody deaths, which have been temporally associated with the deployment of these devices. Most of the deaths have been attributed to specific cardiac and metabolic effects. We hypothesized that prolonged EID exposure in a model animal system would induce clinically significant metabolic acidosis and cardiovascular disturbances. METHODS: Using an Institutional Animal Care and Use Committee-approved protocol, 11 standard pigs (6 experimentals and 5 sham controls) were anesthetized with ketamine and xylazine. The experimentals were exposed to two 40-second discharges from an EID (TASER X26, TASER Intl., Scottsdale, AZ) across the torso. Electrocardiograms, blood pressure, troponin I, blood gases, and electrolyte levels were obtained pre-exposure and at 5, 15, 30, and 60 minutes and 24, 48, and 72 hours postdischarge. p values <0.05 were considered significant. RESULTS: Two deaths were observed immediately after TASER exposure from acute onset ventricular fibrillation (VF). In surviving animals, heart rate was significantly increased and significant hypotension was noted. Acid-base status was dramatically affected by the TASER discharge at the 5-minute time point and throughout the 60-minute monitoring period. Five minutes postdischarge, central venous blood pH (6.86 +/- 0.07) decreased from baseline (7.45 +/- 0.02; p = 0.0004). Pco2 (94.5 mm Hg +/- 14.8 mm Hg) was significantly increased from baseline (45.3 mm Hg +/- 2.6 mm Hg) and bicarbonate levels significantly decreased (15.7 mmol/L +/- 1.04 mmol/L) from baseline (30.4 mmol/L +/- 0.7 mmol/L). A large, significant increase in lactate occurred postdischarge (22.1 mmol/L +/- 1.5 mmol/L) from baseline (1.5 mmol/L +/- 0.3 mmol/L). All values returned to normal by 24 hours postdischarge in surviving animals. A minor, nonsignificant increase in troponin I was seen at 24 hours postdischarge (0.052 ng/mL +/- 0.030 ng/mL, mean +/- SEM). CONCLUSIONS: Immediately after the discharge, two deaths occurred because of ventricular fibrillation. In this model of prolonged EID exposure, clinically significant acid-base and cardiovascular disturbances were clearly seen. The severe metabolic and respiratory acidosis seen here suggests the involvement of a primary cardiovascular mechanism.

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BACKGROUND: Stun guns or electromuscular incapacitation devices (EMIs) generate between 25,000 and 250,000 V and can be discharged continuously for as long as 5 to 10 min. In the United States, over 200,000 individuals have been exposed to discharges from the most common type of device used. EMI devices are being used increasingly despite a lack of objective laboratory data describing the physiological effects and safety of these devices. An increasing amount of morbidity, and even death, is associated with EMI device use. To examine this type of electrical injury, we hypothesized that EMI discharges will induce acute or delayed cardiac arrhythmia and neuromuscular injury in an animal model. METHODS: Using an IACUC approved protocol, from May 2005 through June 2006 in a teaching hospital research setting, 30 Yucatan mini-pigs (24 experimentals and 6 sham controls) were deeply anesthetized with ketamine and xylazine without paralytics. Experimentals were exposed to discharges from an EID (MK63; Aegis Industries, Bellevue, ID) over the femoral nerve on the anterior left hind limb for an 80 s exposure delivered as two 40 s discharges. EKGs, EMGs, troponin I, CK-MB, potassium, and myoglobin levels were obtained pre-discharge and post-discharge at 5, 15, 30, and 60 min, 24, 48, and 72 h (n = 6 animals) and 5, 15, and 30 d post-discharge (n = 6 animals at each time point). Skin, skeletal muscle, and peripheral nerve biopsies were studied bilaterally. Data were compared using one-way analysis of variance and paired t-tests. P-values <0.05 were considered significant. RESULTS: No cardiac arrhythmias or sudden deaths were seen in any animals at any time point. No evidence of skeletal muscle damage was detected. No significant changes were seen in troponin I, myoglobin, CK-MB, potassium, or creatinine levels. There were no significant changes in compound muscle action potentials (CMAP). No evidence of conduction block, conduction slowing, or axonal loss were detected on EMG. M-wave latency (M(lat), ms), amplitude (M(amp), mV), area (M(area), mV-ms), and duration (M(dur), ms) were not significantly affected by MK63 discharge compared with contralateral or sham controls. F-wave latency (F(lat), ms), a sensitive indicator of retrograde nerve conduction and function, was not significantly affected by MK63 discharge compared with contralateral or sham controls. No significant histological changes were seen at any time point in skeletal muscle or peripheral nerve biopsies although mild skin inflammation was evident. CONCLUSIONS: There was no evidence of acute arrhythmia from MK63 discharges. No clinically significant changes were seen in any of the physiological parameters measured here at any time point. Neuromuscular function was not significantly altered by the MK63 discharge. In this animal model, even lengthy MK63 discharges did not induce muscle or nerve injury as seen using EMG, blood chemistry, or histology.

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In this paper, we developed a new deformable model, the charged fluid model (CFM), that uses the simulation of a charged fluid to segment anatomic structures in magnetic resonance (MR) images of the brain. Conceptually, the charged fluid behaves like a liquid such that it flows through and around different obstacles. The simulation evolves in two steps governed by Poisson's equation. The first step distributes the elements of the charged fluid within the propagating interface until an electrostatic equilibrium is achieved. The second step advances the propagating front of the charged fluid such that it deforms into a new shape in response to the image gradient. This approach required no prior knowledge of anatomic structures, required the use of only one parameter, and provided subpixel precision in the region of interest. We demonstrated the performance of this new algorithm in the segmentation of anatomic structures on simulated and real brain MR images of different subjects. The CFM was compared to the level-set-based methods [Caselles et al. (1993) and Malladi et al (1995)] in segmenting difficult objects in a variety of brain MR images. The experimental results in different types of MR images indicate that the CFM algorithm achieves good segmentation results and is of potential value in brain image processing applications.

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BACKGROUND: Little objective laboratory data are available describing the physiologic effects of stun guns or electromuscular incapacitation (EMI) devices, but increasing morbidity and even deaths are associated with their use. We hypothesized that exposure to EMI discharges in a model animal system would induce clinically significant acidosis and cardiac arrhythmia. METHODS: Ten Yucatan mini-pigs, six experimental and four sham controls, were anesthetized with ketamine, xylazine, and glycopyrrolate. Experimental pigs were exposed to two 40-second discharges from an EMI device over the left thorax. Electrocardiograms, troponin I, blood gases, and lactate levels were obtained pre-exposure, at 5, 15, 30, 60 minutes, and at 24, 48, and 72 hours postdischarge. RESULTS: No acute or delayed cardiac arrhythmias were seen. Heart rate was not affected significantly (p>0.05). A subclinical increase in troponin I was seen at 24 hours postdischarge (0.040+/-0.030 ng/mL, p>0.05). Central venous blood pH (7.432+/-0.014) and pCO2 (36.1+/-0.9 mm Hg) were not changed significantly (p>0.05) during the 60-minute postdischarge period. A moderate significant increase in lactate occurred in the 5-minute postdischarge group (4.9+/-0.3 mmol/L, p=0.0179). All blood chemistry and vital signs were normal at 24, 48, and 72 hours postdischarge. CONCLUSIONS: Although significant changes in some parameters were seen, these changes were small and of little clinical significance. Lengthy EMI exposures did not cause extreme acidosis or cardiac arrhythmias. These findings may differ from those seen with other EMI devices because of the unique MK63 waveform characteristics or to specific characteristics of the model systems.

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The segmentation of brain tissue from nonbrain tissue in magnetic resonance (MR) images, commonly referred to as skull stripping, is an important image processing step in many neuroimage studies. A new mathematical algorithm, a model-based level set (MLS), was developed for controlling the evolution of the zero level curve that is implicitly embedded in the level set function. The evolution of the curve was controlled using two terms in the level set equation, whose values represented the forces that determined the speed of the evolving curve. The first force was derived from the mean curvature of the curve, and the second was designed to model the intensity characteristics of the cortex in MR images. The combination of these forces in a level set framework pushed or pulled the curve toward the brain surface. Quantitative evaluation of the MLS algorithm was performed by comparing the results of the MLS algorithm to those obtained using expert segmentation in 29 sets of pediatric brain MR images and 20 sets of young adult MR images. Another 48 sets of elderly adult MR images were used for qualitatively evaluating the algorithm. The MLS algorithm was also compared to two existing methods, the brain extraction tool (BET) and the brain surface extractor (BSE), using the data from the Internet brain segmentation repository (IBSR). The MLS algorithm provides robust skull-stripping results, making it a promising tool for use in large, multi-institutional, population-based neuroimaging studies.

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Normal human brain volume is heritable. The genes responsible for variation in brain volume are not known. Microcephalin (MCPH1) and ASPM (abnormal spindle-like microcephaly associated) have been proposed as candidate genes as mutations in both genes are associated with microcephaly, and common variants of each gene are apparently under strong positive selective pressure. In 120 normal subjects, we genotyped these variants and measured brain volumes using magnetic resonance imaging. We found no evidence that the selected alleles were associated with increases or decreases in brain volume. This result suggests that the selective pressure on these genes may be related to subtle neurobiological effects or to their expression outside the brain.

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The purpose was to design and implement a Web-based telemedicine system for diabetic retinopathy screening using digital fundus cameras and to make the software publicly available through Open Source release. The process of retinal imaging and case reviewing was modeled to optimize workflow and implement use of computer system. The Web-based system was built on Java Servlet and Java Server Pages (JSP) technologies. Apache Tomcat was chosen as the JSP engine, while MySQL was used as the main database and Laboratory of Neuro Imaging (LONI) Image Storage Architecture, from the LONI-UCLA, as the platform for image storage. For security, all data transmissions were carried over encrypted Internet connections such as Secure Socket Layer (SSL) and HyperText Transfer Protocol over SSL (HTTPS). User logins were required and access to patient data was logged for auditing. The system was deployed at Hubert H. Humphrey Comprehensive Health Center and Martin Luther King/Drew Medical Center of Los Angeles County Department of Health Services. Within 4 months, 1500 images of more than 650 patients were taken at Humphrey's Eye Clinic and successfully transferred to King/Drew's Department of Ophthalmology. This study demonstrates an effective architecture for remote diabetic retinopathy screening.

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Brain image analysis often involves processing neuroimaging data with different software packages. Using different software packages together requires exchanging files between them; the output files of one package are used as input files to the next package in the processing sequence. File exchanges become problematic when different packages use different file formats or different conventions within the same file format. Although comprehensive medical image file formats have been developed, no one format exists that satisfies the needs of analyses that involve multiple processing algorithms. The LONI Debabeler acts as a mediator between neuroimaging software packages by automatically using an appropriate file translation to convert files between each pair of linked packages. These translations are built and edited using the Debabeler graphical interface and compensate for package-dependent variations that result in intrapackage incompatibilities. The Debabeler gives neuroimaging processing environments a configurable automaton for file translation and provides users a flexible application for developing robust solutions to translation problems.

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Tumor necrosis factor-alpha (TNF-alpha) is an immunomodulatory cytokine that has exhibited anti-tumor activity in a variety of experimental systems. However, the toxicities associated with systemic administration of TNF-alpha have limited its clinical utility and have led to the investigation of targeted delivery techniques with the ability to present the TNF-alpha dose directly to the vascular bed of the tumor. The intra-arterial (IA) administration of TNF-alpha to patients with liver metastases represents one such approach, and recent work suggests that subsequent ablation of the tumor's arterial supply via embolization may enhance the efficacy of intra-arterial treatments (hepatic chemoembolization). The present study was undertaken to test the hypothesis that IA administration of TNF-alpha is superior to the intravenous (IV) route for inhibition of tumor growth in a regionally confined rat mammary adenocarcinoma model that provides for ablation of the arterial supply to the tumor following cytokine therapy. Rats bearing hind limb mammary adenocarcinomas received single IA or IV infusions of 8 x 10(5), 1 x 10(6), and 1.5 x 10(6) units of TNF-alpha via the common femoral artery (CFA) followed 1 h later by ligation of the artery. Control animals received either no treatment or IA infusion of 2% normal rat serum (NRS) followed by ipsilateral CFA ligation. Tumor size was measured every other day after treatment. Tumor growth inhibition occurred in the first 5 to 10 days after treatment. IV administration of TNF-alpha did not result in visual tumor necrosis or significant reduction in the rate of tumor growth. IA administration of TNF-alpha resulted in statistically significant diminution of tumor size as compared to untreated controls and animals receiving IA 2% normal rat serum (NRS; P<0.05 at days 6, 8 and 10), regardless of the dose employed. The maximum growth inhibition with IA TNF-alpha was a 91% reduction in tumor volume that was achieved with a dose of 1 x 10(6) U TNF-alpha. These results demonstrate improved anti-tumor activity with the IA administration of TNF-alpha over the IV route in a regionally confined mammary adenocarcinoma. IA administration of biologic response modifiers like TNF-alpha may therefore be a useful approach for the hepatic chemoembolization of breast adenocarcinomas metastatic to the liver.

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