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J M Hoffman

Publications and source records attributed to J M Hoffman.

At least 19 recordsLinked to original sources
PubMed2006

Rapid dual-injection single-scan 13N-ammonia PET for quantification of rest and stress myocardial blood flows.

Quantification of myocardial blood flows at rest and stress using 13N-ammonia PET is an established method; however, current techniques require a waiting period of about 1 h between scans. The objective of this study was to test a rapid dual-injection single-scan approach, where 13N-ammonia injections are administered 10 min apart during rest and adenosine stress. Dynamic PET data were acquired in six human subjects using imaging protocols that provided separate single-injection scans as gold standards. Rest and stress data were combined to emulate rapid dual-injection data so that the underlying activity from each injection was known exactly. Regional blood flow estimates were computed from the dual-injection data using two methods: background subtraction and combined modelling. The rapid dual-injection approach provided blood flow estimates very similar to the conventional single-injection standards. Rest blood flow estimates were affected very little by the dual-injection approach, and stress estimates correlated strongly with separate single-injection values (r=0.998, mean absolute difference=0.06 ml min-1 g-1). An actual rapid dual-injection scan was successfully acquired in one subject and further demonstrates feasibility of the method. This study with a limited dataset demonstrates that blood flow quantification can be obtained in only 20 min by the rapid dual-injection approach with accuracy similar to that of conventional separate rest and stress scans. The rapid dual-injection approach merits further development and additional evaluation for potential clinical use.

Ammonia↗
PubMed2006

Operational specifications of the laser illuminated track etch scattering dosemeter reader.

The personnel dosimetry operations team at the Los Alamos National Laboratory (LANL) has accepted the laser illuminated track etch scattering (LITES) dosemeter reader into its suite of radiation dose measurement instruments. The LITES instrument transmits coherent light from a He-Ne laser through the pertinent track etch foil and a photodiode measures the amount of light scattered by the etched tracks. A small beam stop blocks the main laser light, while a lens refocuses the scattered light into the photodiode. Three stepper motors in the current LITES system are used to position a carousel that holds 36 track etch dosemeters (TEDs). Preliminary work with the LITES system demonstrated the device had a linear response in counting foils subjected to exposures up to 50 mSv (5.0 rem). The United States Department of Energy requires that the annual general employee dose not exceed 50 mSv (5.0 rem). On a regular basis, LANL uses the Autoscan-60 reader system (Thermo Electron Corp.) for counting track etch dosemeters. However, LANL uses a 15 h etch process for CR-39 dosemeters, and this produces more and larger track etch pits than the 6 h etch used by many institutions. Therefore, LANL only uses the Autoscan-60 for measuring neutron dose equivalent up to exposure levels of approximately 3 mSv (300 mrem). The LITES system has a measured lower limit of detection of approximately 0.6 mSv (60 mrem), and it has a correlation coefficient of R (2) = 0.99 over an exposure range up to 500 mSv (50.0 rem). A series of blind studies were done using three methods: the Autoscan-60 system, manual counting by optical microscope and the LITES instrument. A collection of track etch dosemeters of unknown neutron dose equivalent (NDE) were analysed using the three methods, and the performance coefficient (PC) was calculated when the NDE became known. The Autoscan-60 and optical microscope methods had a combined PC = 0.171, and the LITES instrument had a PC = 0.194, where a PC less than or equal to 0.300 is considered satisfactory.

Dose-Response Relationship, Radiation↗
PubMed2004

Multisphere default spectra--solution spectrum and dosemeter response implications.

Initial calibration of a multisphere spectroscopy system has been completed at Los Alamos National Laboratory using four standard calibration scenarios. Spectrum unfolding was performed using three methods of constructing the default spectrum: simple parameter models, Monte Carlo calculations and physical measurement. Comparisons of the resulting spectra for each solution method are presented. Implications of the spectral solutions upon dosemeter characterisation are addressed.

Algorithms↗
PubMed2003

Direct text entry in electronic progress notes. An evaluation of input errors.

OBJECTIVES: It is not uncommon that the introduction of a new technology fixes old problems while introducing new ones. The Veterans Administration recently implemented a comprehensive electronic medical record system (CPRS) to support provider order entry. Progress notes are entered directly by clinicians, primarily through keyboard input. Due to concerns that there may be significant, invisible disruptions to information flow, this study was conducted to formally examine the incidence and characteristics of input errors in the electronic patient record. METHODS: Sixty patient charts were randomly selected from all 2,301 inpatient admissions during a 5-month period. A panel of clinicians with informatics backgrounds developed the review criteria. After establishing inter-rater reliability, two raters independently reviewed 1,891 notes for copying, copying errors, inconsistent text, inappropriate object insertion and signature issues. RESULTS: Overall, 60% of patients reviewed had one or more input-related errors averaging 7.8 errors per patient. About 20% of notes showed evidence of copying, with an average of 1.01 error per copied note. Copying another clinician's note and making changes had the highest risk of error. Templating resulted in large amounts of blank spaces. Overall, MDs make more errors than other clinicians even after controlling for the number of notes. CONCLUSIONS: Moving towards a more progressive model for the electronic medical record, where actions are recorded only once, history and physical information is encoded for use later, and note generation is organized around problems, would greatly minimize the potential for error.

Hospital Information Systems↗
PubMed2001

Positron emission tomography in evaluation of dementia: Regional brain metabolism and long-term outcome.

CONTEXT: Deficits in cerebral glucose utilization have been identified in patients with cognitive dysfunction attributed to various disease processes, but their prognostic and diagnostic value remains to be defined. OBJECTIVE: To assess the sensitivity and specificity with which cerebral metabolic patterns at a single point in time forecast subsequent documentation of progressive dementia. DESIGN, SETTING, AND PATIENTS: Positron emission tomography (PET) studies of [(18)F]fluorodeoxyglucose in 146 patients undergoing evaluation for dementia with at least 2 years' follow-up for disease progression at the University of California, Los Angeles, from 1991 to 2000, and PET studies in 138 patients undergoing evaluation for dementia at an international consortium of facilities, with histopathological diagnoses an average of 2.9 years later, conducted from 1984 to 2000. MAIN OUTCOME MEASURES: Regional distribution of [(18)F]fluorodeoxyglucose in each patient, classified by criteria established a priori as positive or negative for presence of a progressive neurodegenerative disease in general and of Alzheimer disease (AD) specifically, compared with results of longitudinal or neuropathologic analyses. RESULTS: Progressive dementia was detected by PET with a sensitivity of 93% (191/206) and a specificity of 76% (59/78). Among patients with neuropathologically based diagnoses, PET identified patients with AD and patients with any neurodegenerative disease with a sensitivity of 94% and specificities of 73% and 78%, respectively. The negative likelihood ratio of experiencing a progressive vs nonprogressive course over the several years following a single negative brain PET scan was 0.10 (95% confidence interval, 0.06-0.16), and the initial pattern of cerebral metabolism was significantly associated with the subsequent course of progression overall (P<.001). CONCLUSION: In patients presenting with cognitive symptoms of dementia, regional brain metabolism was a sensitive indicator of AD and of neurodegenerative disease in general. A negative PET scan indicated that pathologic progression of cognitive impairment during the mean 3-year follow-up was unlikely to occur.

Aged↗
PubMed2001

Enhanced post-ischemic liver injury in iNOS-deficient mice: a cautionary note.

The objective of this study was to assess the role of inducible nitric oxide synthase (iNOS) in ischemia- and reperfusion (I/R)-induced liver injury. We found that partial hepatic ischemia involving 70% of the liver resulted in a time-dependent increase in serum alanine aminotransferase (ALT) levels at 1-6 h following reperfusion. Liver injury at 1, 3, and 6 h post-ischemia was not due to the infiltration of neutrophils as assessed by tissue myeloperoxidase (MPO) activity and histopathology. iNOS-deficient mice subjected to the same duration of ischemia and reperfusion showed dramatic and significant increases in liver injury at 3 but not 6 h following reperfusion compared to their wild type controls. Paradoxically, iNOS mRNA expression was not detected in the livers of wild type mice at any point during the reperfusion period and pharmacological inhibition of iNOS using L-N(6)(iminoethyl)-lysine (L-NIL) did not exacerbate post-ischemic liver injury at any time post-reperfusion. These data suggest that iNOS deficiency produces unanticipated genetic alterations that renders these mice more sensitive to liver I/R-induced injury.

Alanine Transaminase↗
PubMed2001

An apparatus and behavioral training protocol to conduct positron emission tomography (PET) neuroimaging in conscious rhesus monkeys.

Nonhuman primates offer a unique resource in neuroimaging research, providing the opportunity to manipulate appropriate biological and behavioral variables under well-controlled experimental conditions in an animal model that is closely related to humans, both functionally and neuroanatomically. The present report describes the development and standardization of PET neuroimaging protocols in conscious rhesus monkeys and their application to characterize the acute effects of cocaine on cerebral blood flow. Specific attention was devoted to the development of an effective and comfortable head restraint device to be used in the imaging of conscious monkeys. The restraint device was designed to attach to a standard primate chair to facilitate frequent immobilization. Subjects received extensive behavioral training prior to neuroimaging in order to ensure their comfort and minimize potential stress associated with the imaging protocols. Functional changes in cerebral blood flow were characterized in three subjects with the positron-emitting tracer 15O water following acute i.v. administration of cocaine. Regions of interest were defined on MRI scans with a high degree of accuracy. Cocaine caused pronounced increases in cerebral blood flow at 5 min postinjection that diminished markedly within 25 min. The results document the feasibility to conduct PET neuroimaging studies of cerebral blood flow in conscious nonhuman primates. Extension of the methodology to include brain activation during behavioral studies could contribute significantly to the growing discipline of behavioral neuroscience.

Animals↗
PubMed2001

Neural correlates of maternal separation in rhesus monkeys.

BACKGROUND: The neurobiological basis of stress and anxiety in primates remains poorly understood. In this study, we examined the neural response to a naturalistic social stressor: maternal separation. We used rhesus monkeys as an animal model because of their close phylogenetic affinity with humans. METHODS: Six juvenile rhesus monkeys received [(18)F]-fluorodeoxyglucose positron emission tomography scans following 1) a period together with their mothers and again after separation from their mothers 2) with or 3) without visual contact. Image subtraction revealed brain regions that exhibited altered activity during separation. In addition, plasma cortisol concentrations obtained following each condition were tested for correlations with regional brain activity. RESULTS: Maternal separation activated the right dorsolateral prefrontal cortex and the right ventral temporal/occipital lobe. There was also decreased activity in left dorsolateral prefrontal cortex associated with separation stress. Correlational analyses demonstrated these activated and deactivated regions to be positively and negatively correlated with cortisol, respectively. Additionally, correlational analyses revealed cortisol-related activation in brainstem areas previously implicated in stress and anxiety. CONCLUSIONS: In juvenile rhesus monkeys, the stress of maternal separation is associated with activation in the right dorsolateral prefrontal cortex and ventral temporal/occipital lobes and decreased activity in the left dorsolateral prefrontal cortex.

Aggression↗
PubMed2001

Neural activity related to drug craving in cocaine addiction.

BACKGROUND: Crack cocaine dependence and addiction is typically associated with frequent and intense drug wanting or craving triggered by internal or environmental cues associated with past drug use. METHODS: Water O 15 positron emission tomography (PET) studies were used to localize alterations in synaptic activity related to cue-induced drug craving in 8 crack cocaine-dependent African American men. In a novel approach, script-guided imagery of autobiographical memories were used as individualized cues to internally generate a cocaine craving state and 2 control (ie, anger and neutral episodic memory recall) states during PET image acquisition. RESULTS: The mental imagery of personalized drug use and anger-related scripts was associated with self-ratings of robust drug craving or anger, and comparable alterations in heart rate. Compared with the neutral imagery control condition, imagery-induced drug craving was associated with bilateral (right hemisphere amygdala activation greater than left) activation of the amygdala, the left insula and anterior cingulate gyrus, and the right subcallosal gyrus and nucleus accumbens area. Compared with the anger control condition, internally generated drug craving was associated with bilateral activation of the insula and subcallosal cortex, left hippocampus, and anterior cingulate cortex and brainstem. A brain-wide pixel-by-pixel search indicated significant positive and negative correlations between imagery-induced cocaine craving and regional cerebral blood flow (rCBF) in distributed sites. CONCLUSIONS: The collected findings suggest the craving-related activation of a network of limbic, paralimbic, and striatal brain regions, including structures involved in stimulus-reward association (amygdala), incentive motivation (subcallosal gyrus/nucleus accumbens), and anticipation (anterior cingulate cortex).

Adult↗
PubMed2001

Role of nitric oxide in inflammation.

A number of laboratories have sought to elucidate the role of nitric oxide (NO) in both acute and chronic inflammatory diseases. It is now well appreciated that NO can influence many aspects of the inflammatory cascade ranging from its own expression to recruitment of leucocytes to the effected tissue. With the advent of mice selectively deficient in the various isoforms of nitric oxide synthase (NOS), the role that NO may play in various disease states can now be examined in vivo. One such syndrome that has gained much attention in recent years is ischaemia and reperfusion-induced tissue injury. Ischaemia-reperfusion (I/R) injury is an important clinical consideration in situations such as transplantation, trauma, liver or bowel resection and haemorrhagic shock. A hallmark of I/R is the production of reactive oxygen species (ROS) during the reperfusion phase and it is thought that the production of ROS mediate much of the post-ischaemic tissue injury. This review will examine the current state of knowledge regarding the regulatory mechanisms by which NO can influence various aspects of the inflammatory cascade as well as its role in a model of I/R injury in vivo.

Animals↗
PubMed2001

In vivo imaging of gene expression.

Imaging of gene expression is increasingly essential for cancer diagnosis, prediction of tumor response to various available therapies, and for monitoring response to therapy, whether it is gene or nongene therapy. Most of the work on developing techniques and methodologies for imaging gene expression has been performed in mice. Sophisticated small animal imaging technologies have been developed for this purpose. Imaging of gene expression in humans is still very limited. Nuclear medicine, positron-emission tomography, magnetic resonance imaging, and optical methods are the modalities that have shown preliminary utility in imaging gene expression. Two major imaging strategies have been investigated: using marker genes encoding either intracellular enzymes or cell-surface receptors. The first approach exploits the ability of certain enzymes to modify imaging prodrugs, so that tissue accumulation of such drugs reflects the expression. The second approach uses cell-surface expression of ligand-binding receptors that can be detected using imaging tracers. In this review, we summarize some of the imaging techniques that have been developed to detect gene expression.

Animals↗
PubMed2001

New advances in brain tumor imaging.

During the period of this review, there has been continued use and development of neuroimaging techniques in brain tumor diagnosis and management. Although no monumental developments or improvements in neuroimaging techniques or technology have occurred, important studies continue to be published showing the clinical impact and utility of various neuroimaging techniques to improve the care of patients with brain tumors. Several studies have shown the power of functional neuroimaging techniques with both magnetic resonance imaging (MRI) and positron-emission tomography (PET) to map eloquent cortex and assist in the planning of surgical and radiation therapy. New nuclear imaging radiopharmaceuticals, including various PET ligands and single photon emission computed tomography (SPECT) agents, have also been developed and show their potential power in the evaluation of brain tumor patients. New MRI pulse sequences to improve image quality and shorten imaging time have also been developed. Several excellent reviews of the use of fluorodeoxyglucose (FDG)-PET and MRI techniques were also published. This article reviews the relevant and important neuroimaging literature related to brain tumor that was published during the defined time period of November 1, 1999 to October 31, 2000. Discussion is organized by modality, including nuclear imaging techniques (SPECT and PET) and MRI (pulse sequence development, contrast agent development, functional MRI developments, and general MRI-related information).

Brain Neoplasms↗
PubMed2001

Selected contribution: Effects of gender on reduced-size liver ischemia and reperfusion injury.

Hepatic resection with concomitant periods of ischemia and reperfusion (I/R) is a common occurrence in resectional surgery as well as reduced-size liver transplantation (e.g., split liver or living donor transplantation). However, the I/R induced by these types of surgical manipulations may impair liver regeneration, ultimately leading to liver failure. The objectives of the study were to develop a murine model of reduced-size liver I/R and assess the role of gender in this model of hepatocellular injury. We found that 100% of female mice survived the surgery indefinitely, whereas all male mice had greater initial liver injury and died within 5 days after surgery. The protective effect observed in females appeared to be due to ovarian 17beta-estradiol, as ovariectomy of females or administration of a selective estrogen antagonist to female mice resulted in enhanced liver injury and greater mortality following reduced-size liver I/R. Conversely, 17beta-estradiol-treated male mice exhibited less hepatocellular damage and survived indefinitely. Taken together, these data demonstrate an estrogen-mediated protective pathway(s) that limits or attenuates hepatocellular injury induced by reduced-size liver I/R.

Animals↗
PubMed2001

Biodistribution and radiation dosimetry of the dopamine transporter ligand.

UNLABELLED: 18F-labeled 2 beta-carbomethoxy-3beta-(4-chlorophenyl)-8-(-2-fluoroethyl)nortropane ([18F]FECNT) is a recently developed dopamine transporter ligand with potential applications in patients with Parkinson's disease and cocaine addiction. METHODS: Estimates of the effective dose equivalent and doses for specific organs were made using biodistribution data from 16 Sprague-Dawley rats and nine rhesus monkeys. PET images from two rhesus monkeys were used to calculate the residence time for the basal ganglia. The computer program MIRDOSE3 was used to calculate the dosimetry according to the methodology recommended by MIRD. RESULTS: The basal ganglia were the targeted tissues receiving the highest dose, 0.11 mGy/MBq (0.39 rad/mCi). The effective dose equivalent was 0.018 mSv/MBq (0.065 rem/mCi), and the effective dose was 0.016 mSv/MBq (0.058 rem/mCi). CONCLUSION: Our data show that a 185-MBq (5-mCi) injection of [18F]FECNT leads to an estimated effective dose of 3 mSv (0.3 rem) and an estimated dose to the target organ or tissue of 19.4 mGy (1.93 rad).

Animals↗
PubMed2001

Future directions in small animal imaging.

The adaptation and development of imaging technologies for use in small animals has the potential to be a refinement with profound effects on how basic cancer research using animals is conducted. The authors describe how NCI funding is helping to advance research in this area.

Animals↗
PubMed2000

Identification of MK-944a: a second clinical candidate from the hydroxylaminepentanamide isostere series of HIV protease inhibitors.

Recent results from human clinical trials have established the critical role of HIV protease inhibitors in the treatment of acquired immune-deficiency syndrome (AIDS). However, the emergence of viral resistance, demanding treatment protocols, and adverse side effects have exposed the urgent need for a second generation of HIV protease inhibitors. The continued exploration of our hydroxylaminepentanamide (HAPA) transition-state isostere series of HIV protease inhibitors, which initially resulted in the identification of Crixivan (indinavir sulfate, MK-639, L-735,524), has now yielded MK-944a (L-756,423). This compound is potent, is selective, and competitively inhibits HIV-1 PR with a K(i) value of 0.049 nM. It stops the spread of the HIV(IIIb)-infected MT4 lymphoid cells at 25.0-50.0 nM, even in the presence of alpha(1) acid glycoprotein, human serum albumin, normal human serum, or fetal bovine serum. MK-944a has a longer half-life in several animal models (rats, dogs, and monkeys) than indinavir sulfate and is currently in advanced human clinical trials.

Animals↗
PubMed2000

Synthesis, biodistribution, and primate imaging of fluorine-18 labeled 2beta-carbo-1'-fluoro-2-propoxy-3beta-(4-chlorophenyl)tr opanes. Ligands for the imaging of dopamine transporters by positron emission tomography.

2beta-(R)-Carbo-1-fluoro-2-propoxy-3beta-(4-chlorophenyl) tro pane ((R)-FIPCT, R-6) and 2beta-(S)-carbo-1-fluoro-2-propoxy-3beta-(4-chlorophenyl) tro pane ((S)-FIPCT, S-6) were prepared and evaluated in vitro and in vivo for dopamine transporter (DAT) selectivity and specificity. High specific activity [(18)F](R)-FIPCT and [(18)F](S)-FIPCT were synthesized in 5% radiochemical yield (decay-corrected to end of bombardment (EOB)) by preparation of the precursors 2beta-carbo-R-1-mesyloxy-2-propoxy-3beta-(4-chlorop hen yl)tropane (R-12) and 2beta-carbo-S-1-mesyloxy-2-propoxy-3beta-(4-chlorop hen yl)tropane (S-12) followed by treatment with no carrier-added potassium[(18)F]fluoride and kyrptofix K222 in acetonitrile. Competition binding in cells stably expressing the transfected human DAT and serotonin transporter (SERT) labeled by [(3)H]WIN 35428 and [(3)H]citalopram, respectively, demonstrated the following order of DAT affinity (K(i) in nM): GBR 12909 (0.36) > CIT (0.48) > (S)-FIPCT (0.67) >> (R)-FIPCT (3.2). The affinity of (S)-FIPCT and (R)-FIPCT for SERT was 127- and 20-fold lower, respectively, than for DAT. In vivo biodistribution studies were performed in male rats and demonstrated that the brain uptake of [(18)F](R)-FIPCT and [(18)F](S)-FIPCT were selective and specific for DAT rich regions (caudate and putamen). PET brain imaging studies in monkeys demonstrated high [(18)F](R)-FIPCT and [(18)F](S)-FIPCT uptake in the caudate and putamen which resulted in caudate-to-cerebellum and putamen-to-cerebellum ratios of 2.5-3.5 at 115 min. [(18)F](R)-FIPCT uptake in the caudate/putamen achieved transient equilibrium at 75 min. In an imaging experiment with [(18)F](S)-FIPCT in a rhesus monkey with its left hemisphere lesioned with MPTP, radioactivity was reduced to background in the caudate and putamen of the lesioned hemisphere. The high specific activity one-step radiolabeling preparation and high specificity and selectivity of [(18)F](R)-FIPCT and [(18)F](S)-FIPCT for DAT indicate [(18)F](R)-FIPCT and [(18)F](S)-FIPCT are potential radioligands for mapping brain DAT in humans using PET.

Animals↗