Dr. David Eisenberg
Box 951570
Los Angeles, CA 90095-1570
Phone: 310-825-3754
Fax: 310-206-3914
Email: david@pauling.mbi.ucla.edu
Projects are approved by an IRB located at: University of California, Los Angeles.
The approving IRB operates under a Multiple Project Assurance (MPA) recognized by DOE or by the Department of Health and Human Services (HHS).
MPA number of the IRB: M-1127
Number of Human Subjects Projects reported: 8
Project Identifier: UCLA-47-87ER60615
Project Title:
Structural Biology and Molecular Medicine Research Program/Nuclear Medicine Applications
Principal Investigator:
Dr. David Eisenberg
Project started in: 1947
This project ended in Fiscal Year 1996.
Project Funding Information:
Project received funding in Fiscal Year 1996.
Project used human subjects in Fiscal Year 1996.
Funding Sources:
Funding last year indicated total dollars awarded by DOE to entire Lab not funding associated with use of human subjects only.
Project involves use of multiple protocols/subprojects.
Number of protocols/subprojects associated with this project: 6
Protocol/Subproject # 1
Protocol/Subproject Identifier: 91-12-543-4
IRB Review:
Type of Review: Expedited
Most Recent Approval: February 07, 1995
IRB Approval Number: 91-12-543-4
Number of Human Subjects who participated in this project/protocol during
FY 1996 (10/1/95 - 9/30/96): 0
Type of Human Subjects Involvement:
TITLE: "Metabolic tissue characterization in patients with acute myocardial infarction by positron emission tomography". The PI on this project is Heinrich R. Schelbert, MD. No studies were performed in FY96.
The benefit of the study is primarily directed toward medical science. The study is expected to provide information on the metabolic pattern of infarcted and ischemically injured myocardium in humans. An early differentiation between viable and necrotic tissue during an evolving infarct will then allow better definition of patients who will benefit from therapeutic interventions such as angioplasty or surgical revascularization. For the individual patient, there will be the benefit of assessing the severity and extent of disease which may be important information for further management.
For the study early after the acute infarction, the patient will be transported from the UCLA Coronary Care Unit (CCU) to the UCLA Nuclear Medicine Clinic where the positron tomograph is located. He/she will be escorted by a CCU nurse and cardiologist or cardiologist fellow. The follow-up study will be performed electively on an outpatient basis approximately 6 weeks later. For the study later after an acute myocardial infarction, patients will be examined first at the time of hospital discharge, 10-14 days post myocardial infarction and then again at 3 months. Concurrent with the PET studies will be gated MRI evaluation of the heart in terms of tissue characterization and regional function. This protocol seeks to examine the predictive value of residual metabolic abnormality as seen on PET for subsequent characterization. The study will be performed jointly with the cardiology group at Cedars Sinai Medical Center, where the gated MRI studies will be obtained. Both scintigraphic studies include the injection of 82Rubidium, 18Fluorodeoxyglucose and 11Carbon palmitate.
During the 1st study, the patient will be continuously monitored electrocardiographically, and hemodynamical monitoring will be performed periodically. The cardiologist will be present throughout the stay of the patient in the Nuclear Medicine Clinic. The scanner room is equipped with all standard cardiac monitoring and emergency devices including defibrillator. The additional risk to the patient by participating in the study is considered minimal, since no intervention is involved which significantly stresses the cardiovascular system. However, sudden arhythmias can occur in patients with acute infarct. Therefore, care will be taken to continuously monitor the patient.
Patients' diagnoses of acute myocardial infarction must be established by ECG and enzyme criteria. Hemodynamically and clinically unstable patients will be excluded. Patients with life threatening dysrhythmias will not be considered. Additionally, patients who are deemed unable to comprehend the context of the study either due to the disease or drug intervention will be excluded. The selection will be discussed with the referring physician of the patient and the attending staff of the CCU.
The identity of the participants in this research study will remain confidential. Any identifying information will be securely locked in a file cabinet, and only personnel related to the study will have access to these records. No information that identifies any participant will be released without that subject's separate consent except as specifically required by law.
IRB Review:
Type of Review: Expedited
Most Recent Approval: April 17, 1995
IRB Approval Number: 92-11-639-3
Number of Human Subjects who participated in this project/protocol during
FY 1996 (10/1/95 - 9/30/96): 0
Type of Human Subjects Involvement:
This project was previously reported under UCLA1-47-87ER60615, subproject 92-11-639, with Dr. Lewis Baxter as principal investigator. Dr. Baxter has since left the University and relinquished responsibility for the project to Drs. Gary W. Small and Jorge Barrio.
This protocol uses a trace amount of a compound which binds specifically to key sites in the brain that have been implicated in a variety of disease processes involving mental illness and neurological disorders. Some of the illnesses that affect these receptor sites include depression, schizophrenia, movement disorders and behavioral abnormalities following head trauma. To measure these receptors, we administer a trace amount of a radioactive compound into the subjects vein while sampling blood from a vein or artery. While this is happening, the subject is lying on a couch with their head in a large machine that records the radioactivity from the compound as it passes through the brain. These serial pictures, plus the information about the behavior of the compound in the blood, allow for the precise and accurate measurement of these receptors in the brain. Once known in normal subjects, changes associated with diseases can be determined. Such information will provide insights into the basic disorders as well as provide direction as to the proper therapy of such patients.
Each year, up to 20 normal volunteers will be recruited and 30 patients. Ages will be 18 and older.
IRB Review:
Type of Review: Expedited
Most Recent Approval: January 25, 1995
IRB Approval Number: 92-12-676-2
Number of Human Subjects who participated in this project/protocol during
FY 1996 (10/1/95 - 9/30/96): 0
Type of Human Subjects Involvement:
TITLE: "Study of hemodynamics and metabolism with compounds labeled with short-lived positron emitting radionuclides (heart)" The PI on this project is Heinrich R. Schelbert, MD. The protocol was discontinued in FY96. In FY95, four human subjects were studied.
The objective of these study protocols is to develop non-invasive techniques for accurate and specific measurements of regional myocardial metabolism and blood flow. This information will potentially be useful for early diagnosis and acquisition of highly specific information that is of potential clinical value for early disease detection, characterization of extent and severity of disease, and patient management. These studies will include evaluation and measurement of myocardial blood flow (with N-13 ammonia, rubidium-82 or O-15 carbon monoxide), myocardial fatty acid metabolism (with C-11 palmitic acid) and/or regional myocardial glucose utilization (with F-18 fluorodeoxyglucose) as well as of myocardial oxidative metabolism (with C-11 acetate). These studies will be performed in normal volunteers and in patients with cardiovascular disease (i.e., with coronary artery disease, ischemic heart disease and/or cardiomyopathy).
The tracer amounts of radioactivity used are well within the guidelines for permissible exposure. Additional potential risks include blood sampling.
We expect to study 100 patients and 50 normal subjects, male and female. Ages will be 18 or older.
The identity of the participants in this research study will remain confidential. Any identifying information will be securely locked in a file cabinet, and only personnel related to the study will have access to these records. No information that identifies any participant will be released without that subject's separate consent except as specifically required by law.
IRB Review:
Type of Review: Expedited
Most Recent Approval: January 26, 1995
IRB Approval Number: 92-12-683
Number of Human Subjects who participated in this project/protocol during
FY 1996 (10/1/95 - 9/30/96): 0
Type of Human Subjects Involvement:
TITLE: "Noninvasive quantification of regional myocardial blood flow reserve and glucose metabolism by myocardial imaging during dipyridamole or adenosine hypermia". The PI on this project is Heinrich R. Schelbert, MD. Please refer to UCLA1-95-117 for current study derived from this subproject.
The objectives of this research proposal include investigation of the effect of maximal coronary artery vasodilation on regional myocardial blood flow and metabolism in patients with suspected or known coronary artery disease and in normal volunteers. This research will attempt not only to investigate the pathophysiology of maximal coronary artery vasodilation but also to determine whether high-risk patients can be identified so that irreversible myocardial damage can be prevented.
Significant coronary artery disease and myocardial disease remain undetected until the occurrence of a catastrophic event such as sudden death or acute myocardial infarction. Even when angina or congestive symptoms herald the presence of significant disease, accurate, predictive diagnostic tools are not currently available to determine which patients require immediate aggressive intervention in order to prevent irreversible myocardial damage.
The quantification of myocardial blood flow, oxygen consumption and myocardial metabolism in cardiac disease is of considerable clinical interest. Such measurements are important in order to gain insights into disease mechanisms for assessing diagnostic and therapeutic efficacy. PET is the only technique at this time which can noninvasively assess regional myocardial metabolism. Although perfusion defects may be observed under conditions of rest, the detection of a hemodynamic significant coronary artery lesion frequently requires conditions of increased myocardial workload and hence, blood flow. Pharmacological coronary vasodilation is an alternative to exercise. One pharmacological stress agent proven in more than 1,000 patients with PET and thallium-201 (Tl-201) imaging for the diagnosis of coronary artery disease is dipyridamole. Adenosine is a relatively new potent coronary vasodilator with clear potential as a pharmacological stress agent in cardiac imaging. Its rapid onset of action and extremely short elimination half-life suggest it may be superior to dipyridamole in this regard.
The tracer amounts of radioactivity used are well within the guidelines for permissible exposure. Additional potential risks include blood sampling.
We expect to study 500 patients with proven/suspected cardiac disease and 100 normal subjects, male and female, ages 18 and older.
Radionuclides injected into arm or inhaled: Nitrogen-13 ammonia; Carbon-11 palmitate/acetate; Fluorine-18-deoxyglucose; Oxygen-15, water, carbon monoxide, carbon dioxide.
IRB Review:
Type of Review: Expedited
Most Recent Approval: January 26, 1995
IRB Approval Number: 93-11-654-2
Number of Human Subjects who participated in this project/protocol during
FY 1996 (10/1/95 - 9/30/96): 1
Type of Human Subjects Involvement:
TITLE: "In-vivo measurement of regional myocardial blood flow and metabolism at different cardiac workloads using tracers of blood flow and metabolism with positron emission tomography" The PI's on this project are Heinrich R. Schelbert, MD. and Johannes Czernin, MD. One human subject was studied in FY96 before the project closed; thirteen human subjects were studied in FY95.
This study investigates blood flow and metabolism at different cardiac workloads in patients with coronary artery disease. In addition, patients with other cardiac diseases, such as hypertrophic or dilated cardiomyopathy, will be studied, and normal values determined in volunteers. Methods of increasing cardiac workload and/or demand that will be utilized include exercise, intravenous dipyridamole, dobutamine and pacing. Pacing will not be utilized in normal volunteers. The study will provide improvement in the non-invasive diagnosis and characterization of cardiovascular disease and better understanding of the human heart's physiology and pathophysiology.
A baseline PET imaging study will be obtained following the first group of injections of the tracers. Cardiac workload and/or demand will be increased by exercise (walking on a treadmill or using a cycle ergometer), intravenous dipyridamole, intravenous dobutamine or pacing, and a second study will be obtained following the second group of injections of the tracers. The study may include arterial or venous blood sampling.
Echocardiography will be performed during dobutamine stimulation in healthy subjects as well as in patients with coronary artery disease, to evaluate changes in regional wall motion induced by pharmacologic stress.
The protocol will be performed on 20 patients per year, both male and female, will be studied, age 18 or older, and 10 normal volunteers per year, both male and female, age 18 or older.
The tracer amounts of radioactivity used are well within permissible guidelines for exposure. Additional potential risks include blood sampling, discomfort to the patient due to rapid arterial pacing or mild chest pain in patients with coronary artery disease.
Radionuclides used: Rubidium-82 chloride; Nitrogen-13 ammonia; Carbon-11 acetate or palmitate; Fluorine-18 deoxyglucose.
The identity of the participants in this research study will remain confidential. Any identifying information will be securely locked in a file cabinet, and only personnel related to the study will have access to these records. No information that identifies any participant will be released without that subject's separate consent except as specifically required by law.
IRB Review:
Type of Review: Full Board
Most Recent Approval: August 07, 1995
IRB Approval Number: 95-01-036
Number of Human Subjects who participated in this project/protocol during
FY 1996 (10/1/95 - 9/30/96): 1
Type of Human Subjects Involvement:
TITLE: "Dopamine transport and storage measured with 4-[18F] fluoro-L-metatyrosine". The PI's on this project were Jorge Barrio, Ph.D. and Sam Gambhir, MD., Ph.D. Dr. Gambhir relinquished his authority over the project to Dr. Gary Small, and the protocol is now being reported as a separate project. Please see UCLA1-036.
The objective of this study is to perform in vivo quantitative measurements of regional L-DOPA transport and storage in the brain of human subjects using Positron Emission Tomography (PET), both in normal volunteers and patients with certain neurological and psychiatric disorders. Abnormalities in the dopamine system with changes in dopamine receptor binding have been demonstrated in animal models and human autopsy studies of many neurological and psychiatric illnesses. Over recent years, major institutions throughout the world have developed radiopharmaceuticals to label precursors of dopamine in the living human brain.
Initially, the use of 4-FMT will be directed at control subjects of both sexes with ages greater than 19. These subjects will provide a database for the distribution, magnitude and range for quantitative values for 6-FMT in the normal brain at various ages. From this database, we will compare patients with a variety of disorders, including epilepsy, Huntington's disease, tardive dyskinesia, Parkinson's disease, progressive supranuclear palsy, dystonia, affective disorders, schizophrenia, Gilles de La Tourette syndrome, obsessive compulsive disorders, individuals exposed to toxins that may produce Parkinsonian-like symptoms (e.g., MPTP, carbon monoxide, manganese), and others.
Thirty normal volunteers and thirty patients will be studied initially.
Project Identifier: UCLA-92-639
Project Title:
Mapping Dopamine Receptors with F-188 fluoroethylspiperone (see project UCLA1-47-87ER60615, subproject 92-11-639-3 in 1995 and 1996 database)
Principal Investigator:
Dr. Gary W. Small
Project started in: 1992
Project Funding Information:
Project received funding in Fiscal Year 1996.
Project did not use human subjects in Fiscal Year 1996.
Explanation:
Project was inactive in this fiscal year; no human subjects were studied.
Funding Sources:
Project does not involve use of multiple protocols/subprojects.
IRB Review:
Type of Review: Full Board
Most Recent Approval: October 03, 1996
IRB Approval Number: 92-11-639-04
Number of Human Subjects who participated in this project/protocol during
10/03/95 - 10/03/96: 0
Type of Human Subjects Involvement:
This project was previously reported under UCLA1-47-87ER60615, subproject 92-11-639, with Dr. Lewis Baxter as principal investigator. Dr. Baxter has since left the University and relinquished responsibility for the project to Drs. Gary W. Small and Jorge Barrio.
This protocol uses a trace amount of a compound which binds specifically to key sites in the brain that have been implicated in a variety of disease processes involving mental illness and neurological disorders. Some of the illnesses that affect these receptor sites include depression, schizophrenia, movement disorders and behavioral abnormalities following head trauma. To measure these receptors, we administer a trace amount of a radioactive compound into the subjects vein while sampling blood from a vein or artery. While this is happening, the subject is lying on a couch with their head in a large machine that records the radioactivity from the compound as it passes through the brain. These serial pictures, plus the information about the behavior of the compound in the blood, allow for the precise and accurate measurement of these receptors in the brain. Once known in normal subjects, changes associated with diseases can be determined. Such information will provide insights into the basic disorders as well as provide direction as to the proper therapy of such patients.
Each year, up to 20 normal volunteers will be recruited and 30 patients. Ages will be 18 and older.
The identity of the participants in this research study will remain confidential. Any identifying information will be securely locked in a file cabinet, and only personnel related to the study will have access to these records. No information that identifies any participant will be released without that subject's separate consent except as specifically required by law.
Project Identifier: UCLA-92-640
Project Title:
Dopamine Transport and Storage Measured with DOPA
Principal Investigator:
Dr. Gary W. Small
Project started in: 1992
Project Funding Information:
Project received funding in Fiscal Year 1996.
Project did not use human subjects in Fiscal Year 1996.
Explanation:
Human subjects were studied under previous IRB approval with funding through NIH. No human subjects have yet been studied under the new IRB approval.
Funding Sources:
Project does not involve use of multiple protocols/subprojects.
IRB Review:
Type of Review: Full Board
Most Recent Approval: October 02, 1996
IRB Approval Number: 92-11-640-04
Number of Human Subjects who participated in this project/protocol during
FY 1996 (10/1/95 - 9/30/96): 0
Type of Human Subjects Involvement:
NOTE: This project was previously funded by NIH with former LSBMM investigator Dr. John Mazziotta as principal investigator. Dr. Mazziotta relinquished responsibility for the project to Drs. Gary Small and Jorge Barrio, LSBMM investigators, and funding is now under the DOE cooperative agreement.
Dopamine is a major neurotransmitter in the central nervous system which is involved in mediating thoughts, emotions and motor behaviors. L-DOPA, which we have labelled with 18F, is a precursor in the synthesis of dopamine. By injecting trace amounts of 18F-L-DOPA in subjects and using PET technologies, we are able to measure the rates at which the dopamine neurons synthesize and excrete dopamine.
Cocaine produces its euphoric effects, at least in part, through its effects on the dopamine neuron. Other substances of abuse, such as alcohol and opiates, may have dopamine mechanisms too. In Parkinson's disease, the dopamine neurons are slowly destroyed. With continued cocaine or amphetamine use in animals, there is evidence for damage of the dopamine secreting neurons. Our PET studies so far in humans and monkeys have also shown this. Drug abusers trying to synthesize narcotics in Northern California a number of years ago accidentally made a compound (referred to as MPTP) which induced Parkinson's disease.
We are doing fluorodopa PET scans of Parkinson's disease patients, cocaine abusers, amphetamine abusers, opiate abusers with and without MPTP exposure, alcoholics and normal controls to better understand the effects of these drugs on the presynaptic dopamine neuron. Damage that these patients sustained to their dopamine system may explain their difficulty in getting of drugs. Subjects undergo fluorodopa scanning after first stopping the drug and then after at least 6 months abstinence to see if there is any recovery. We correlate this with their symptoms. We are doing parallel studies in monkeys where drug use and amounts can be controlled to better understand this problem. Drug abusers come from UCLA Neuropsychiatric Hospital and populations. MPTP exposed individuals are sometimes referred by Dr. William Langston in San Jose. Patients who are not UCLA outpatients come into the CRC under an approved CRC protocol.
Project Identifier: UCLA-95-036
Project Title:
Dopamine Transport and Storage Measured with [18F] Fluoro-L-m-Tyrosine (see project UCLA1-47-87ER60615, sub-project 95-01-036 in 1995 and 1996 database)
Principal Investigator:
Dr. Gary W. Small
Project started in: 1995
Project Funding Information:
Project received funding in Fiscal Year 1996.
Project did not use human subjects in Fiscal Year 1996.
Explanation:
Project was inactive in FY96; no human subjects were studied.
Funding Sources:
Project does not involve use of multiple protocols/subprojects.
IRB Review:
Type of Review: Full Board
Most Recent Approval: October 02, 1996
IRB Approval Number: 95-01-036-02
Number of Human Subjects who participated in this project/protocol during
FY 1996 (10/1/95 - 9/30/96): 0
Type of Human Subjects Involvement:
This project was previously reported under UCLA1-47-87ER60615, subproject 95-01-036, with Drs. Sanjiv Gambhir and Jorge Barrio as principal investigators. Dr. Gambhir has relinquished responsibility for the project to Dr. Gary Small. Dr. Barrio continues as co-investigator.
The objective of this study is to perform in vivo quantitative measurements of regional L-DOPA transport and storage in the brain of human subjects using Positron Emission Tomography (PET), both in normal volunteers and patients with certain neurological and psychiatric disorders. Abnormalities in the dopamine system with changes in dopamine receptor binding have been demonstrated in animal models and human autopsy studies of many neurological and psychiatric illnesses. Over recent years, major institutions throughout the world have developed radiopharmaceuticals to label precursors of dopamine in the living human brain.
Initially, the use of 4-FMT will be directed at control subjects of both sexes with ages greater than 19. These subjects will provide a database for the distribution, magnitude and range for quantitative values for 6-FMT in the normal brain at various ages. From this database, we will compare patients with a variety of disorders, including epilepsy, Huntington's disease, tardive dyskinesia, Parkinson's disease, progressive supranuclear palsy, dystonia, affective disorders, schizophrenia, Gilles de La Tourette syndrome, obsessive compulsive disorders, individuals exposed to toxins that may produce Parkinsonian-like symptoms (e.g., MPTP, carbon monoxide, manganese), and others.
Thirty normal volunteers and thirty patients will be studied initially.
Project Identifier: UCLA-95-117
Project Title:
Measurement of Myocardial Blood Flow with N-13 Ammonia (see project numbered UCLA1-47-87ER60615, sub-project 92-12-683 for previous year information)
Principal Investigator:
Dr. Heinrich R. Schelbert
Project started in: 1995
Project Funding Information:
Project received funding in Fiscal Year 1996.
Project used human subjects in Fiscal Year 1996.
Funding Sources:
Project does not involve use of multiple protocols/subprojects.
IRB Review:
Type of Review: Full Board
Most Recent Approval: September 20, 1996
IRB Approval Number: 95-03-117-02
Number of Human Subjects who participated in this project/protocol during
FY 1996 (10/1/95 - 9/30/96): 13
Type of Human Subjects Involvement:
Co-investigator is Johannes Czernin, MD.
This project was formerly part of UCLA1-47-87ER60615, sub-project 92-12-683.
The aim of this study is to determine, non-invasively, coronary artery disease in healthy subjects, individuals at risk for, and patients with the disease using Positron Emission Tomography (PET). PET can assess these problems noninvasively and can identify individuals with early abnormalities in coronary vasomotion or endothelial function. This is of importance because life style modifications such as smoking cessation or a low lipid diet might reverse the course of the disease.
All subjects will undergo PET imaging of the heart at rest and during cold pressor stress under baseline conditions and during intravenous L-arginine. L-arginine, a physiologically occurring amino acid, is a precursor of nitric oxide and might induce a small increase in the blood flow to the heart. L-arginine is used clinically to test the pituitary function.
The cold pressor test will be performed by immersing the patients hand in ice water for about 2 minutes. Cold pressor testing induces a modest increase in heart rate and systolic blood pressure and is therefore considered a very mild stressor.
On the first day, radioisotope N-13 ammonia will be injected when the subject is at rest, and then again during cold pressor testing.
On the second day, the radioisotope N-13 ammonia will be injected when the subject is at rest with the simultaneous application of intravenous L-arginine.
On the third day, the radioisotope N-13 ammonia will be injected during cold pressor testing with the simultaneous application of intravenous L-arginine.
Patients aged 18 years or older, males and non pregnant females after giving written consent and proving to be within the study criteria will be accepted in the study.
Normal control subjects ages 18 years and older, male and non pregnant females will be given a normal resting electrocardiogram after giving written consent and proving to be within the study criteria will be accepted in the study.
Twenty normal controls and 40 patient volunteers will be studied.
This is an open trial.
Johannes Czernin, MD., Assistant Professor Nuclear Medicine and H.R. Schelbert, MD., Professor Pharmacology/Nuclear Medicine will be responsible for this research. The research will be conducted in the PET Center, AR-115, CHS, UCLA.
Project Identifier: UCLA-96-082
Project Title:
Sparing/Recovery of Function after Hemispherectomy: Analysis with Functional Imaging
Principal Investigator:
Dr. Sanjiv Gambhir
Project started in: 1996
Project Funding Information:
Project received funding in Fiscal Year 1996.
Project did not use human subjects in Fiscal Year 1996.
Explanation:
Funding Sources:
Project does not involve use of multiple protocols/subprojects.
IRB Review:
Type of Review: Full Board
Most Recent Approval: June 11, 1996
IRB Approval Number: 96-02-082-01B
Number of Human Subjects who participated in this project/protocol during
FY 1996 (10/1/95 - 9/30/96): 0
Type of Human Subjects Involvement:
Co-investigators are Harley Kornblum, MD., Ph.D., and Sarah Copeland, Ph.D.
In this proposal, we will examine patterns of cerebral blood flow during rest or during movement or sensory stimulation using positron emission tomography (PET) and functional magnetic resonance imaging (fMRI). The goal of this project is to investigate the mechanisms which allow subjects to retain certain motor and sensory abilities after cerebral hemispherectomy, the removal of the cerebral cortex of an entire hemisphere. If this surgery is performed at an early age (typically prior to 7-8 years), sensory and motor performance is usually better than performance seen after damage in adulthood. Although some motor deficits remain following surgery (e.g. the loss of fine finger movements and foot tapping) gross motor performance (e.g. walking) can be relatively spared. Despite the presence of some sensory deficits, there is also evidence for the preservation of these functions after early brain damage in humans has not been determined, although they may involve recruitment of some already existing motor pathways, and/or formation of new connections between the remaining hemisphere and subcortical structures involved in control of movement on the affected side. Both of these mechanisms have been shown to play roles in the recovery of function after hemispherectomy in the cat and the rat. In this study, patterns of cerebral activation during movement and sensory stimulation of the affected and unaffected limbs in patients and of the two limbs in normal control volunteers will be related to the recovery of motor and sensory function after hemispherectomy.
A brief neurological examination will be administered to each patient prior to scanning. Additionally, handedness will be assessed by means of a standard questionnaire. Subsequently, functional neuroimaging techniques will be employed to examine areas activated during motor performance and sensory stimulation in patients and normal volunteers. For PET studies, each scan will involve an injection of radioactive water, which will be adjusted for the subject's weight. A single session will consist of 5-7 scans, with 3 baseline (resting) scans and 2-3 activation scans for the right and left limbs in either a sensory or motor activation condition. Motor activation tasks will consist of simple, repetitive arm or leg movements, and sensory conditions will involve repeated sensory stimulation of an arm or leg. MRI sessions will include of a set of scans to obtain images of brain anatomy which will be used for co-registration of PET and fMRI data, and a set of functional MRI images obtained during both rest and the same activation conditions as are used in PET scans. Both functional imaging techniques are designed to demonstrate areas of local cerebral blood flow increase in the brain during activation.
The study population will consist of up to 40 patients, both male and female, ranging in age from 10 to 25 years, who have undergone cerebral hemispherectomy for epilepsy at the UCLA Medical Center. After HSPC approval, an ad will be placed in local newspapers to solicit up to 40 volunteers aged 18 or over and matched with subjects for gender to serve as a control population. Control subjects will be neurologically normal, and not on medication. Any subject who is suspected of being pregnant will be excluded from the study. We propose to reimburse the volunteers at the rate of $25/hour for involvement in the procedures described above. The volunteers will be asked to read and sign the enclosed normal volunteer consent forms which will be explained to them in detail by one of the investigators. Patients will also be asked to read and sign the patient consent forms, or in the case of patients under age 12, the child assent forms.
Sam Gambhir, MD., Ph.D., Harley Kornblum, MD., Ph.D, and Sarah Copeland, Ph.D. will be conducting the research and will be responsible for obtaining informed consent from all subjects. PET scanning will be conducted at the UCLA clinical PET center (CHS A-level), and MRI scanning will take place either at the UCLA clinical MRI suite (CHS B-level) or at 200 Medical Plaza.
Project Identifier: UCLA-96-426
Project Title:
Response of Coronary Vasomotion to Intravenous L-Arginine
Principal Investigator:
Dr. Johannes Czernin
Project started in: 1996
Project Funding Information:
Project received funding in Fiscal Year 1996.
Project did not use human subjects in Fiscal Year 1996.
Explanation:
Project was approved by IRB but no human subjects were studied.
Funding Sources:
funds for personnel and supply costs
Project does not involve use of multiple protocols/subprojects.
IRB Review:
Type of Review: Full Board
Most Recent Approval: February 09, 1996
IRB Approval Number: 95-09-426-01A
Number of Human Subjects who participated in this project/protocol during
FY 1996 (10/1/95 - 9/30/96): 0
Type of Human Subjects Involvement:
This three day study protocol will be performed using N-13 ammonia PET at rest (baseline), during Cold Pressor testing, during baseline and intravenous application of L-arginine and during Cold Pressor testing and intravenous L-arginine. This study is aimed at identifying early abnormalities in myocardial blood flow and their potential reversibility by intravenous application of L-arginine. Early identification of individuals with abnormal coronary vasomotion is important because these abnormalities have been shown to precede the development of coronary artery disease.
N-13 ammonia, diluted in saline, is a radiolabeled compound which will be administered intravenously. There are no known side effects of N-13 ammonia. However, the participants will be aware that a small amount of radioactivity will be involved in this study which is comparable to less than 1% of what California law deems an acceptable amount of exposure during the course of one year for a radiology technologist. Women of child bearing age will only be enrolled if they undergo a pregnancy test. Women who are or have been on contraceptive medication until 4 weeks prior to the study will be excluded from the study because estrogen might alter the baseline measurements of myocardial blood flow. However, women using a barrier method such as an intrauterine device or women who agree to take birth control pills for three months following the study will be able to participate in this study.
The cold pressor test involves the immersion of one hand in ice water for 90-120 seconds. This evokes the release of local and adrenal catecholamines resulting in a modest, about 20-30% increase in cardiac work as evidenced by modest increases in the rate pressure product (heart rate x systolic blood pressure). The most common adverse effect of cold is local pain. Other side effects occur rarely. However, episodes of low heart rate and low blood pressure have been observed. This was ascribed to increases in parasympathetic nerve activity. The side effects can be reversed promptly by the intravenous application of atropine, a drug that blocks parasympathetic activity. Cold might induce coronary vasospasm. However, the risk for vasospasm to occur is very small and not greater than induced by cold weather. Some patients with coronary artery disease might develop chest pain. If this occurs, oral nitroglycerine will be administered.
L-arginine is a physiologically occurring amino-acid. It is a known precursor of nitric oxide, a strong physiologic coronary vasodilator. It has been used to test human pituitary function. Few side effects are known. For instance, mild allergic reactions such as flushing, vomiting, headache, or numbness might occur and will pass. Other possible side effects are skin rash, swelling of the hands and the face which will be treated by anti-histamines.
Both N-13 ammonia and L-arginine will be administered intravenously. Therefore, a intravenous line (butterfly) will be placed on day I and day II and III of the study. This might be associated with local pain and a blue discoloration of the skin (hematoma).
Twenty patients with known coronary artery disease will be recruited through the division of Cardiology/Department of Medicine at UCLA. Both, the attending physician and the home officer will need to agree in writing to the participation in this study.
Twenty healthy individuals, matched in age to the patients will be recruited through advertising the study in local newspapers.
Twenty individuals with elevated total or LDL cholesterol will also be enrolled. They will be recruited through the Division of Cardiology/Department of Medicine at UCLA. Both the attending physician and the home officer will need to agree in writing to the participation of their patients in this study.
All participants will be paid 25 Dollars/hour. They also will be compensated for travelling time and parking.
The Principal Investigator (Johannes Czernin, MD.) will obtain the informed consent in the presence of a consent monitor provided by the volunteer office at UCLA. He will also be present throughout the entire study.
Project Identifier: UCLA-96-450
Project Title:
Significance of Cardiac Allograft Vasculopathy
Principal Investigator:
Dr. Johannes Czernin
Project started in: 1996
Project Funding Information:
Project received funding in Fiscal Year 1996.
Project did not use human subjects in Fiscal Year 1996.
Explanation:
IRB approved the project, but no human subjects have been studied.
Funding Sources:
Total Funding: $0
Project does not involve use of multiple protocols/subprojects.
IRB Review:
Type of Review: Full Board
Most Recent Approval: October 23, 1996
IRB Approval Number: 95-10-450-01C
Number of Human Subjects who participated in this project/protocol during
FY 1996 (10/1/95 - 9/30/96): 0
Type of Human Subjects Involvement:
Study #1
The aim of this study is to determine, non-invasively with positron emission tomography (PET) the effects the amino acid L-arginine on myocardial blood flow and flow reserve in cardiac transplant recipients. PET can assess these problems noninvasively and can identify individuals with early abnormalities in coronary vasomotion or endothelial function. This is of importance because early abnormalities in coronary vasomotion and blood flow might be reversible indicating that transplant vasculopathy is a reversible process.
All subjects will undergo PET imaging of the heart at rest and during cold pressor stress under baseline conditions and during intravenous L-arginine. L-arginine, a physiologically occurring amino acid, is a precursor of nitric oxide and might induce a small increase in the blood flow to the heart. L-arginine is used clinically to test the pituitary function.
The cold pressor test will be performed by immersing the patients hand in ice water for about 2 minutes. Cold pressor testing induces a modest increase in heart rate and systolic blood pressure and is therefore considered a very mild stressor.
On the first day, the radioisotope N-13 ammonia will be injected when the subject is at rest, and then again during cold pressor testing while the amino acid L-arginine is infused for 45 minutes.
On the second day, the cold pressor test will be performed first followed by the radioisotope injection when the patient is at rest with the simultaneous application of intravenous L-arginine.
Patients aged 18 years or older, males and non pregnant females after giving written consent and proving to be within the study criteria will be accepted in the study.
Normal control subjects ages 18 years and older, male and non pregnant females will be given a normal resting electrocardiogram after giving written consent and proving to be within the study criteria will be accepted in the study.
Twenty normal controls and 20 transplant recipients will be studied.
This is an open trial.
Johannes Czernin, MD., Assistant Professor, Nuclear of Medicine will be responsible for this research. The research will be conducted in the PET Center, AR-115, CHS, UCLA.
Study #2
The aim of this study is to determine, non-invasively, in cardiac transplant recipients the presence and severity of transplant coronary artery disease using Positron Emission Tomography (PET). In addition, early abnormalities in the blood flow to the heart will be determined and related to future clinical events such as recurrent heart failure or sudden cardiac death. Patients will undergo N-13 ammonia PET at rest, during cold pressor test and during intravenous dipyridamole.
PET can assess blood flow to the heart noninvasively and can identify individuals with early abnormalities in coronary vasomotion. This is of importance because a) such abnormalities might precede transplant coronary artery disease and b) might be modulated by acute or chronic pharmacologic interventions.
A total of 300 cardiac transplant recipients will be studied for this 5-year study: 60 patients/year within 4-6 weeks after cardiac transplantation. They will be restudied annually for 5 years.
The cold pressor test will be performed by immersing the patients hand in ice water for about 2 minutes. Cold pressor testing induces a modest increase in heart rate and systolic blood pressure and is therefore considered a very mild stressor. Dipyridamole, a commonly used pharmacologic stress agent, will be given intravenously at a rate of 0.56 mg/kg over 4 minutes.
Patients aged 18 years or older, males and non pregnant females after giving written consent and proving to be within the study criteria will be accepted in the study.
Normal control subjects ages 18 years and older, male and non pregnant females will be given a normal resting electrocardiogram after giving written consent and proving to be within the study criteria will be accepted in the study.
Twenty normal controls and 60 transplant recipients/year will be studied.
This is an open trial.
Johannes Czernin, MD., Assistant Professor Nuclear Medicine. The research will be conducted in the PET Center, AR-115, CHS, UCLA.