Mr. David R. Schwoegler
Public Affairs Office
7000 East Avenue, L-404
Livermore, CA 94551
Phone: 925-422-6900
Fax: 925-424-2780
Email: newsguy@llnl.gov
Projects are approved by an IRB located at: Lawrence Livermore National Laboratory.
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-1415-01
Number of Human Subjects Projects reported: 49
Project Identifier: LLNL-88-105
Project Title:
Radiation Genotoxicity from Chernobyl Accident
Principal Investigator:
Dr. Irene M. Jones
Project started in: 1988
Project Funding Information:
Project received funding in Fiscal Year 1998.
Project used human subjects in Fiscal Year 1998.
Funding Sources:
Total Funding: $2,040,000
Project involves use of multiple protocols/subprojects.
Number of protocols/subprojects associated with this project: 2
Protocol/Subproject # 1
Protocol/Subproject Identifier: 88-105
IRB Review:
Type of Review: Full Board
Most Recent Approval: May 20, 1998
IRB Approval Number: 88-105
Number of Human Subjects who participated in this project/protocol during
FY 1998 (10/1/97 - 9/30/98): 231
Type of Human Subjects Involvement:
a. Objectives
This project applies three somatic mutation assays to a human population exposed to low-dose, whole-body, ionizing radiation for the purpose of defining the exposure and evaluating the dosimetric assays alone and in combination. In addition, the ability of low dose radiation exposure to induce inherited changes in mini-satellite DNA sequence is studied. Over a four year period, the project will study approximately 300 Russians exposed to doses in the range of ~5-25 cGy while working on the containment and cleanup of the Chernobyl nuclear power plant accident in Chernobyl, Ukraine after April 1986, and 300 controls for somatic effects. Fifty control and 25 liquidator families will be studied for heritable effects. Workers who were exposed during cleanup of the site and sarcophagus construction for the reactor, termed "liquidators" by the Soviets, were recruited from throughout the Soviet Union. Each person's work was planned to limit their exposure to 25 cGy. The somatic cell assays are: 1) stable chromosome aberrations in lymphocytes detected by fluorescence in situ hybridization; 2) glycophorin A mutation in red blood cells; and 3) hypoxanthine phosphoribosyltransferase (HPRT) mutation in lymphocytes. Information from each assay will be analyzed independently for the exposed average and variability, alone and in relation to control, and in relationship to variables such as age, smoking and diet. The results of this study should determine: the utility of these biological dosimeters in the study of low-dose human radiation biology; and the advisability of subsequent pursuit of health effects in this population.
b. Methodology
All laboratory analyses start with cells in blood samples. The cytogenetic and HPRT studies both require that white blood cells be cultured. Cytogenetic (chromosomal) changes are studied by microscope studies using fluorescent in situ hybridization methods. For HPRT studies cells are evaluated by microscopic inspection to determine how many cells are mutated; DNA of mutated cells is studied to define any deletions of the HPRT gene. The glycophorin A assay studies red blood cells by treating them first with a preservative, then with a fluorescent label for glycophorin A markers; a flow cytometer determines the number of mutated cells. The germinal mutation studies process DNA from peripheral blood so that a large number of mini-satellite DNA sequences are detected in each person. The patterns of these sequences are compared to determine if there are any sequences in a child that are not present in a parent; such alterations are inherited mutations.
c. List any agents to which subjects are exposed.
The people studied are not exposed to any agent as a consequence of this study. The liquidators we are studying were exposed to radiation during the cleanup of radiation after the Chernobyl nuclear power reaction accident.
d. Involvement of Human Subjects.
Blood samples are collected by our Russian collaborators at St. Petersburg and Tula. All of the contact with the subjects including obtaining informed consent and collection of blood samples is provided by our Russian collaborators in conjunction with the Russian Ministry of Health, the agency charged with providing health care to these individuals. The risks to the individual from the drawing of the blood sample are bruising at the site of venipuncture and minor infection. Any adverse effects will be treated by the appropriate Russian health service. The volume of blood drawn is 25-45 ml for adults, and 10 ml for children. Informed consent is obtained from both the exposed and the control individual, and spouses, by standard means, using forms and explanations in their native language. Consent on behalf of minor children is required by a parent or legal guardian. The inclusion of children is necessary for the identification of germinal mutations.
In addition, each control and liquidator completes a brief questionnaire that provides information on their date of birth, current health status, medications they take, medical treatments involving radiation exposure, their current occupation, the dates they were at Chernobyl and the work assignment they had when at Chernobyl.
IRB Review:
Type of Review: Full Board
Most Recent Approval: May 20, 1998
IRB Approval Number: 98-110
Number of Human Subjects who participated in this project/protocol during
FY 1998 (10/1/97 - 9/30/98): 0
Type of Human Subjects Involvement:
a. Objectives
To provide quality control, this project tests reagents and develops methods for studies of genetic alterations of the hypoxanthine phosphoribosyltransferase (HPRT) gene in lymphocytes in another project, Radiation Genotoxicity from the Chernobyl Accident (LLNL-88-105). The latter project is described below.
This larger project Radiation Genotoxicity from the Chernobyl Accident (LLNL-88-105) applies three somatic mutation assays to a human population exposed to low-dose, whole-body, ionizing radiation for the purpose of defining the exposure and evaluating the dosimetric assays alone and in combination. In addition, the ability of low dose radiation exposure to induce inherited changes in a mini-satellite DNA sequence is studied. Over a four year period, the project will study approximately 300 Russians exposed to doses in the range of ~5-25 cGy while working on the containment and cleanup of the Chernobyl nuclear power plant accident in Chernobyl, Ukraine after April 1986, and 300 controls for somatic effects. Fifty control and 25 liquidator families will be studied for heritable effects. Workers who were exposed during clean up of the site and sarcophagus construction for the reactor, termed "liquidators" by the Soviets, were recruited from throughout the Soviet Union. Each person's work was planned to limit their exposure to 25 cGy. The somatic cell assays are: 1) stable chromosome aberrations in lymphocytes detected by fluorescence in situ hybridization; 2) glycophorin A mutation in red blood cells; and 3) hypoxanthine phosphoribosyltransferase (HPRT) mutation in lymphocytes. Information from each assay will be analyzed independently for the exposed average and variability, alone and in relation to control, and in relationship to variables such as age, smoking and diet. The results of this study should determine: the utility of these biological dosimeters in the study of low-dose human radiation biology; and the advisability of subsequent pursuit of health effects in this population.
b. Methodology
All laboratory analyses start with cells in blood samples. The HPRT studies require that white blood cells be cultured. For HPRT studies, cells are evaluated by microscopic inspection to determine how many cells are mutated; DNA of mutated cells is studied to define any deletions of the HPRT gene.
c. List any agents to which subjects are exposed.
The people studied are local, LLNL controls, and are not exposed to any agent as a consequence of this study. They provide blood samples that are used only to test reagents and develop methods in support of the larger project, Radiation Genotoxicity from the Chernobyl Accident (LLNL-88-105)
d. Involvement of Human Subjects.
Blood samples are collected by the Medical Department of LLNL. The risks to the individual from the drawing of the blood sample are bruising at the site of venipuncture and minor infection. Any adverse effects will be treated by the Medical Department of LLNL. The volume of blood drawn is 25-45 ml. Informed consent is obtained from all individuals.
Project Identifier: LLNL-88-111
Project Title:
Cytogenetic Studies
Principal Investigator:
Dr. James D. Tucker
Project started in: 1988
Project Funding Information:
Project received funding in Fiscal Year 1998.
Project used human subjects in Fiscal Year 1998.
Funding Sources:
Project does not involve use of multiple protocols/subprojects.
IRB Review:
Type of Review: Full Board
Most Recent Approval: December 03, 1997
IRB Approval Number: 88-111
Number of Human Subjects who participated in this project/protocol during
FY 1998 (10/1/97 - 9/30/98): 6
Type of Human Subjects Involvement:
A. Objectives. To provide human peripheral blood and DNA for cytogenetic and DNA analyses for use in calibration, validation, and quality control for laboratory purposes. Metaphase chromosomes will be utilized for mapping or verifying DNA probes, and developing or evaluating potential new methods.
B. Methodology. Phlebotomy of normal, healthy subjects. In some cases we may elect to have donors complete a questionnaire inquiring about lifestyle factors which may affect the results.
C. Radiation or chemical exposures. None.
D. Involvement of human subjects. Phlebotomy, followed by DNA isolation and/or cell culture to provide material to be used as described in "A" above. Cells are grown under commonly-used conditions to promote growth for subsequent analysis by a variety of molecular and genetic methods. Risks to the subjects are those associated with routine phlebotomy. All samples are processed encoded, and identifying information is kept in a locked file cabinet in the Principal Investigator's office; no identifier is published. All subjects provide fully informed consent.
Project Identifier: LLNL-89-106
Project Title:
Protective Breathing Equipment (Respirators) Testing
Principal Investigator:
Dr. Art Biermann
Project started in: 1989
Project Funding Information:
Project received funding in Fiscal Year 1998.
Project used human subjects in Fiscal Year 1998.
Funding Sources:
Total Funding: $280,000
Project does not involve use of multiple protocols/subprojects.
IRB Review:
Type of Review: Full Board
Most Recent Approval: April 14, 1998
IRB Approval Number: 89-106
Number of Human Subjects who participated in this project/protocol during
FY 1998 (10/1/97 - 9/30/98): 17
Type of Human Subjects Involvement:
For Respirator protection testing
The objective of this research is to measure the degree of protection offered by various respirators to a challenge agent while the wearer, a human subject, is performing movements or exercises designed to simulate specific workplace operations. To evaluate the performance of the respirator during the movements, a human subject will don a respirator and enter a test chamber containing the challenge agent. The challenge may be an aerosol, gas, or combination of the two. Leakage of the challenge agent into the respirator is measured to quantify the respirator performance during the simulated operations. In these experiments, testing is performed on the respirator, not the subject; involvement of the subject is required to adequately simulate the workplace activities.
Respirators being tested may include half masks, full face masks, powered air purifying respirators, supplied air line respirators, and self-contained breathing apparatus. For experiments being conducted in fiscal years 1997-98, the research studies focus on several types of powered air purifying and supplied air line respirators supplied by a variety of manufacturers. Also, for these studies, a submicron aerosol of polyethylene glycol (molecular weight of 400) is used as the challenge agent. Concentrations of the aerosol in the test chamber can range from 10 to 50 mg/m3. However, the subject is not exposed to these levels since they enter the test chamber donning the respirator and there is a high degree of protection provided by the respirator. Once in the chamber the subjects execute the planned exercise protocol. Exercises include standing still while breathing normally, bending forward and touching toes, raising arms above head and looking upward, bending knees and squatting, running in place, standing while twisting at the waist, moving the head side-to-side and up and down, hand scooping of oiled pebbles, and the building of a concrete block wall. Subjects are in the test chamber for no longer than 45 minutes. In addition to measurements of aerosol leakage, the pressure difference between the chamber and inside the face piece and the air flow provided by the respirator will be measured.
For the current studies, it is envisioned that 12 to 20 human subjects will eventually be qualified to participate. All subjects will be LLNL employee volunteers and LLNL-respirator qualified. There are no significant risks resulting from using polyethylene glycol as a challenge agent. Many years of human experience in the workplace and in consumer products consisting of polyethylene glycol have not indicated any adverse health effects. No carcinogenic effects have been reported. Further, no specific industrial hygiene inhalation limits have been established for the compound. Subjects may experience fatigue or sore muscles due to the exercise, or respiratory distress if there is a hypersensitivity to the aerosol. Total exposure will not exceed that permitted for an 8-hr workday under current workplace exposure guidelines for a nuisance oil mist. As of the end of fiscal year 1998, 17 subjects have qualified for participation, and, at the most, one subject will have participated in an actual experiment.
Project Identifier: LLNL-90-105
Project Title:
LLNL Human Genome Center
Principal Investigator:
Dr. Anthony V. Carrano
Project started in: 1990
Project Funding Information:
Project received funding in Fiscal Year 1998.
Project used human subjects in Fiscal Year 1998.
Funding Sources:
Project does not involve use of multiple protocols/subprojects.
IRB Review:
Type of Review: Expedited
Most Recent Approval: January 21, 1998
IRB Approval Number: 90-105
Number of Human Subjects who participated in this project/protocol during
FY 1998 (10/1/97 - 9/30/98): 1
Type of Human Subjects Involvement:
As part of the research carried out by members of the Human Genome Center, we occasionally need metaphase preparations of human chromosomes to localize probes (small segments of DNA) back on the chromosomes. Our current need for these chromosomes preparations is quite small, so we are obtaining samples only 1 - 3 times per year.
To generate the metaphase chromosomes preparations, a small aliquot of human peripheral blood is obtained from a donor, drawn by a qualified phlebotomist at the LLNL Health Services facility. White blood cells contained therein are cultured for 2-3 days. Chromosomes are harvested from the white blood cells and placed on microscope slides for the analyses. No long term cultured cells are preserved, nor is any personal data collected from the individual providing the blood sample. The donors are not exposed to any hazardous materials as part of this protocol. A human consent form is signed prior to sample collection.
There is minimal risk or discomfort to the individual donating the blood sample, but may including temporary pain, bruising, localized infection, and/or fainting. This activity does not involve medical treatment.
Project Identifier: LLNL-90-108
Project Title:
Detection of Aneuploid Human Sperm by in situ Hybridization and Image Analysis
Principal Investigator:
Dr. Andrew J. Wyrobek
Project started in: 1990
Project Funding Information:
Project received funding in Fiscal Year 1998.
Project used human subjects in Fiscal Year 1998.
Funding Sources:
Project does not involve use of multiple protocols/subprojects.
IRB Review:
Type of Review: Full Board
Most Recent Approval: April 14, 1998
IRB Approval Number: 90-108
Number of Human Subjects who participated in this project/protocol during
FY 1998 (10/1/97 - 9/30/98): 10
Type of Human Subjects Involvement:
a. Objectives:
The objectives of this research are to investigate the risk factors of paternally transmitted genetic damage. New methods will be developed for detecting chromosomal abnormalities in human sperm using multi-probe FISH. In addition, computer assisted image analysis systems will be developed for automatic scoring.
b. Methodology:
A small amount of human semen is smeared onto glass slides and is analyzed for sperm aneuploidy and structural aberrations by fluorescence in situ hybridization (FISH) using chromosome specific DNA probes.
c. Ionizing Radiation, Radioactive Substances, or Chemical Substances.
No person is exposed to these substances for the purpose of the study. Most of the men used in this study are healthy normal men. For validation of our assays, we also utilize a small number of archived semen samples provided by cancer patients before, during and after they have been treated with drug and/or radiation therapies.
d. Involvement of Human Subjects.
Men are invited to be volunteers for providing semen samples and some choose to participate in our studies. Samples are delivered to the laboratory and all samples are coded to protect the confidentiality of the donors. Either frozen or fresh samples are used as dictated by the requirements of the specific laboratory methods. There is no known risk to the semen donors.
Project Identifier: LLNL-91-102
Project Title:
Glycophorin A-based Somatic Cell Mutation Measurements in Blood Samples from Normal Individuals
Principal Investigator:
Dr. Richard G. Langlois
Project started in: 1991
Project Funding Information:
Project received funding in Fiscal Year 1998.
Project used human subjects in Fiscal Year 1998.
Funding Sources:
Project does not involve use of multiple protocols/subprojects.
IRB Review:
Type of Review: Full Board
Most Recent Approval: April 14, 1998
IRB Approval Number: 91-102
Number of Human Subjects who participated in this project/protocol during
FY 1998 (10/1/97 - 9/30/98): 50
Type of Human Subjects Involvement:
A) Objectives
The glycophorin A (GPA) human mutation assay was developed at LLNL, and this assay is now being extensively used for studies of genetic damage in human populations with exposure to potentially mutagenic agents and populations that are potentially unusually susceptible to mutational damage. Thus, the GPA assay provides an important approach for studying the human risk from exposure to genotoxic agents. Blood samples from normal donors are required for both quality control, and for defining the distribution of GPA variant frequencies in unexposed individuals for comparison with individuals with potential mutagen exposure.
B) Methodology
Blood samples (5-30 ml) from volunteers at LLNL will be obtained by standard venipuncture done by members of the LLNL Medical Department. All samples will first be M,N typed to identify which samples are of blood type MN, as the assay can only be performed on samples of this blood type. Blood samples will be fixed, labeled with monoclonal antibodies and propidium iodide, and analyzed by flow cytometry. The flow cytometer data will be used to calculate the frequency of variant phenotype erythrocytes in each sample.
C) Ionizing Radiation, Radioactive Substances, or Chemical Substances
None
D) Involvement of Human Subjects
Blood samples will be obtained from normal donors in the LLNL employee population for use in the GPA assay for somatic cell mutations in humans. Samples from normal donors will be used for instrument calibration, quality control tests on assay performance, and as test samples for modifications of the GPA assay method. Assay data from normal donors will also be combined with data from other normal donors to provide information on the distribution of variant cell frequencies in unexposed individuals.
Each donor will be assigned a code number by the principal investigator, Dr. Richard G. Langlois. Subject names will be known only to him and appropriate laboratory personnel. Data obtained from individual subjects will be referred to only by the code number so that the identity of donors will be protected.
Blood samples are obtained by standard venipuncture procedures, and it is expected that the subject will be able to function normally immediately. Possible risks and discomforts that may result from the procedure are considered unlikely but include:
a. Temporary pain
b. Bruising and/or soreness of the affected tissue or surrounding tissue
c. Formation of scar tissue
d. Infection
e. Fainting
Project Identifier: LLNL-91-109
Project Title:
Ultratrace Hair Analysis
Principal Investigator:
Dr. Brian D. Andresen
Project started in: 1991
Project Funding Information:
Project received funding in Fiscal Year 1998.
Project used human subjects in Fiscal Year 1998.
Funding Sources:
Project does not involve use of multiple protocols/subprojects.
IRB Review:
Type of Review: Full Board
Most Recent Approval: May 20, 1998
IRB Approval Number: 91-109
Number of Human Subjects who participated in this project/protocol during
FY 1998 (10/1/97 - 9/30/98): 30
Type of Human Subjects Involvement:
Objective
Hair can possibly be a biological sample that will reveal chemical exposures in humans. Incidental inhalation and ingestion of particles over extended periods of time may result in the formation of a diagnostic chemical fingerprint in hair samples. Methods will be explored to ascertain if routine chemical exposures in the work environment can be revealed through ultratrace analysis of human hair samples.
Methodologies
Human hair from individuals known to have been exposed to chemicals in the workplace will be analyzed. New analytical methods will be developed to assay for ultralow levels of certain organics (e.g., high explosives) and specific elements (e.g., actinides).
The focus of the hair analysis program centers first on reviewing the literature concerning the extraction of target analytes in laboratory-fortified hair samples. Several approaches will be reviewed in detail. For example, enzymatic digestion, organic solvent extractions, and mild acidic extractions. Depending on the harshness of the extraction, solid phase extraction (SPE) may be proposed as a partial method to clean up the extracts. Every extraction technique will be evaluated on its efficiency and ease of use.
The work also includes the development of a laboratory protocol for organic extracts of hair that will either pre-concentrate the sample prior to analysis, or evaporate the sample to dryness and then derive the isolated compounds and elements. It will be proposed to analyze each sample utilizing gas chromatography-mass spectrometry (GC-MS) and inductively coupled plasma mass spectrometry (ICP-MS). We will recommend equipment that is readily available to most analytical chemistry laboratories.
The use of matrix assisted laser desorption and ionization (MALDI) mass spectrometry will be evaluated for sectional hair analysis. Because hair grows at approximately 1 cm/month it may be used to detect a history of chemical exposures. We plan to review the application of MALDI-MS for hair analysis of HE and actinide incorporation. MALDI-MS will enable us to precisely focus laser power on a selected portion of a hair strand utilizing a miniaturized video camera with newly designed laser optics to monitor the ionization points on the hair shaft. The ions created should allow an ion trap mass spectrometer (with MS/MS option) to detect target species. We will consider in our studies the level of concentration of chemicals in the hair and if at what level the target species must be present in order to be seen with MALDI-MS. Most of the preliminary work will be performed with laboratory fortified hair samples.
Ionizing Radiation
No radiation experiments are anticipated in these studies. Only hair samples from individuals who work with radioactive materials will be utilized in these studies. No human experiments are anticipated.
Involvement of Human Subjects
1. Hair samples from selected volunteers will be obtained for these studies. Typically hair is obtained during routine hair cuts at the local barber shops. The hair samples are placed in suitable containers and collected for analysis.
2. There is very little risk of injury in obtaining hair samples. The information obtained following the analysis is maintained confidential to all and only available to selected researchers as coded data. No names are associated with the analytical chemistry findings.
Project Identifier: LLNL-92-105
Project Title:
The Effects of Ergonomically Designed Computer Keyboards on the Incidence of Cumulative Trauma Disorders among VDT Workers
Principal Investigator:
Dr. Pat Tittiranonda
Project started in: 1992
Project Funding Information:
Project received funding in Fiscal Year 1998.
Project used human subjects in Fiscal Year 1998.
Funding Sources:
Total Funding: $172,000
Project does not involve use of multiple protocols/subprojects.
IRB Review:
Type of Review: Full Board
Most Recent Approval: July 15, 1998
IRB Approval Number: 92-105
Number of Human Subjects who participated in this project/protocol during
FY 1998 (10/1/97 - 9/30/98): 50
Type of Human Subjects Involvement:
Recruited heavy keyboard users (>4 hours per day) involved with data entry and word processing will be eligible for the keyboard trials. Ergonomic keyboard evaluation will be administered to identify various causes of Carpal Tunnel Syndrome (CTS) and/or tendinitis. CTS subjects will be randomized into 3 different groups where they will be assigned to use different keyboards for a 12 week trial period. Selected subjects will also be asked to participate in a laboratory based experiment to measure their wrist deviation patterns using a video analysis system. Subjects will be asked to type from a pangrammic text as their hand and arm movements are monitored using a camera system that relays positional information to a computer for motion analysis.
Standard clinical care will be given regardless of selection into the study.
Project Identifier: LLNL-94-105
Project Title:
Investigation of the Relationship between Numerical Chromosomal Aneuploidy in Sperm and Offspring
Principal Investigator:
Dr. Andrew J. Wyrobek
Project started in: 1994
Project Funding Information:
Project received funding in Fiscal Year 1998.
Project used human subjects in Fiscal Year 1998.
Funding Sources:
Project does not involve use of multiple protocols/subprojects.
IRB Review:
Type of Review: Full Board
Most Recent Approval: September 16, 1998
IRB Approval Number: 94-105
Number of Human Subjects who participated in this project/protocol during
FY 1998 (10/1/97 - 9/30/98): 2
Type of Human Subjects Involvement:
a. Objectives:
The objective of this study is to study the relationship between numerical chromosomal abnormalities in semen and the chance of fathering a child with a chromosomal defect (e.g., Klinefelter syndrome, 47,XXY).
b. Methodology:
Blood from the parents and child was used to determine the parental origin of the abnormal chromosome and sperm from the father was used to determine the frequency of aneuploidy in the sperm.
c. Ionizing Radiation, Radioactive Substances, or Chemical Substances.
None
d. Involvement of Human Subjects.
1. Families were identified who have a child with Klinefelter syndrome. A genetic counselor approached the family to request participation in our study and obtained the questionnaire information and arranged for the visit by the nurse. A nurse went to the family residence to draw the blood and to pick-up the semen sample which were provided by the father. All samples were be coded to protect the identity of the family.
2. There is a small risk to the puncture area associated with drawing blood and a certified nurse performed this procedure. There are no known risks for the semen donor.
Project Identifier: LLNL-95-115
Project Title:
Determining Metabolism Differences by Urine Analysis
Principal Investigator:
Dr. James S. Felton
Project started in: 1995
Project Funding Information:
Project received funding in Fiscal Year 1998.
Project used human subjects in Fiscal Year 1998.
Funding Sources:
Project does not involve use of multiple protocols/subprojects.
IRB Review:
Type of Review: Full Board
Most Recent Approval: July 15, 1998
IRB Approval Number: 95-115
Number of Human Subjects who participated in this project/protocol during
FY 1998 (10/1/97 - 9/30/98): 3
Type of Human Subjects Involvement:
subjects will eat cooked meat that naturally contains up to 400 parts-per-billion of PhIP.
The objective of this work is to understand human susceptibility to cooked food containing carcinogenic heterocyclic amines. Individuals will eat normally cooked meat products, primarily chicken, and their urine will be collected over a 10 h time period. Subjects will be exposed (ingest) to food. Unfortunately, cooked food contains 1-500 ppb of very potent carcinogens and the subjects will be exposed up to 200 ug of compounds similar to PhIP (2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine) at a single meal. Individuals will undergo the risk of eating carcinogens, but no more than they do if they are not vegetarians.
Project Identifier: LLNL-95-119
Project Title:
Background Translocation Frequencies in Humans (former title is "Chromosome Painting")
Principal Investigator:
Dr. Joe N. Lucas
Project started in: 1995
Project Funding Information:
Project did not receive funding in Fiscal Year 1998.
Project did not use human subjects in Fiscal Year 1998.
Explanation:
Samples were collected in 1995 and 1996. No funding was available in FY98; however, PI expects funding in FY99.
Project does not involve use of multiple protocols/subprojects.
IRB Review:
Type of Review: Full Board
Most Recent Approval: September 16, 1998
IRB Approval Number: 95-119
Number of Human Subjects who participated in this project/protocol during
FY 1998 (10/1/97 - 9/30/98): 0
Type of Human Subjects Involvement:
The present study to measure background translocation frequencies in humans evolved from early studies that began in the mid 80's, soon after we developed chromosome painting and began to measure chromosome translocations with that technique. Most of the early donors were from Bio Med, however, we expanded to lab wide in the late 80's and early 90's. The translocation frequencies are measured in blood lymphocytes of unexposed individuals. Peripheral blood samples will be drawn by sterile venipuncture from human volunteers at the LLNL medical Department. The samples are taken from LLNL employees, retirees, and their relatives. All donors will be unexposed, and range in ages from 18 to healthy elderly relatives of LLNL employees.
Peripheral blood samples (~5ml) will be taken from volunteers or during routine medical examination for analysis of chromosome aberration frequencies. Blood samples from volunteers will be taken at LLNL. Blood samples will be drawn from LLNL donors, cultured, and cells stored on glass slides for analysis. All volunteer donors will be informed of the purpose of the blood work and of the (minimal) risk involved. They will be asked to sign an informed consent form prior to blood drawing. The consent form will be kept on file by the principal investigator. The samples will be coded, and the codes will be kept confidential so that only the chief medical personnel knows the donor identity.
Project Identifier: LLNL-95-126
Project Title:
Influence of Heterocyclic Amine Metabolic Polymorphisms on Bioactivation of PhIP in the Human Colon
Principal Investigator:
Dr. Kenneth Turteltaub
Project started in: 1995
Project Funding Information:
Project received funding in Fiscal Year 1998.
Project used human subjects in Fiscal Year 1998.
Funding Sources:
Project does not involve use of multiple protocols/subprojects.
IRB Review:
Type of Review: Full Board
Most Recent Approval: December 03, 1997
IRB Approval Number: 95-126
Number of Human Subjects who participated in this project/protocol during
FY 1998 (10/1/97 - 9/30/98): 5
Type of Human Subjects Involvement:
The aim of this study is to determine if a well-characterized mutagen that is present in the human diet, primarily from cooked meat consumption, binds to DNA in human tissue and how this binding differs among humans. Additionally it is a goal of this work to establish the minimal amount of isotope-labeled compound that can be administered and still measured quantitatively by accelerator mass spectrometry (AMS). It has been established that prolonged dietary intake of well-cooked meats increases the risk for colorectal cancer. Well-cooked meats contain significant quantities of heterocyclic aromatic amines (HAAs), which have been established as mutagens. The compound present in the highest concentrations (30-50 ng/g) is 2-amino-1-methyl-6-phenylimidazo-[4,5-b]pyridine (PhIP). In fact, PhIP-DNA adducts have been detected by us in animal experiments using AMS.
The primary benefit from this study is determining if PhIP binding can be detected in humans and how the binding compares to what has been seen in animal studies. This comparison is very important for determining if these compounds contribute to the incidence of colon cancer in the western world since rodents have been used to assess the potential carcinogenicity of these compounds. Importantly, these compounds are carcinogenic in rodents and produce tumors at multiple sites in both rats and mice. This comparison will help establish how the rodents used in cancer studies compare to the human response and will thus increase the confidence in the human risk assessments made using animal models. Further, this study will demonstrate for the first time that DNA adducts are formed in human tissues with these compounds. DNA adducts are believed to be a critical early step in the process of tumorigenesis. Finally, it will help establish if there are individuals with a genetic predispostion (based on phenotype and genotype) for sensitivity to this compound and will lead to studies to attempt to reduce risk by chemical or dietary intervention.
The study is a collaboration between LLNL, and Dr. N. Lang (University of Arkansas, Medical Center). Administration of the compound, blood collection, urine collection and surgeries will be supervised and carried out by Dr. Lang at the UAMS University Hospital and the J.L. McClellan Memorial Veterans Administration Medical Center (VAMC) in Little Rock. Samples of tissue sections removed during the course of colon surgery will be sent to LLNL for analysis. DNA will be isolated at LLNL and analyzed for DNA adducts. Only the tissue and purified DNA will be handled and analyzed at LLNL. Briefly, VAMC patients who have been previously diagnosed with colon cancer and who are scheduled for colon resection at the UAMS University Hospital and the VAMC will be informed as to the nature of the study and then asked to participate. A total of 10 human subjects will be enrolled into this study. They will be asked to read and sign the consent form (on file). Patients may be of either sex and must be 18 yrs old. Twenty-four (24) hours prior to surgery patients who consent to participate will be administered 14C-PhIP in a gelatin capsule, per os, (0.07 - 1 µg/kg; maximum activity 15.6 µCi/person). Lactose powder will be used as a bulking agent in the capsule. Blood will be drawn (50 mls by vein puncture) 12 hr after PhIP administration, 24 hr after PhIP administration, and 36 hr after PhIP administration to determine the circulating levels of the compound and its metabolites. Additionally, urine and feces will be collected from approximately 12 hours prior to PhIP administration and for up to 96 hr after administration of the PhIP containing capsule to determine clearance rates and metabolic profiles. Approximately 24 hrs after the capsule is given the patients will undergo colon surgery and the tissue removed during surgery will be placed on dry ice. Specimens will then be divided into four portions, labeled, quick frozen in liquid nitrogen, and then stored at -70°C until sufficient quantities are collected for overnight shipment to LLNL (see time line).
Approximately 6 - 8 wks after surgery, patients who participate in this study will be phenotyped and genotyped for enzymes potentially involved in the metabolism of the heterocyclic amines. These polymorphic genes include the cytochrome P450s (cyp1A1 and cyp1A2), N-acetyl-transferase (NAT-1 and NAT-2), sulfotransferase and glutathione-S-transferase genes (GSTM1 and GSTP1). In the case of the cyp and NAT genes, caffeine metabolism will be examined. Caffeine is used because it is an indicator of cyp phenotype and N-acetyltransferase phenotype which are significant enzymes involved in PhIP metabolism. Results from this test will be used to assess human variation in metabolism capability. At this time, the participants will be asked to take 200 mg caffeine (2 No-Doz tablets). The patients will be asked to empty his/her bladder 4 hours later. This specimen will be discarded. The bladder will again be emptied one hour later (a total of 5 hrs after taking the caffeine) and this urine will be treated with HCl to preserve metabolites and frozen at -20°C until extraction and analysis can be performed. High performance liquid chromatography (HPLC) will be used to quantitatively measure caffeine urinary metabolites. Phenotype will be assigned based on characteristic peak ratio calculations which have been previously described. In the case of sulfotransferase, a platelet based activity test will be used to determine phenotype. Finally, the glutathione-S-transferase genotype will be determined by PCR using lymphocyte DNA obtained from the pre-dose blood draw.
Project Identifier: LLNL-96-103
Project Title:
Does Tamoxifen cause DNA Damage in Human Tissues
Principal Investigator:
Dr. Kenneth W. Turteltaub
Project started in: 1996
Project Funding Information:
Project received funding in Fiscal Year 1998.
Project used human subjects in Fiscal Year 1998.
Funding Sources:
Project does not involve use of multiple protocols/subprojects.
IRB Review:
Type of Review: Full Board
Most Recent Approval: April 14, 1998
IRB Approval Number: 96-103
Number of Human Subjects who participated in this project/protocol during
FY 1998 (10/1/97 - 9/30/98): 6
Type of Human Subjects Involvement:
The question of an increased cancer risk to women taking tamoxifen as a chemotherapeutic agent is a major public health issue. This study addresses whether or not there are DNA adducts present in human tissues after tamoxifen administration. The results will provide better information on the risk-benefit ratio for tamoxifen as a chemopreventive drug.
Women admitted to the Leicester Royal Infirmary, UK, for breast, endometrial, colon or liver surgery will be fully informed of the purpose of the study and will be asked to participate. Those willing to take part will be asked to provide written informed consent and to fill in a simple questionnaire which will center particularly on which drugs they are currently taking. They are administered 50 µCi [1.85 MBq] of 14C-tamoxifen diluted in unlabeled tamoxifen to provide a dose of 20 mg/person, which is the normal daily therapeutic dose. The radiation dose based will be 170.9 µSv and is less than the natural background radiation to which people are exposed in daily life during the course of a month. The tamoxifen will be taken orally by women in the form of a capsule 12 to 18 hours prior to surgery. Surgical specimens and blood samples [no more than 30 ml] will be taken at the time of surgery. Urine will be collected for up to 48 hours following capsule administration. It is planned to study up to 20 subjects in this study (10 dosed with 14C-labeled tamoxifen and 10 controls).
This study is a collaboration between LLNL, Professor Kent Woods [Leicester Royal Infirmary], Mr. F. Al-Azzawi [Leicester Royal Infirmary] and Professor L.L. Smith [MRC Toxicology Unit, Leicester]. Administration of the tamoxifen capsules, blood collection and surgery will be supervised and carried out at Leicester Royal Infirmary. Samples will be taken to the MRC Toxicology Unit (Professor L.L. Smith) for further processing. DNA, protein and tamoxifen metabolites will be extracted from the tissue and sent to LLNL for analysis by AMS.
Project Identifier: LLNL-96-104
Project Title:
Do Trace Levels of Aflatoxin B1 cause DNA Damage in Human Tissues
Principal Investigator:
Dr. Kenneth W. Turteltaub
Project started in: 1996
This project ended in Fiscal Year 1998.
Project Funding Information:
Project received funding in Fiscal Year 1998.
Project did not use human subjects in Fiscal Year 1998.
Explanation:
No subjects were involved in the wrap-up work on this study
Funding Sources:
Project does not involve use of multiple protocols/subprojects.
IRB Review:
Type of Review: Full Board
Most Recent Approval: May 21, 1997
IRB Approval Number: 96-104
Number of Human Subjects who participated in this project/protocol during
FY 1998 (10/1/97 - 9/30/98): 0
Type of Human Subjects Involvement:
Aflatoxin B1 is a fungal metabolite which is a naturally occurring dietary contaminant. Human epidemiology and animal studies have indicated that aflatoxin B1 may be a human liver and colon carcinogen. However, the human studies have been hampered by a lack of accurate intake information, poor cancer incidence data and various confounding factors. Therefore, the objective of this project is to investigate if aflatoxin B1 is likely to be a human cancer risk at levels which may be encountered in the diet.
This is a study in collaboration with Professor Colin Garner (University of York, United Kingdom) and Mr Steve Leveson (York District Hospital, United Kingdom) in which human volunteers are administered a small amount of 14C-labeled aflatoxin B1. Human subjects are patients at York District Hospital who are about to undergo colon or liver surgery for cancer or other diagnostic purposes. The objectives and health consequences of the study are explained to the subjects and then they are asked if they are willing to participate. Participating volunteers are asked to fill in a detailed informed consent document and to complete a brief questionnaire. Pre-dose blood and urine samples are then collected for analysis. Four to six hours prior to surgery, the volunteers are administered 1 mg [14C]aflatoxin B1 in the form of a capsule, which is swallowed with water. The dose of aflatoxin B1 is equivalent to consuming 250g of peanut butter at the maximum levels of contamination permitted by current regulations. The radiation dose is 0.13 mSv, which approximates to 0.15% of the radiation dose from a chest X-ray. There are no foreseen, or so far encountered, health risks associated with either the chemical or radiation exposures. All urine is collected until 24 hours post-dosing and at the time of surgery a second blood sample is collected, together with a tissue sample. Twenty-four hours post-surgery, a third and final blood sample is collected.
Albumin and hemoglobin are extracted from the blood and DNA is extracted from the tissue. These samples are coded and sent to LLNL, where they are analyzed for carbon-14 content by accelerator mass spectrometry. Urine is analyzed by HPLC with scintillation counting, which is performed at York University, United Kingdom. Results from these analyses are used to indicate if aflatoxin B1 binds to DNA in the colon and liver and whether binding to blood proteins or levels of urinary metabolites could be used as markers of exposure and/or metabolism.
Project Identifier: LLNL-96-105
Project Title:
A Comparison of the use of 41Ca Tracer and Conventional Biomarkers to Assess Bone Turnover in Healthy Adults.
Principal Investigator:
Dr. Stewart Freeman
Project started in: 1996
Project Funding Information:
Project received funding in Fiscal Year 1998.
Project used human subjects in Fiscal Year 1998.
Funding Sources:
Project does not involve use of multiple protocols/subprojects.
IRB Review:
Type of Review: Full Board
Most Recent Approval: April 14, 1998
IRB Approval Number: 105
Number of Human Subjects who participated in this project/protocol during
FY 1998 (10/1/97 - 9/30/98): 16
Type of Human Subjects Involvement:
Objectives
Novel methodologies for measuring human calcium kinetics are being pursued. The development at LLNL of technology capable of measuring the very long-lived isotope of calcium 41Ca (104,000 yr halflife) at environmental levels, enables this isotope to be added to the cannon of calcium isotopic tracers. 41Ca tracer might be employed where others are precluded for radiological, physiological and/or economical reasons, permitting unique long-term studies of resorbing labeled bone and so-called continuous feeding studies. This experiment tests 41Ca protocols against conventional calcium isotope tracers.
Methodology
In all cases, 41Ca is administered to experimental subjects managed at a collaborating institution: UC Davis, the Palo Alto VA, 96-105. The tracer is either administered as a single bolos dissolved in food or as many smaller amounts with meals for up to a month for the continuous feeding studies. Excreta samples from the period of tracer administration and up to six months later are analyzed for 41Ca and the kinetics are calculated. The conventional isotope tests involve a day of IV and PO tracer administration, and urine collection and a blood draw for tracer analysis. Subjects are maintained in a metabolic ward for a week for the mass balance determinations, or to stabilize their kinetics prior to providing urine and blood samples for measurement of the biomarkers in that test.
Radioactive and Chemical Substances
Each subject consumes approximately 5 nCi 41Ca @ 10-6 of total calcium in the form of the carbonate dissolved in orange juice. The standard isotope tests involve the administration of 5 µCi 45Ca or stable isotopes tested for sterility and pyrogenicity.
Human Subject Involvement
A total of 16 adult male and post-menopausal female subjects have been or will be recruited into these studies. Eight subjects will consume a single bolos of 41Ca and another eight will continuously consume the tracer for a month. Subjects will provide occasional urine samples during and after tracer administration until the urine tracer level has stabilized. Then, about 100 days after beginning the experiment, the subjects will be admitted to a metabolic ward where they will provide further urine samples and blood samples while on a measured diet.
The risks to the subjects as a consequence of these studies are those associated with the lifetime radiation dose from the subsequent decay of 41Ca absorbed by bone. Normalized to the 5 nCi oral dose, the International Commission on Radiological Protection calculates the 50 year integrated committed effective dose to be 6 µrem, with an associated risk for all stochastic effects (fatal cancers, non-fatal cancers and severe hereditary effects) of 3*10-9. The 0.1 µrem per year dose is 1 three-millionth of the average background radiation dose of 360 mrem per year. A typical chest X-ray is 10-15 mrem.
Project Identifier: LLNL-96-106
Project Title:
Chernobyl Dosimetry
Principal Investigator:
Dr. Joe N. Lucas
Project started in: 1996
Project Funding Information:
Project did not receive funding in Fiscal Year 1998.
Project did not use human subjects in Fiscal Year 1998.
Explanation:
This protocol has been on hold for the past 2 years due to funding issues. The PI expects to receive funding and begin working on this protocol in FY99.
Project does not involve use of multiple protocols/subprojects.
IRB Review:
Type of Review: Full Board
Most Recent Approval: January 21, 1998
IRB Approval Number: 96-106
Number of Human Subjects who participated in this project/protocol during
FY 1998 (10/1/97 - 9/30/98): 0
Type of Human Subjects Involvement:
The overall goal of this project is to apply our expertise in chromosome painting doses reconstruction to validate the micronucleus (MW) technology for liquidators and populations exposed to Chernobyl radiation in the Ukraine. In preliminary data we have shown that the dose for 23 liquidators was elevated based on chromosome translocations compared to unexposed controls. Chromosome painting biodosimetry will be performed on a subset of the total number of people evaluated by MW to validate the micronucleus assay.
The translocation frequencies are measured in blood lymphocytes of individuals. Peripheral blood samples (~20 ml) taken during routine physical examination will be cultured and spread on glass slides for chromosome translocation analysis. All volunteer donors will be informed of the purpose of the blood work and the (minimal) risk involved. They will be asked to sign an informed consent form prior to blood drawing. The consent form will be kept on file by the principal investigator. The samples will be coded, and the codes will be kept confidential so that only the chief medical personnel knows the donor identity.
Project Identifier: LLNL-96-108
Project Title:
Genetic and Molecular Analysis of a Normal Human Population
Principal Investigator:
Dr. Janice Pluth
Project started in: 1996
Project Funding Information:
Project did not receive funding in Fiscal Year 1998.
Project did not use human subjects in Fiscal Year 1998.
Explanation:
PI is waiting for grant funding to come through so that she can continue with project.
Project does not involve use of multiple protocols/subprojects.
IRB Review:
Type of Review: Full Board
Most Recent Approval: May 19, 1998
IRB Approval Number: 96-108
Number of Human Subjects who participated in this project/protocol during
FY 1998 (10/1/97 - 9/30/98): 0
Type of Human Subjects Involvement:
The central focus of this investigation is to determine whether maternal environments induce detectable levels of chromosome damage in human newborns. This study is designed to address the hypothesis that maternal environmental exposures, specifically to active and passive tobacco smoke, impose a significant genotoxic burden on the developing fetus that can be quantitated by measuring chromosome damage in placental blood lymphocytes. This study also seeks to identify the relationship between sensitivity to environmental exposures, chromosome damage and exposure to maternal tobacco smoke and other maternal lifestyle factors.
This project builds upon work completed in the past year which looked at the complex association between an individual's (both adult and fetal) environmental exposures, genetic makeup and relationship to chromosome damage. It will also confirm preliminary work completed 5 years ago which showed maternal exposure to tobacco smoke increased the frequency of chromosome damage in utero.
This effort involves a close collaboration with an ongoing study in the laboratory of Dr. William L. Bigbee, which is funded by the National Institute of Child Health and Human Development (NICHD). This work incorporates the study design of Dr. Bigbee's grant and will use aliquots of the placental and maternal blood samples currently being acquired by Dr. Bigbee's staff. We began receiving samples from Dr. Bigbee in October of 1997 and have received 110 samples to date. We plan on collecting about 600 additional samples in the upcoming year. Samples received from Dr. Bigbee's laboratory are being cultured for cytogenetics and the microscope slides prepared are being stored until the necessary additional funds are received to analyze this material. The IRB at the University of Pittsburgh has approved Dr. Bigbee's work and all proper procedures with regards to human subjects privacy, confidentiality and consent are being followed.
Project Identifier: LLNL-96-109
Project Title:
Age Effects on the Incidence of Genetic and Physiological Defects in Human Sperm
Principal Investigator:
Dr. Andrew J. Wyrobek
Project started in: 1996
Project Funding Information:
Project received funding in Fiscal Year 1998.
Project used human subjects in Fiscal Year 1998.
Funding Sources:
Project does not involve use of multiple protocols/subprojects.
IRB Review:
Type of Review: Expedited
Most Recent Approval: August 13, 1998
IRB Approval Number: 96-109
Number of Human Subjects who participated in this project/protocol during
FY 1998 (10/1/97 - 9/30/98): 97
Type of Human Subjects Involvement:
Objective: The specific aim for this study was to determine whether there is an effect of a man's age on the types and proportions of genetic damage in sperm measured by sperm aneuploidy and semen quality using semen chromatin structure assay, CASA (computer assisted sperm analyses) motility, and nuclear morphometry.
This research will provide fundamental information on the effects of paternal age on genetic damage to human sperm. These findings will also provide the critical data needed for the design and interpretation of studies of paternal effects of exposure to environmental agents.
Methodology: The following laboratory analyses are being performed: sperm concentration, visual motility, and CASA (computer-assisted sperm analysis) motility; nuclear morphometry assay; sperm chromatin assay, sperm chromosomal aneuploidy and aberration assay.
Ionizing Radiation, Radioactive Substances or Chemical Substances: None
Involvement of Human Subjects: Recruiting steps included: screening for eligibility; obtaining a self-administered questionnaire about dietary habits; obtaining a self-administered questionnaire about medical history and sociodemographic characteristics; obtaining consent for their dosimetry record; and collecting one semen sample for assessment of sperm and semen quality (any additional samples will be collected only in the event of damage to the original). We recruited 97 non-smoking men in the following age groups: 21 men 20-29 years old; 19 men 30-39 years old; 16 men 40-49 years old; 16 men 50-59 years old; and 25 men 60+ years old.
The subjects received $25 in compensation for their time and effort, the results of the dietary questionnaire, and the results of the conventional semen parameters (volume, count, and motility). Possible risks and discomforts that may have resulted from the procedure were considered unlikely.
Project Identifier: LLNL-96-110
Project Title:
Characterization of Dentin
Principal Investigator:
Dr. John H. Kinney
Project started in: 1996
Project Funding Information:
Project received funding in Fiscal Year 1998.
Project used human subjects in Fiscal Year 1998.
Funding Sources:
Project does not involve use of multiple protocols/subprojects.
IRB Review:
Type of Review: Full Board
Most Recent Approval: August 13, 1998
IRB Approval Number: 96-110
Number of Human Subjects who participated in this project/protocol during
FY 1998 (10/1/97 - 9/30/98): 26
Type of Human Subjects Involvement:
Characterization of Dentin will lead to improved adhesion and bonding of restorations and improved clinical treatment of caries.
We will collect teeth from 30 patients this year. Patients will be asked if they wish to participate in the study, and will be asked to read and then sign a consent form that describes the study in detail.
Teeth will be extracted following normal oral surgery procedures, each tooth will be stored in a coded vial containing distilled water and thymal to prevent bacterial growth (teeth subsequently irradiated for sterilization). Each patient will be asked to complete a form requesting his or her places of residence so we may obtain water fluoridation data for each tooth. This form will be coded corresponding to the vial. A copy of the patient's dental record will be examined to obtain pertinent information from dental history which may have influenced the dentin as well as sex and age. The patient name and address will be replaced with the same code as on the vial(s) containing the tooth (teeth).
Project Identifier: LLNL-96-111
Project Title:
MIR Speech Science Experiments on the Human Vocal Tract.
Principal Investigator:
Dr. Larry Ng
Project started in: 1996
Project Funding Information:
Project received funding in Fiscal Year 1998.
Project used human subjects in Fiscal Year 1998.
Funding Sources:
Project does not involve use of multiple protocols/subprojects.
IRB Review:
Type of Review: Full Board
Most Recent Approval: July 16, 1998
IRB Approval Number: 111
Number of Human Subjects who participated in this project/protocol during
07/16/97 - 07/16/98: 20
Type of Human Subjects Involvement:
The involvement of most of the subjects (those participating in the set of experiments referred to as Study A) will be limited to the utilization of the MIR radar to observe the movements of the tissues surrounding the glottis (Adam's Apple) as they speak several different sentences and words. The plastic case of the radar will be in light contact with the skin on the neck as they speak into a microphone. A second sensor may be used in conjunction with the glottal sensor that will attempt to detect jaw and tongue movement. This secondary sensor will be placed under the jaw and may or may not be in contact with the skin. The entire procedure will normally take less than 30 minutes. There are no significant risks that may result from this procedure. The strength of the radio waves utilized is many thousands of times lower than the strictest international standards for exposure to such waves. No biological specimens will be collected. The number of subjects involved will be 30-40, with roughly equal numbers of men and women. For our other studies (referred to as Study B) there will only be 2 to 5 subjects (most likely from the MIR lab itself, some will be patients with vocal fold pathologies), and the studies will involve the use of the radar in conjunction with standard speech industry tools such as an electroglottograph, laryngoscope, and airflow mask. These procedures will be done at either the University of Iowa's National Center for Voice and Speech or the University of California at Davis Medical Center's Department of Otolaryngology. Approvals to do human subjects research with the MIR radar have been received from both institutions. No information will be solicited from the subjects except for their name, gender, and age.
The benefit to society could be quite large if the MIR radar can be proven to substantially improve man-to-machine communication (which includes speech recognition, synthesis, and speaker verification). There could also be substantial benefit to individuals through speech training (for the hearing disabled) and speech-driven appliances (for the physically disabled).
Project Identifier: LLNL-96-113
Project Title:
The Dynamics of Folate Metabloism in Adults
Principal Investigator:
Dr. John S. Vogel
Project started in: 1996
Project Funding Information:
Project received funding in Fiscal Year 1998.
Project did not use human subjects in Fiscal Year 1998.
Explanation:
Funding Sources:
Total Funding: $20,000
Project does not involve use of multiple protocols/subprojects.
IRB Review:
Type of Review: Full Board
Most Recent Approval: July 15, 1998
IRB Approval Number: 96-113
Number of Human Subjects who participated in this project/protocol during
FY 1998 (10/1/97 - 9/30/98): 0
Type of Human Subjects Involvement:
Nutrition research
Folate chemicals are necessary B vitamins for development, growth, and health. Isotopic labeling was not possible in healthy humans because the radioactivity to produce a signal above the large body folate pool would produce unsatisfactory risk to volunteers. This study uses sensitive detection of 14C by accelerator mass spectrometry to trace labeled folate metabolites in a health volunteer to establish the fate and distribution of a single, sub-RDA dose of folic acid. Nutritional studies, in general, provide data for better estimation of daily requirements of specific nutrients.
Folic acid (35 µg) is labeled with 14C (100 nCi) and is consumed in a single dose with food by a human volunteer. Blood, urine, and fecal samples are collected at frequent convenient time points, starting 10 minutes after the dose to 200 days. Blood and urine samples are fractionated to give metabolite identities. 14C levels in the measured components are fit to distribution models in order to deduce the chemical folate levels in unavailable tissues.
Human metabolism in the folic acid cycle is unlike that of any common animal host. Whole body metabolism must be studied because the effects metabolism occur within the intestine, while the separation, purification, and storage of folates takes place in the liver. No tissue culture can faithfully replicate this cycle. The labeled compound is a nutrient and is supplied at a fraction of the normal daily dose, no chemical toxicity endangers the volunteer. Volunteers receive a total radiation dose of approximately 1 µSievert, equivalent to the normal exposure to cosmic radiation at mid-latitudes on the earth's surface for a single day. The added risk of illness is so small that it cannot be calculated.
Volunteers are from the Davis, CA community and are provided with a description of the research and risks. They sign an approved consent form. All human contact is through the Nutrition Department at UCD. The samples measured at LLNL contain no label revealing the volunteer's identity.
Project Identifier: LLNL-96-114
Project Title:
Optical Diagnosis of Periodontal Disease (Protocol 97-111 was formally LLNL-97-111 in FY97 Database)
Principal Investigator:
Dr. Bill Colston
Project started in: 1996
Project Funding Information:
Project received funding in Fiscal Year 1998.
Project used human subjects in Fiscal Year 1998.
Funding Sources:
Project involves use of multiple protocols/subprojects.
Number of protocols/subprojects associated with this project: 2
Protocol/Subproject # 1
Protocol/Subproject Identifier: 96-114
IRB Review:
Type of Review: Expedited
Most Recent Approval: September 16, 1998
IRB Approval Number: 96-114
Number of Human Subjects who participated in this project/protocol during
FY 1998 (10/1/97 - 9/30/98): 3
Type of Human Subjects Involvement:
The volunteer will sit in a chair. A sterile cheek retractor will be used to pull back the subject's lips to expose her/his teeth and gums. Focused near infra-red light from a super luminescent diode coupled through a single mode fiber will be scanned across her/his teeth and gums using a hand-held scanning device. Light scattered by the gums and teeth will be collected by the same device and used to produce a tomographic image of the gums and tissue. Standard infection control guidelines for dental procedures will be followed. Any material placed inside the subject's mouth will have been disinfected or sterilized. The subject will be able to stop the procedure at any time if he or she feels any discomfort or does not wish to continue with the procedure for any reason.
To make certain that no damage or discomfort occurs to the subject's gums or teeth, the light incident upon the subject's mouth will always be kept at a power level below the maximum permissible exposures (MPEs) limits for skin exposure to a laser beam as given by the ANSI Z-136.1 Standard, Safe Use of Lasers 1993. Although the typical exposure of light to any location on the gums or teeth will only be a few seconds, the limit used will assume a continuous (up to eight hours) exposure to further safeguard the subject.
As the intensity of light considered safe for direct exposure to the eye is generally below the level considered safe for skin, steps will be taken to avoid sending light into the eye. If the power level of the light being used is at or above the ANSI direct eye exposure limits, once again assuming up to eight hours of continuous direct exposure, appropriate laser goggles will be worn to block any stray probe light from reaching the eyes.
The wavelengths of light which will be used in this diagnostic are 0.85 µm, 1.3 µm, and 1.51 µm. The MPEs limits for up to eight hours of continuous exposure to skin at these wavelengths are 38.5 milliwatts, 96.2 milliwatts, and 9.62 milliwatts, respectively, in any region of less than 3.5 mm diameter. We have chosen a cautious approach in using these limits which assumes an eight hour exposure time as light from the superluminescent diode will typically only be focused on any one location for a few seconds and the whole procedure will last under an hour.
A person's eyes are more vulnerable to harm from exposure to light than skin tissue is. Typically in a laser lab, one assumes that the eye may be exposed to a misdirected laser beam for up to 10 seconds. The MPE's are then calculated accordingly in order to determine if one needs laser safety goggles. However, when a beam of light is being used to probe a person's mouth, the principal investigator, Matthew Everett, and the Environment Safety and Health department, as represented by Gordon Miller, feel that the more cautious assumption of the possibility of continuous exposure to the eye is more appropriate. The MPEs for up to eight hours of continuous exposure to the eye are 246 µW at 0.85 µm, 4.9 milliwatts at 1.3 µm, and 9.6 milliwatts at 1.51 µm. Thus, if the probe light from the super luminescent diode is at or above 246 µW at 0.85 µm or 4.9 milliwatts at 1.3 µm, appropriate laser goggles will be worn by the subject to block any stray reflections from the eyes. The light level at 1.51 µm, will be kept below 9.6 milliwatts, so that danger to the eyes is not an issue.
After the teeth and gums have been scanned with the near infra-red light, a dentist, Dr. Linda Otis, may probe the periodontal tissues with a Michigan probe to determine periodontal pocket depths. Standard infection control guidelines for dental procedures will be followed. Any material placed inside the subject's mouth will have been disinfected or sterilized. The subject will be able to stop the procedure at any time if he or she feels any discomfort or does not wish to continue with the procedure for any reason.
IRB Review:
Type of Review: Full Board
Most Recent Approval: September 17, 1997
IRB Approval Number: 97-111
Number of Human Subjects who participated in this project/protocol during
FY 1998 (10/1/97 - 9/30/98): 15
Type of Human Subjects Involvement:
The goal of this project is to demonstrate that an optical coherence tomography (OCT) system can be used to image the gums and teeth in the human mouth. In particular, we wish to determine what the differences are between the images of healthy tissue and diseased tissue (periodontal disease).
This project will involve in vivo imaging of the periodontal tissues of 25 volunteers with near infrared light (1310 mn wavelength) at the University of Connecticut Health Center. There will be no chemical or radiation exposure, and no biological samples will be collected from the subjects. The light exposure will be below the exposure limits for skin exposure from a laser beam as given by the ANSI Z-136.1 Standard, Safe Use of Lasers 1993. There are no known detrimental side effects to the light of this wavelength being directed on the gum tissue or teeth.
Patients who have documented periodontal disease will be recruited at the University of Connecticut Health Center. The principal investigator, Dr. Linda Otis, will use the dental records of each subject to obtain information about the condition of their gums. The front surface of no more than 18 or each subject's teeth will then be scanned at the University of Connecticut Health Clinic with a hand-held optical imaging device operating at 1310 nm. This procedure will take approximately 30 minutes of the subject's time. The subject will be able to stop the procedure at any time if he or she feels any discomfort or does not wish to continue with the procedure for any reason.
The volunteer will sit in a chair. A sterile cheek retractor will be used to pull back the subject's lips to expose their teeth and gums. Focused near infra-red light from a super luminescent diode coupled through a single mode fiber will be scanned across the teeth and gums using a hand-held scanning device. Light scattered by the gums and teeth will be collected by the same device and used to produce a tomographic image of the gums and tissue. Standard infection control guidelines for dental procedures will be followed. Any material placed inside the subject's mouth will have been disinfected or sterilized. The subject will be able to stop the procedure at any time if he or she feels any discomfort or does not wish to continue with the procedure for any reason.
To make certain that no damage or discomfort occurs in the subject's gums or teeth, the light incident upon the subject's mouth will always be kept at a power level below the maximum permissible exposure (MPEs) limits for skin exposure to a laser beam as given by the ANSI Z-136.1 Standard, Safe Use of Lasers, 1993. Although the typical exposure of light to any location of the gums or teeth will only be a few seconds, the limit used will assume a continuous (up to eight hours) exposure to further safeguard the subject.
As the intensity of light that is considered safe for direct exposure to the eye is generally below the level considered safe for skin, steps will be taken to avoid sending light into the eye. If the power level of the light being used is at or above the ANSI direct eye exposure limits, once again assuming up to eight hours of continuous direct exposure, appropriate laser goggles will be worn to block any stray probe light from reaching the eyes.
The wavelengths of light which will be used in this diagnostic are 0.85 µm, 1.3µm, and 1.51 µm. The MPEs for up to eight hours of continuous exposure to skin at these wavelengths are 38.5 milliwatts, 96.2 milliwatts, and 9.62 milliwatts, respectively, in any region of less than 3.5 mm diameter. We have chosen a cautious approach in using these limits which assume an eight hour exposure time as light from the superluminescent diode will typically only be focused on any one location for a few seconds and the whole procedure will last under an hour.
A person's eyes are more vulnerable to harm from exposure to light than skin tissue. Typically in a laser lab, one assumes that the eye may be exposed to a misdirected laser beam for up to 10 seconds. The MPEs are then calculated accordingly in order to determine if one needs laser safety goggles. However, when a beam of light is being used to probe a person's mouth, the principal investigator and the Environmental Safety and Health department feel that the more cautious assumption of the possibility of continuous exposure to the eye is more appropriate. The MPEs for up to eight hours of continuous exposure to the eye are 246 µW at 0.85, 4.9 milliwatts at 1.3 µm and 9.6 milliwatts at 1.51 µm. Thus, if the probe light from the super luminescent diode is at or above 246 µm at 0.85 µm or 4.9 milliwatts at 1.3 µm, appropriate laser goggles will be worn by the subject to block any stray reflections from the eyes. The light level at 1.51 µm will be kept below 9.6 milliwatts, so danger to the eyes is not an issue.
After the teeth and gums have been scanned with the near infra-red light, a dentist, Dr. Linda Otis, may probe the periodontal tissues with a Michigan probe to determine periodontal pocket depths. Standard infection control guidelines for dental procedures will be followed. Any material placed in the subject's mouth will have been disinfected or sterilized. The subject will be able to stop the procedure at any time if he or she feels any discomfort or does not wish to continue with the procedure for any reason.
Project Identifier: LLNL-97-100
Project Title:
Biochemical Analysis of Individual Human Sperm for IVF
Principal Investigator:
Dr. Rodney L. Balhorn
Project started in: 1997
This project ended in Fiscal Year 1998.
Project Funding Information:
Project did not receive funding in Fiscal Year 1998.
Project did not use human subjects in Fiscal Year 1998.
Explanation:
PI did not receive funding as anticipated.
Project does not involve use of multiple protocols/subprojects.
IRB Review:
Type of Review: Full Board
Most Recent Approval: February 07, 1997
IRB Approval Number: 100
Number of Human Subjects who participated in this project/protocol during
FY 1998 (10/1/97 - 9/30/98): 0
Type of Human Subjects Involvement:
The objective of this study is to determine if a sub-population of sperm in the semen of infertile males possesses a biochemical composition that correlates with normal DNA packaging. Using an imaging technique called PIXE (particle induced X-ray emission spectroscopy), we will conduct measurements of the phosphorus, sulfur and metal content of pools of sperm and individual sperm heads isolated from Percoll gradient fractions of semen produced by fertile and infertile males. This will allow us to determine if the nuclear protein (sulfur content), DNA (phosphorus content) and metal (zinc) content of the sperm head are normal or deficient. By coupling this data with histological, morphological and functional assessments of individual sperm, motility assessments and biochemical analyses performed on pools of sperm, this work will provide data clinicians need in order to select sperm with normal nuclear composition for in vitro fertilization, rather than relying only on motility and shape. We also hope to identify a range of defects in sperm chromatin organization involving protamine 1, protamine 2 and metals (such as zinc) that can cause male infertility. This will provide a better understanding of the biochemical causes for male infertility and should provide the clinician with a means of identifying certain types of male infertility.
We will receive and analyze only semen and Percoll gradient fractionated sperm samples. The samples will be identified by a code number and we will only have access to previous motility and morphological data that have been obtained by analyzing pools of sperm from the individuals. Frozen pooled semen and Percoll gradient samples that we receive will be thawed, the sperm will be rinsed in a buffer, and aliquots of the suspended, sperm heads will be applied to nylon foils to be analyzed by PIXE. Total mass (using an oxygen beam), phosphorus, sulfur and metal content data will be obtained for the heads of individual sperm cells (20-300 cells) in each sample. The morphology of the analyzed heads will be assessed from the total mass image and confirmed by light microscopy. Aliquots of the seminal fluid obtained after sedimenting the sperm by centrifugation will be analyzed for their metal content by atomic absorption spectroscopy and DNA and protamine content by gel electrophoresis.
These studies will be conducted in collaboration with Dr. Nongnuj Tanphaichitr, University of Ottawa/Ottawa Medical Clinic, Canada. All semen samples used in the proposed work will be collected via masturbation. These samples will be collected at the donors own request when they enter the clinic to assess their fertility or lack of fertility. There is no potential physical, psychological or social risk to the patient. The individuals will not be exposed to ionizing radiation, radioactive substances or chemicals. The donors will be mature male adults of age 20 and upwards. Fertile donors and infertile patients will not be excluded on the basis of minority groups or their sub-populations and represent a cross-section of the demographic society that is available to the medical clinic. The health status of the individuals supplying semen samples also represents a cross-section of the same demographic society apart from the fact that most infertile patient donors are infertile.
Project Identifier: LLNL-97-101
Project Title:
Physiological Responses of the Eye during Video Display Terminal (VDT) Work
Principal Investigator:
Paul Bommarito
Project started in: 1997
This project ended in Fiscal Year 1998.
Project Funding Information:
Project received funding in Fiscal Year 1998.
Project used human subjects in Fiscal Year 1998.
Funding Sources:
Project does not involve use of multiple protocols/subprojects.
IRB Review:
Type of Review: Full Board
Most Recent Approval: March 19, 1997
IRB Approval Number: 97-101
Number of Human Subjects who participated in this project/protocol during
FY 1998 (10/1/97 - 9/30/98): 25
Type of Human Subjects Involvement:
Eye irritation and dryness are among the most common eye strain symptoms reported by people who normally perform near visual work. Over fifty percent of video display terminal (VDT) users experience eye strain, and it continues to rise as the use of VDT proliferates in the U.S. Vision professionals attribute the symptoms partly to the faster evaporation of tear film in the eyes due to a reduction in blink rates, to a decrease in eye blink amplitude, and to wider opening of the eyes during VDT work. The purpose of this study is to find out if there is an effect on eye blinking rates and amplitudes due to changes in viewing angle during VDT work. Blink rates and amplitudes will be measured with electrooculography (EGO) at four different suspended viewing angles: eye level (0°), normal line of sight (-15°), below eye level, (-30°), above eye level (+15°). Materials and Devices:
Text from a classical novel will be displayed on a standard desktop personal computer (PC) screen. The novel is displayed continuously, the subjects are to scroll down to the next page using a mouse. The PC will also be used to perform signal processing on data from the BioMuse. The BioMuse is an eight channel bioelectrical signal processing device. The BioMuse uses an optically isolated analog-to-digital section to sample subject data, and a digital signal processor that is used to perform preliminary filtering on the data. The BioMuse is connected to the PC via a standard serial port. A height adjustable monitor arm will be used to adjust the VDT height and hence the suspended viewing angles.
A digital camera will be used to video record the experiment. Head postures will be analyzed using the digital video and computer aided design (CAD) software. A photometer will be used to measured illumination at the workstation where experiments will be performed.
The BioMuse is a stretchy velcro headband with five self-adhesive sensors (electrodes) mounted on the inner part of the band, which are to be applied to the subject's forehead with gel. The subjects forehead will be cleaned with an alcohol wipe to clean off sweat and dead skin.
Procedures:
The illumination in the experimental room will be measured before subjects arrive. The subjects will be seated in front of the computer table facing the VDT monitor. Chair adjustments will be made to ensure that each subject is seated comfortably at the appropriate height from the floor. The eye level height from the floor will be measured and recorded on their tracking sheets. At eye level, suspended viewing angle (0°), the distance from the floor to the very top of the monitor screen equals the subjects eye level height. Monitor height adjustments will be calculated using the desired suspended angle and distance from screen. The mouse will be placed at the appropriate height and distance from body for comfortable handling of the mouse.
Once seating and workstation adjustments are done, the experimenter will carefully wipe the subjects forehead where the headband will be placed. The headband is then placed, and the experimenter ensures that the signals are picked-up correctly by the BioMuse program. The video camera is also turned on to begin recording. Instructions are then given to the subjects. The subjects will be asked to gaze at a distance and to try to relax for 5 minutes while the program is being set; eye blink data from this time period will be used as a baseline for the subjects blinking rate.
The subjects will then be asked to read the text displayed on the VDT screen continuously (at their normal pace) until instructed to stop, and to keep their eyes on the VDT screen during each trial. They will also be asked to try to maintain good but comfortable posture, and avoid large head and body movements. They will be asked to read the text entirely and told that a brief questionnaire would be administered at the end of each trial. There will be a total of four trials per subject, each trial lasting 10 minutes. After each trial, the subjects will be given a brief questionnaire for two minutes regarding simple facts from the reading material. Then the subjects will given a two minutes break before the next trial. During this time the monitor height is adjusted.
Experimental conditions will be assigned to subjects in a random counterbalanced order. At the completion of all trials, the subjects will be asked to fill out a questionnaire on potential visual discomforts experienced during the trials.
Project Identifier: LLNL-97-102
Project Title:
Assessment of Dermal Exposure to Metals and Metal Compounds
Principal Investigator:
Dr. Graham Bench
Project started in: 1997
Project Funding Information:
Project received funding in Fiscal Year 1998.
Project used human subjects in Fiscal Year 1998.
Funding Sources:
Project does not involve use of multiple protocols/subprojects.
IRB Review:
Type of Review: Full Board
Most Recent Approval: September 16, 1998
IRB Approval Number: 102
Number of Human Subjects who participated in this project/protocol during
FY 1998 (10/1/97 - 9/30/98): 13
Type of Human Subjects Involvement:
The growing accumulation of metals and metal-based compounds in occupational or environmental settings raises concerns about their potential effects on human health. Several metals are known or suspected carcinogens, and a large number of metals and metal compounds can induce dermal allergic and/or hypersensitivity reactions. Xenobiotic metal ions can also affect the balance of trace elements critical for maintenance of normal function and injury repair. Skin contact represents an important rout of exposure for some hazardous metals/metal compounds, since: (a) they are absorbed through it, (b) skin can act as a reservoir for metals, (c) skin surface deposition can be an important source of secondary contamination, and (d) impairment/loss of skin barrier function can occur as the result of exposure. Proton induced X-ray emission (PIXE) is a well-characterized analytical technique based on X-ray spectrometry that can be used to localize metals with micron resolution and quantitate them with ppm sensitivity. It is ideal for detecting and identifying metals on the outer layers of the skin and can be used as a valuable tool for risk assessment, in the assay of exposure following dermal contact, and as an aid in the diagnosis of metal-induced allergic or contact hypersensitivity.
In this study, our goal is to characterize the average metal background in the stratum corneum (the outer, dead layer of the skin) of healthy volunteers. Stratum corneum samples will be obtained by tape-stripping with a special adhesive tape and the analysis of these tape samples will be performed by PIXE.
The selected skin site (appx. 10x3 cm; volare forearm, or abdomen, or back only one site will be selected per volunteer) will be cleaned with distilled water, and wiped dry with a tissue. A 10x1 cm piece of a low-metal, hypoallergenic tape will be adhered to one selected skin site and then be peeled off. This procedure will be repeated for up to a maximum of 20 times from the one selected skin site. The time required for this procedure will be 15 minutes.
There are no anticipated risks associated with the procedures described above. If unusual discomfort other than local skin reddening or itching is experienced, the experiment will be discontinued immediately.
Subjects will be identified, through coding of data sheets by alphanumeric strings.
Project Identifier: LLNL-97-103
Project Title:
Genetic Variation in Genes of DNA Repair
Principal Investigator:
Dr. Harvey Mohrenweiser
Project started in: 1997
This project ended in Fiscal Year 1998.
Project Funding Information:
Project received funding in Fiscal Year 1998.
Project used human subjects in Fiscal Year 1998.
Funding Sources:
Project does not involve use of multiple protocols/subprojects.
IRB Review:
Type of Review: Full Board
Most Recent Approval: May 21, 1997
IRB Approval Number: 97-103
Number of Human Subjects who participated in this project/protocol during
FY 1998 (10/1/97 - 9/30/98): 60
Type of Human Subjects Involvement:
Although smoking is a known risk factor for lung cancer, only ~10% of all smokers develop lung cancer during their lifetime. Several investigators have identified the reduced ability to repair damaged DNA as a risk factor for developing cancer. Smokers with reduced repair will have approximately twice the frequency of lung cancer as smokers with normal capacity to repair damaged DNA. The reduced repair capacity detected in these studies is not sufficient to cause either genetic disease or cancer. Our colleague, Dr Gloria Petersen of the Department of Epidemiology at Johns Hopkins University (JHU), is conducting a study of the lung cancer patients, including the role of reduced DNA repair capacity as a risk factor for lung cancer. She has collected white blood cells from a series of lung cancer patients and appropriate controls. In collaboration with Dr Petersen, we are screening samples from 30 lung cancer patients and 30 controls for variation in the sequence or structure of genes involved in repairing DNA damage. All samples to be analyzed by LLNL and related information have been previously collected under a protocol approved by Johns Hopkins University for the study the relationship of DNA repair and cancer, thus no contact with the patients is required to obtain material for this analysis. The samples are provided with a code known only to the JHU investigator.
We have sequenced the regions of genes of 9 DNA repair genes where differences in sequence may have a role in determining the functionality of the protein or enzyme. Variation in the DNA sequence is being noted and the results sent to Dr. Petersen. Preliminary statistical analysis suggests that several of the variants are associated with an increased risk of smoking related cancers. These data could be very useful in the identification of individuals at elevated risk of lung and other smoking related cancers.
Project Identifier: LLNL-97-105
Project Title:
Pesticides: Health, Fertility and Reproductive Risks
Principal Investigator:
Dr. James Tucker
Project started in: 1997
Project Funding Information:
Project received funding in Fiscal Year 1998.
Project used human subjects in Fiscal Year 1998.
Funding Sources:
Project does not involve use of multiple protocols/subprojects.
IRB Review:
Type of Review: Full Board
Most Recent Approval: July 15, 1998
IRB Approval Number: 97-105
Number of Human Subjects who participated in this project/protocol during
FY 1998 (10/1/97 - 9/30/98): 1
Type of Human Subjects Involvement:
A. Objectives. To determine the health risks associated with the use of pesticides and herbicides in agricultural workers. In particular, we are interested in the risks of chemical exposure that may lead to cancer. There is some evidence that pesticide and herbicide workers have an elevated frequency of cancer.
B. Methodology. Phlebotomy of normal, healthy subjects. In some cases we may elect to have donors complete a questionnaire inquiring about lifestyle factors which may affect the results.
C. Radiation or chemical exposures. None.
D. Involvement of human subjects. Phlebotomy, followed by cell culture. Cells are grown under commonly-used conditions to promote growth for subsequent analysis by molecular cytogenetic methods. Risks to the subjects are those associated with routine phlebotomy. All samples are processed encoded, and identifying information is kept in a locked file cabinet in the Principal Investigator's office; no identifier is published. All subjects provide fully informed consent.
Project Identifier: LLNL-97-106
Project Title:
Dosimetry of Aflatoxin B2 in Humans
Principal Investigator:
Ken Turteltaub
Project started in: 1997
This project ended in Fiscal Year 1998.
Project Funding Information:
Project received funding in Fiscal Year 1998.
Project used human subjects in Fiscal Year 1998.
Funding Sources:
Project does not involve use of multiple protocols/subprojects.
IRB Review:
Type of Review: Full Board
Most Recent Approval: July 16, 1997
IRB Approval Number: 106
Number of Human Subjects who participated in this project/protocol during
FY 1998 (10/1/97 - 9/30/98): 4
Type of Human Subjects Involvement:
Aflatoxin B2 is a fungal metabolite which is a naturally occurring dietary contaminant. The natural abundance of aflatoxin B2 in contaminated food is approximately 150 times lower than aflatoxin B1, which is being studied under IRB#96-104. Although aflatoxin B2 has not been widely studied in laboratory animals, it is weakly active in inducing liver tumors at doses more than 100 times higher than aflatoxin B1. Therefore, the objective of this project is to investigate if the trace levels of aflatoxin B2 found in the diet may cause damage to human colon and liver and to determine how this varies between individuals. In addition, we aim to establish if adducts of aflatoxin B2 with serum albumin and hemoglobin can be used as dosimeters of exposure and to examine the urinary metabolites of aflatoxin B2. This project will, therefore, determine if the levels of aflatoxin B2 permitted in the diet may pose a human cancer risk.
This is a study in collaboration with Professor Colin Garner (University of York, United Kingdom) and Mr Steve Leveson (York District Hospital, United Kingdom) in which human volunteers are administered a small amount of 14C-labeled aflatoxin B2. Human subjects are patients at York District Hospital who are about to undergo colon or liver surgery for cancer or other diagnostic purposes. The objectives and health consequences of the study are explained to the subjects and then they are asked if they are willing to participate. Participating volunteers are asked to fill in a detailed informed consent document and to complete a brief questionnaire. Pre-dose blood and urine samples are then collected for analysis. Four to six hours prior to surgery, the volunteers are administered 1 mg [14C]aflatoxin B2 in the form of a capsule, which is swallowed with water. The dose of aflatoxin B2 is equivalent to consuming 250g of peanut butter at the maximum levels of contamination permitted by current regulations. The radiation dose is 0.13 mSv, which approximates to 0.15% of the radiation dose from a chest X-ray. There are no foreseen health risks associated with either the chemical or radiation exposures. All urine is collected until 24 hours post-dosing and at the time of surgery a second blood sample is collected, together with a tissue sample. Twenty-four hours post-surgery, a third and final blood sample is collected.
Albumin and hemoglobin are extracted from the blood and DNA is extracted from the tissue. These samples are coded and sent to LLNL, where they are analyzed for carbon-14 content by accelerator mass spectrometry. Urine is analyzed by HPLC with scintillation counting, which is performed at York University, United Kingdom. Results from these analyses are used to indicate if aflatoxin B2 binds to DNA in the colon and liver and whether binding to blood proteins or levels of urinary metabolites could be used as markers of exposure and/or metabolism.
Project Identifier: LLNL-97-108
Project Title:
Electronic Steghoscope with Digital Signal Processing
Principal Investigator:
Dr. Patrick Fitch
Project started in: 1997
This project ended in Fiscal Year 1998.
Project Funding Information:
Project did not receive funding in Fiscal Year 1998.
Project did not use human subjects in Fiscal Year 1998.
Explanation:
This protocol has been cancelled and no human subjects were used in FY98
Project does not involve use of multiple protocols/subprojects.
IRB Review:
Type of Review: Full Board
Most Recent Approval: September 17, 1997
IRB Approval Number: 97-108
Number of Human Subjects who participated in this project/protocol during
FY 1998 (10/1/97 - 9/30/98): 0
Type of Human Subjects Involvement:
Our goal is to develop an accurate, inexpensive screening tool for the detection of carotid artery stenosis (blockage of an artery to the brain by atherosclerotic plaque that could result in a stroke of death) that could be used in every physician's office to detect disease before a stroke or TIA occurs.
The subjects will not be placed at any risk, either through chemical or radiation exposure.
The transducer array (a strip about two inches long by 1/2 inch wide) will be held against the neck, parallel with the carotid pulse (anterior border of the sternomastoid muscle, just above the clavicle). The subject will be asked to hold their breath for approximately 10 seconds while data is collected by an array of small microphones. Data will be collected within approximately 5 minutes on each subject and then they will be dismissed. If the subject had a previous carotid ultrasound or arteriogram, the results will be compared.
Confidentiality will be ensured by having the subjects identified by number, rather than by name. There will be a closed cross-reference of number assignment in a locked file.
Project Identifier: LLNL-97-110
Project Title:
Generation of Contiguous Sequence-ready DNA Clones in Human and Mouse
Principal Investigator:
Dr. Anne Olsen
Project started in: 1997
Project Funding Information:
Project received funding in Fiscal Year 1998.
Project did not use human subjects in Fiscal Year 1998.
Explanation:
This project uses an existing cosmid library and genomic BAC libraries. No human subjects are contacted for this study.
Funding Sources:
Project does not involve use of multiple protocols/subprojects.
IRB Review:
Type of Review: Full Board
Most Recent Approval: September 16, 1998
IRB Approval Number: 97-110
Number of Human Subjects who participated in this project/protocol during
FY 1998 (10/1/97 - 9/30/98): 0
Type of Human Subjects Involvement:
This project is a subcontract to LLNL on an NIH grant to the University of Wisconsin (Lloyd Smith, PI). The grant is for sequencing 2 Mb of DNA (1 Mb each of human and mouse DNA) in two years in conjunction with development of an improved sequencing system. Maps of human and mouse clones will be constructed at LLNL; sequencing of the mapped clones will be done at the University of Wisconsin; and annotation and submission of the completed sequence to the public database will be done at LLNL. The cloned fragments of human DNA that will be mapped and sequenced are from two sources: a human chromosome 19 cosmid library previously constructed at LLNL and human total genomic BAC libraries constructed at Caltech (commercially available from Research Genetics). Maps of overlapping clones spanning a 1 Mb region of human chromosome 19 will be constructed at LLNL, and a subset of minimally overlapping clones spanning the region will be selected for sequencing at the University of Wisconsin. The completed sequence will be annotated (analyzed for content of genes or other features of interest) and submitted to the public database by LLNL. This project will determine the sequence of 1 million bases of human DNA (out of a total of 3 billion bases in the human genome). A knowledge of the sequence of human DNA will contribute to our understanding of the genetic basis of human biology and the role of various genes in health and disease. This will ultimately lead to prevention strategies and improved therapies for a number of diseases.
Project Identifier: LLNL-97-112
Project Title:
Metabolism and Macromolecular Adduct Formation of the Food Mutagen MelQx in Humans
Principal Investigator:
Dr. Kenneth W. Turteltaub
Project started in: 1997
This project ended in Fiscal Year 1998.
Project Funding Information:
Project received funding in Fiscal Year 1998.
Project used human subjects in Fiscal Year 1998.
Funding Sources:
Project does not involve use of multiple protocols/subprojects.
IRB Review:
Type of Review: Full Board
Most Recent Approval: September 17, 1997
IRB Approval Number: 97-112
Number of Human Subjects who participated in this project/protocol during
FY 1998 (10/1/97 - 9/30/98): 3
Type of Human Subjects Involvement:
MeIQx is a heterocyclic amine which is a naturally occurring dietary contaminant formed during the cooking of meat. Laboratory animal and human epidemiology studies have linked exposure to heterocyclic amines, including MeIQx, to an increased risk of colon cancer. Therefore, the objective of this project is to investigate if the trace levels of MeIQx found in the diet may cause damage to the human colon and to determine how this varies between individuals. In addition, we aim to establish if adducts of MeIQx with serum albumin and hemoglobin can be used as dosimeters of exposure and to examine the urinary metabolites of MeIQx. This project will, therefore, determine if the levels of MeIQx in the diet may pose a human cancer risk.
This is a study in collaboration with Professor Colin Garner (University of York, United Kingdom) and Mr Steve Leveson (York District Hospital, United Kingdom) in which human volunteers are administered a small amount of 14C-labeled MeIQx. Human subjects are patients at York District Hospital who are about to undergo colon surgery for cancer. The objectives and health consequences of the study are explained to the subjects and then they are asked if they are willing to participate. Participating volunteers are asked to fill in a detailed informed consent document and to complete a brief questionnaire. Pre-dose blood and urine samples are then collected for analysis. Four to six hours prior to surgery, the volunteers are administered 50 mg [14C]MeIQx in the form of a capsule, which is swallowed with water. The dose of MeIQx has been estimated to correspond to 19 days of exposure to MeIQx in the diet based upon upper estimates of human dietary exposure. The radiation dose is 3 mSv, which presents no radiological risk to the volunteer. There are no foreseen health risks associated with the chemical exposure. All urine is collected until 24-48 hours post-dosing and at the time of surgery a second blood sample is collected, together with a tissue sample. Twenty-four hours to 48 hours post-surgery, a third and final blood sample is collected.
Albumin and hemoglobin are extracted from the blood and DNA is extracted from the tissue. These samples are coded and sent to LLNL, where they are analyzed for carbon-14 content by accelerator mass spectrometry. Urine is analyzed by HPLC with scintillation counting, which is performed at York University, United Kingdom. Results from these analyses are used to indicate if MeIQx binds to DNA in the colon and whether binding to blood proteins or levels of urinary metabolites could be used as markers of exposure and/or metabolism.
Project Identifier: LLNL-98-100
Project Title:
Study to Establish if DNA Damage is caused through Ingesting Secondary Amines together with Sodium Nitrate or Nitrite and if it can be Prevented with Chemopreventive Agents
Principal Investigator:
Dr. Kenneth W. Turteltaub
Project started in: 1998
Project Funding Information:
Project received funding in Fiscal Year 1998.
Project used human subjects in Fiscal Year 1998.
Funding Sources:
Project does not involve use of multiple protocols/subprojects.
IRB Review:
Type of Review: Full Board
Most Recent Approval: January 21, 1998
IRB Approval Number: 98-100
Number of Human Subjects who participated in this project/protocol during
FY 1998 (10/1/97 - 9/30/98): 3
Type of Human Subjects Involvement:
The aim of this study is to establish if methyl-DNA and methyl-protein adducts can be detected in humans exposed to a quantity of methylurea that may occur in the diet, and to establish the urinary metabolites of methylurea in humans. Methylurea belongs to a group of compounds known as amides, which react with nitrite to form nitroso compounds (NOCs). NOCs can be found naturally in foods and beverages (Hotchkiss et al. {1989} Cancer Surv. 8: 295-321), are occasionally generated by industrial processes (Tricker et al. {1989} Cancer Surv. 8: 251-272), and are formed endogenously in the stomach as well as other sites within the body from dietary precursors (Gough et al. {1983} Food Chem. Toxicol. 21: 151-156).
Subjects admitted to York District Hospital for either gastrectomy or biopsy during endoscopy will be fully informed of the objectives and health consequences of the study and asked to participate. Volunteers will have any medical condition requiring surgical intervention, although surgical patients normally have gastric cancer. Volunteers will not have a biopsy taken unless it is required for their treatment. Patients with a previous history of psychiatric illness will not be asked to participate. Volunteers will be asked to sign a detailed informed consent document and a brief questionnaire about diet, alcohol consumption and smoking habits. Lifestyle ( i.e. diet, smoking habits, environmental exposure, etc.) have been linked with gastric carcinogenesis (Correa, 1992). The patient questionnaire will help us to establish the patient's previous exposure to cancer causing agents, and see how this relates to their response to the compounds administered. The volunteers will be allowed to withdraw from the study at any time. Up to 50 volunteers (male and female) ages 18-80, will take a gelatin capsule filled with lactose containing no more than 22 mg (16 mCi of 54 mCi/mmol) [14C]methylurea, 2 to 4 hours prior to their medical procedure (Dosing regimen 1). The daily intake of methylurea in the average diet is approximately 1 mg (Shephard and Lutz, {1989} Cancer Surv. 8: 402-421). For example, alkylating agents of the nitrosourea type are found in quantities up to 371 mg per portion of fermented milk products (yogurt, etc.), wine, and smoked fish (Groenen and Busink, {1988} Food Chem. Toxicol. 26: 215-225).
It has been proposed that stomach cancer may arise from nitrosation of nitroso compound precursors such as methylurea by nitrate and nitrite, leading to the production of N-methyl-N-nitrosourea (MNU) (Correa {1992} Cancer Research, (54) 6735-6740). We hope to gain some information on the nitrosation reaction of methylurea to MNU in humans. Thirty minutes prior to taking the 14C-methylurea capsule, some volunteers will be administered 5 mg nitrite or 300 mg nitrate in the form of a sodium salt (Dosing regimen 2). This is equivalent to the Acceptable Daily Intake of these compounds as set by the World Health Organization. The yield of MNU formed from methylurea and sodium nitrite in the rat stomach has been found to be 0.46% after 3 hours (Mirvish et al {1977} IARC Scientific Publications No.19). When administered to animals at high doses (mg/kg), MNU induced benign and malignant tumors at different sites, including the stomach.
Some volunteers will also be asked to take possible chemopreventive agents (vitamin C, E, and b-carotene (Dosing regimen 3). Those volunteers involved will take up to 1 g of vitamin C per day, as a daily dose, up to one month prior to methylurea administration and subsequent surgery. For other chemopreventive agents involved, the Recommended Daily Allowance will be used. Use of chemopreventive agents will be phased in once dosing with methylurea has shown generation of detectable adducts in the DNA of the volunteers.
At the time of capsule administration, a blood sample (no more than 30 ml) and a urine sample (mid-stream sample) will be obtained. A complete collection of urine from 0-48 hrs post-dosing will be collected. Feces will not be collected and so the levels of methylurea will not be used to generate total clearance data. During the medical procedures, a second blood sample (no more than 30 ml) will be obtained together with a tissue sample (where appropriate, normal and tumor tissue will be obtained), and gastric juice. The surgeon will determine the amount of tissue to take, for reasons unrelated to the experiment (i.e. patient care). Before having a gastrectomy, any gastric juice must be removed from the patient's stomach in order for the doctor to see properly through the endoscope. The amount of gastric juice in a fasting stomach can be as much as 50ml, but is usually under 10ml. The gastric juice is normally thrown away, but for our study, it will be saved. The pH, nitrite concentration, ascorbic acid concentration, and the Helicobacter pylori status of the patient (from histology of the biopsy, performed at the York District Hospital) will all be measured. All of these factors can influence adduct formation and gastric cancer causation. Finally, a post-surgery blood sample (no more than 30 ml) will be obtained.
Project Identifier: LLNL-98-102
Project Title:
Evaluation of Chromosome Damage to Uranium Workers in Namibia for Assessment of Health Risk.
Principal Investigator:
Dr. Joe N. Lucas
Project started in: 1998
Project Funding Information:
Project did not receive funding in Fiscal Year 1998.
Project did not use human subjects in Fiscal Year 1998.
Explanation:
Funding for this project has been approved by all parties, but not yet received.
Project does not involve use of multiple protocols/subprojects.
IRB Review:
Type of Review: Full Board
Most Recent Approval: July 15, 1998
IRB Approval Number: 98-102
Number of Human Subjects who participated in this project/protocol during
FY 1998 (10/1/97 - 9/30/98): 0
Type of Human Subjects Involvement:
The purpose of this work is to measure stable chromosomal aberrations in uranium miners at Rossing Uranium, Ltd. compared to controls. The results of this study will be compared to the findings of a study on chromosomal aberrations performed by Reinhard Zaire et al. (Rad. Res. 1996) on Rossing employees and controls.
Summary of work: This work, requested by Rossing Uranium, Ltd., Namibia (RTZ, UK), will be accomplished by measuring chromosome translocation frequencies in a small group of miners, and comparing the data with the frequencies measured in a small control group of unexposed individuals with similar lifestyles. The endpoint of our work is to test whether we see an excess of translocations in the miners compared to controls. Because the control group will be well selected for factors such as smoking, age, social class, etc., it will then be reasonable to conclude that if a statistically significant excess in translocations is observed in the miners, it is due to occupational radiation. We can then make an estimate of the average dose.
The translocation frequencies are measured in blood lymphocytes of unexposed individuals. Peripheral blood samples (~20 ml) will be drawn by sterile venipuncture from volunteer employees of Rossing Uranium, Ltd. at the medical department of the Rossing plant, cultured and spread on glass slides. A physician will be available for consultation. All volunteer donors will be informed of the purpose of the blood work and of the (minimal) risk involved. They will be asked to sign an informed consent form prior to blood drawing. The consent form will be kept on file by the principal investigator or by the medical department at Rossing. The samples will be coded, and the codes will be kept confidential so that only the chief medical personnel knows the donor identity.
Project Identifier: LLNL-98-104
Project Title:
Elucidating Dynamics of Beta-carotene Metabolism in Adults
Principal Investigator:
Dr. John S. Vogel
Project started in: 1998
Project Funding Information:
Project received funding in Fiscal Year 1998.
Project used human subjects in Fiscal Year 1998.
Funding Sources:
Total Funding: $74,271
Project does not involve use of multiple protocols/subprojects.
IRB Review:
Type of Review: Full Board
Most Recent Approval: January 20, 1998
IRB Approval Number: 98-104
Number of Human Subjects who participated in this project/protocol during
FY 1998 (10/1/97 - 9/30/98): 1
Type of Human Subjects Involvement:
For nutrition research
Beta carotene produces Vitamin A, needed for development, growth and health. Isotopic labeling was not possible in healthy humans because the radioactivity to produce a signal would produce unsatisfactory risk to volunteers. This study uses sensitive detection of 14C by accelerator mass spectrometry to trace labeled carotene metabolities in a healthy volunteer to establish the fate and distribution of a single, sub-Recommended Daily Allowance (RDA) dose of folic acid. Nutritional studies, in general, provide data for better estimation of daily requirements of specific nutrients.
Beta carotene (300 µg) is labeled with 14C (200 nCi) and is consumed in a single dose with food by a human volunteer. Blood, urine and fecal samples are collected at frequent convenient time points, starting 10 minutes after the dose to 200 days. Blood and urine samples are fractionated to give metabolite identities. 14C levels in the measured components are fit to distribution models in order to deduce the chemical carotene levels in unavailable tissues.
Human metabolism of beta carotene is unlike that of any common animal host. No tissue culture can faithfully replicate this cycle. The labeled compound is a nutrient and is supplied at a fraction of the normal daily dose, no chemical toxicity endangers the volunteer. A volunteer receives a total radiation dose of approximately 2 µSievert, equivalent to the normal exposure to cosmic radiation at mid-latitudes on the earth's surface for two days. The added risk of illness is so small that it cannot be calculated.
Volunteers are from the Davis, CA community and are provided with a description of the research and risks. They sign an approved consent form. All human contact is through the Nutrition Department at University of California - Davis. The samples measured at LLNL contain no label revealing the volunteer's identity.
Project Identifier: LLNL-98-105
Project Title:
Optical Diagnosis through Blood
Principal Investigator:
Dr. Matthew J. Everett
Project started in: 1998
Project Funding Information:
Project received funding in Fiscal Year 1998.
Project used human subjects in Fiscal Year 1998.
Funding Sources:
Project does not involve use of multiple protocols/subprojects.
IRB Review:
Type of Review: Full Board
Most Recent Approval: April 14, 1998
IRB Approval Number: 98-105
Number of Human Subjects who participated in this project/protocol during
FY 1998 (10/1/97 - 9/30/98): 2
Type of Human Subjects Involvement:
We required fresh normal blood to measure in vitro the effects of optical scattering of blood on an optical coherence tomography (OCT) imaging system. This information was necessary for determining whether imaging systems based on optical coherence tomography are feasible as an alternative/improvement to intervascular ultrasound (IVUS) systems for in vivo diagnosis of the human arterial system. To make this determination, we took fresh human blood and placed it in excised pig arteries. We then generated cross-sectional images of the pig artery by imaging through the human blood with the OCT system. We used small amounts of fresh peripheral human blood for this study. When blood was required an appointment was made by one of the volunteers to have blood drawn at LLNL Health Services. The venipunctures were performed by the LLNL Health Services Department using normal procedures and thus not incurring any unusual risks. To retain confidentiality, names were not recorded with the blood samples taken.
Project Identifier: LLNL-98-106
Project Title:
Melanoma and other Mortality Rates in LLNL Employees
Principal Investigator:
Dr. Mortimer L. Mendelsohn
Project started in: 1998
Project Funding Information:
Project received funding in Fiscal Year 1998.
Project did not use human subjects in Fiscal Year 1998.
Explanation:
Overhead funding was used to prepare data and submit application to the National Death Index. Data, however, have not yet left LLNL - hence human subjects have yet to be affected
Funding Sources:
Project does not involve use of multiple protocols/subprojects.
IRB Review:
Type of Review: Full Board
Most Recent Approval: April 14, 1998
IRB Approval Number: 98-106
Number of Human Subjects who participated in this project/protocol during
FY 1998 (10/1/97 - 9/30/98): 0
Type of Human Subjects Involvement:
This study will use the National Death Index (NDI) of the Centers of Disease Control to determine the death rate from melanoma and all other major causes of death in employees who worked at LLNL any time during the period from January 1984 to December 1996. The primary purpose is to assess the effectiveness of the Laboratory's melanoma prevention efforts; the secondary purpose is to provide an alert for any unusual mortality events that bear on health and safety at the Laboratory. The study involves assembly and analysis of approximately 8500 records of identifying information, including such things as name(s), date of birth and social security number of each employee. The NDI will identify those who have died and will assign the cause of death. The Laboratory will make no approach to families or medical records. We will carefully safeguard the identifying information and the causes of death, keeping such material under lock and key. The overall results will be made available through LLNL publications and the scientific literature, but only in the form of blanket information on death rates. Likewise, NDI has careful safeguards in place to protect the information. They themselves will not use the data, and they will destroy their files shortly after the study is completed.
Project Identifier: LLNL-98-107
Project Title:
Measurement of Historically Administered 41Ca
Principal Investigator:
Dr. Stewart Freeman
Project started in: 1998
Project Funding Information:
Project did not receive funding in Fiscal Year 1998.
Project did not use human subjects in Fiscal Year 1998.
Explanation:
Project has not received funding and no contact has been made with human subjects
Project does not involve use of multiple protocols/subprojects.
IRB Review:
Type of Review: Full Board
Most Recent Approval: July 15, 1998
IRB Approval Number: 98-107
Number of Human Subjects who participated in this project/protocol during
FY 1998 (10/1/97 - 9/30/98): 0
Type of Human Subjects Involvement:
In 1997 I discovered and made public that short-lived calcium radiotracers contain the previously unrecognized impurity 41Ca (41Ca has a 104,000 years halflife decaying with the emission of soft x-rays.) The 45Ca and 47Ca radiotracers have been and continue to be used in standard tests of human calcium kinetics, such as of the absorption of dietary calcium. As a consequence of this, an estimated 10,000 one time experimental subjects have been inadvertently administered 41Ca. The 41Ca poses a negligible health risk and may indeed prove a boon to scientists and the subjects concerned as 41Ca resorbing from bone and excreted, even many years after administration, may provide a good indicator of skeletal health. Creighton University scientists have administered 45Ca and 47Ca radiotracers over many years and have stored subject excreta samples. We propose to now analyze some of these historical samples from up to 10 subjects for the presence of 41Ca by accelerator mass spectrometry (the only technique sensitive enough). This is to characterize the signal of excreted 41Ca to investigate its utility as a marker of bone calcium loss. (We have previously measured historical 45Ca and 47Ca dosing solutions to characterize inadvertent 41Ca administration in the first place.)
There is no new subject involvement in this protocol. The original subjects will not be informed of the new protocol and their consent will not be sought. The subjects previously gave informed consent to the administration of the radioisotopes and the analysis of samples for such tracers, and this is deemed sufficient. Subject identities are know to the Creighton University collaborators and subjects shown to be excreting experimentally useful levels of 41Ca may subsequently be contacted for enrollment in further protocols, for which IRB approval and subject informed consent would be sought in due course.
The 41Ca impurities are due to the nuclear activation genesis of the radiotracers and may be estimated. We conclude that, depending on the tracer used, subject 41Ca radiological doses have been about a millionth or a billionth of that from the deliberately administered isotopes, which in turn is a thousandth of the annual ~3 mSv natural dose; the ICRP (pub 60 - 1990) whole population probability coefficient for all stochastic effects (all cancers and severe hereditary effects) is 0.073/Sv. However, should measurements indicate that a subject is receiving an anticipated lifelong radiological dose from 41Ca that is more than 1% of the dose from the deliberately administered radiotracer then I will inform LLNL IRB of this and seek guidance on continued measurement and informing the subject. In any case, there is no risk to the subjects because of this protocol.
Project Identifier: LLNL-98-109
Project Title:
Development of Improved Methods for the Detection of Individual Sensitivity to Beryllium and Identification of Immunologic and Genetic Factors
Principal Investigator:
Ms. Kathleen A. Noonan
Project started in: 1998
This project ended in Fiscal Year 1998.
Project Funding Information:
Project received funding in Fiscal Year 1998.
Project used human subjects in Fiscal Year 1998.
Funding Sources:
Project does not involve use of multiple protocols/subprojects.
IRB Review:
Type of Review: Full Board
Most Recent Approval: July 15, 1998
IRB Approval Number: 98-109
Number of Human Subjects who participated in this project/protocol during
FY 1998 (10/1/97 - 9/30/98): 16
Type of Human Subjects Involvement:
A. Objective:
This is a research study conducted by Kathleen Noonan, R.N., LLNL, Babetta L. Marrone, Ph.D, and Hugh Smith, M.D. from LANL. The LANL researchers will use the blood sample to develop improved methods and reagents for performing pre-screening and medical surveillance on beryllium worker groups and to understand the factors that contribute to individual sensitivity to beryllium. Information about the baseline percentages of selected white blood cells will be obtained. The LANL researchers will use this information to analyze if there are a certain proportion of types of white blood cells that are predictive of beryllium disease.
B. Methodology:
The participant will agree to give one sample (4 teaspoons) of blood. The blood sample will be sent to LANL for developing improved methods and reagents for performing pre-screening and medical surveillance on beryllium worker groups and to understand the factors that contribute to individual sensitivity to beryllium. The purpose of performing these procedures is to obtain blood for biomedical, and genetic tests outside the human body. Specifically the blood will be used to develop improved methods and reagents for beryllium and to characterize the content of the blood for differences in gene structure and immunological factors to help in the understanding of individual differences in beryllium sensitivity.
C. None
D. Involvement of Human Subjects:
1) The employee will give one sample of 20 mls (4 teaspoons) of blood. The blood sample will be sent to Los Alamos National Laboratory for: (1) development of improved methods and reagents for performing pre-screening and medical surveillance on beryllium worker groups and (2) understanding the factors that contribute to individual sensitivity (immunological and genetic)to beryllium.
The purpose of performing these procedures is to obtain blood for biomedical, and genetic tests outside the human body. Specifically the blood will be used to: 1) develop improved methods and reagents for beryllium, and 2) characterize the content of the blood for differences in gene structure and immunological factors to help in understanding individual differences in beryllium sensitivity.
Inherited traits, in addition to environmental factors such as exposure to beryllium, may play an important part in the development of sensitivity to beryllium and Chronic Beryllium Disease (CBD). A portion of the blood sample will be used to study the inheritance factors (chromosomes and genes) contributing to beryllium sensitivity, specifically to characterize the contents of the blood cells gene structure and differences in gene structure. It is currently not known whether sensitivity to beryllium prevails in a particular population or ethnic group. The results of the genetic study will be analyzed in reference to the results of the beryllium sensitivity tests and in reference to my ancestry. The researchers will use this information to test whether there is a genetic factor that contributes to beryllium sensitivity and to learn whether individuals of specific ethnic extraction are more or less susceptible to beryllium sensitivity.
2) Blood drawing can involve risks. Possible risks and discomforts that may result from obtaining the blood sample are considered unlikely but include: temporary pain, bruising and/or soreness of the affected tissue or surrounding tissue, formation of scar tissue, infection and/or fainting.
3) Any publication arising from this study will be made without specific reference to any participants name. Lawrence Livermore National Laboratory, Health Services Department will encode the blood sample to protect the participant's identity and will not disclose any name to the individuals performing the research, or to anyone else.
Project Identifier: LLNL-98-111
Project Title:
Chromosome Aberration Persistence Study
Principal Investigator:
Dr. James D. Tucker
Project started in: 1998
Project Funding Information:
Project did not receive funding in Fiscal Year 1998.
Project did not use human subjects in Fiscal Year 1998.
Explanation:
Funding is being pursued via an NIH R01 grant application.
Project does not involve use of multiple protocols/subprojects.
IRB Review:
Type of Review: Full Board
Most Recent Approval: May 20, 1998
IRB Approval Number: 98-111
Number of Human Subjects who participated in this project/protocol during
FY 1998 (10/1/97 - 9/30/98): 0
Type of Human Subjects Involvement:
A. Objectives. To determine whether chromosome translocations in human cells exposed to low levels of ionizing radiation decline with time.
B. Methodology. Phlebotomy of normal, healthy subjects, followed by in vitro exposure to ionizing radiation and analysis of structural chromosome aberrations.
C. Radiation or chemical exposures. None.
D. Involvement of human subjects. Phlebotomy, followed by cell culture. Cells are grown under commonly-used conditions to promote growth for subsequent analysis by molecular cytogenetic methods. Risks to the subjects are those associated with routine phlebotomy. All samples are processed encoded, and identifying information is kept in a locked file cabinet in the Principal Investigator's office; no identifier is published. All subjects provide fully informed consent.
Project Identifier: LLNL-98-112
Project Title:
Perchloroethylene Exposure Study
Principal Investigator:
Dr. James D. Tucker
Project started in: 1998
Project Funding Information:
Project received funding in Fiscal Year 1998.
Project used human subjects in Fiscal Year 1998.
Funding Sources:
Project does not involve use of multiple protocols/subprojects.
IRB Review:
Type of Review: Full Board
Most Recent Approval: May 20, 1998
IRB Approval Number: 98-112
Number of Human Subjects who participated in this project/protocol during
FY 1998 (10/1/97 - 9/30/98): 20
Type of Human Subjects Involvement:
A. Objectives. To determine whether humans exposed to perchloroethylene (PCE) in an occupational setting experience adverse health effects.
B. Methodology. Phlebotomy of normal, healthy subjects, followed by cell culture and analysis of structural chromosome aberrations.
C. Radiation or chemical exposures. None.
D. Involvement of human subjects. Phlebotomy, followed by cell culture. Cells are grown under commonly-used conditions to promote growth for subsequent analysis by molecular cytogenetic methods. Risks to the subjects are those associated with routine phlebotomy. All samples are processed encoded, and identifying information is kept in a locked file cabinet in the Principal Investigator's office; no identifier is published. All subjects provide fully informed consent.
Project Identifier: LLNL-98-116
Project Title:
Thermospectrometry for Body Temperature Measurement
Principal Investigator:
Dr. James E. Trebes
Project started in: 1998
Project Funding Information:
Project received funding in Fiscal Year 1998.
Project used human subjects in Fiscal Year 1998.
Funding Sources:
Project was undertaken using borrowed equipment and conducted by a summer student
Project does not involve use of multiple protocols/subprojects.
IRB Review:
Type of Review: Full Board
Most Recent Approval: July 15, 1998
IRB Approval Number: 98-116
Number of Human Subjects who participated in this project/protocol during
FY 1998 (10/1/97 - 9/30/98): 20
Type of Human Subjects Involvement:
In situations where large numbers of people are being moved rapidly, such as military troop movements or emergency evacuations, there is a need for a non-contact, remote, passive system to determine deviations in the human body temperature from normal as an indicator of the presence of infectious disease. The thermal camera can be used to passively and remotely determine the surface temperature of exposed areas of the body. If this surface temperature can be correlated with internal body temperatures, then thermal spectrometry will be a potential candidate as a tool for assessing the presence of diseases that result in fevers.
Specifically, we will look at the correlation between the surface temperature near the carotid artery and in and around the eyes. These areas have sufficient blood flow near the surface to be potential indicators of core body temperature. Human subjects will have thermal images produced using a passive commercial thermal camera. The images will be analyzed for the temperatures at the location of the eyes and the carotid artery. These temperatures will be compared to the body temperature obtained from a disposable oral thermometer. There is no risk to the human subject. The subject will be informed of the temperature measurement procedure, that all data will be stored and analyzed by a confidential subject number, and that all images obtained will be confidential. The subject will be informed that they can stop the procedure at any time.
If a correlation between body temperature and temperature inferred from thermal images is found to exist, then further studies can be designed and executed to investigate the effects of fatigue, emotional and physical state, and the effect of normal medication, drug and alcohol use, and ambient background temperature conditions. This experiment is a first proof-of-concept to evaluate if there is any feasibility at all for the technique.
Project Identifier: LLNL-98-120
Project Title:
Measurement of Previously Administered 41Ca
Principal Investigator:
Dr. Stewart Freeman
Project started in: 1998
Project Funding Information:
Project did not receive funding in Fiscal Year 1998.
Project did not use human subjects in Fiscal Year 1998.
Explanation:
Funding has not yet been received for this protocol.
Funding Sources:
Funding has not yet been received for this project
Project does not involve use of multiple protocols/subprojects.
IRB Review:
Type of Review: Full Board
Most Recent Approval: July 15, 1998
IRB Approval Number: 98-120
Number of Human Subjects who participated in this project/protocol during
FY 1998 (10/1/97 - 9/30/98): 0
Type of Human Subjects Involvement:
In 1997 I discovered and made public that short-lived calcium radiotracers contain the previously unrecognized impurity 41Ca (41Ca has a 104,000 years half-life decaying with the emission of soft x-rays.) The 45Ca and 47Ca radiotracers have been and continue to be used in standard tests of human calcium kinetics, such as of the absorption of dietary calcium. As a consequence of this, an estimated 10,000 one time experimental subjects have been inadvertently administered 41Ca. The 41Ca poses a negligible health risk and may indeed prove a boon to scientists and the subjects concerned as 41Ca resorbing from bone and excreted, even many years after administration, may provide a good indicator of skeletal health. University of Texas Southwestern Medical Center scientists have administered 45Ca and 47Ca radiotracers over many years. We propose to use accelerator mass spectrometry (the only technique sensitive enough) to measure contemporary levels of 41Ca excreted by up to 10 historically dosed subjects. This is to characterize the signal of excreted 41Ca to investigate its utility as a marker of bone calcium loss. If available, we will also measure archived historical samples from the original dosing experiments.
The 41Ca impurities are due to the nuclear activation genesis of the radiotracers and may be estimated. We conclude that, depending on the tracer used, subject 41Ca radiological doses have been about a millionth or a billionth of that from the deliberately administered isotopes, which in turn is a thousandth of the annual ~3 mSv natural dose; the ICRP (pub 60 - 1990) whole population probability coefficient for all stochastic effects (all cancers and severe hereditary effects) is 0.073/Sv. However, should measurements indicate that a subject is receiving an anticipated lifelong radiological dose from 41Ca that is more than 1% of the dose from the deliberately administered radiotracer then I will inform the LLNL IRB of this and seek guidance on continued measurement and informing the subject. In any case, there is no risk to the subjects because of this protocol.
Dr Howard Heller will recruit up to 10 historically 41Ca dosed subjects based on estimations of historical dose, the presence of archived historical samples and subject availability. As may be agreed to, the subjects will provide occasional urine samples for up to a year. These and any archived samples will be forwarded to LLNL for analysis.
Project Identifier: LLNL-98-121
Project Title:
Optical Diagnosis of Skin Abnormalities
Principal Investigator:
Dr. Ujwal S. Sathyam
Project started in: 1998
Project Funding Information:
Project received funding in Fiscal Year 1998.
Project did not use human subjects in Fiscal Year 1998.
Explanation:
This is a new project that just received IRB approval. Human subjects are expected to be used in fiscal year 1999
Funding Sources:
Project does not involve use of multiple protocols/subprojects.
IRB Review:
Type of Review: Full Board
Most Recent Approval: August 13, 1998
IRB Approval Number: 98-121
Number of Human Subjects who participated in this project/protocol during
FY 1998 (10/1/97 - 9/30/98): 0
Type of Human Subjects Involvement:
The ultimate goal of this project is to develop a high resolution imagining system based on Optical Coherence Tomography to be used in screening for skin cancers and other skin abnormalities. The data resulting from this study will be to locate small structural abnormalities in the skin that are currently not resolvable by existing techniques. Applications of this device include diagnosis of basal and squamous cell carcinomas and the differentiation between benign and malignant abnormalities. Skin cancer is the biggest cancer nationwide. The development of a screening tool will aid in an early diagnosis and defray treatment costs.
Subject involvement in this study will be to provide skin tissue samples following surgery at UC Davis Medical Center. Subjects will be drawn from a pool of patients who have already elected to undergo surgery for various types of skin disorders. The surgery involves removal of some skin tissue, not for the specific purpose of this study. The surgical margins will remain the same and are not influenced by this research. There is no additional risk to the subject other than those associated with a surgical procedure arising specifically from this project.
The removed tissue will be transported to LLNL for high resolution optical imaging. There is no further involvement of the human subjects. Surgeries are performed twice a week at the UC Davis Medical Center. Approximately 10 human subjects will be involved in the coming year.
Research records will be handled so that confidentiality is maintained. All records associating any subject with particular skin samples will be coded and kept in locked files.
Project Identifier: LLNL-98-122
Project Title:
Design of a Knee Immobilizer
Principal Investigator:
Dr. William W. Colston
Project started in: 1998
Project Funding Information:
Project received funding in Fiscal Year 1998.
Project used human subjects in Fiscal Year 1998.
Funding Sources:
Project does not involve use of multiple protocols/subprojects.
IRB Review:
Type of Review: Full Board
Most Recent Approval: August 13, 1998
IRB Approval Number: 98-122
Number of Human Subjects who participated in this project/protocol during
FY 1998 (10/1/97 - 9/30/98): 1
Type of Human Subjects Involvement:
The goal of this project is to develop self-contained, wireless orthopedic devices that incorporate transcutaneous electrical nervous stimulation (TENS) for the temporary relief of acute pain. In so doing, plastic parts must be produced that conform to the shape of human joints and limbs. Since these shapes are often very complex, it is impractical and economically unfeasible to produce prototype parts through conventional machining and molding. Plaster casts will therefore be made of the limbs of a human subject. The casts will be used to create rubber molds around which plastic parts could be formed. The use of humans subjects is limited to the production of casts.
The procedure follows: The limb or joint is comfortably supported in the correct position while the casting procedure takes place. The procedure takes approximately one hour. A release film such as Saran Wrap or Vasoline is placed on the limb/joint prior to casting. Gypsona Brand plaster bandages are wetted with water and placed onto the limb/joint. Several layers are applied to ensure structural integrity of the cast. Once the cast has hardened, it is removed from the subject. The cast is then filled with a casting silicone rubber, Sylastic "J". When this is cured and removed from the cast, we will have a silicone rubber model of the limb/joint. This rubber model is then used as the forming tool in a vacuum thermforming process. With this process or similar processes, a sheet of plastic material is formed around the tooling. The sheet is then trimmed and cut to make the final part. No confidential information is collected or distributed, and risks are very minimal.
Project Identifier: LLNL-98-123
Project Title:
Optically Parallel Ultrasound System
Principal Investigator:
Mr. Jeffrey S. Kallman
Project started in: 1998
Project Funding Information:
Project did not receive funding in Fiscal Year 1998.
Project did not use human subjects in Fiscal Year 1998.
Explanation:
PI needs IRB approval prior to receiving grant funding
Funding Sources:
Project does not involve use of multiple protocols/subprojects.
IRB Review:
Type of Review: Full Board
Most Recent Approval: September 16, 1998
IRB Approval Number: 98-123
Number of Human Subjects who participated in this project/protocol during
FY 1998 (10/1/97 - 9/30/98): 0
Type of Human Subjects Involvement:
The objective of this experiment is to determine the usefulness of a new ultrasound sensor for diffraction tomographic mammography (breast imaging).
In this experiment the human subject will lay on a table, inserting one breast at a time into a receptacle filled with an ultrasound couplant (probably oil). The breast will be insonified by an ultrasound source, and the transmitted ultrasound will be sensed and recorded by our new sensor.
We will use no ionizing radiation or radioactive substances. The only chemical substances to which the subjects will be exposed will be either medical ultrasound couplants or vegetable oils. The only potential risk will be allergic reaction to the coupling medium. Ultrasound levels will be kept under the limits imposed by the FDA. It is anticipated that the scans will take less than 10 minutes per side.
The data will be encoded to protect the subject's identity, and their name will not be disclosed to the individuals who are not involved in performing the research. The record of names/numbers will be maintained in a locked file by the investigators, should they be required for future use.
Project Identifier: LLNL-98-97-116
Project Title:
LLNL/AHS Study of Home-Cooked Foods
Principal Investigator:
Dr. David Layton
Project started in: 1998
Project Funding Information:
Project received funding in Fiscal Year 1998.
Project used human subjects in Fiscal Year 1998.
Funding Sources:
Total amount refers to total budget for human subjects study. Amount associated with use of human subjects mostly for collaborator costs to enroll subjects in study.
Project does not involve use of multiple protocols/subprojects.
IRB Review:
Type of Review: Full Board
Most Recent Approval: December 03, 1997
IRB Approval Number: 97-116
Number of Human Subjects who participated in this project/protocol during
FY 1998 (10/1/97 - 9/30/98): 104
Type of Human Subjects Involvement:
The objective of the study is to assess the intake of heterocyclic amines (HAs, carcinogenic by-products formed during the cooking of meat) in the U.S. diet. Acquiring data on the level of HAs in food prepared in the homes of human subjects will provide a better estimate of these carcinogenic by-products in the U.S. diet.
Human subjects in Iowa will provide samples of cooked meat prepared in their residences for analysis of HA content at LLNL. Anonymous (to LLNL) individuals will be asked by random telephone survey what their preferences are for the cooking method and level of doneness for beef steak and hamburger. Those indicating a preference for medium, well-done and very well done pan-fried steak and hamburger will be asked to provide samples of these meats from meals cooked in their residence. Enrolled subjects will be sent sampling kits, instructions, and a questionnaire. The instructions will inform the subject that he/she should prepare the meat as they indicated in the telephone survey, photograph the meat before during and after it is cooked with a disposable camera, complete the questionnaire and place the sample and sampling kit materials in the freezer. The questionnaire will ask how the meat was acquired, how it was prepared before cooking, how and to what degree of done-ness it was cooked and whether or not the subject cooked the meat. Staff members will go to the subject's residence, acquire the sample and provide the reimbursement.
Human subjects personal information is being held confidentially by the University of Iowa collaborator as part of a larger NCI study and will not be divulged to LLNL or any other investigators. No consent form was required for this use of human subjects on the basis that providing the subjects with a verbal and written statement of the research and allowing subjects to decide whether or not to participate in the study constitutes implied consent from the human subjects.
The subjects are not required to perform any procedures other than normal food preparation activities and will incur no additional risk from their involvement in the study.