Datasets:

pat-jj

/

ClinicalTrialSummary

like 0

Bacterial vaginosis is a syndrome manifested by adverse alterations in vaginal microbial flora. It is present in 10 to 25% of women in the general population, and is the most common vaginal infection. It has been associated with a number of adverse sequelae in reproductive health including acquisition of HIV, pelvic inflammatory disease, cervical dysplasia, and complications of gynecological procedures. During pregnancy it has been associated with an increased risk of preterm birth and postpartum maternal infection. However, the vaginal microbial flora remains poorly understood. Information on variation in microbial flora and its association with BV from a longitudinal study is unavailable. This prospective observational study aims to advance our knowledge of the natural history and abnormal alteration in vaginal microbial flora, and to identify risk factors that are associated with these changes. A total of 5500 healthy, non-pregnant women of reproductive age will be enrolled and followed up in Birmingham, Alabama, for one year (baseline visit plus once every three months afterwards, totaling 5 visits). Detailed information on sociodemographic status, medical history, hygiene practice, sexual behavior and psychosocial stress will be collected through in-person interviews. Routine gynecological and dental examinations will be carried out during the study visits. Samples of vaginal secretion and blood will be collected. Laboratory tests to quantify vaginal microbial flora and to identify infection of bacterial vaginosis as well as common sexually transmitted diseases will be conducted. This project is expected to complete in 5 years.

Bacterial vaginosis is a syndrome manifested by adverse alterations in vaginal microbial flora. It is present in 10 to 25% of women in the general population, and is the most common vaginal infection. It has been associated with a number of adverse sequelae in reproductive health including acquisition of HIV, pelvic inflammatory disease, cervical dysplasia, and complications of gynecological procedures. During pregnancy it has been associated with an increased risk of preterm birth an postpartum maternal infection. However, the vaginal microbial flora remains poorly understood. Information on variation in microbial flora and its association with BV from a longitudinal study is unavailable. This prospective observational study aims to advance our knowledge of the natural history and abnormal alteration in vaginal microbial flora, and to identify risk factors that are associated with these changes. A total of 5500 healthy, non-pregnant women of reproductive age will be enrolled and followed up in Birmingham, Alabama, for one year (baseline visit plus once every three months afterwards, totaling 5 visits). Detailed information on sociodemographic status, medical history, hygiene practice, sexual behavior and psychosocial stress will be collected through in-person interviews. Routine gynecological and dental examinations will be carried out during the study visits. Samples of vaginal secretion and blood will be collected. Laboratory tests to quantify vaginal microbial flora and to identify infection of bacterial vaginosis as well as common sexually transmitted diseases will be conducted. This project is expected to complete in 5 years.

Teens are at high risk for traffic violations and motor vehicle crashes because of their young age, lack of driving experience, and exposure to high-risk driving conditions. Crash risk is greatest during the first two years of driving, and especially elevated during the first months of driving. Increasing parent involvement is becoming an important target of young driver education; however, little attention has been devoted to parental management of teen driving after teen licensure. Increased parental management of teen driving could reduce the risk of serious injury during the first months of driving and establish clear expectations for their teens' safe driving thereafter. In two randomized trials, the Checkpoints Program has been demonstrated to increase parental restrictions on teen driving through at least four months post-licensure. In this proposed research, we will evaluate the efficacy of the Checkpoints Program as applied to driver education. The purpose of this study is to assess the extent to which exposure to the Checkpoints Program during driver education classes in Michigan results in increased restrictions on young drivers during the first year of provisional licensure. The design is a randomized trial in which 24-30 commercial driver education classes will be randomly assigned to be either standard driver education or driver education that integrates the Checkpoints Program, Approximately 400 teens enrolled in driver education and one of their parents will be recruited and will complete written surveys at baseline and telephone surveys one month after teens obtained provisional licenses. Teens will complete additional telephone surveys one, three, six, and 12 months after provisional licensure. Study outcomes include parent management practices of teen driving, teen driving experience including the amount and conditions of driving during the first 12 months of licensure, and teen risky driving behaviors.

Teens are at high risk for traffic violations and car crashes because of their young age, lack of driving experience, and exposure to high-risk driving conditions. The Checkpoints Program has used increased parental restrictions on teen driving through at least the first 4 months after their children obtain a driver's permit.~The purpose of this study is to evaluate the efficacy of the Checkpoints Program.~Approximately 400 teens in Michigan will participate in one of two study groups. One group will take standard driver education classes; the other group will take driver education classes that incorporate the Checkpoints Program. Teens and their parents will complete a written survey after completing the classes and a telephone survey after teens obtain a driver's permit. Teens will complete additional telephone surveys 1, 3, 6, and 12 months after obtaining a driver's permit. Researchers will use this information to study how parents manage teen driving practices, teen driving experiences (amount and conditions of), and high-risk teen driving behaviors.

Adults treated with X-rays in childhood for benign conditions such as enlarged tonsils and adenoids have an increased risk of developing nervous system tumors. The risk is highest for schwannomas (RR of 33.1, 95% CI of 9.4-116.5), intermediate for meningiomas (RR of 9.5, 95% CI of 3.5-25.7) and lowest for gliomas (RR of 2.6, 95% CI of 0.8-8.6).~Studies of sporadic tumors of these types have demonstrated the presence of somatic mutations in the NF2 gene. Because these mutations are not usually seen in other types of tumors, they are believed to be what caused the sporadic neural tumors to develop. Germline mutations in the same gene are responsible for the autosomal dominant disorder known as neurofibromatosis 2 (NF2) which is characterized by the development of similar types of neural tumors.~The purpose of the proposed study is to determine if neural tumors that developed in people who were treated with X-rays in childhood also have somatic NF2 mutations. This will be done using DNA from paraffin-embedded neural tumors that developed in ~ 112 individuals treated with X-rays in childhood for benign head and neck conditions. These individuals are from a cohort of over 4,000 irradiated persons followed by Michael Reese Hospital in Chicago since 1974. If we find NF2 mutations in the radiation-related tumors, we will determine whether they are somatic or germline by looking for NF2 mutations in DNA from buccal cells of the patients with the studied tumors. We expect that most patients will have NF2 mutations only in tumor DNA. However, there is a remote possibility that one or more patients may have a germline NF2 mutation and thus an increased risk of developing neural tumors even in the absence of X-ray treatment. We will then compare the types and frequencies of the somatic NF2 mutations with those found in sporadic neural tumors. If we do not find somatic NF2 mutations in the radiation-related tumors, we will conclude that X-rays caused neural tumors to develop through interactions with another gene or genes. Either result will contribute to our knowledge of radiation tumorigenesis.~We will send letters describing this study to patients from the Michael Reese Hospital cohort who have developed radiation-related neural tumors. Those who consent to take part in it will be asked for permission to obtain paraffin blocks from any neural tumor that they have had removed and to donate buccal cells for NF2 mutation studies. Finally, they will also be asked to complete a questionnaire that will help us update their medical history and obtain a medical history on close blood relatives.

Adults treated with X-rays in childhood for benign conditions such as enlarged tonsils and adenoids have an increased risk of developing nervous system tumors. The risk is highest for schwannomas (RR of 33.1, 95% CI of 9.4-116.5), intermediate for meningiomas (RR of 9.5, 95% CI of 3.5-25.7) and lowest for gliomas (RR of 2.6, 95% CI of 0.8-8.6).~Studies of sporadic tumors of these types have demonstrated the presence of somatic mutations in the NF2 gene. Because these mutations are not usually seen in other types of tumors, they are believed to be what caused the sporadic neural tumors to develop. Germline mutations in the same gene are responsible for the autosomal dominant disorder known as neurofibromatosis 2 (NF2) which is characterized by the development of similar types of neural tumors.~The purpose of the proposed study is to determine if neural tumors that developed in people who were treated with X-rays in childhood also have somatic NF2 mutations. This will be done using DNA from paraffin-embedded neural tumors that developed in ~ 112 individuals treated with X-rays in childhood for benign head and neck conditions. These individuals are from a cohort of over 4,000 irradiated persons followed by Michael Reese Hospital in Chicago since 1974. If we find NF2 mutations in the radiation-related tumors, we will determine whether they are somatic or germline by looking for NF2 mutations in DNA from buccal cells of the patients with the studied tumors. We expect that most patients will have NF2 mutations only in tumor DNA. However, there is a remote possibility that one or more patients may have a germline NF2 mutation and thus an increased risk of developing neural tumors even in the absence of X-ray treatment. We will then compare the types and frequencies of the somatic NF2 mutations with those found in sporadic neural tumors. If we do not find somatic NF2 mutations in the radiation-related tumors, we will conclude that X-rays caused neural tumors to develop through interactions with another gene or genes. Either result will contribute to our knowledge of radiation tumorigenesis.~We will send letters describing this study to patients from the Michael Reese Hospital cohort who have developed radiation-related neural tumors. Those who consent to take part in it will be asked for permission to obtain paraffin blocks from any neural tumor that they have had removed and to donate buccal cells for NF2 mutation studies. Finally, they will also be asked to complete a questionnaire that will help us update their medical history and obtain a medical history on close blood relatives.

At fertilization, the binding of sperm to the zona pellucida induces the acrosome reaction releasing lytic enzymes that facilitate the passage of the sperm through the zona. The sperm then fuses with the egg s plasma membrane and enters the egg s cytoplasm. The zona pellucida, an extracellular matrix composed of three or four glycoproteins, mediates the species-specific binding of sperm to egg. Although homologous proteins are present in mouse and humans, human sperm will not bind to the mouse zona pellucida and when the zona pellucida is experimentally removed, human sperm will not bind or fuse to the mouse egg's plasma membrane. We have established transgenic mouse lines that express one or more human or rat zona proteins. We wish to determine if human sperm will bind to these chimeric zonae and if this binding will induce the human sperm acrosome reaction. Sperm and devitalized eggs will be collected by collaborating institution(s) under protocols and consent forms approved by that institution's IRB. Alternatively, anonymous fertile human sperm will be obtained from a commercial sperm bank using a donor consent agreement. Only procedures already being performed on subjects for diagnostic or treatment purposes will be used.

At fertilization, the binding of sperm to the zona pellucida induces the acrosome reaction releasing lytic enzymes that facilitate the passage of the sperm through the zona. The sperm then fuses with the egg's plasm membrane and enters the egg's cytoplasm. The zona pellucida, an extracellular matrix composed of three glycoproteins (ZP1, ZP2, ZP3), mediates the species-specific binding of sperm to egg. Although homologous proteins are present in mouse and humans, human sperm will not bind to the mouse zona pellucida and when the zona pellucida is experimentally removed, human sperm will not bind or fuse to the mouse egg's plasm membrane. We have created transgenic mouse lines that express one or more human zona proteins. We wish to determine if human sperm will bind to these chimeric zonae and if this binding will induce the human sperm acrosome reaction. Sperm and devitalized eggs will be collected by collaborating institution(s) under protocols and consent forms approved by that institution's IRB. Only procedures already being performed on subjects for diagnostic or treatment purposes will be used.

In a collaborative effort with the IBN AL-NAFEES Hospital (Damascus, Syrian Arab Republic), individuals from multiplex families determined to have hereditary oral clefts will be studied. Healthy Syrian individuals with no family history of oral clefts will also be enrolled as a comparison group. The purpose of this study is to identify the gene(s) involved in heritable oral clefts by linkage analysis and gene mapping strategies. Characterization of genes involved in inherited oral clefts could provide important insight into the inheritance and pathogenesis of this disease. All families are enrolled into the study by our Syrian collaborators (under Ethics Board approval from the IBN AL-NAFEES Hospital) and only coded phenotype data and coded biospecimens are ever received at the NIH.

In a collaborative effort with the IBN AL-NAFEES Hospital (Damascus, Syrian Arab Republic), individuals from multiplex families determined to have hereditary oral clefts will be studied. The purpose of this study is to identify the gene(s) involved in heritable oral clefts by linkage analysis and gene mapping strategies. Characterization of genes involved in inherited oral clefts could provide important insight into the inheritance and pathogenesis of this disease.

America's greatest resource is its youth, but that resource is increasingly threatened by violence. Recommendations for violence prevention have highlighted the need to focus on youth and to explore targeted interventions. Nowhere is the need greater than in our nation's capital where the intentional injury fatality rate for youth age 14-19 is higher than any of the 50 states. This study builds on the CDC-supported project Adolescent Violence: A Community-Based Strategy which instituted citywide surveillance on injuries, conducted by researchers at the Children's National Medical Center. In this study, the same researchers will extend that work by testing an individualized intervention to reduce violent behavior among a sample of assault-injured youth, age 9-15, who present at the Emergency Department (ED). 196 youths and their families will be included in this randomized trial, with 98 families assigned to the individualized intervention condition and 98 families assigned to the control condition. Families will be followed for 18 months. To address issues of attrition over the 18 months that the study follows, approximately twice as many families, or 400 families, will be recruited to participate in the study.

America's greatest resource is its youth, but that resource is increasingly threatened by violence. Recommendations for violence prevention have highlighted the need to focus on youth and to explore targeted interventions Nowhere is the need greater than in our nation's capital where the intentional injury fatality rate for youth age 14-19 is higher than any of the 50 states. This study builds on the CDC-supported project Adolescent Violence: A Community-Based Strategy which instituted citywide surveillance on injuries, conducted by researchers at the Children's National Medical Center. In this study, the same researchers will extend that work by testing an individualized intervention to reduce violent behavior among a sample of assault-injured youth, age 9-15, who present at the Emergency department (ED). 196 youths and their families will be included in this randomized trial, with 98 families assigned to the individualized intervention condition and 98 families assigned to the control condition. Families will be followed for 18 months. To address issues of attrition over the 18 months that the study follows, approximately twice as many families, or 400 families, will be recruited to participate in the study.

This evaluation of the reproducibility of serum sex steroid measurements has two components. The first is the evaluation of reproducibility of laboratory measurements of steroid sex hormones in men. This is an ancillary study to serve as a quality control (QC) measure for the ongoing DCEG Prostate Tissue Study (ORSH#: OH99-C-N025; principal investigator: Dr. Ann Hsing) so that high-quality assays can be chosen to quantify steroids in tissue. Pending satisfactory performance in serum, we will then evaluate the reproducibility of tissue hormone measurements by Gas Chromatography-Mass Spectrometry (GC-MS) or by Liquid Chromatography - Mass Spectrometry-(GC-MS) or by Liquid Chromatography- Mass Spectrometry- Mass Spectrometry (LC-MS-MS) before incorporating them into the Prostate Tissue Study. The second component of this study involves evaluation of the reproducibility of sex steroid hormone measurements in pre- and postmenopausal women. This component, although not part of the Prostate Tissue Study, is included in this summary because the laboratory, assay methods, and blood collection procedures used in the female component are identical to those in the male component and these two components will run in parallel.~The present study will evaluate the reproducibility of serum sex steroid assays using two different assay methods in different laboratories. Specifically, the study will investigate assay reproducibility at Dr. Fernand Labrie's laboratory using GC-MS and LC-MSMS and at Dr. Frank Stanczyk's laboratory using radioimmunoassay (RIA). We propose to collect overnight fasting blood from 60 healthy subjects (20 men aged 50-65, 20 premonopausal women, and 20 postmenopausal women). Once collected, the blood will be separated and aliquotted into multiple vials. Serum from each subject will be sent to Dr. Labrie, who will perform CG-MS or LC-MSMS assays, and to Dr. Stanczyk, who will perform RIA, at four different time intervals. Subject recruitment and blood collection will be performed by Westat. BBI Biotech will ship and store the specimens after they have been collected.

The purpose of this study is to evaluate the reproducibility of measurements of sex hormone levels in serum samples. Researchers will collect blood from 60 healthy adults, including 20 men, 20 premenopausal women, and 20 postmenopausal women. Blood samples will be collected after study participants have fasted overnight.

The CCCH tandem zinc finger proteins are members of a small family of proteins that regulate the stability of certain types of mRNA containing so-called class II AU-rich elements in their 3'-untranslated regions. The best studied member of this protein family, tristetraprolin (TTP), exerts this destabilizing effect on at least two mRNAs coding for physiologically and medically important cytokines, tumor necrosis factor alpha and granulocyte macrophage colony stimulating factor. The physiological functions of the other two members of this protein family in mammals, 11B and 11D, are not known, but in experimental transfection studies they too can destabilize mRNAs containing this type of AU-rich element.~As part of the Environmental Genome Project, we resequenced the protein coding portions of the human genes encoding these three proteins, and uncovered a dinucleotide splice site mutation in the 11B gene in one of 144 alleles sequenced. We showed that this mutation created a novel restriction fragment length polymorphism, and that this mutation resulted in the failure of splicing and expression of the mRNA encoded by the mutant allele. Based on our previous data with mice completely deficient in TTP, we anticipate that complete deficiency of this protein, and possibly its partial deficiency, would result in human disease.~The mutant allele was from an anonymous adult Aka Pygmy women from the Central African Republic. We propose to genotype up to 1000 members of this ethnic group after obtaining buccal cell DNA from them. This will give us an approximate idea of the prevalence of this mutation in this population. If the mutation is found in a significant number of living individuals in this initial screen, then we will propose a later study of the individuals who have this genotype and their families. This second study, which will be reviewed separately, will attempt to correlate this genotype with a human trait or phenotype and possible treatable human disease.

The CCCH tandem zinc finger proteins are members of a small family of proteins that regulate the stability of certain types of mRNA containing so-called class II AU-rich elements in their 3'-untranslated regions. The best studied member of this protein family, tristetraprolin (TTP), exerts this destabilizing effect on at least two mRNAs coding for physiologically and medically important cytokines, tumor necrosis factor alpha and granulocyte macrophage colony stimulating factor. The physiological functions of the other two members of this protein family in mammals, 11B and 11D, are not known, but in experimental transfection studies they too can destabilize mRNAs containing this type of AU-rich element.~As part of the Environmental Genome Project, we resequenced the protein coding portions of the human genes encoding these three proteins, and uncovered a dinucleotide splice site mutation in the 11B gene in one of 144 alleles sequenced. We showed that this mutation created a novel restriction fragment length polymorphism, and that this mutation resulted in the failure of splicing and expression of the mRNA encoded by the mutant allele. Based on our previous data with mice completely deficient in TTP, we anticipate that complete deficiency of this protein, and possibly its partial deficiency, would result in human disease.~The mutant allele was from an anonymous adult Aka Pygmy women from the Central African Republic. We propose to genotype up to 1000 members of this ethnic group after obtaining buccal cell DNA from them. This will give us an approximate idea of the prevalence of this mutation in this population. If the mutation is found in a significant number of living individuals in this initial screen, then we will propose a later study of the individuals who have this genotype and their families. This second study, which will be reviewed separately, will attempt to correlate this genotype with a human trait or phenotype and possible y treatable human disease.

The Norway Mother and Child study is a collaborative venture among health researchers in Norway funded by the Norwegian government. The study is being coordinated by the National Institute of Public Health (aka Folkehelsa) in Oslo and the Medical Birth Registry (MBR) in Bergen. NIEHS has the unique opportunity to participate through the collection of additional tubes of blood during the blood sample collection; these two tubes of blood and a urine sample will allow NIEHS and collaborators to explore environmental determinants for disease among women and their children. These additional samples will remain in the Biobank in Oslo, Norway, with other samples from cohort members and will be used under collaboration with Norwegian investigators.~To achieve better health for mothers and children in the future, the Norway Mother and Child study is designed to test specific hypotheses about the causes of a number of serious diseases by recruiting 110,000 pregnant women to a cohort study. As part of the primary aim of the study, women will be asked to provide a blood sample at 17 weeks gestation, at birth, and 4 days after birth. The NIEHS samples will be collected at the blood draw at 17 weeks gestation. Likely causal factors will be linked to information obtained from questionnaires, blood samples, and medical registers.~The Norway Mother and Child study has multiple endpoints. Primarily those associated with adverse pregnancy outcomes will be studied, but also diseases affecting mother, father or child. Endpoints will be taken from questionnaires and medical registers. The study will be carried out nationally and any research groups with relevant questions will be able to participate. The Norway Mother and Child study has been approved by the Norwegian Parliament as well as their Data Inspectorate to ensure that the study and all protocols conform to Norwegian ethical standards as well as appropriate research ethical criteria. Further, the project has been evaluated by the Regional Ethics Committee for Medical Research which has approved all modifications to the project.~Other researchers, nationally and internationally, will have access to the cohort on request and following approval from the project's executive group. NIEHS has the opportunity to add additional biological specimens for blood and urine to the base cohort. Two additional tubes of blood (total volume 9 ml) and a urine sample will be collected as part of the routine prenatal ultrasound visit and blood sample collection included in the overall study protocol. As part of a reliability sub-study, blood and urine samples will also be collected an additional two times, at weeks 23 and 29 of gestation. These samples are designed to allow investigators to explore environmental contributors to the health of women and their children. Low level exposure to environmental contaminants occurs in all industrialized countries, though the level of exposure may differ as the result of diet, cooking practices and pollution sources. However, the ability to explore the role of environmental exposure on health is often more limited by good population-based information on health and disease then by exposure level. Thus, by creating a biological specimen repository in a country with excellent disease registries, it will allow NIEHS to explore risk factors for disease relevant to US populations. All samples will be stored in Norway and will be used in collaboration with Norwegian and other investigators. NIEHS investigators will not have access to identifying information. NIEHS samples will not be used for genetic analyses.

The Norway Mother and Child study is a collaborative venture among health researchers in Norway funded by the Norwegian government. The study is being coordinated by the National Institute of Public Health (aka Folkehelsa) in Oslo and the Medical Birth Registry (MBR) in Bergen. NIEHS has the unique opportunity to participate through the collection of additional tubes of blood during the blood sample collection; these two tubes of blood and a urine sample will allow NIEHS and collaborators to explore environmental determinants for disease among women and their children. These additional samples will remain in the Biobank in Oslo, Norway, with other samples from cohort members and will be used under collaboration with Norwegian investigators.~To achieve better health for mothers and children in the future, the Norway Mother and Child study is designed to test specific hypotheses about the causes of a number of serious diseases by recruiting 110,000 pregnant women to a cohort study. As part of the primary aim of the study, women will be asked to provide a blood sample at 17 weeks gestation, at birth, and 4 days after birth. The NIEHS samples will be collected at the blood draw at 17 weeks gestation. Likely causal factors will be linked to information obtained from questionnaires, blood samples, and medical registers.~The Norway Mother and Child study has multiple endpoints. Primarily those associated with adverse pregnancy outcomes will be studied, but also diseases affecting mother, father or child. Endpoints will be taken from questionnaires and medical registers. The study will be carried out nationally and any research groups with relevant questions will be able to participate. The Norway Mother and Child study has been approved by the Norwegian Parliament as well as their Data Inspectorate to ensure that the study and all protocols conform to Norwegian ethical standards as well as appropriate research ethical criteria. Further, the project has been evaluated by the Regional Ethics Committee for Medical Research which has approved all modifications to the project.~Other researchers, nationally and internationally, will have access to the cohort on request and following approval from the project's executive group. NIEHS has the opportunity to add additional biological specimens for blood and urine to the base cohort. Two additional tubes of blood (total volume 9 ml) and a urine sample will be collected as part of the routine prenatal ultrasound visit and blood sample collection included in the overall study protocol. As part of a reliability sub-study, blood and urine samples will also be collected an additional two times, at weeks 23 and 29 of gestation. These samples are designed to allow investigators to explore environmental contributors to the health of women and their children. Low level exposure to environmental contaminants occurs in all industrialized countries, though the level of exposure may differ as the result of diet, cooking practices and pollution sources. However, the ability to explore the role of environmental exposure on health is often more limited by good population-based information on health and disease then by exposure level. Thus, by creating a biological specimen repository in a country with excellent disease registries, it will allow NIEHS to explore risk factors for disease relevant to US populations. All samples will be stored in Norway and will be used in collaboration with Norwegian and other investigators. NIEHS investigators will not have access to identifying information. NIEHS samples will not be used for genetic analyses.~...

In 1976 an accidental explosion in a chemical plant 16 miles north of Milan resulted in contamination of the local population with 2, 3, 7, 8-tetrachlorodibenzo-para-dioxin (TCDD). There is evidence that TCDD and related phenoxy herbicides act as teratogens, tumor promoters, and carcinogens in experimental animals. In human, TCDD causes chloracne in those exposed. Associations with various cancers have been reported, but the precise role in human toxicity, immune and reproductive dysfunction, and cancer is controversial.~The Seveso accident provides a unique opportunity for an epidemiological investigation in that the exposures are the highest recorded in humans, the exposure involves TCDD without other contaminants, and a cohort in the involved and surrounding area has been enumerated.~There is inter-individual variation in the action of genes involved in TCDD effect in human cells. The quality of human AH receptor, and the CYP1A1 and arnt genotypes are examples of susceptibility markers that may identify subjects at high risk for TCDD-related disease. A hypothesis that could explain the inconsistent association of TCDD exposure with cancer is that genetic susceptibility may influence which individuals are adversely affected by TCDD exposure.~The study is in three phases. The first is a pilot/validation study of 126 highly exposed and not exposed subjects. The second is a case-control study of 100 individuals with chloracne and 100 controls. The field components of phase one and two are complete. The third and final phase is a planned case-control study of TCDD-related cancers that will include approximately 125 cases and 125 controls.~Using different methods to estimate TCDD levels below the detection limit, we found that, approximately 20 years after the accident, plasma TCDD was still elevated in subjects from the exposed areas, particularly in women, and was negatively associated with IgG plasma levels. Subjects who developed chloracne after the accident had high TCDD levels, and no evidence of TCDD-related long-term toxicity.~The analyses of the expression of key genes in the aryl hydrocarbon receptor (AhR) pathway, which is necessary for most TCDD effects, showed a significant reduction in AhR expression by increasing plasma dioxin levels. Cytochrome P450 gene SNPs and haplotypes were associated with variable TCDD-related gene inducibility.~On-going studies are examining the proteomics and gene expression pattern (by microarray) in exposed subjects compared with not exposed individuals, and the frerquency of t(14;18) translocations in lymphocytes from the same subjects.~The study includes a questionnaire/interview and a biospecimen collection; 73 ml of blood were obtained from each participant.

In 1976 an accidental explosion in a chemical plant 16 miles north of Milan resulted in contamination of the local population with 2, 3, 7, 8-terachlorodibenzo-para-dioxin (TCDD). There is evidence that TCDD and related phenoxy herbicides act as teratogens, tumor promoters, and carcinogens in experimental animals. In human, TCDD causes chloracne in those exposed. Associations with various cancers have been reported, but the precise role in human toxicity, immune and reproductive dysfunction, and cancer is controversial.~The Seveso accident provides a unique opportunity for an epidemiological investigation in that the exposures are the highest recorded in humans, the exposure involves TCDD without other contaminants, and a cohort in the involved and surrounding area has been enumerated.~There is inter-individual variation in the action of genes involved in TCDD effect in human cells. The quality of human AH receptor, and the CYP1A1 and arnt genotypes are examples of susceptibility markers that may identify subjects at high risk for TCDD-related disease. A hypothesis that could explain the inconsistent association of TCDD exposure with cancer is that genetic susceptibility may influence which individuals are adversely affected by TCDD exposure.~The study is proceeding in three phases. The first is a pilot/validation study that is complete (field activities) and involved 126 subjects. The second is a case-control study of about 100 individuals with chloracne and 100 controls. The field components of phase one and two are complete, and analyses of results are underway. The third and final phase is a planned case-control study of TCDD-related cancers that will include approximately 125 cases and 125 controls.~The study includes a questionnaire/interview and a biospecimen collection; 73 ml of blood are obtained from each participant.

The Environmental Genome Project (EGP) has completely or partially resequenced the protein coding and regulatory regions of 53 environmentally sensitive genes from 72 anonymous individuals of varying ethnic backgrounds to date. Some of the same genes have been resequenced in an additional set of 20 samples, and, in a subset of these, the introns and promoter regions have been sequenced as well. Within this population, 523 allelic variants (genetic polymorphisms), mostly single nucleotide polymorphisms (SNPs), have been found to date. If the polymorphism alters the behavior or expression of the encoded protein, it might be of clinical significance.~The Program in Clinical Research is planning to establish a large resource bank of frozen DNA samples (20,000) and make it available to NIEHS intramural investigators involved in the EGP to screen for the presence of these SNPs and other mutations by standard genotyping methods. To investigate the feasibility of such a large collection of samples,~we plan to first conduct a pilot study to estimate the accrual rate and uncover potential problems that may be encountered in the larger effort. This IRB proposal is for the pilot study in which we will collect whole blood samples (EDTA-anticoagulated) from 481 patients at UNC Medical Center. Once the pilot study is complete, we will decide whether to proceed with the larger, 20,000 sample collection and if so, develop and submit for review a new IRB protocol for its implementation taking data from the pilot study into account.~For both the pilot study and larger, 20,000 sample collection, only blood left over from patients already having their blood drawn for hematology (complete blood count or CBC) and hemoglobin A1c (HbA1c) assays as part of their routine clinical management will be used, thus eliminating the need to collect extra blood. Once the samples have been obtained from the clinical laboratory and processed, they will be identifiable only with a unique identification number and sent to an NIEHS contractor (BioServe Biotechnlolgies, Laurel, MD) for DNA isolation.~During recruitment, interviewers will explain the study to potential participants, obtain their signatures on the informed consent documents, and answer any questions they have concerning this study. At this time, potential participants will be informed that, depending on the results of the genetic analyses of their blood samples, they may be recontacted at a later date and asked to participate in follow-up genotype/phenotype studies. These follow-up studies will be separate from this protocol and the subjects of future IRB proposals. The ultimate objective of these sample collections, combined with the follow-up genotype/phenotype studies, is to identify groups of individuals with genetic polymorphisms in environmentally sensitive genes, and to correlate their genotype with their clinical phenotype, a process known as ascertainment by genotype.

The Environmental Genome Project (EGP) has completely or partially resequenced the protein coding and regulatory regions of 53 environmentally sensitive genes from 72 anonymous individuals of varying ethnic backgrounds to date. Some of the same genes have been resequenced in an additional set of 20 samples, and, in a subset of these, the introns and promoter regions have been sequenced as well. Within this population, 523 allelic variants (genetic polymorphisms), mostly single nucleotide polymorphisms (SNPs), have been found to date. If the polymorphism alters the behavior or expression of the encoded protein, it might be of clinical significance.~The Office of Clinical Research is planning to establish a large resource bank of frozen DNA samples (20,000) and make it available to NIEHS intramural investigators involved in the EGP to screen for the presence of these SNPs and other mutations by standard genotyping methods. To investigate the feasibility of such a large collection of samples, we plan to first conduct a pilot study to estimate the accrual rate and uncover potential problems that may be encountered in the larger effort. This IRB proposal is for the pilot study in which we will collect whole blood samples (EDTA-anticoagulated) from 481 patients at UNC Medical Center. Once the pilot study is complete, we will decide whether to proceed with the larger, 20,000 sample collection and if so, develop and submit for review a new IRB protocol for its implementation taking date from the pilot study into account.~For both the pilot study and larger, 20,000 sample collection, only blood left over from patients already having their blood drawn for hematology (complete blood count or CBC) assays as part of their routine clinical management will be used, thus eliminating the need to collect extra blood. Once the samples have been obtained from the clinical hematology laboratory and processed, they will be identifiable only with a unique identification number and sent to an NIEHS contractor (BioServe Biotechnlolgies, Laurel, MD) for DNA isolation.~During recruitment, interviewers will explain the study to potential participants, obtain their signatures on the informed consent documents, and answer any questions they have concerning this study. At this time, potential participants will be informed that, depending on the results of the genetic analyses of their blood samples, they may be recontacted at a later date and asked to participate in follow-up genotype/phenotype studies. These follow-up studies will be separate from this protocol and the subjects of future IRB proposals. The ultimate objective of these sample collections, combined with the follow-up genotype/phenotype studies, is to identify groups of individuals with genetic polymorphisms in environmentally sensitive genes, and to correlate their genotype with their clinical phenotype, a process known as ascertainment by genotype.

Fibroblasts can be cultured from human skin biopsies using fetal bovine serum and artificial growth medium. Fibroblasts cultured in this way retain the genetic characteristics of their donor but can be used for experiments where study conditions are much more precisely controlled than they can be in in vivo studies. We plan to culture fibroblasts from Pima Indians for two purposes: 1) to look for an in vitro system to measure insulin resistance, the underlying abnormality in Pima diabetics; and 2) to look for biochemical markers of diabetes or obesity in Pimas employing two-dimensional electrophoresis techniques.

Fibroblasts can be cultured from human skin biopsies using fetal bovine serum and artificial growth medium. Fibroblasts cultured in this way retain the genetic characteristics of their donor but can be used for experiments where study conditions are much more precisely controlled than they can be in in vivo studies. We plan to culture fibroblasts from Pima Indians for two purposes. Firstly, to look for an in vitro system to measure insulin resistance, the underlying abnormality in Pima diabetics. Secondly, to look for biochemical markers of diabetes or obesity in Pimas employing two dimensional electrophoresis techniques.

Research and development in genetic testing for cancer susceptibility genes has advanced rapidly in recent years, allowing healthy individuals, cancer patients, and their families to determine if they carry mutations which increase their risk of breast, ovarian, prostate, colon, and other cancers. Initial efforts have unfolded primarily in academic medical centers targeting families at high risk for cancer. There is currently no information available for assessing the prevalence of genetic testing for cancer susceptibility genes at the national level, or for evaluating the knowledge of and attitudes toward such testing among primary care physicians. The objectives of this survey are to determine the utilization of genetic tests by physicians at the national level; to ascertain physician knowledge of available genetic tests for specific cancer susceptibility genes, to examine physicians' general attitudes toward testing, and; to explore possible variation in utilization and knowledge/attitudes by medical specialty, type of practice, year of training completion, board status, urbanicity, and geographic region. The primary research question that this survey will address is what is the prevalence of use of genetic testing for cancer susceptibility among primary care physicians in the U.S.? The survey will also assess whether there are statistically significant differences in 1) self-reported knowledge, current use of, and future intentions to use genetic testing for cancer susceptibility, and 2) perceptions of barriers to testing, among primary care physicians by their type and location of practice, and recency of training. Primary care physicians (general internists, obstetrician/gynecologist, family and general practitioners) will also be compared with specialty groups (gastroenterologists, surgeons, urologists) and oncologists with respect to their use, attitudes towards, and knowledge of, genetic testing for cancer susceptibility. A questionnaire was administered by mail, telephone, facsimilie or Internet to a nationally representative sample of 1,251 primary care physicians and specialists. Study participants are primary care and specialty physicians with active licenses to practice medicine in the U.S. A data file with personal identifiers deleted will be prepared for statistical analysis to estimate the prevalence and determine predictors of use and intentions to genetic tests for inherited cancer susceptibility.

Research and development in genetic testing for cancer susceptibility genes has advanced rapidly in recent years, allowing healthy individuals, cancer patients, and their families to determine if they carry mutations which increase their risk of breast, ovarian, prostate, colon, and other cancers. Initial efforts have unfolded primarily in academic medical centers targeting families at high risk for cancer. There is currently no information available for assessing the prevalence of genetic testing for cancer susceptibility genes at the national level, or for evaluating the knowledge of and attitudes toward such testing among primary care physicians. The objectives of this survey are to determine the utilization of genetic tests by physicians at the national level; to ascertain physician knowledge of available genetic tests for specific cancer susceptibility genes, to examine physicians' general attitudes toward testing, and; to explore possible variation in utilization and knowledge/attitudes by medical specialty, type of practice, year of training completion, board status, urbanicity, and geographic region. The primary research question that this survey will address is what is the prevalence of use of genetic testing for cancer susceptibility among primary care physicians in the U.S.? The survey will also assess whether there are statistically significant differences in 1) self-reported knowledge, current use of, and future intentions to use genetic testing for cancer susceptibility, and 2) perceptions of barriers to testing, among primary care physicians by their type and location of practice, and recency of training. Primary care physicians (internists, obstetrician/gynecologist, family and general practitioners) will also be compared with specialty groups (gastroenterologists, surgeons, urologists) and oncologists with respect to their use, attitudes towards, and knowledge of, genetic testing for cancer susceptibility. A questionnaire is being administered by mail, telephone, facsimilie or Internet to a nationally representative sample of 2,100 physicians. Responding physicians select their preferred response mode. Study participants are primary care and specialty physicians with active licenses to practice medicine in the U.S. A data file with personal identifiers deleted will be prepared for statistical analysis to estimate the prevalence and determine predictors of use and intentions to genetic tests for inherited cancer susceptibility.

Evidence suggests that exposure to cockroach allergen might be the most important risk factor for asthma in inner-city households. Contrary to other students in the literature, we recently reported that cockroach extermination alone-without professional cleaning or occupant education-reduced cockroach allergen levels in inner-city homes. This was an important finding because extermination alone would be much less expensive and easier to implement than a more comprehensive intervention. The primary objective of this study is to validate our previous finding that cockroach extermination alone can significantly reduce cockroach allergen levels in inner-city homes. The secondary objective is to determine the level of expertise and effort in extermination that would be required to achieve significant allergen reductions. The study design will be a 3-arm, randomized control trial. Sixty cockroach-infested, multi-unit rental homes will be randomly assigned to either a control group or one of two treatment groups. The Treatment-1 group, which will test the efficacy of extermination, will receive insecticide bait placement by staff from the Urban Entomology Department at North Carolina State University (the gold standard for this study). The Treatment-2 group, which will test the effectiveness of extermination, will receive extermination from 1 to 5 commercial pest control companies randomly assigned to the homes. Study staff will assist home occupants in obtaining a 12-month, prepaid contract. Periodically in all homes, study staff will administer a questionnaire, set cockroach traps to monitor cockroach numbers, and sample dust to monitor cockroach allergen levels. Treatment-1 homes will receive exterminations by NCSU staff at baseline and then as needed, as determined by cockroach trap counts. Treatment-2 homes will receive extermination by commercial applicators according to the terms of the contract. In the NIEHS laboratory of Dr. Zeldin, dust samples will be analyzed for concentrations of cockroach allergens Bla g 1 and Bla g 2. Statistical analyses will compare cockroach allergen concentration changes in each of the treatment groups relative to changes in the control group. The percentage of homes for which concentrations are reduced below 8.0 and 2.0 units of allergen per gram of dust-the proposed thresholds for asthma morbidity and allergic sensitization, respectively-will also be compared between groups. The results from this study, if they prove to be consistent with our previous work, will be used by NIEHS to plan future primary and secondary asthma prevention trials. With the exception of NCSU staff, the field and laboratory work will be carried out by staff from Dr. Zeldin's clinical program.

The most important risk factor for asthma in inner-city homes may be exposure to cockroach allergen. In a previous study, the researchers reported that extermination alone, without resident education or professional cleaning, reduced allergen levels in inner-city homes. This result contradicted earlier findings by other scientists. This study seeks to confirm the researchers' earlier results, and to determine how intensive an effective extermination must be.~The study will last one year and include 60 infested, multi-unit rental homes in North Carolina, divided into three groups. In the Treatment-1 group, researchers from North Carolina State University will set insecticide bait in initial and follow-up visits, as the highest standard for treatment. In the Treatment-2 group, one of five commercial pest-control companies will be randomly assigned to treat each home according to a 12-month, pre-paid contract. The third group will be a control group that receives no extermination treatment. In all homes, researchers will periodically survey the residents, monitor cockroach numbers, and monitor allergen levels in dust samples. If this study is successful, it will be used to plan future asthma prevention trials.

Family history of cancer is an important possible indicator of inherited cancer susceptibility, which has helped identify individuals and families at high risk of inherited cancers in research studies and clinical practice. While there are also various potential uses of family history of cancer data in cancer surveillance, the completeness and accuracy of family history of cancer data collected from the general population is unclear. In an effort to evaluate the feasibility of conducting a national surveillance study to determine the prevalence of family history of cancer in the U.S. population, the Risk Factor Monitoring and Methods Branch will undertake a pilot study, entitled the Family Health Study, that examines issues of data quality. In this study, a family history of cancer questionnaire (FHCQ) will be developed for surveillance purposes and administered to a random digit dial (RDD) sample of households in the state of Connecticut. Positive and negative reports of common cancers in the respondent's families will be validated against records of the Connecticut Tumor Registry (CTR) and other data sources.~The objectives are to: 1) assess the agreement between respondent reports of specific cancers in first and second degree relatives and medical record-based reports, as measured by percent concordance; 2) quantify the sensitivity, specificity and predictive value of the FHCQ by cancer site; 3) evaluate the possible predictors of reporting accuracy, including cancer site, year of diagnosis, kinship relation of the relative to the respondent and the frequency and quality of their contact, overall family cohesiveness, respondent's own history of cancer, and demographic factors; 4) describe the completeness and reliability of family structure data.~Validation of selected relatives' cancer status will be done through data linkage to the Connecticut Tumor Registry, other selected cancer registries, the National Death Index, Medicare claims data bases, state death certificate registries, or by obtaining consent to review available medical records from physicians and health care facilities. Self-reports of respondents' cancer status will also be validated since this may be a predictor of ability to accurately report family history. A pre-established tracing algorithm will be used to triage cancer reports into the medical records systems where true cancer status is most likely to be verified by the highest quality data. Validated cancer outcomes will be assigned ICD-9 codes by a nosology team following a double-blinded protocol. A certainty level will be assigned to each cancer outcome based on the type of confirming medical record, with evidence of microscopic confirmation of malignancy considered the most certain. Statistical analyses to determine FHCQ1 sensitivity, specificity, and predictive value, will be performed, accounting for level of certainty. Predictors of cancer reporting accuracy will be examined using multivariate regression.

Family history of cancer is an important possible indicator of inherited cancer susceptibility, which has helped identify individuals and families at high risk of inherited cancers in research studies and clinical practice. While there are also various potential uses of family history of cancer data in cancer surveillance, the completeness and accuracy of family history of cancer data collected from the general population is unclear. In an effort to evaluate the feasibility of conducting a national surveillance study to determine the prevalence of family history of cancer in the U.S. population, the Risk Factor Monitoring and Methods Branch will undertake a pilot study, entitled the Family Health Study, that examines issues of data quality. In this study, a family history of cancer questionnaire (FHCQ) will be developed for surveillance purposes and administered to a random digit dial (RDD) sample of households in the state of Connecticut. Positive and negative reports of common cancers in the respondent's families will be validated against records of the Connecticut Tumor Registry (CTR) and other data sources.~The objectives are to: 1) assess the agreement between respondent reports of specific cancers in first and second degree relatives and medical record-based reports, as measured by percent concordance; 2) quantify the sensitivity, specificity and predictive value of the FHCQ by cancer site; 3) evaluate the possible predictors of reporting accuracy, including cancer site, year of diagnosis, kinship relation of the relative to the respondent and the frequency and quality of their contact, overall family cohesiveness, respondent's own history of cancer, and demographic factors; 4) describe the completeness and reliability of family structure data.~Validation of selected relatives' cancer status will be done through data linkage to the Connecticut Tumor Registry, other selected cancer registries, the National Death Index, Medicare claims data bases, state death certificate registries, or by obtaining consent to review available medical records from physicians and health care facilities. Self-reports of respondents' cancer status will also be validated since this may be a predictor of ability to accurately report family history. A pre-established tracing algorithm will be used to triage cancer reports into the medical records systems where true cancer status is most likely to be verified by the highest quality data. Validated cancer outco...

Obesity is the consequence of an imbalance between energy intake and energy expenditure. Recent studies have suggested that the sympathetic nervous system (SNS) may be an important determinant of the rate of energy expenditure in man. Indirect assessments of the sympathetic nervous activity in Pima Indians have recently shown impaired SNS-mediated energy expenditure in this obesity-prone population. We plan to perform direct microelectrode nerve recording of the sympathetic innervation of the lower leg to directly assess SNS activity and examine its potential role in the regulation of metabolic rate and the development of obesity. Measurements will be performed in the basal state, in response to glucose feeding (75 g OGTT), in response to a standard meal, and in response to glucose/insulin infusion. These studies also will help to disassociate the effect of insulin and glucose on the stimulation of SNS activity. The association between postprandial changes in SNS activity and subjective ratings of hunger and fullness also will be studied. Energy expenditure measurements will be performed over 24 hours in the respiratory chamber and for 2 1/2 hours before and during the euglycemic clamp. Results also will be used to determine possible racial differences between Pimas and Caucasians, since the risk for obesity is markedly different in these populations. To exclude the possibility of a normal SNS activity but with peripheral resistance to the action of norepineprine, we will perform adrenergic stimulation by isoproterenol to measure peripheral adrenergic sensitivity.

Obesity is the consequence of an imbalance between energy intake and energy expenditure. Recent studies have suggested that the sympathetic nervous system (SNS) may be an important determinant of the rate of energy expenditure in man. Indirect assessments of the sympathetic nervous activity in Pima Indians have recently shown impaired SNS-mediated energy expenditure in this obesity-prone population. We plan to perform direct microelectrode nerve recording of the sympathetic innervation of the lower leg to directly assess SNS activity and examine its potential role in the regulation of metabolic rate and the development of obesity. Measurements will be performed in the basal state, in response to glucose feeding (75 g OGTT) and in response to glucose/insulin infusion. These studies also will help to disassociate the effect of insulin and glucose on the stimulation of SNS activity. Energy expenditure measurements will be performed over 24 hours in the respiratory chamber and for 2 1/2 hours before and during the euglycemic clamp. Results also will be used to determine possible racial differences between Pimas and Caucasians, since the risk for obesity is markedly different in these populations. To exclude the possibility of a normal SNS activity but with peripheral resistance to the action of norepineprine, we will perform adrenergic stimulation by isoproterenol to measure peripheral adrenergic sensitivity.

This study is divided into two stages. In Stage I, all women registered in the antenatal clinics at the Namakkal District Hospital or at the Rasipuram Government Hospital in the state of Tamil Nadu in India will be offered the opportunity to participate in an educational session on HIV infection and transmission. With informed consent, a systematic sample of the population will be asked to participate in a pre-educational session assessment of knowledge, attitudes, and beliefs, and in a post-educational assessment of knowledge, regarding HIV infection and transmission. All women will be offered voluntary HIV counseling and testing, irrespective of participation in the education session (those who refuse to participate although education offered) and in the pre- and post-educational assessments (those among the systematic sample who do not provide signed informed consent). The objectives of Stage I are: (1) to assess the acceptance of education regarding HIV infection and transmission among antenatal women at the participating clinical sites and, among a systematic sample of those offered such education, to assess knowledge, attitudes, and beliefs, as well as changes in knowledge; (2) to assess the acceptance of voluntary counseling and HIV testing among antenatal women at the participating clinical sites; and (3) to describe the HIV seroprevalence among antenatal women at the participating clinical sites who accept HIV testing. The main outcomes of interest are the proportions of women in the antenatal clinics who agree to undergo HIV testing and, of these, the proportion who are seropositive for HIV.~HIV seropositive women will be offered enrollment in Stage II (a prospective cohort study). All women enrolled in the prospective cohort study will be offered education and counseling regarding infant feeding, i.e. the risks and benefits of breastfeeding, factors which are likely to increase the risk of transmission through breastfeeding, and the potential advantages and disadvantages of early weaning from breastmilk and replacement feeding.~Women enrolled in the prospective cohort study at Rasipuram Government Hospital who meet eligibility criteria will be offered Protocol ZDV/NVP: zidovudine prophylaxis beginning at 28 weeks gestation (or as soon as possible thereafter up to 36 weeks gestation if late presentation for antenatal care or other reasons preclude initiation at 28 weeks) and continuing through labor until delivery, and one dose of nevirapine at the onset of labor or as soon as possible thereafter. Their infants will receive zidovudine beginning within the first 24 hours of life and continuing through the end of the sixth week of life, and one dose of nevirapine within 24 hours after birth. Those women who decline protocol ZDV/NVP, or who enroll after 32 weeks gestation, can receive the standard of care: the two dose nevirapine regimen. (Women enrolled at Namakkal District Hospital could receive the two-dose nevirapine regimen.)~The primary objectives of Stage II are: (1) to assess the safety and tolerability of protocol ZDV/NVP; (2) to assess the acceptance of, and adherence to, protocol ZDV/NVP; (3) to assess the acceptance of education and counseling regarding infant feeding; and (4) to describe the mother-to-child transmission rates, among HIV-infected women and their infants enrolled in the prospective cohort study. The secondary objectives of Stage II are: (1) to describe morbidity and mortality rates through 12 months after delivery/birth; and (2) to describe risk factors for mother-to-child transmission of HIV, among HIV-infected women and their infants enrolled in the prospective cohort study. The primary outcomes of interest are the safety and tolerability of protocol ZDV/NVP, the proportion of HIV-infected women who agree to receive protocol ZDV/NVP, the mother-to-child HIV transmission rate (overall as well as according to receipt of protocol ZDV/NVP and infant feeding modality), and risk factors for transmission.

This study, conducted in Tamil Nadu, India, was initiated in response to the developing epidemic of HIV/AIDS in India. It is divided into two stages, as follows:~Stage I~All women registered in the pregnancy clinics at the Namakkal District Hospital or the Rasipuram Government Hospital in the state of Tamil Nadu in India will be offered participation in an educational session on HIV infection and transmission. It will include a pre-educational assessment of knowledge, attitudes, and beliefs, and a post-educational assessment of knowledge about HIV infection and transmission. All women at the clinic, regardless of whether or not they participate in the educational and assessment sessions, will be offered HIV counseling and testing. The objectives of this stage of the study are to:~Assess the acceptance of education about HIV infection and transmission among pregnant women at the participating sites and their knowledge, attitudes, and beliefs about HIV~Assess the acceptance of voluntary counseling and HIV testing among pregnant women at these sites~Determine the prevalence of infection among women who accept HIV testing at these sites~Stage II~Pregnant HIV-infected women at the pregnancy clinics at the Namakkal District Hospital or the Rasipuram Government Hospital who are 18 years of age or older will be offered enrollment in Stage II of this study. Participants will be followed during their pregnancy and until their baby is a year old. The baby will be a part of the study from birth to one year of age. After delivery, both the mother and baby will be followed with regularly scheduled visits that include a physical examination and blood test.~Treatment with the anti-AIDS drug zidovudine will be offered for both the mother and child. For the study protocol, the mother will receive the drug starting the 28th week of pregnancy and continuing through labor and delivery. The infants will start drug treatment within the first 24 hours of life and continue for 6 weeks. Women who do not choose to take zidovudine according to this schedule will be offered standard treatment with a shorter course of drug, beginning with the 36th week of pregnancy, and no preventative treatment for their infants. All women will be offered education and counseling about the risks and benefits of breastfeeding and the risk of HIV transmission through breastfeeding. The objectives of this stage of the study are to:~Assess the safety and tolerability of zidovudine given according to this protocol~Assess the acceptance of and adherence to the zidovudine regimen in the protocol~Assess the acceptance of education and counseling about breastfeeding~Determine the mother-to-child HIV transmission rates in this study~Determine the rates of illness and death through 12 months after delivery~Determine risk factors for mother-to-child transmission of HIV

We propose to conduct a study to increase our understanding of farming practices and of the potential for previous exposure to DDT in North Carolina African American male agricultural workers, a group especially likely to have had high DDT exposure. Because of potentially widespread DDT exposure from agricultural activities, African American farmers and farm workers may be uniquely at risk for any associated health effects. However, little is known about levels of pesticide exposure in African American farming populations. Three hundred and eighty-nine African American men who are current or former farmers or farm workers will be asked to participate in the study. These men are members of the Supplemental Minority Cohort of the NCI/NIEHS/EPA Agricultural Health Study (AHS). The AHS is a prospective study of the potential health effects associated with agricultural exposures. Men in the supplemental cohort were recruited in 1996. At that time, they completed an enrollment questionnaire that focused on lifetime agricultural exposures, demographics, lifestyle factors and health. In this new study, a follow-up questionnaire will be administered by telephone by a trained interviewer to all men. Following the interview, the participant will be asked to donate a blood specimen, to have anthropometric indices (e.g., height, weight, waist and hip circumference, etc.) measured, and to have a top- and side view Polaroid photograph of their head taken during one visit to a central community location, such as the local church or health clinic. We will quantitatively document serum p,p'-DDE levels, correlate these with self-reported farming activities and DDT exposure, and describe the health status of these men. We will also correlate serum p,p'-DDE levels and androgen concentrations, since p,p'-DDE is thought to be a potent androgen receptor antagonist. This exploration of the potential link between levels is important because the demonstration of any subclinical physiological effects of p,p'-DDE would increase the plausibility of a wide range of health effects that have been postulated to be associated with the endogenous endocrine environment and the so-called endocrine disrupters. In addition, we will evaluate the relationship between several important physiological parameters which can be easily and accurately measured in serum, and physical characteristics including hair patterning and distribution of body fat in these African American men.

We propose to conduct a study to increase our understanding of farming practices and of the potential for previous exposure to DDT in North Carolina African American male agricultural workers, a group especially likely to have had high DDT exposure. Because of potentially widespread DDT exposure from agricultural activities, African American farmers and farm workers may be uniquely at risk for any associated health effects. However, little is known about levels of pesticide exposure in African American farming populations. Three hundred and eighty-nine African American men who are current or former farmers or farm workers will be asked to participate in the study. These men are members of the Supplemental Minority Cohort of the NCI/NIEHS/EPA Agricultural Health Study (AHS). The AHS is a prospective study of the potential health effects associated with agricultural exposures. Men in the supplemental cohort were recruited in 1996. At that time, they completed an enrollment questionnaire that focused on lifetime agricultural exposures, demographics, lifestyle factors and health. In this new study, a follow-up questionnaire will be administered by telephone by a trained interviewer to all men. Following the interview, the participant will be asked to donate a blood specimen, to have anthropometric indices (e.g., height, weight, waist and hip circumference, etc.) measured, and to have a top- and side view Polaroid photograph of their head taken during one visit to a central community location, such as the local church or health clinic. We will quantitatively document serum p,p'-DDE levels, correlate these with self-reported farming activities and DDT exposure, and describe the health status of these men. We will also correlate serum p,p'-DDE levels and androgen concentrations, since p,p'-DDE is thought to be a potent androgen receptor antagonist. This exploration of the potential link between levels is important because the demonstration of any subclinical physiological effects of p,p'-DDE would increase the plausibility of a wide range of health effects that have been postulated to be associated with the endogenous endocrine environment and the so-called endocrine disrupters. In addition, we will evaluate the relationship between several important physiological parameters which can be easily and accurately measured in serum, and physical characteristics including hair patterning and distribution of body fat in these African American men.

We will test the following hypotheses:~The activity of the desaturating/elongating enzymes assessed by the in vivo conversion of deuterated a-linolenic and linoleic acids to DHA and AA, respectively, will be related to the duration of gestation and to postnatal age.~Dietary w-3 and w-6 LCPUFAs in human milk or DHA and AA supplemented formula will inhibit the desaturation/elongation of deuterated a-linolenic and linoleic acids demonstrating in vivo inhibition of the metabolic pathway by respective products.~Present evidence suggests that the parent essential fatty acids (EFA), linoleic acid (18:2 w-6) and a-linolenic acids (18:3 w-3) are insufficient to fully satisfy EFA nutrition during early life in the human. A possible need for long chain (LC, longer than 18 C chain length) EFAs in the human is suggested by the accretion rates of elongated and desaturated products in the developing fetus; the altered plasma and red cell fatty acid patterns, and the abnormal visual function observed in infants receiving solely the parent EFAs; and by the relatively high concentration of LC EFAs in human milk. Most milk formula, as compared to human milk, are lower in oleic acid, higher in linoleic, have little a-linolenic acid and virtually no LC w-3 or w-6 polyunsaturated FA (LC PUFA). This study will evaluate the capacity of human infants to form w-3 and w-6 LCPUFAs from the parent EFAs as affected by developmental stage and dietary EFA supply. The precursors will be labeled with deuterium and the products analyzed by gas chromatography / mass spectrometry GC/MS. The main products of the desaturation / elongation pathway are docosahexaenoic (DHA) and arachidonic (AA) acids for the w-3 and w-6 series, respectively. Infants will be fed human milk or formulas with or without supplemental LCPUFAs as part of a study to evaluate the effect of EFAs on CNS functional development. Infants included in this study of the effect of developmental stage on EFA desaturation/elongation will be 2-5 days of age (before any fat is administered enterally or parenterally) and 28, 32, 36 or 40 weeks gestation. In addition, infants born at 28 and 40 weeks gestation will be studied 2 and 6 weeks postnatally after dietary fat has been provided for at least 7 days and energy intake is sufficient to assure growth. To evaluate the effect of dietary EFA on DHA and AA formation we will assess elongation/ desaturation in infants receiving 3 diets: human milk (which contains w-3 and w-6 LCPUFAs); cow milk based formula providing 18:2 w-6 and 18:3 w-3 but no LCPUFAs; or formula supplemented with added LCPUFAs (DHA and AA). Also, the relative efficiency of conversion of the 18-C precursors will be compared to the 20-C precursors with respect to their metabolic endpoints. This study should provide new information on the effects of developmental stage and w-3 and w-6 LCPUFA supply in determining the activity of EFA elongation/desaturation in the human. This knowledge may help in improving early neonatal nutritional practices to assure meeting the EFA needs of the developing CNS.

We will test the following hypotheses:~The activity of the desaturating/elongating enzymes assessed by the in vivo conversion of deuterated a-linolenic and linoleic acids to DHA and AA, respectively, will be related to the duration of gestation and to postnatal age.~Dietary w-3 and w-6 LCPUFAs in human milk or DHA and AA supplemented formula will inhibit the desaturation/elongation of deuterated a-linolenic and linoleic acids demonstrating in vivo inhibition of the metabolic pathway by respective products.~Present evidence suggests that the parent essential fatty acids (EFA), linoleic acid (18:2 w-6) and a-linolenic acids (18:3 w-3) are insufficient to fully satisfy EFA nutrition during early life in the human. A possible need for long chain (LC, longer than 18 C chain length) EFAs in the human is suggested by the accretion rates of elongated and desaturated products in the developing fetus; the altered plasma and red cell fatty acid patterns, and the abnormal visual function observed in infants receiving solely the parent EFAs; and by the relatively high concentration of LC EFAs in human milk. Most milk formula, as compared to human milk, are lower in oleic acid, higher in linoleic, have little a-linolenic acid and virtually no LC w-3 or w-6 polyunsaturated FA (LC PUFA). This study will evaluate the capacity of human infants to form w-3 and w-6 LCPUFAs from the parent EFAs as affected by developmental stage and dietary EFA supply. The precursors will be labeled with deuterium and the products analyzed by gas chromatography / mass spectrometry GC/MS. The main products of the desaturation / elongation pathway are docosahexaenoic (DHA) and arachidonic (AA) acids for the w-3 and w-6 series, respectively. Infants will be fed human milk or formulas with or without supplemental LCPUFAs as part of a study to evaluate the effect of EFAs on CNS functional development. Infants included in this study of the effect of developmental stage on EFA desaturation/elongation will be 2-5 days of age (before any fat is administered enterally or parenterally) and 28, 32, 36 or 40 weeks gestation. In addition, infants born at 28 and 40 weeks gestation will be studied 2 and 6 weeks postnatally after dietary fat has been provided for at least 7 days and energy intake is sufficient to assure growth. To evaluate the effect of dietary EFA on DHA and AA formation we will assess elongation/ desaturation in infants receiving 3 diets: human milk (which contains w-3 and w-6 LCPUFAs); cow milk based formula providing 18:2 w-6 and 18:3 w-3 but no LCPUFAs; or formula supplemented with added LCPUFAs (DHA and AA). This study should provide new information on the effects of developmental stage and w-3 and w-6 LCPUFA supply in determining the activity of EFA elongation/desaturation in the human. This knowledge may help in improving early neonatal nutritional practices to assure meeting the EFA needs of the developing CNS.

This protocol describes an exposure assessment study of farmers in North Carolina and Iowa who personally apply the fungicides captan, thiophanate-methyl, and benomyl to apple and peach orchards. The exposure assessment will include environmental measurements as well as biological monitoring data. The biomonitoring data will be based on 24-hour urinary metabolites of the three fungicides selected for study. The study is being done in collaboration with the Agricultural Health Study (AHS), a large prospective health study of licensed private (farmer) and commercial applicators, and the spouses of private applicators. The AHS is sponsored by the National Cancer Institute, the National Institute of Environmental Health Sciences and the Environmental Protection Agency. The study described here will be conducted by the National Institute of Occupational Safety and Health.~Retinal degeneration among applicators in the AHS has been associated with cumulative days of use of five fungicides, including captan and benomyl, which are or have been heavily used in orchards. Minimal monitoring data are available on fungicide exposures among orchard applicators in the U.S. Agent-specific exposure classification in the AHS is based primarily on questionnaire data, supplemented by exposure monitoring data from non-cohort studies in the literature. An algorithm has been developed by AHS to estimate an individual's cumulative exposure using information on duration, frequency and intensity of exposure from questionnaires. The intensity piece of this algorithm identifies factors that either increase or decrease exposure and a weight is assigned to each factor to reflect the relative impact of that factor on exposure. Exposure data are need to validate these algorithms, to identify major exposure determinants, and to evaluate the appropriateness of the assigned weights.~Fungicides are applied at regular intervals throughout the spring and summer in orchards. Captan is a frequently applied fungicide that will serve as the primary marker for fungicide exposures in orchards. Participants from the AHS will be selected based on planned use of captan. A benzimidazole fungicide, such as thiophanate-methyl or benomyl, is often applied with captan and exposure to thiophanate-methyl and benomyl will also be monitored. Applicator exposure will be measured using both environmental (air, dermal patch, hand) and biological monitoring methods. Captan is metabolized to tetrahydrophthalimide, which is excreted into the urine. Thiophanate-methyl an benomyl share a common metabolite, methyl (5-hydroxy-1H-benzimidazol-2-yl)-carbamate, which is also excreted into the urine. Dupont is voluntarily withdrawing its benomyl product from the market as of December 31, 2001; however, existing supplies of benomyl may be used in 2002. Due to this carryover use of benomyl and the presence of a metabolite in the urine common to thiophanate-methyl, it is prudent to monitor benomyl exposure among participating applicators. A repeated measures design has been proposed to address the likelihood of high within-worker variability for exposure measures.~In summary, the objectives of this study are 1) to measure actual exposures to the target fungicides using both environmental and biological measures of exposure, 2) to identify and quantify major determinants of exposure, 3) to describe within- and between-worker exposure variability, and 4) to evaluate, to the extent possible, agreement between exposure estimates computed using the AHS exposure algorithms and exposure estimates based on actual measurements.

This protocol describes an exposure assessment study of farmers in North Carolina and Iowa who personally apply the fungicides captan, thiophanate-methyl, and benomyl to apple and peach orchards. The exposure assessment will include environmental measurements as well as biological monitoring data. The biomonitoring data will be based on 24-hour urinary metabolites of the three fungicides selected for study. The study is being done in collaboration with the Argicultural Health Study (AHS), a large prospective health study of licensed private (farmer) and commercial applicators, and the spouses of private applicators. The AHS is sponsored by the National Cancer Institute, the National Institute of Environmental Health Sciences and the Environmental Protection Agency. The study described here will be conducted by the National Institute of Occupational Safety and Health.~In summary, the objectives of this study are 1) to measure actual exposures to the target fungicides using both environmental and biological measures of exposure, 2) to identify and quantify major determinants of exposure, 3) to describe within- and between-worker exposure variability, and 4) to evaluate, to the extent possible, agreement between exposure estimates computed using the AHS exposure algorithms and exposure estimates based on actual measurements.

Peripheral blood mononuclear cells (PBMC) will be collected from healthy volunteers and patients who present with different diseases that involve or implicate the immune system dysregulation (HIV infection, autoimmune diseases and cancer). These PBMC will be studied in vitro for a number of functional parameters, including generating soluable factors that inhibit HIV infection, developing patterns of immune dysregulation, and inducing apoptotic T cell death. The purpose of such studies is to obtain insight into the mechanisms of natural resistance to viral infections, AIDS pathogenesis, and disease-induced immune dysregulation.

Peripheral blood mononuclear cells (PBMC) will be collected from healthy volunteers and patients who present with different diseases that involve or implicate the immune system dysregulation (HIV infection, autoimmune diseases and cancer). These PBMC will be studied in vitro for a number of functional parameters, including generating soluable factors that inhibit HIV infection, developing patterns of immune dysregulation, and inducing apoptotic T cell death. The purpose of such studies is to obtain insight into the mechanisms of natural resistance to viral infections, AIDS pathogenesis, and disease-induced immune dysregulation.

We propose to analyze a DNA sample for mutations in the estrogen receptor gene from a patient who appears insensitive to estrogen hormone treatment.

We propose to analyze a DNA sample for mutations in the estrogen receptor gene from a patient who appears insensitive to estrogen hormone treatment.

Two large, nutritional intervention trials were conducted in Linxian, China between 1985-1991. These trials tested the effect of multiple vitamins and minerals in the prevention of esophageal cancer in a population with the highest known rate for this disease in the world. Results from the trials showed that Beta-carotene + Vitamin E + selenium reduced total mortality, total cancer mortality, and stomach cancer incidence and mortality. Multivitamins/minerals also showed reduction in premalignant lesions. Preliminary follow-up data obtained for the time period after cessation of intervention in 1991 suggests that the observed benefit for total and cancer mortality is reduced but that the benefit for stomach cancer remains.~The objectives of the follow-up study are: (1) to continue to determine cancer incidence and all causes of mortality in trial participants after intervention to permit examination of potential effects of the interventions on total and cause-specific mortality and cancer incidence in the post-intervention period; (2) to conduct a cross-sectional nutritional survey in a subsample of living trial participants to evaluate their nutritional status, asses the validity of dietary questionnaires, and relate neurologic status to vitamin B12 plasma levels; (3) to collect a blood sample from all living trial participants to permit further etiologic investigations of genetic and environmental hypotheses; and (4) to perform nested case-control studies of selected genetic and environmental hypotheses.~To accomplish the objectives of the follow-up study, we will: (1) determine updated vital status and cancer status data on all trial participants via monthly checks of village doctor records and quarterly checks of the Linxian Cancer Registry; conduct a Vital/Cancer Status Interview Survey among all (n approximately 34,000 trial participants (or their surrogates); identify, collect, and store all available diagnostic materials for trial participants identified as having developed cancer or died with cancer during the follow-up period; (2) conduct a Nutritional Survey on a subsample (n approximately 1000) of living trial participants that will include (a) a physical exam and brief medical history, (b) a neurologic history, (c) a cognitive function exam, (d) a hair/mouth skin exam, (e) a neurological exam, (f) a nutritional questionnaire, and (g) collection of a blood sample for hematologic/ biochemical analyses; (3) conduct a Blood Collection Survey of all living trial participants (n approximately 23,000) to obtain (a) a physical exam and brief medical history and (b) a single 10-ml blood sample for separation and preservation as WBCs (both viable and nonviable), RBCs, and plasma for genetic (e.g., xenobiotic polymorphisms) and environmental (e.g., plasma ascorbic acid) hypothesis testing; and (4) perform Nested Case-Control Studies of selected genetic and environmental hypothesis related to the etiology and prevention of esophageal cancer and stroke. These will be done using serum from the new cancer and stroke cases (approximately 2500) and controls (approximately 2500) previously identified from 1991-1996, as well as using new cancer and stroke cases and controls for the period 1996-2004 (approximately 9000).~The followup for endpoints will continue monthly for an additional 5 years (through the year 2003). The Nutritional Survey and Blood Collection Survey will be conducted in the spring of 1999. The Nested Case-Control studies will be performed annually beginning in 2000, and the Vital/Cancer Interview Survey will be conducted in the Spring of 2001.

Two large, nutritional intervention trials were conducted in Linxian, China between 1985-1991. These trials tested the effect of multiple vitamins and minerals in the prevention of esophageal cancer in a population with the highest known rate for this disease in the world. Results from the trials showed that Beta-carotene + Vitamin E + selenium reduced total mortality, total cancer mortality, and stomach cancer incidence and mortality. Multivitamins/minerals also showed reduction in premalignant lesions. Preliminary follow-up data obtained for the time period after cessation of intervention in 1991 suggests that the observed benefit for total and cancer mortality is reduced but that the benefit for stomach cancer remains.~The objectives of the follow-up study are: (1) to continue to determine cancer incidence and all causes of mortality in trial participants after intervention to permit examination of potential effects of the interventions on total and cause-specific mortality and cancer incidence in the post-intervention period; (2) to conduct a cross-sectional nutritional survey in a subsample of living trial participants to evaluate their nutritional status, asses the validity of dietary questionnaires, and relate neurologic status to vitamin B12 plasma levels; (3) to collect a blood sample from all living trial participants to permit further etiologic investigations of genetic and environmental hypotheses; and (4) to perform nested case-control studies of selected genetic and environmental hypotheses.~To accomplish the objectives of the follow-up study, we will: (1) determine updated vital status and cancer status data on all trial participants via monthly checks of village doctor records and quarterly checks of the Linxian Cancer Registry; conduct a Vital/Cancer Status Interview Survey among all (n-34,000 trial participants (or their surrogates); identify, collect, and store all available diagnostic materials for trial participants identified as having developed cancer or died with cancer during the follow-up period; (2) conduct a Nutritional Survey on a subsample (n-1000) of living trial participants that will include (a) a physical exam and brief medical history, (b) a neurologic history, (c) a cognitive function exam, (d) a hair/mouth skin exam, (e) a neurological exam, (f) a nutritional questionnaire, and (g) collection of a blood sample for hematologic/biochemical analyses; (3) conduct a Blood Collection Survey of all living trial participants (n-23,000) to obtain (a) a physical exam and brief medical history and (b) a single 10-ml blood sample for separation and preservation as WBCs (both viable and nonviable), RBCs, and plasma for genetic (e.g., xenobiotic polymorphisms) and environmental (e.g., plasma ascorbic acid) hypothesis testing; and (4) perform Nested Case-Control Studies of selected genetic and environmental hypothesis related to the etiology and prevention of esophageal cancer and stroke. These will be done using serum from the new cancer and stroke cases (-2500) and controls (-2500) previously identified from 1991-1996, as well as using new cancer and stroke cases and controls for the period 1996-2004 (-9000).~The followup for endpoints will continue monthly for an additional 5 years (through the year 2003). The Nutritional Survey and Blood Collection Survey will be conducted in the spring of 1999. The Nested Case-Control studies will be performed annually beginning in 2000, and the Vital/Cancer Interview Survey will be conducted in the Spring of 2001.

Early life exposures now appear to be important in modulation of the immune response and tendency to develop asthma. We plan to enroll a cohort of children at birth to study early life factors in the development of wheezing and respiratory illness during the first six years of life in Mexico City. In particular, we will consider the role of early diet (particularly antioxidant intake, lactation and obesity), infections, dust mite and cockroach antigens, traffic related air pollution, and environmental tobacco smoke. We will also consider the potential modifying effect of genetic predisposition with respect to the exposures of interest.~Approximately 6,800 children will be enrolled at birth. The goal is to follow the cohort though age 6. To increase the number of expected cases of asthma, we will partially enrich the cohort for increased risk of asthma by virtue of having a parent with doctor diagnosis of asthma or allergies; the remaining cohort will not be enriched to preserve generalizability.~Pregnant women enrolled in a prepaid health plan in Mexico City (the Insituto Mexicano de Seguridad Social, henceforth referred to as IMSS) will be screened for the study and invited to enrolled their newborns when they come for delivery at one of two IMSS hospitals. An initial home visit during the first three months of life will include assessment of environmental exposures and infant diet. Children will be followed through age six with yearly home visits, monitoring of acute lower respiratory illness during the first year of life and periodic review of the IMSS medical records.~We have chosen Mexico City because of the relatively low rates of asthma in the face of prevalent exposures to factors that are thought to increase asthma risk in urban areas in the United States. These include dust mites, cockroach, airborne pollutants and social factors such as low income and young maternal age. This pattern suggests that protective factors may be operating in Mexico City that could shed light on the etiology of worldwide childhood asthma epidemic. Potential candidates include exposure to certain early infections that shift the developing immune system away from the pattern of allergic asthmatic response. We are also especially interested in potential protective effects of early nutrition. Exposure to ozone in this population is the highest in North American and thus antioxidant intake may be especially important. In order to evaluate these protective hypotheses, we will also collect information on risk factors believed to be related to increased risk of asthma in US cities such as allergens, traffic related air pollutants, and lower respiratory infection with respiratory syncytial virus.

Early life exposures now appear to be important in modulation of the immune response and tendency to develop asthma. We plan to enroll a cohort of children at birth to study early life factors in the development of wheezing and respiratory illness during the first six years of life in Mexico City. In particular, we will consider the role of early diet (particularly antioxidant intake, lactation and obesity), infections, dust mite and cockroach antigens, traffic related air pollution, and environmental tobacco smoke. We will also consider the potential modifying effect of genetic predisposition with respect to the exposures of interest.~Approximately 6,800 children will be enrolled at birth. The goal is to follow the cohort though age 6. To increase the number of expected cases of asthma, we will partially enrich the cohort for increased risk of asthma by virtue of having a parent with doctor diagnosis of asthma or allergies; the remaining cohort will not be enriched to preserve generalizability.~Pregnant women enrolled in a prepaid health plan in Mexico City (the Insituto Mexicano de Seguridad Social, henceforth referred to as IMSS) will be screened for the study and invited to enrolled their newborns when they come for delivery at one of two IMSS hospitals. An initial home visit during the first three months of life will include assessment of environmental exposures and infant diet. Children will be followed through age six with yearly home visits, monitoring of acute lower respiratory illness during the first year of life and periodic review of the IMSS medical records.~We have chosen Mexico City because of the relatively low rates of asthma in the face of prevalent exposures to factors that are thought to increase asthma risk in urban areas in the United States. These include dust mites, cockroach, airborne pollutants and social factors such as low income and young maternal age. This pattern suggests that protective factors may be operating in Mexico City that could shed light on the etiology of worldwide childhood asthma epidemic. Potential candidates include exposure to certain early infections that shift the developing immune system away from the pattern of allergic asthmatic response. We are also especially interested in potential protective effects of early nutrition. Exposure to ozone in this population is the highest in North American and thus antioxidant intake may be especially important. In order to evaluate these protective hypotheses, we will also collect information on risk factors believed to be related to increased risk of asthma in US cities such as allergens, traffic related air pollutants, and lower respiratory infection with respiratory syncytial virus.

The chemopreventive efficacy of Se was tested in a 10-year human intervention trial; total and lung cancer mortality, total cancer incidence, colorectal cancer and prostate cancer incidence decreased. This study is designed to compare, via stable isotope tracer studies the kinetics of inorganic and organic Se before and following two years of oral supplementation with L-selenomethionine, to measure forms of Se in the plasma (extracellular Se-dependent glutathione peroxidase [GSHPx], selenoprotein-P [SeP], albumin-bound Se [AlbSe] and nonprotein-bound low molecular weight [LMWSe] fractions), and to determine the effects of supplementation on the ecology of the hindgut microflora. The forms of Se were chosen to resemble the metabolism of the principal forms of Se in mixed American diets. Sodium selenite, an inorganic form, is metabolized by reduction to selenide which is then either used in the co-translational synthesis of SeCys in specific Se-containing proteins (e.g., glutathione peroxidases, diodinases, selenoproteins P and W), or is converted to methylated excretion products; in this sense it resembles the food form selenocysteine (SeCys) which is metabolized to the selenide level. Selenomethionine (SeMet), an organic form, is a major form of Se in many foods, particularly those of plan origin. In addition to being metabolized to selenide, SeMet also enters the metabolic protein pool by competing with the sulfur-containing amino acid, methionine. A study is proposed to assess the impact of selenium (Se) supplementation on its metabolism in humans.~A pilot study will be conducted to test recruitment strategies and sample collection, preparation and analysis and to assess the detectability of two stable isotopes given together. Four subjects will receive two 300 ug oral doses consisting of 150 ug of the stable isotope 76Se as selenite and 150 ug of the stable isotope 74Se as selenomethionine on study days one and twelve. Subjects will be followed for six weeks.~In the first pharmacokinetics tracer study (PK1), twenty-eight subjects will receive the same two labeled stable isotope doses, and will be followed for 4 months. In addition, two subjects who have been self-supplementing with 200 ug of Se as selenized yeast for two years will take part in PK1 to assess the sensitivity over time of the tracer assay in supplemented subjects. PK1 will be followed by a 2-yr supplementation period, in which all 28 subjects will receive daily doses of 200 ug of L0SeMet; subjects = metabolism is expected to approach a new steady state reflective of long-term supplementation. A second 4-month pharmacokinetic tracer study (PK2) will then be conducted while subjects remain on Se-supplementation with an extension of six monthly blood samples. Extensive sampling of plasma, urine, and feces during PK1 and PK2 will permit both the refinement of existing baseline models for selenite and selenomethionine metabolism in humans and the investigation of changes in metabolism arising from Se-supplementation. The study is designed to detect a difference of 0.75 standard deviation units in pre-versus post-supplementation rate parameters, assuming a two-sided test with an alpha level of 0.05 and a power of 0.80.~The non-absorbed portion of Se may favor portions of the normal colonic bacterial microflora that produce certain short-chain fatty acids that colon cells use for energy. To test this hypothesis, fecal specimens will be analyzed for short-chain fatty acids over the course of Se-supplementation. In addition, the sampling of buccal cell-Se and of toenail-Se on a quarterly basis over the course of the study and assay of thyroid hormone levels during the first year of the study will permit the investigation of possible changes in levels resulting from supplementation.

The chemopreventive efficacy of Se was tested in a 10-year human intervention trial; total and lung cancer mortality, total cancer incidence, colorectal cancer and prostate cancer incidence decreased. This study is designed to compare, via stable isotope tracer studies the kinetics of inorganic and organic Se before and following two years of oral supplementation with L-selenomethionine, to measure forms of Se in the plasma (extracellular Se-dependent glutathione peroxidase [GSHPx], selenoprotein-P [SeP], albumin-bound Se [AlbSe] and nonprotein-bound low molecular weight [LMWSe] fractions), and to determine the effects of supplementation on the ecology of the hindgut microflora. The forms of Se were chosen to resemble the metabolism of the principal forms of Se in mixed American diets. Sodium selenite, an inorganic form, is metabolized by reduction to selenide which is then either used in the co-translational synthesis of SeCys in specific Se-containing proteins (e.g., glutathione peroxidases, diodinases, selenoproteins P and W), or is converted to methylated excretion products; in this sense it resembles the food form selenocysteine (SeCys) which is metabolized to the selenide level. Selenomethionine (SeMet), an organic form, is a major form of Se in many foods, particularly those of plan origin. In addition to being metabolized to selenide, SeMet also enters the metabolic protein pool by competing with the sulfur-containing amino acid, methionine. A study is proposed to assess the impact of selenium (Se) supplementation on its metabolism in humans.~A pilot study will be conducted to test recruitment strategies and sample collection, preparation and analysis and to assess the detectability of two stable isotopes given together. Four subjects will receive two 300 ug oral doses consisting of 150 ug of the stable isotope 76Se as selenite and 150 ug of the stable isotope 74Se as selenomethionine on study days one and twelve. Subjects will be followed for six weeks.~In the first pharmacokinetics tracer study (PK1), twenty-eight subjects will receive the same two labeled stable isotope doses, and will be followed for 4 months. In addition, two subjects who have been self-supplementing with 200 ug of Se as selenized yeast for two years will take part in PK1 to assess the sensitivity over time of the tracer assay in supplemented subjects. PK1 will be followed by a 2-yr supplementation period, in which all 28 subjects will receive daily doses of 200 ug of L0SeMet; subjects = metabolism is expected to approach a new steady state reflective of long-term supplementation. A second 4-month pharmacokinetic tracer study (PK2) will then be conducted while subjects remain on Se-supplementation with an extension of six monthly blood samples. Extensive sampling of plasma, urine, and feces during PK1 and PK2 will permit both the refinement of existing baseline models for selenite and selenomethionine metabolism in humans and the investigation of changes in metabolism arising from Se-supplementation. The study is designed to detect a difference of 0.75 standard deviation units in pre-versus post-supplementation rate parameters, assuming a two-sided test with an alpha level of 0.05 and a power of 0.80.~The non-absorbed portion of Se may favor portions of the normal colonic bacterial microflora that produce certain short-chain fatty acids that colon cells use for energy. To test this hypothesis, fecal specimens will be analyzed for short-chain fatty acids over the course of Se-supplementation. In addition, the sampling of buccal cell-Se and of toenail-Se on a quarterly basis over the course of the study and assay of thyroid hormone levels during the first year of the study will permit the investigation of possible changes in levels resulting from supplementation.

Our purpose is to evaluate the changes in quality of life parameters after LASIK surgery. We intend to create a questionnaire to delineate the changes that occur in LASIK patients at the pre-operative visit and at the 1-month and 3-month post-operative visits. Additional questionnaires will be administered to demonstrate the validity of the new questionnaire. The approximate time the patient will be required to spend in clinic will be approximately 45 minutes at each of the three visits.

To evaluate the changes in quality of life parameters after LASIK surgery.

The purpose of this research is to compare the on-eye performance of 12 month daily wear versus 6-night extended wear and 30-night extended wear of novel hyper-oxygen permeable contact lenses on bacterial binding to corneal cells and central epithelial thickness. Usual and customary care will be given in the form of eyeglasses and contact lenses. To compare long-term Daily wear vs. immediate Overnight wear (Extended wear) of a new hyper-oxygen permeable silicone hydrogel contact lens on binding of Pseudomonas Aeruginosa to exfoliated human surface corneal cells collected from the eyes of human patients and on central corneal thickness, as follows: 1) a hyper Dk/t lens for 12 months of daily wear, 2) a hyper Dk/t lens for 12 months of de novo 6 night extended wear, and 3) a hyper Dk/t lens for 12 months of de novo 30 night extended wear.

The purpose of this research is to compare the on-eye performance of 12 month daily wear versus 6-night extended wear and 30-night extended wear of novel hyper-oxygen permeable contact lenses by studying its effects on human eyes. Usual and customary care will be given in the form of eyeglasses and/or contact lenses.

Umbilical cord often becomes encircled around portions of the fetus, usually the neck. The incidence ranges from 1 loop in 21% to 3 loops in 0.2%. In this study we wish to assessed the practice of severing the cord, which was encircled once around the neck of the fetus, after delivery of the anterior shoulder and prior to extraction of the body. The study and the control groups will include 30 women, each one. After diagnosis of cord around the neck during labor by ultrasound, the women will inter a randomization process. After delivery of the head, it will be cut intentionally in the study group and left intact in the control group. Neonatal outcome will be assessed.

Umbilical cord often becomes encircled around portions of the fetus, usually the neck. The incidence ranges from 1 loop in 21% to 3 loops in 0.2%. In this study we wish to assessed the practice of severing the cord, which was encircled once around the neck of the fetus, after delivery of the anterior shoulder and prior to extraction of the body. The study and the control groups will include 30 women, each one. After diagnosis of cord around the neck during labor by ultrasound, the women will inter a randomization process. After delivery of the head, it will be cut intentionally in the study group and left intact in the control group. Neonatal outcome will be assessed.

Despite the fact that lung cancer is attributed almost entirely to cigarette smoking and smoking cessation substantially decreases the risk for lung cancer, many smokers are not significantly motivated to quit smoking. A loved one's diagnosis of terminal lung cancer diagnosis presents a time when relatives who smoke are in need of and may be especially receptive to smoking cessation interventions.~The overarching aim of the study is to evaluate in a randomized trial the impact of delivering a coping-focused intervention as an adjunct to a state-of-the-science self-help program to promote smoking cessation among relatives of lung cancer patients. The specific aims are as follows:~To evaluate the impact of a coping-focused self-help intervention on relatives' rates of abstinence from cigarettes at 2 weeks, 6- and 12-months post-treatment follow-ups.~To evaluate whether any observed intervention effect on abstinence rates is mediated by improvements in relative's cognitive appraisals specifically self-efficacy, and perceived control over health outcomes, adaptive coping responses, and decreases in stress and depression~To evaluate the cost-effectiveness of the standard self-help and coping-focused interventions.~Patient diagnosed with lung cancer will be contacted and asked to enumerate their relatives (i.e., immediate family, extended family, spouses, and anyone perceived as family) and asked the smoking status of each of these relatives. Patients will then be asked for permission to send their relatives who smoke a letter that describes the study and provides a telephone number to call to decline participation. Patients who are current smokers may receive materials to help them stop smoking.~The relatives who do not call to decline participation will be contacted by the survey company to ask them to participate in a telephone survey. If eligible and willing, verbal consent will be obtained from relatives who smoke to complete the 20-30 minute baseline survey. During the telephone contact, relatives will have the opportunity to decline to complete the survey and to be further involved in the research study.~The first relative in a family who participates will be randomized to one of two intervention arms: Standard self-help (N=240) or Coping-focused self-help (N=240). Once randomized, patients will receive the following intervention:~STANDARD SELF-HELP: Relatives who smoke will receive a letter from the clinic where their family member receives care to encourage smoking cessation and to introduce the study. A tailored booklet that encourages the relative to quit smoking will introduce a self-help quit kit (e.g., written cessation booklet, audio relaxation tape, over-the-counter nicotine patches, if applicable).~COPING-FOCUSED SELF-HELP: Participants in this arm will receive a letter from the clinic where their family member receives care (i.e. TOP, MTOP, or MTOC), tailored booklet and self-help quit kit. In addition, these relatives will receive a total of six counseling phone calls that will be delivered in tandem with the tailored materials. Optimally these phone calls will be scheduled once a week for a total of six weeks in order to retain participation and to encourage practice and use of skills covered during the phone calls. All calls must be completed with a 12-week period. Each intervention component will emphasize: the salience of the patient's diagnosis as a prompt for smoking cessation or to maintain abstinence and the importance of coping in ways that promote successful smoking cessation.~All family members will be surveyed at baseline, 2 weeks, 6 months and 12- months follow-up.

The purpose of this study is to evaluate the impact of delivering a coping-focused intervention as an adjunct to a self-help program to promote smoking cessation among relatives of lung cancer patients.

Women with a family history of breast cancer have several menopausal therapy options, including tamoxifen, hormone therapy, alternative medications, or no treatment. This complex decision should be based on each woman's risk to develop breast cancer, menopausal symptoms, preferences, and risks for other conditions. Current models in use for menopausal therapy counseling do not include pedigree analysis, personalized risk assessment or genetic testing in this process. The purpose of this multi-center study is to determine the effects of a personalized risk assessment and genetic counseling intervention on knowledge, risk perception, and decision-making in a group of healthy women who had a first-degree relative with breast cancer. Intervention participants will be given a personalized risk assessment for breast cancer, heart disease, osteoporosis, and uterine cancer based on family history and personal health data.

The purpose of this study is to determine the effects of a personalized menopausal therapy risk assessment and genetic counseling intervention on knowledge, risk perception, and decision-making in healthy women at increased risk for breast cancer.

The purpose of this study is to test if temperature homeostasis in football players can be improved by circulating cool, dry air underneath shoulder pads between periods of intense physical activity. To assess the efficacy of this intervention, several dependent variables will be tested: core body temperature, skin temperature, infrared skin temperature, heart rate, sweating rate, urine color, urine specific gravity, physiological strain index, visual analog thirst, rate of perceived exertion, thermal sensation scale, and fluid intake. The two independent variables (test variables) are treatment which has two levels (Control - no air blown under the shoulder pads, COOL - cool, dry air blown under the shoulder pads) and time (pre-exercise and post-exercise cycles, rest break and recovery).~Specific Aim 1: To assess differences in physiological parameters when cooled dry air is blown under football shoulder pads as a means of cooling football players between periods of exercise and after exercise. Limited research is available to demonstrate the efficacy of cooling methods alternated with vigorous exercise. Football players are at particular risk for heat-related illness because they frequently practice and compete in hot, humid conditions in uniforms that limit the body's natural thermoregulation. To study this specific aim, three hypotheses will be addressed during the data collection process of this investigation: (1) a significantly lower increase in core body temperature, heart rate, skin temperature, and infrared skin temperature will be noted during the COOL testing sessions as compared to the Control sessions; (2) significantly lower measurements of urine color, urine specific gravity, and sweat rate will be noted in the COOL testing sessions as compared to the Control sessions; and (3) significant associations will be noted between core body temperature and infrared temperature during both testing sessions.~Specific Aim 2: To assess differences in subjective ratings of exertion and heat stress during and after exercise sessions when cooled dry air is blown under football shoulder pads as compared to no air during rest breaks between the exercise bouts. The rationale behind Specific Aim 2 is that the cooling method (COOL) will aid in improving the body's blunted cooling mechanisms. The sensation of the cool, dry air will be more prominent than the sensation of warmth (during the COOL trials), the decrease in physiological strain, and the decrease in core body temperature will cause the subject to experience lower perceived exertion; thus, subjects' subjective response to exertion in subsequent exercise cycles will be decreased. One hypothesis will be addressed related to this specific aim: cool, dry air blown under football shoulder pads (COOL) as a cooling method between exercise bouts will significantly lower physiological strain index score, visual analog thirst score, rate of perceived exertion, and thermal sensation score as compared to no cool, dry air being blown under the shoulder pads (Control).

The purpose of this study is to test if temperature homeostasis in football players can be improved by circulating cool, dry air underneath shoulder pads between periods of intense physical activity.

Current European Best Practice Guidelines and the KDOQI Committee in the USA recommend preferential subcutaneous (SC) twice- to thrice-weekly epoetin administration. SC route significantly reduces epoetin requirements and therefore costs, compared to the intravenous (IV) route. Additionally, there is solid evidence showed once-weekly SC administration of epoetin beta to be equally efficient and well tolerated in hemodialyzed (HD) patients. Clinical studies suggest that the effects of epoetin alpha are sustained for more than one week, enabling less frequent schedules in pre-dialysis chronic kidney disease (CKD) patients. A recent European multicenter study in peritoneal dialysis (PD) patients confirmed that once-every-two-weeks SC epoetin beta is efficient and safe in the maintenance phase of anemia treatment for PD patients11. Thus, the optimum epoetin dosing regimen is still yet to be determined despite over a decade of clinical use.~All these data also suggest that the pharmacodynamic effects of epoetins could last longer than their plasma half-lives. The survival half-life of erythrocytes produced after exogenous epoetin administration is longer than that of erythrocytes produced in the absence of exogenous stimulation.~Apart of the academic interest, this issue has also direct implications on cost savings and increased patients' convenience. Furthermore, less frequent administration would reduce epidemiological hazards associated with populations at high risk of blood-borne viral infections such as hepatitis, particularly important in less developed countries, with a high prevalence of viral hepatitis infections (hepatitis B/C markers prevalences: 15.7%/45% in Romania versus 3%/13.5% in EuroDOPPS patients). While the potential benefits of less frequent dosing are clear, the efficacy and safety of such regimens must be fully investigated before adoption as standard treatment.~The present study investigates for the first time the equivalence of once-weekly versus once-every-two-weeks SC epoetin beta dosing regimens, in the maintenance phase of anemia therapy, in stable HD patients. The aim of the study is to assess whether once-every-other-week SC administration of the same total epoetin beta dose is as effective and as safe as SC once-weekly dosing.~In order to avoid a carry-over effect of the weekly schedule of epoetin treatment received prior to randomization, we defined a run-in period (weeks 1-12). Statistical analyses will be performed for the efficacy parameters determined during the assessment period only. The average for weeks 13-24 will be obtained by adding all values and dividing the sum by the number of time points for each patient during this period.~The two treatment schedules will be considered equivalent if the primary efficacy parameters will be simultaneously similar for both groups and in the predefined range of variation. Confidence intervals (CIs) will be used to compare groups. Since the target Hb in dialyzed patients is defined as 11g/dL (110 g/L) by the European Guidelines and as >10 g/dL (100 g/L) by the National Guidelines, with a recommended upper limit of 13 g/dL (130 g/L), the efficacy range for Hb in this study was predefined as 10-12 g/dL (100-120 g/L). The two treatment schedules will be considered to have similar efficacy if the mean Hb in Group 2w will not differ by more than ±0.5 g/dL (±5 g/L) compared to Group 1w during the assessment period. Once similar efficacy established, drug requirements will be compared calculating the ratio of the mean weekly epoetin doses in Group 2w/Group 1w. A range of 0.8 to 1.25 for the ratio is considered sufficient to define bioequivalence. Equivalence of drug usage in the two arms will be accepted if the whole 95% CI for this ratio will be within the above limits.~Lack of difference between group means does not imply similar distribution of treatment effects within each group. The individual hemoglobin change will be used to assess if response to treatment was similarly variable in the two arms. The change in Hb will be calculated for each patient as the difference between the mean Hb during the assessment period and the mean Hb during the baseline phase. The percentages of patients with target Hb and not requiring any increase in epoetin dose during the assessment period will be compared with chi-squared statistic.~The study is designed to detect a difference in Hb between the study groups of at least 0.5 g/dL (5 g/L), with a probability of 95% and a power of 0.9021, assuming a standard deviation of Hb in the HD population of 1.0 g/dL (10 g/L). A sample size of 85 patients is required in each arm of the trial. Since the study design includes epoetin doses variations in order to maintain target hemoglobin, it would have been expected that Hb would be constant and epoetin dose would vary. Therefore, the power calculations using epoetin doses as the outcome measure seem to be more appropriate. Considering a standard deviation of 39 IU/kg per week, a probability of 95% and a power of 90%, a sample size of 70 patients in each arm is required to detect a ± 20% difference in epoetin dose between groups. Because of an anticipated drop-out proportion of 15%, a minimum of 100 patients have to be enrolled in each group to satisfy both Hb and epoetin doses power conditions.

Currently, less frequent than once weekly subcutaneous epoetin administration regimens were shown to be equally effective and safe as the once-weekly schedules in stable pre-dialyzed and peritoneal dialyzed patients Bioequivalence of once-every-two-weeks and once-weekly subcutaneous administration of the same total dose of epoetin beta for the maintenance phase of anemia treatment in stable, iron-replete, chronic hemodialyzed patients was therefore prospectively investigated.~two treatment schedules will be considered equivalent if the primary efficacy parameters will be simultaneously similar for both groups and in the predefined range of variation. Confidence intervals (CIs) will be used to compare groups. Since the target Hb in dialyzed patients is defined as 11g/dL (110 g/L) by the European Guidelines and as >10 g/dL (100 g/L) by the National Guidelines, with a recommended upper limit of 13 g/dL (130 g/L), the efficacy range for Hb in this study was predefined as 10-12 g/dL (100-120 g/L). The two treatment schedules will be considered to have similar efficacy if the mean Hb in Group 2w will not differ by more than ±0.5 g/dL (±5 g/L) compared to Group 1w during the assessment period. Once similar efficacy established, drug requirements will be compared calculating the ratio of the mean weekly epoetin doses in Group 2w/Group 1w. A range of 0.8 to 1.25 for the ratio is considered sufficient to define bioequivalence. Equivalence of drug usage in the two arms will be accepted if the whole 95% CI for this ratio will be within the above limits.~Lack of difference between group means does not imply similar distribution of treatment effects within each group. The individual hemoglobin change will be used to assess if response to treatment was similarly variable in the two arms. The change in Hb will be calculated for each patient as the difference between the mean Hb during the assessment period and the mean Hb during the baseline phase.

Background: Bi-, tri- and multi- focal ('multifocal') glasses have been associated with increased rates of falls in older people (Lord et al 2002).~Study Aim: To determine whether the provision of supplementary plain distance glasses for outdoor use to older users multifocal glasses will reduce falls rates over a 12 month period.~Study Design: A randomised controlled assessor-blinded trial with two parallel groups in 580 participants. Study inclusion criteria are: outdoor use of multifocal glasses 3 or more times per week, community-dwelling persons aged 65+ years with a recent fall OR persons aged 80+ years regardless of falls history, Folstein Mini Mental score of 24+, and adequate visual contrast sensitivity (Melbourne Edge Test score of 16+dB). All participants will receive an optometry assessment and updated multifocal glasses (if required) at baseline. Intervention group subjects will receive a pair of plain distance glasses and counselling for their use in predominantly outdoor situations. Control group participants will use their multifocal glasses in their usual manner. Falls rates and compliance with the intervention will be recorded on monthly falls diaries returned by the participants.

The purpose of this study is to determine whether the provision of supplementary plain distance glasses for outdoor use to older users multifocal glasses will reduce falls rates over a 12 month period.

The purpose of this study is to evaluate the safety and effectiveness of a steroid-free and calcineurin-inhibitor free treatment regimen for patients who are receiving a kidney transplant from a living donor that is HLA - identical, or in other words, has a similar immune system. The immune system is a defense system that the body uses to fight foreign substances that enter the body, such as a transplanted kidney. Two people with similar immune systems are less likely to fight off or reject an organ donated from one to the other. HLA-identical kidney transplant recipients are less likely to need large amounts of immunosuppression because they are immunologically similar. In this study, you will be treated with the immunosuppressive medications, Cellcept, Rapamune, and Prograf and after a rejection free period will remain on Cellcept alone. This treatment regimen is currently being used at The University of Cincinnati for all HLA-identical living donor kidney transplant recipients. This study is being conducted to determine if the protocol currently being used results in beneficial outcomes for HLA-identical kidney transplant recipients.~Only recently have transplant centers considered avoiding steroid therapy (prednisone) in any transplant patient because steroids have been used successfully for so long, but with many side effects. The ability to stop steroids has occurred due to the availability of newer more effective immunosuppressive medications. Stopping steroids has been tried in patients who are considered to be at both low and higher risk of kidney rejection. Patients considered at risk for rejection may typically be left on steroids forever or no attempts to stop the steroids would be made until the patient is one year after transplant and has already received a lot of steroid therapy resulting in side effects. This study will be conducted in patients that are low risk for rejection and can potentially benefit from steroid avoidance.~Overall, the concept of steroid avoidance in patients that are at low risk for rejection is now much more acceptable because newer, more potent medications have recently become available to prevent acute rejection. These newer medications include Prograf (tacrolimus), Cellcept (mycophenolate mofetil), and Rapamune (sirolimus). Currently, most kidney transplant recipients receive medications consisting of tacrolimus or cyclosporine, mycophenolate mofetil or azathioprine, and steroids. However, recently, the combination of Prograf (tacrolimus) and Rapamune (sirolimus) with steroid withdrawal 3 months after transplantation was studied in patients receiving liver, liver/kidney, and kidney/pancreas transplants. This study showed a low rate of acute rejection with excellent patient and kidney survival.~The addition of Cellcept to Prograf and Rapamune is thought to be a safe and effective alternative to the use of steroids in transplant patients. Due to the low risk of rejection for HLA-identical kidney transplant recipients, patients in this study will be slowly withdrawn from both Rapamune and Prograf over a rejection free period of time. Withdrawal of these medications and avoidance of steroids could decrease the development of high blood pressure, high cholesterol, diabetes, tremors, and infection after transplant. This study will determine if this medication regimen is safe, effective, and able to produce beneficial post transplant outcomes.

The purpose of this study is to evaluate the safety and effectiveness of a steroid-free and calcineurin-inhibitor free treatment regimen for patients who are receiving a kidney transplant from a living donor that is HLA-identical (has a similar immune system).

Objective The supermarket industry now services many customers through online food shopping over the Internet. The Internet shopping process offers a novel opportunity for the modification of dietary patterns. The aim of this study was to evaluate the effects on consumers' purchases of saturated fat of a fully automated computerised system that provided real-time, personally tailored advice recommending foods lower in saturated fat.~Design Blinded, randomized controlled trial.~Setting & Participants Consumers using a commercial on-line Internet shopping site between February and June 2004.~Intervention Individuals assigned to intervention received fully automated individually tailored advice that recommended specific switches from selected products higher in saturated fat to alternate similar products lower in saturated fat. Participants assigned to control received general non-specific advice about how to eat a diet lower in saturated fat.~Outcome measure The percent of food purchased that was saturated fat. Results There were 497 randomised participants, mean age 40 each shopping for an average of about 3 people. The amount of saturated fat in the foods purchased by the intervention group was 0.66% lower (95% confidence interval 0.48-0.84, p<0.0001) than in the control group. The effects of the intervention were sustained over time and there was no difference in the average cost of the food bought by each group.~Conclusions Fully automated, personally tailored dietary advice offered to customers doing Internet shopping can bring about changes in food purchasing habits that are likely to have significant public health implications. Because implementation is simple to initiate and maintain this strategy would likely be highly cost-effective.

The supermarket industry now services many customers through online food shopping over the Internet. The Internet shopping process offers a novel opportunity for the modification of dietary patterns. The aim of this study was to evaluate the effects on consumers' purchases of saturated fat of a fully automated computerised system that provided real-time, personally tailored advice recommending foods lower in saturated fat.

The immunosuppressant sirolimus is a substrate for the drug efflux pump p-glycoprotein~(Pgp) and the hepatic and intestinal drug metabolizing enzyme cytochrome P450 3A4/5~(CYP3A4/5). Single nucleotide polymorphisms (SNPs) in the multi-drug resistance (MDR)-1~gene which encodes for the Pgp, CYP3A4, and CYP3A5 genes have been shown to be associated with altered metabolism of various drugs including the immunosuppressants cyclosporine and tacrolimus. This protocol will evaluate the effects of MDR-1, CYP3A4, and CYP3A5 gentotypes/haplotypes on the pharmacokinetics and pharmacodynamics of sirolimus in patients with renal transplantation. All patients who had kidney transplantation at the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) Transplant Branch, participated in one of the NIDDK therapeutic protocols, and have received sirolimus will be enrolled in this study. Selected MDR-1, CYP3A4, and CYP3A5 SNPs will be determined by polymerase chain reaction based methods using existing patient blood samples. Demographic, pharmacokinetic, and pharmacodynamic data will be collected from the medical information system, NIDDK transplant database, and medical records of these patients. Population pharmacokinetic parameters and pharmacodynamic measurements will then be compared among patients with different MDR-1, CYP3A4, and CYP3A5 genotypes/haplotypes. Results from this study will help to understand the effects of pharmacogenetics on sirolimus pharmacokinetics and pharmacodynamics, and will provide information for rationalizing sirolimus dosing in patients with renal transplantation.

This study will evaluate the effects of certain genes (MDR-1, CYP3A4, and CYP3A5) on metabolism of the drug sirolimus, an immune-suppressing drug given to transplant recipients to prevent organ rejection. Individual differences in metabolism and excretion of sirolimus affect the patient's response to treatment.~Patients who have undergone kidney transplantation at the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) Transplant Branch and have received sirolimus treatment will be enrolled in this study.~DNA (genetic material) will be extracted from blood samples collected from transplant recipients to determine their MDR-1, CYP3A4, and CYP3A5 genotypes. Patient demographic information and data on sirolimus metabolism and excretion will be collected from the medical information system, NIDDK transplant database, and the patients' medical records. The data will be compared among patients with different genotypes (genetic constitution of an individual) and haplotypes (set of genes that code for different proteins but are inherited as a unit) to determine the effect of these gene variations on sirolimus metabolism.~Information from this study may be applied to developing better dosing strategies, and thus, treatment outcomes for transplant patients receiving sirolimus.

This study is divided in two steps:~Step 1 (20 volunteers): IMP321 will be given alone and tested versus placebo (physiological saline)~In this first step, 4 group doses (of four subjects each) will be evaluated versus a placebo group of 4 subjects:~Group IMP321 alone at 3 µg,~Group IMP321 alone at 10 µg,~Group IMP321 alone at 30 µg,~Group IMP321 alone at 100 µg.~In order to complete these groups, four successive cohorts of volunteers will be studied:~Cohort A will correspond to the dose 3 µg and will include:~4 subjects treated by IMP321 3 µg alone~1 subject treated by placebo~If the tolerability of this cohort is acceptable, the following cohort will be done.~Cohort B will correspond to the dose 10 µg and will include:~4 subjects treated by IMP321 10 µg alone~1 subject treated by placebo~If the tolerability of this cohort is acceptable, the following cohort will be dose.~Cohort C will correspond to the dose 30 µg and will include:~4 subjects treated by IMP321 30 µg alone~1 subject treated by placebo~If the tolerability of this cohort is acceptable, the following cohort will be done.~Cohort D will correspond to the dose 100 µg and will include:~4 subjects treated by IMP321 100 µg alone~1 subject treated by placebo~Step 2 (40 volunteers): The association IMP321 + Agrippal will be tested versus the Agrippal alone.~In this second step, 4 group doses (of eight subjects each) will be evaluated versus a reference group (Agrippal + physiological saline) of 8 subjects:~Group Agrippal + 3 µg of IMP321,~Group Agrippal + 10 µg of IMP321,~Group Agrippal + 30 µg of IMP321,~Group Agrippal + 100 µg of IMP321.~In order to complete these groups, four successive cohorts of volunteers will be studied.~Cohort A will correspond to the dose 3 µg of IMP321 and will include:~8 subjects treated by Agrippal + IMP321 3 µg~2 subjects treated by Agrippal + physiological saline~If the tolerability of this cohort is acceptable, the following cohort will be done.~Cohort B will correspond to the dose 10 µg of IMP321 and will include:~8 subjects treated by Agrippal + IMP321 10 µg~2 subjects treated by Agrippal + physiological saline~If the tolerability of this cohort is acceptable, the following cohort will be done.~Cohort C will correspond to the dose 30 µg of IMP321 and will include:~8 subjects treated by Agrippal + IMP321 30 µg~2 subjects treated by Agrippal + physiological saline~If the tolerability of this cohort is acceptable, the following cohort will be done.~Cohort D will correspond to the dose 100 µg of IMP321 and will include:~8 subjects treated by Agrippal + IMP321 100 µg~2 subjects treated by Agrippal + physiological saline.~This study will be a single centre, single blind, placebo (step 1) or reference (step 2) randomised study.~Healthy young male volunteers will receive single ascending dose of IMP321 in each step. Treatments will be administered as a subcutaneous injection on the mornings of Day 1. The injection will be done subcutaneously (s.c.) in the deltoid area of the non dominant arm.~The pharmacokinetic analysis will be performed by IMP321-specific ELISA testing of the samples collected from the 4 volunteers receiving 100 µg IMP321 alone. Blood samples will be taken on the morning of Day 1 before dosing then at 0.5, 1, 4, 24 and 48 h after dosing.~Blood samples (for T cell assays) and serum samples (for hLAG-3Ig- and HA-specific antibody detection by ELISA) will be taken on the morning of Days 1, 29 and 57.~Monitoring for the occurrence of adverse events (AE), changes in physical examination, vital signs (blood pressure, pulse rate, respiration), electrocardiograms (ECG) and clinical laboratory tests (biochemistry, haematology, urinalysis) will be performed before and after each dose of the study drug to assess safety and tolerability.

This study is a single centre, single blind, placebo (step 1) or reference (step 2) randomised study. Healthy young male volunteers will receive single ascending dose of IMP321 in each step (4 doses tested: 3, 10, 30 and 100 µg). In step 1, IMP321 will be given alone and tested versus placebo (physiological saline). In step 2, the association IMP321 + Agrippal (commercially available flu vaccine) will be tested versus Agrippal alone.

Resistance to antibiotics is a major public-health problem and studies linking antibiotic use and resistance have shown an association not a causal effect. Utilizing the newer macrolides, azithromycin and clarithromycin that are commonly prescribed for respiratory infections, we investigated the direct impact of antibiotic exposure on resistance at the individual level. 203 healthy cohorts were treated with azithromycin, clarithromycin, or a placebo in a randomised, double-blind trial. Pharyngeal swabs were collected pre- (day 0) and post-antibiotic administration (days 8, 14, 28, 42, 180) and proportions of macrolide-resistant streptococci (MRS) were determined at each time-point.

Resistance to antibiotics is a major public-health problem and studies linking antibiotic use and resistance have shown an association not a causal effect. Utilizing the newer macrolides, azithromycin and clarithromycin that are commonly prescribed for respiratory infections, we investigated the direct impact of antibiotic exposure on resistance at the individual level.

Cervical spine stabilization is usually achieved by a semi-rigid collar. While these collars achieve the goal of supporting the cervical spine, they limit the possibilities for jaw thrust or other airway manipulations. Definitive airway protection usually must be achieved by orotracheal intubation. Thee Lubo collar is a device that simultaneously maintains cervical spine control and keeps an open airway in a non-invasive manner that is simple to operate. The objective of the study is to test the safety of the collar volunteers. The study is composed of two stages:1.healthy volunteers that will not undergo any intervention except testing the LCC.2. second group of patients scheduled to undergo an operation under general anesthesia with endotracheal intubation or laryngeal mask airway.

The Lubo cervical collar is a device that simultaneously maintains cervical spine control and keeps an open airway in a non-invasive manner. The purpose of the device is to manage cervical spine control and airway protection in the trauma patient.

The susceptibility to gain weight is highly variable even when caloric intake and physical activity are well controlled. Because basal metabolic rate (BMR) represents ~70% of total daily energy expenditure (TDEE), even a small difference in BMR can affect daily energy balance, thereby increasing the susceptibility for gaining weight. Our preliminary data indicate that high-normal growth hormone (GH) secretion is associated with resistance to weight-gain in rats when overfed and greater weight-loss in humans when underfed. Given that GH influences many of the key metabolic processes that contribute to BMR, the investigators hypothesize that persons with high-normal GH will be resistant to weight-gain because of a high BMR, resulting from accelerated rates of these processes. The investigators will measure basal 24h GH secretion and BMR in 106 non-obese men and women. The investigators will also measure protein synthesis, proteolysis, triglyceride/fatty acid cycling (all measured using stable isotope tracer methods) to determine the relationships among these processes, BMR, and GH [Specific Aim 1]. Subjects identified as having low-normal (<1.5 ug/L) and high-normal (>3 ug/L) 24h GH will then be admitted to the hospital for a 2 wk overfeeding protocol (~2000 kcal/d >TDEE - with restricted physical activity), immediately followed by a 4 wk caloric restriction protocol (~750 kcal/d <TDEE) to compare changes in weight, body composition and intra-abdominal adiposity between these groups that differ markedly in their GH secretion (GH measured before the diet) [Specific Aim 2]. A subset of subjects with low-normal GH will receive intravenous GH throughout the 2 wk overfeeding period at either: 1. a constant rate or 2. as a pulsatile infusion (to mimic endogenous secretion). BMR will be assessed daily and protein synthesis, proteolysis, and triglyceride/fatty acid cycling will be measured at the end of the 2 wks [Specific Aim 3]. The investigators anticipate that a higher GH pulsatility (peak amplitude), rather than elevated GH concentration, per se, will increase protein synthesis, proteolysis, and triglyceride/fatty acid cycling with a resultant increase in BMR and resistance to weight-gain. Identifying factors responsible for predisposing individuals to weight-gain will help combat the alarming rise in the prevalence of obesity.

With the alarming increase in the prevalence of obesity, identifying factors that predispose individuals to weight-gain is of critical importance. Even when caloric intake and physical activity levels are well controlled, susceptibility for weight-gain is heterogeneous. Basal metabolic rate (BMR) represents the largest portion of daily energy expenditure in normal adults, and as such, variability in BMR among individuals can be a major factor in determining the susceptibility for gaining weight. However, factors responsible for this variability in BMR and resistance to weight-gain remain unclear. Our preliminary data indicate that high-normal growth hormone (GH) concentration is associated with resistance to weight-gain in rats when overfed and greater weight-loss in humans when underfed. In addition, the investigators have found that the pulsatility of GH secretion has profound effects on several metabolic processes. Therefore, together these findings suggest that endogenous GH secretion is associated with body weight regulation, and the pulsatility (peak amplitude) of GH secretion, rather than the absolute GH concentration, per se, may be responsible for this effect. Because GH influences many of the key metabolic processes that contribute to BMR (e.g.; protein synthesis, proteolysis, substrate cycling), the investigators anticipate that the resistance to weight-gain in persons with elevated GH concentrations will be associated with an increase in BMR due to acceleration of some or all of these processes. Our overall hypothesis is that increased GH secretion can protect against weight-gain due to an augmentation of major metabolic processes that contribute to BMR. Identifying factors responsible for predisposing individuals to weight-gain will lead to establishing improved methods for reducing the prevalence of obesity.

In blind individuals, the occipital cortex becomes capable of processing tactile and auditory information, a phenomenon described as crossmodal plasticity. GABA is the major inhibitory neurotransmitter in the brain and a possible candidate to mediate this form of human plasticity. We intend to use magnetic resonance spectroscopy (MRS) to measure GABA and hypothesize that GABA levels in the occipital cortex of blind humans will be lower than in sighted controls. Such decrease could possibly mediate compensatory changes in the occipital cortex of the blind.~Objective~Early blind subjects exhibit better tactile acuity than late blinds or sighted individuals. The purpose of the study is the determine GABA levels in the human occipital cortex after long-term light deprivation (blindness).~Study Population~Our experiments will make use of early blind, late blind, and sighted control subjects.~Design~Subjects will be identified and will receive clinical and neurological examinations at the NIH. MRS studies will be performed at NIH MRI Center with 3Tesla Magnet. Each subject head will be positioned in an adjustable holder (designed for minimal motion and maximal comfort) such that a flat coil lay just below the occipital cortex. The sequence has been described before. The individuals who perform the data analysis will be blind to the purpose of the experiments.~Outcome measures~The concentration of GABA from the 14 ml voxel over the visual cortex will be measured. Edited proton spectrum of GABA will be compared with the edited sub spectrum of creatine for a concentration reference.

In blind individuals, the occipital cortex becomes capable of processing tactile and auditory information, a phenomenon described as crossmodal plasticity. GABA is the major inhibitory neurotransmitter in the brain and a possible candidate to mediate this form of human plasticity. We intend to use magnetic resonance spectroscopy (MRS) to measure GABA and hypothesize that GABA levels in the occipital cortex of blind humans will be lower than in sighted controls. Such decrease could possibly mediate compensatory changes in the occipital cortex of the blind.~Objective~Early blind subjects exhibit better tactile acuity than late blinds or sighted individuals. The purpose of the study is the determine GABA levels in the human occipital cortex after long-term light deprivation (blindness).~Study Population~Our experiments will make use of early blind, late blind, and sighted control subjects.~Design~Subject will be identified and will receive clinical and neurological examinations at the NIH. MRS studies will be performed at NIH MRI Center with 3Tesla Magnet. Each subject head will be positioned in an adjustable holder (designed for minimal motion and maximal comfort) such that a flat coil lay just below the occipital cortex. The sequence has been described before [33]. The individuals who perform the data analysis will be blind to the purpose of the experiments.~Outcome measures~The concentration of GABA from the 14 ml voxel over the visual cortex will be measured. Edited proton spectrum of GABA will be compared with the edited sub spectrum of creatine for a concentration reference.

This is a Phase III open-label, roll-over trial to evaluate the long term tolerability, safety, antiviral and immunological effect of TMC125 as part of an individually optimized antiretroviral therapy including TMC114/rtv in HIV-1 infected patients who participated in one of the DUET (TMC125-C206 or TMC125-C216) trials. Also the change in HIV-1 resistance over time will be evaluated. This trial offers patients meeting the definition of virologic failure at Week 24 or beyond the option to roll-over to an open-label trial where they will receive TMC125 and TMC114/rtv. Three hundred patients are estimated to enroll into this trial. The withdrawal visit of the DUET trial will be the first visit of this trial. From this visit onward, all patients will receive 200 mg twice daily TMC125 and 600/100 mg twice daily TMC114/rtv until both TMC114 and TMC125 are commercially available or the therapy is no longer of clinical benefit to the patient. Patients will receive an antiretroviral therapy consisting of TMC125 as the only non-nucleoside reverse transcriptase inhibitor (NNRTI), TMC114/rtv as the only protease inhibitor (PI) and an optimized background, which will be selected by the investigator according to the local standard of care, the patient's experience with previous therapies and most recent resistance testing. The most recent HIV-1 genotype-analysis system report results from the DUET trial will be made available. TMC125 will be dosed at 200 mg twice daily, administered orally as 2 tablets twice daily with food.TMC114/rtv will be dosed at 600/100 mg twice daily, administered orally as 2 tablets TMC114 and 1 capsule ritonavir twice daily with food.The optimized background will comprise of at least 1 approved ARV drug: 1 or more NRTI(s), with or without ENF. Administration will continue until both TMC114 and TMC125 are commercially available or therapy is no longer of clinical benefit to the patient.

The purpose of this trial is to evaluate the long-term safety and tolerability of TMC125 200 mg twice daily as part of an antiretroviral therapy including TMC114/rtv and an investigator selected optimized background in HIV-1 infected patients who have participated in a DUET trial (TMC125-C206 or TMC125 C216) and have met the definition of virologic failure at Week 24 or later in these trials.

Because genetic evolutionary changes occur slowly in Homo sapiens, and because the traditional diet of Homo sapiens underwent dramatic changes within recent times, modern humans are better physiologically adapted to a diet similar to the one their hominid ancestors evolved on than to the diet typical of modern industrialized societies. The investigators developed a computational model to estimate the net acid load of diets from the nutrient composition of the diet's component ingredients, and suggest that the majority of these hominid diets yield a negative net acid load (that is, yield a net base load), in addition to being low in sodium chloride, high in potassium-containing fruits and vegetables, and low in saturated fats, with the majority of the non-animal-source calories coming from fruits and vegetables, not from acid-producing grains, separated fats and oils, starches and refined sugars. According to paleonutritionists, Homo sapiens' recent switch from their ancestral Paleolithic-type diet to the modern Western diet has contributed in a major way to so-called age-related diseases of civilization. The investigators hypothesize and will test whether:~consuming a high-potassium, low-sodium, net base-producing Paleolithic-type diet, even in the short term, has detectable beneficial effects on cardiovascular physiology, serum lipid profiles, insulin sensitivity, and exercise performance; and~their computational model predicts the measured negative net acid loads of a net base-producing Paleolithic-type diet, using steady-state values of renal net acid excretion as the measure of the diet net acid load (a.k.a., net endogenous acid production), which will be of value in constructing net-base producing diets for modern consumption.~The long term complications of the combination of high blood pressure, high blood sugar and high fat and cholesterol levels, sometimes called the metabolic syndrome, has been termed the number one medical problem in modern society today. If eating a Paleolithic diet helps improve these diseases, this would be the first step in both improving people's health as they get older as well as contributing to future national dietary guidelines for Americans.

If eating a Paleolithic diet helps improve these diseases, this would be the first step in both improving people's health as they get older as well as contributing to future national dietary guidelines for Americans.

Research and theory concur in suggesting that certain maternal activities have both immediate and protracted consequences for children's cognitive development in the first years of life. Two conceptually distinct categories of caretaker-child interactions can be identified: social and didactic. These encompass much of the everyday behavior of infants' caretakers. There are data linking both of these types of behavior to cognitive development in children. In previous work we have investigated these relations in early infancy using samples of convenience. In the proposed study set, this work will be replicated and extended by focusing on the extent to which the characteristics of maternal age, employment status, parenthood status and birthorder of the child influence observed relations between maternal, social and didactic caretaking on the one hand and infant, toddler, preschool age, and middle childhood, and adolescent social and cognitive competencies on the other. For a subset of infants of employed mothers, their substitute caregivers will be added to the sample. Understanding the full range of experience for those infants with multiple caregivers is important in the context of a study designed to elucidate dimensions of experience that influence social and cognitive development. Naturalistic mother-infant interaction will be observed when infants are 5 months old. When study participants are 20 months old, measures of toddler functioning (e.g., play competence and language development) and maternal behavior (e.g., encouragement of attention to the environment, I.Q.) will be obtained. At 48 months, measures of preschooler psychosocial functioning (e.g., I.Q., cognitive and social competencies) and maternal behavior (e.g., scaffolding) will be obtained. At age 10 and 14 years, data assessing the child's adjustment, development, and functioning in multiple areas will be obtained from the child, both parents, and the schoolteacher (age 10 only). Measures of parental attitudes and family functioning will also be obtained. Theoretical formulations about how specific parent-child interactions may contribute to cognition have challenged investigators to look beyond demographic variables as markers of parental stimulation and to consider specific relations between types of interactions and the acquisition of particular skills at different points in time. Understanding the mechanisms linking experience in early infancy through toddlerhood, the preschool years, middle childhood and early adolescence with intellectual and social functioning is an essential aspect of normative developmental research. In addition, examining these phenomena cross-culturally will contribute importantly to our understanding of children and their families.

Research and theory tend to agree when suggesting that certain activities done by mothers have both immediate and delayed consequences for children's mental development in the first years of life.~The everyday interaction between an infant and a caregiver can be broken down into many categories. There are data linking both of these types of interaction to the mental development of children.~The study will focus on the extent to which maternal characteristics (age, employment status, parenthood status, and birth order of the child) influence the relation between maternal social and didactic caregiving and the social and mental development of children.~Mother-infant interaction will be observed when the infants are 5 months old.~When the children are 20 months old, measures of toddler function (e.g., ability to play and language development) and maternal behavior (e.g., encouragement of attention to the environment and I.Q.) will be obtained.~When the children are 48 months old, researchers will measure preschooler psychosocial functioning (e.g., I.Q., cognitive and social competencies) and maternal behavior (e.g., scaffolding).~Understanding the relation between children's experiences as infants, toddlers, and preschoolers and their eventual intellectual and social functioning is an essential part of normal developmental research.<TAB>...

The purpose of the study is to determine the safety and efficacy of two dosing regimens of daclizumab as an adjunctive immunosuppressive agent in simultaneous kidney/pancreas transplant recipients receiving tacrolimus, mycophenolate mofetil, and steroids as primary maintenance immunosuppression.

The purpose of the study is to determine the safety and efficacy of two dosing regimens of daclizumab in simultaneous kidney/pancreas transplant recipients.

Rationale and Objectives. A multitude of risk factors for falls has been reported, however many of these risk factors are not applicable to persons who use a wheelchair for mobility. Specific objectives include: (1) Describe the incidence and prevalence of wheelchair tips (near falls), falls, and fall-related injuries, (2) Describe the epidemiology of the wheelchair tip or fall event. (3) Create models for predicting wheelchair tips, falls, and fall-related injuries for elderly persons who use a wheelchair for mobility. (4) Determine healthcare utilization and direct costs associated with wheelchair-related fall injuries. (5) Describe patient perceived short- and long-term consequences of wheelchair-related falls.~Research Design. This 3-year prospective cohort study includes qualitative and quantitative data collected at baseline data and through monthly follow-up phone interviews over a 12-month period. Data Source. Baseline data on demographics, intrinsic risk factors, and extrinsic risk factors will be collected through interviews. We will assess functional status, cognition, and home management skills through standardized tools. Administrative databases will be used to gather data regarding comorbidities, Veterans Health Administration (VHA) health care utilization and direct costs. A physical therapy assistant will also conduct a wheelchair inventory and wheelchair skills test. Monthly follow-up phone interviews will include number of falls, description of the fall event/mechanism and nature of the injury, changes in modifiable risk factors, and description of injury and treatment. A separate phone interview will be conducted with a subset of subjects at 6 months post fall, using open-ended questions to gather data about patient-perceived long-term consequences of falls. At the end of the 12-month data collection, we will reassess patient's functional status and cognition. Sample. Inclusion criterion includes all veterans who (1) are aged 62 and older, (2) use a wheelchair for their primary means of mobility, (3) have used a wheelchair for at least 12 months previous to enrollment, and (4) will be using a wheelchair for at least the next 12 months. Exclusion criteria (1) no longer living in a community-based setting (e.g., admitted to nursing home), (2) do not have a telephone. We will over sample women and minorities. A total of 882 subjects are needed for a power of 0.8 and an alpha of 0.05 with an anticipated drop out rate of 30%. Analysis. Bivariate analysis will be performed to determine relationships between outcomes and risk factors. Logistic regression models for predicting wheelchair-related tips, falls and fall-related injuries will be developed based on the most important intrinsic and extrinsic risk factors, controlling for possible confounders. Falls will also be analyzed according to a survival-analysis technique. Univariate and multiple Cox regression will be used to assess the associations of different independent variables with the injurious fall. The cost analysis estimates the net or marginal costs of wheelchair users who experience a wheelchair fall accident and seek medical advice or treatment. We use a dichotomous fall (generating medical expense) variable for a with or without analysis to compare the average cost of medical care for wheelchair users without a fall involving medical observation or care to the average cost of those that did have a serious fall (including death). The difference between these two groups is a proxy of the cost of utilization due to the fall. Multivariate regression analysis will be used to gauge the net effects of a fall on costs, controlling for the wider array of factors that drive cost of treatment and thereby potentially confound univariate analysis. The control variables are demographic including co-morbid conditions and healthcare related.~Anticipated Impact. Our project is expected to identify previously unaccounted for factors that predispose persons who use a wheelchair to falls and fall-related injuries. We will create models for predicting wheelchair tips, falls, and fall-related injuries. These models will be used to develop an evidence-based, patient centered wheelchair falls prevention program targeting modifiable risk factors. Findings from this study will be so used to develop an instrument to identify fall risk in elderly wheelchair users as well as an evidenced-based prevention program. We will partner with the VA National Center for Patient Safety to disseminate these products nationally in the VHA.

The purpose of this study is to find out about the risk factors for wheelchair-related falls among elderly veterans, and to find out about the costs and consequences of those falls.

Experimental headache model open a unike opportunity to study the pathophysiological mechanisms behind headache in general and migrane in particular. Previous studies have used various techniques to study the cerebral haemodynamics as a basis for the headache pathophysiology. We wish to use a 3-Tesa MRI so study the cerebral haemodynamics after application of various pharmacological substances.~The most used experimental headache model is the glyceryl trinitrate model (GTN). Where infusion of the NO donor GTN induces headache and changes in the cerebral arteries. On the other hand injection of Diamox (Acetazolamide) apparently causes increase of the cerebral blod flow with out dilation of the arteries. We wish to study the precise effect of GTN and diamox on the cerebral haemodynamics such as Cerebral blod flow (CBF) and Cerebral blod volume (CBV) via a 3-Tesla MRI.

After infusion / injection of Glyceryl trinitrate and Diamox it is wished to study the effect of drugs on the cerebral haemodynamics such as Cerebral blod flow and cerebral blod volume.

Experimental headache models give a unike opportunity to study pathophysiological mechanisms of prim. headache types such as migraine. Previous studies have used different methods that have had limitations and none of them have had the opportunity to study neuronal activation. But that is possible with the application of functional magnetic resonance (fMRI).~Before we apply fMRI to our experimental headache models it is needed to determine how the BOLD response is influenced and changed by the infusion of different drugs such as the NO donor Glyceryl Trinitrate (GTN) and Diamox (acetazolamide). It is known that GTN causes dilation of the cerebral arteries without having any effect on the regional cerebral blood flow. It is not known what effect GTN has on the BOLD response. Diamox (azetazolamide) increases the CBF but it is uncertain what effect the drug has on the BOLD response. Previous studies disagree gravely on this point.~In this study we will be giving infusion of GTN and Diamox in healty subjects to determine:~Blood-oxygenation-level-Dependent-signal (BOLD-signal) after visual stimulation.~Changes in the diameter of a. cerebri media.~Changes in the regional and global cerebral blodd flow (CBF) with the help of the arterial Spin labeling (ASL) methode.~For the study we will be using a 3-Tesla MRI-scan.

In healthy subjects different cerebral haemodynamic values wished to be determined after infusion of the NO donor Glyceryl trinitrate (GTN) and Diamox. The different values we wish to determine are:~Blood-oxygenation-level-Dependent-signal (BOLD-signal) after visual stimulation.~Changes in the diameter of a. cerebri media.~Changes in the regional and global cerebral blodd flow (CBF) with the help of the arterial Spin labeling (ASL) method.

The objective for this retrospective clinical study is to describe the incidence of CMV infection in orthoptic liver transplant recipients who receive oral valganciclovir or ganciclovir as their CMV prophylactic anti-viral therapy.~Endpoints:~Primary Endpoint~CMV infection will be characterized as viremia, syndrome or disease by the abovementioned methods for up to one year post-transplantation.~Secondary Endpoints~Patient and allograft survival based on donor/recipient CMV status~Incidence of graft rejection and loss associated with CMV infection~Time to hepatitis C virus (HCV) occurrence~Incidence of HSV, EBV and VZV reactivations~Severity of HCV occurrence based on biopsy reports based on the Knodell score~Safety and tolerability of oral valganciclovir and ganciclovir

Null Hypothesis:~There is no significant difference in the incidence of CMV infection when using oral valganciclovir or ganciclovir as prophylactic anti-viral therapy.~Alternate Hypothesis:~There exists a significant difference in the incidence of CMV infection when oral valganciclovir is used for CMV prophylaxis rather than oral ganciclovir. A formal hypothesis to be tested should be defined.

This is a Phase I dose-escalation study of intravenous administration of IHL-305 in patients with advanced solid tumors. Patients will receive IHL-305 as an intravenous infusion over 60 minutes on Day 1 followed by a 27-day observation period for a total of 28 days (4 weeks) per cycle. Two patient populations will be evaluated separately; patients with UGT1A1*28 genotype homozygous wild-type (wt/wt) and heterozygous (wt/*28) variants as one group, and patients with UGT1A1*28 homozygous variant (*28/*28) as another group.

The purpose of this study is to determine whether IHL-305 (irinotecan liposome injection) is safe and effective in the treatment of advanced solid tumors.

this study will try to determine whether serum levels of insulin like growth factor are higher in fertile women than infertile women.The women will over 40 years old.

this study will try to determine whether serum levels of insulin like growth factor are higher in fertile women than infertile women.

Colonoscopy is widely used for the investigation of lower gastrointestinal tract disease.However,colonoscopy remains a technically difficult procedure. As the colon is a mobile organ, looping may occur when the colonoscope passes through.Hence,reducing looping during procedure is very improtant to achieve succes as well as patient acceptance.Recently,some studies shown that cap-assisted colonoscopy(CAC)allow better visualisation of the colonic folds, thus increase success rate.However, previous studies shown that magnetic endoscope imaging (MEI)is useful as an adjunct to assist endoscopist in performing the procedure and as a modality to look for the mechanism of looping. Because of such concern,our study is to compare the mechanism of looping formation and acceptance of CAC and regular colonoscopy by MEI.

The aim of this study is to compare the mechanism of loop formation and acceptance of CAC and regular colonoscopy by MEI.

The primary efficacy objective of this study is to compare the time to emergence of inadequate analgesia of 8 mg Hydromorphone Hydrochloride Extended-Release taken once every 24 hours versus placebo in the treatment of patients with persistent pain who require an opioid medication for control of their pain.

The objective of this study is to assess the efficacy and safety of 8 mg Hydromorphone Hydrochloride Extended-Release.

Induction of labor is indicated when the benefit to either the mother or fetus outweighs that of continuing the pregnancy. Labor induction in the presence of an unripened cervix is associated with prolonged labor, chorioamnionitis, and cesarean delivery. Numerous mechanical and pharmacological methods have been used for cervical ripening. There are limited numbers of rigorous studies comparing the efficacy of the various methods. One of the most common mechanical methods for cervical ripening is placement of a Foley catheter with a 30 cc balloon inside the cervix, with or without the use of oxytocin. The Foley balloon will disrupt the amniotic membrane surface and cause the release of prostaglandin, a natural chemical from the cervix, to facilitate the ripening process. Oxytocin will be used concurrently as the induction agent. Recently, a modification of this method, extraamniotic saline infusion (EASI) has become more popular. The EASI method involves similar procedure including the placement of Foley catheter inside the cervix; in addition, saline solution will be infused through the catheter. This additional step is thought to further facilitate the disruption of amniotic membrane surface. Both methods are safe and become the standard treatment for cervical ripening. However, there are no published trials so far comparing the two methods. The objective of this study is to compare the efficacy and safety of Foley catheter with oxytocin and EASI with oxytocin for induction of labor requiring cervical ripening. The study is designed to be a single masked randomized trial.

Our purpose was to compare the efficacy and safety of Foley catheter with oxytocin and extraamniotic saline infusion with oxytocin for induction of labor requiring cervical ripening.

Anti-tobacco media campaigns in many states are motivating large numbers of smokers to seek advice, assistance, and support to make their cessation efforts more successful. Like many other states, Oregon has sponsored the implementation of a statewide telephone quitline to provide information, referrals, and cessation support for callers. Two investigators on this proposal (Hollis and McAfee) have a contract with the State of Oregon to provide the Oregon Quitline (OQL) services. The purpose of the proposed research effort is to collaborate further with State representatives to answer key policy questions about how to most effectively support smokers who call the OQL for assistance.~Our overall aim is to recruit 4,500 callers to the OQL to participate in a 3 x 2 randomized trial to compare the cost and cost effectiveness of three levels of behavioral intervention. We will also test two different policies regarding the availability of nicotine patch therapy. Subjects will be interviewed by telephone at 6 and 12 months to assess smoking status, quit attempts, and use of health plan and community cessation services. Costs will be assessed separately from the perspective of the patients, health plan, the State (i.e., OQL), and society. The specific aims are described below:~Compare the efficacy of three policies for supporting OQL callers:~Brief counseling with referral to caller's health plan cessation services (standard service);~Moderate counseling, referral to health plan, and one follow-up call to reinforce use of health plan services;~Moderate counseling, referral, and availability a multi-session telephonic intervention.~Compare the efficacy of two policies regarding the provision of nicotine replacement:~No offer of nicotine replacement (current policy);~An offer of free nicotine replacement patches.~Determine the costs and cost per quit of the additional policy interventions relative to usual care (i.e., standard service) from the following perspectives:~Societal perspective (total incremental costs per incremental quit);~State perspective (incremental cost per quit for OQL services);~Health plan perspective (based on differences in use of health plan cessation services);~Participant's perspective (based on differences in out-of-pocket expenses).~Determine the incremental cost per year-of-life saved for the alternative policies relative to usual care.

State-sponsored anti-tobacco campaigns are motivating large numbers of smokers to seek advice, assistance, and support to make their cessation efforts more successful. Like many states, Oregon has sponsored the implementation of a statewide telephone quitline to provide information, referrals, and cessation support for callers. This study will answer key policy questions about how to most effectively support smokers who call the Oregon Quitline for assistance. The specific aims are to recruit 4,500 callers to participate in a 3 x 2 randomized trial comparing the cost and cost effectiveness of three levels of behavioral intervention. We will also test two different policies on the availability of nicotine patch therapy. Subjects will be interviewed by telephone at 6 and 12 months to assess smoking status, quit attempts, and use of health plan anc community cessation services. Costs will be assessed separately from the perspectives of the patients, health plans, the State (i.e., Oregon Quitline), and society. Cost per quit and cost per year quality-adjusted years of life saved will be calculated from each of these perspectives.

Currently, only 32% of adults in the United States participate in regular physical activity. Several healthcare organizations, including the Centers for Disease Control and Prevention, the National Institutes of Health, and the American Heart Association recommend that adults engage in a minimum of 2 ½ hours of physical activity each week. In a previous study, individuals who received motivational print materials in the mail increased their weekly physical activity more than individuals who received no motivational materials or who received motivational support over the telephone. However, about half of those who were mailed the print materials still did not reach the recommended goal of 2 ½ hours of physical activity per week. The purpose of this study is to compare the effectiveness of an enhanced version of an individualized, print-based motivational program versus a previously tested print-based motivational program at increasing physical activity levels in sedentary individuals.~This study will enroll healthy, sedentary individuals. Participants will be randomly assigned to either a print-based, individually tailored motivational program or an enhanced version of the same program. All participants will attend a baseline study visit, which will include body measurements, physical activity assessments, and health and psychological questionnaires. A select group of participants will also take part in an exercise test. Participants will then document their monthly physical activity. Study researchers will use this information, as well as the completed questionnaires, to develop individualized reports, manuals, and tip sheets that include feedback and strategies for increasing physical activity for each participant. Materials will be mailed to participants 14 times throughout the year. Participants in the enhanced intervention will receive additional materials that focus on increasing social support, self regulation, and outcome expectations, as well as materials on how to effectively monitor physical activity levels. They will also attend one study visit to assess their goals with the research staff. At Months 6 and 12, baseline evaluations will be repeated and all participants will be interviewed to assess physical activity levels.

Individuals who are not physically active are at risk for developing heart disease, stroke, and diabetes. Using motivational print materials is one way to encourage individuals to increase their physical activity. This study will evaluate the effect that an enhanced version of an individualized, print-based motivational program has on increasing physical activity among sedentary individuals.

The deleterious effects of institutionalized care on the health and growth and development of children have been described. Early studies have shown that the effects of institutionalized care on a child's growth and development may not be fully reversible. The exact mechanism through which these early stresses affect bio-behavioral outcomes has yet to be determined. A likely mechanism in which environmental influences could regulate both biological and psychosocial development may be through the hypothalamic pituitary adrenal axis (HPA). Recent advances in the area of brain research have enriched our understanding of the importance of early life experiences on physical, cognitive, developmental, mental and behavioral health outcomes. Children adopted from orphanages in countries as diverse as the former Soviet Union and Guatemala provide an opportunity to learn more about the effect of deprivation on neuro-endocrine function, physical growth, and developmental outcomes, including cognitive and behavioral measures.~This protocol proposes to study the changes of the HPA axis of the post-institutionalized adoptive child, ages 10 months to 4 years, which may help elucidate the etiology of the complex findings in this population. We will recruit 60 adopted children who experienced institutionalized care and were recently adopted by a US family and 60 controls. Our primary hypothesis is that a number of adopted children will have biochemical evidence of stress-induced activation of the HPA axis and sympathetic adrenal medullary system. HPA dysfunction will be evident by abnormal diurnal salivary cortisol levels, increased cortisol and/or catecholamine excretion in 24 hours urine measurements, and dysregulation of autonomic nervous system activity We also hypothesize that many of these responses will not normalize with time and that there will be a correlation between these responses and growth and behavioral disorders. In addition, we will examine nutritional intake and sleep patterns to determine their effect on growth and developmental outcome.

The deleterious effects of institutionalized care on the health and growth and development of children have been described. Early studies have shown that the effects of institutionalized care on a child's growth and development may not be fully reversible. The exact mechanism through which these early stresses affect bio-behavioral outcomes has yet to be determined. A likely mechanism in which environmental influences could regulate both biological and psychosocial development may be through the hypothalamic pituitary adrenal axis (HPA). Recent advances in the area of brain research have enriched our understanding of the importance of early life experiences on physical, cognitive, developmental, mental and behavioral health outcomes. Children adopted from orphanages in countries as diverse as the former Soviet Union and Guatemala provide an opportunity to learn more about the effect of deprivation on neuro-endocrine function, physical growth, and developmental outcomes, including cognitive, and behavioral measures.~This protocol proposes to study the changes of the HPA axis of the post-institutionalized adoptive child, ages 10 months to 4 years, which may help elucidate the etiology of the complex findings in this population. We will recruit 60 adopted children who experienced institutionalized care and were recently adopted by a US family and 60 controls. Our primary hypothesis is that a number of adopted children will have biochemical evidence of stress-induced activation of the HPA axis and sympathetic adrenal medullary system. HPA dysfunction will be evident by abnormal diurnal salivary cortisol levels, increased cortisol and/or catecholamine excretion in 24 hours urine measurements, and dysregulation of autonomic nervous system activity We also hypothesize that many of these responses will not normalize with time and that there will be a correlation between these responses and growth and behavioral disorders. In addition, we will examine nutritional intake and sleep patterns to determine their effect on growth and developmental outcome.

The frequency of post-operative permanent vision loss has been recently estimated to be 1:61,0001,2 , although the majority of these cases involve surgical trauma to the eye or brain. Prolonged vision loss not attributable to direct trauma has been estimated to occur with a frequency of approximately 1:125,0003 and has been given a broad classification termed ischemic optic neuropathy. This rare but catastrophic outcome has most commonly been associated with operations performed under circumstances in which there may be increased intraocular pressure (IOP), either due to positioning4 or due to insufflation of the abdomen with carbon dioxide (laparoscopy).5~There are two factors predisposing the robotic prostatectomy patient to an increase in IOP: step head-down (Trendelenburg) position and abdominal carbon dioxide (CO2) insufflation. The Trendelenburg position will increase central venous pressure within the thorax, which may reduce the drainage of blood flow from the head, thus increasing IOP. The CO2 insufflation may increase IOP via two mechanisms. First, by increasing intra-abdominal pressure there is a further increase in intrathoracic pressure. Secondly, insufflation the CO2 may increase the carbon dioxide content of the blood, to which the brain reacts by vasodilating and increasing blood volume. Thus while flow into the eye is increased, flow out of the eye is decreased leading to an increase in pressure inside the eye which eventually may reduce the inflow enough to cause retinal or optic nerve ischemia.~Because the pressure within the eye is an important factor in determining the blood flow to the eye, prevention of a dramatic increase in IOP may make patients less vulnerable to peri-operative ischemic optic neuropathy and vision loss. Because permanent vision loss is such a rare event after surgery, this study will measure more subtle (and most likely, temporary) vision changes (subjective blurriness, visual field deficits, decreased acuity), which occur more frequently and are thus a more easily measured outcome.6~As robotic procedures are gaining in popularity, we should determine whether they are subjecting this patient population, and perhaps more likely the patient with a preoperative diagnosis of glaucoma, to an increased likelihood of postoperative visual disturbance.

Our goal is to study the relationship between intraocular pressure during robotic prostatectomy surgery and visual deficiencies/vision loss after surgery. We believe the risk of vision loss from this surgery to be due to positioning during the operation, as well as abdominal carbon dioxide insufflation. As robotic procedures are gaining in popularity, we should determine whether they are subjecting this patient population, and perhaps more likely the patient with a preoperative diagnosis of glaucoma, to an increased likelihood of postoperative visual disturbance.If our hypothesis that intraocular pressure is increased in these patients is confirmed, future studies will assess therapeutic modalities to maintain the IOP near baseline.

To assess the efficacy and safety of 100 mg and 150 mg of DVS SR in comparison to placebo for the treatment of moderate to severe VMS associated with menopause, as well as additional outcome indicators such as sleep disruptions, overall climacteric symptoms, mood changes, somatic symptoms, and overall satisfaction with DVS SR in postmenopausal women.

The purpose of this study is to evaluate the efficacy and safety of 100 mg and 150 mg of DVS SR, an extended release form of desvenlafaxine succinate, in comparison to placebo for the treatment of Vasomotor Symptoms (VMS) associated with menopause in a population of postmenopausal women.

Objective~There have been no studies in developing countries assessing the safety of midlevel providers (MLP) compared to physicians in performing first-trimester manual vacuum aspiration abortion. In South Africa and Viet Nam, MLP (midwives and physician assistants) are trained and accredited to perform first trimester abortions to increase women's access to safe abortion services. Complication rates of first-trimester manual vacuum aspiration are compared between types of providers in the two countries.~Methods:~A randomized, two-sided controlled equivalence trial was conducted to compare rates of abortion complications. An a priori margin of equivalence of 4.5% with 80% power and a 95% CI ( = 0.025) was used. Women presenting for an induced abortion at up to 12 weeks' gestation were randomly assigned to a physician or a midlevel provider for manual vacuum aspiration and followed-up 10 to 14 days later. Complications were recorded during the abortion procedure, before discharge from the clinic and at follow-up. The study included 25 providers and 2894 cases, 1160 in South Africa and 1734 in Viet Nam.~Results:~Complication rates were 1.4 per 100 for MLP and 0 for physicians in South Africa. In Viet Nam, complication rates were 1.2 per 100 for MLP and 1.1 per 100 for physicians. In both countries, complication rates satisfied the pre-determined statistical criteria for equivalence. In South Africa, the difference in complication rates for mid-level providers and physicians was 1.4 per 100 (CI=0.4 to 2.7). In Viet Nam, the difference in complication rates for mid-level providers and physicians was 0.1 per 100 (CI= -1.0 to 1.2). There were no major immediate complications. Delayed complications were retained products and infection.~Conclusions:~First trimester manual vacuum aspiration abortions performed by trained and accredited midlevel providers in South Africa and Viet Nam were comparable in safety to those performed by physicians. Given appropriate training, midlevel health care providers can provide first trimester manual vacuum aspiration abortions as safely as physician abortion providers.

There have been no studies in developing countries assessing the safety of midlevel providers (MLP) compared to physicians in performing first-trimester manual vacuum aspiration abortion. In South Africa and Viet Nam, MLP (midwives and physician assistants) are trained and accredited to perform first trimester abortions to increase women's access to safe abortion services. To assess the safety of abortions performed by midlevel provider compared to physicians, complication rates of first-trimester manual vacuum aspiration are compared between types of providers in the two countries. We test the null hypothesis that the two types of providers provide abortions equally safely.

This is a Phase 2 multiple site, single-arm, open-label study designed to evaluate the safety of rThrombin in subjects of age 2 to 75 years who are receiving a partial- or full-thickness autologous sheet or mesh grafts following burn or traumatic skin injury. After establishing eligibility, study participants will be treated with topical spray rThrombin at the skin graft recipient site during autologous skin graft surgery. There will be a 1-month follow-up period after the surgery.

The purpose of this study is to evaluate whether rThrombin is safe when used for controlling bleeding during skin graft surgery.

The purpose of this study is to determine whether the timing of the clamping of the umbilical cord after delivery has an impact on neonatal hemoglobin and hematocrit, tests that determine the number of red cells in the blood and their ability to carry oxygen. The study hypothesis is that delaying cord clamping until cord pulsation has ceased will increase the neonatal blood volume and thereby increase the hemoglobin and hematocrit.~As the communication between the placenta and fetus, the umbilical cord provides oxygen and nutrients until the time of delivery. Even after delivery, placental respiration continues for a short time and the newborn infant continues to receive blood from the placenta until physiologic closure of the cord vessels terminates the transfusion. While most term infants can tolerate variations in blood volume, those who are compromised by prematurity, cesarean delivery or cord compression in utero may require blood transfusions if the cord is clamped before pulmonary perfusion is established. Delayed cord clamping is believed to provide a greater supply of blood to perfuse the lungs without robbing blood from the other organs.~In uncomplicated vaginal deliveries the umbilical cord traditionally has been clamped immediately after delivery, more for the doctor's convenience than for any consideration regarding the health of the infant. Both immediate and delayed cord clamping are accepted as routine standard of care at delivery, depending on the circumstances. However, some clinicians and researchers have suggested that by delaying the clamping of the umbilical cord, the placental transfusion to the newborn is maintained, optimizing blood volume and hemostasis.~Several European research studies have suggested that delayed cord clamping increases newborn hemoglobin and hematocrit. However, these studies were not performed under properly controlled conditions and thus have failed to gain general acceptance.~We propose to recruit 150 women who present for vaginal delivery at Tulsa Regional Medical Center. We believe this number of volunteers is possible to enroll in the allotted five months for data collection. A power analysis for this sample size was performed by Dr. Mark Payton, professor of statistics at the OSU Stillwater campus. He estimated that a difference of 0.3 standard deviations has a power of just over 95%.~OSU medical students will explain the study and recruit patient volunteers during routine third trimester prenatal care visits at the OSU OB/Gyn resident clinic at Houston Parke. Study investigators Drs. Beal and Carnett will determine the eligibility of those patients who agree to participate. The ethnic mix of the resident clinic population is not available because race information is not routinely entered in the MegaWest Practice Management Program currently in use.~When a volunteer presents for delivery, the resident in charge of the labor and delivery unit will remind the patient of her previous consent to participate and assign her to either the control group or the study group in an alternating fashion. Women who have agreed to participate in the study will have an identifying mark on their prenatal records which are sent from the clinic. In the control group, the umbilical cord will be clamped immediately after delivery. In the study group, the umbilical cord will be clamped once cord pulsation ceases. Patients also will be advised at this time that they can withdraw from the study at any time, regardless of the reason. The physician making group assignments and performing deliveries on a given day may not be one of the study investigators.~The inability to mask the patients and study personnel will not affect the outcome of the study as strict guidelines regarding the timing of cord clamping will be applied. Immediate clamping will entail clamping of the umbilical cord within six seconds of delivery of the fetal shoulders. Delayed clamping will be performed by clamping the cord after a palpable pulse has ceased, or after 10 minutes. Cord pulsation generally stops within two minutes of delivery. The physician performing the delivery will determine when cord pulsation stops and the clamp times, immediate or delayed will be recorded by delivery room personnel who routinely record times of delivery of infant, delivery of placenta, infant weight and APGARs. Therefore, prior knowledge of group assignment will not affect the behavior of the patient or the physician at the time of delivery.~The infants of mothers in both groups will have blood drawn for a hemoglobin and hematocrit at the time of the routine PKU heel stick. There will be no additional heel sticks to collect blood. The PKU test usually is performed within 18-24 hours of delivery. All infant study data will be collected at this time and no further blood draws will be necessary. The total amount of blood drawn from the baby will be approximately 8-10 drops, or about two teaspoons, which will include blood for the PKU test and the study tests. The results of the blood tests will then be analyzed and compared between the two groups. This comparison will also involve analysis of the mothers' admitting hemoglobin and hematocrit, blood type and demographic data, including age and smoking history, to look for possible exclusion or confounding factors. Maternal blood is routinely tested at the time of admission for blood type, hemoglobin and hematocrit. This involves the collection of approximately two test tubes of blood. No additional testing or blood collections will be performed on participating mothers other than those routinely done.~There are no increased risks to mothers or their infants who agree to participate in the study. Likewise, there are no direct benefits to participation to either mothers or babies aside from the contribution their participation makes in furthering medical knowledge. Adverse events and serious adverse events will be recorded and reported to the IRB under the policies and procedures provided by OSUCHS.~Our tentative timetable is to recruit 25 patients per month so that the data collection can be completed within five months. Tulsa Regional typically delivers about 1,000 babies monthly. Approximately 23 percent of these deliveries are cesarean sections. Of the remaining deliveries, it is reasonable to estimate that 25 patients per month could be recruited to the study.~The study population will include 150 women and their newborn infants delivered at Tulsa Regional Medical Center. Mothers must be between the ages of 18 and 34 and be full term, 37 to 41 weeks, with a singleton pregnancy at the time of delivery. Women will be excluded from the study if their delivery is complicated by non-reassuring fetal heart tones, preeclampsia, eclampsia, chronic hypertension, meconium-stained amniotic fluid, fetal anomalies or any other condition which could require immediate newborn evaluation by nursery personnel at the time of delivery. Infants requiring operative delivery by forceps or vacuum also will be excluded.~Analysis Statistical differences between the blood counts of infants in the control and study groups will be compared using independent samples t tests.

The purpose of this study is to determine whether the timing of the clamping of the umbilical cord after delivery has an impact on neonatal hemoglobin and hematocrit, tests that determine the number of red cells in the blood and their ability to carry oxygen. The study hypothesis is that delaying cord clamping until cord pulsation has ceased will increase the neonatal blood volume and thereby increase the hemoglobin and hematocrit.~We propose to recruit 150 women who present for vaginal delivery at Tulsa Regional Medical Center. Half of the women will be randomly assigned to the immediate clamping group, which will entail clamping of the umbilical cord within six seconds of delivery of the fetal shoulders. The other half of the volunteers will be assigned to the delayed clamping group, which will entail clamping the cord after a palpable pulse has ceased, or after 10 minutes. The infants of mothers in both groups will have blood drawn for a hemoglobin and hematocrit at the time of the routine PKU heel stick, usually is performed within 18-24 hours of delivery.~Statistical differences between the blood counts of infants in the control and study groups will be compared using independent samples t tests.

This study is designed to examine the effects of hatha yoga on autonomic, immune, and endocrine function. The data from both inexperienced and experienced groups will help us better understand how longer-term practice of yoga may be beneficial. The study consists of one 3-hour screening session and three 6-hour activity sessions with 30 minute follow-up appointments the following morning scheduled 2 - 4 weeks apart. Each participant will complete the 3 activity sessions, which will consist of either yoga, mild movement, or a neutral activity (watching a videotape), in randomly assigned order. Thus, both novices and experts will participate in 3 activity sessions each (yoga, movement control, video control). The order in which each participant goes through the activity sessions is counterbalanced. Data for each activity session will be aggregated by group (i.e. novice or expert). We will measure responses to tape stripping to assess skin barrier repair, and evaluate responses to computer tasks, self-report measures, and a battery of unobtrusive behavioral measures. We will also collect blood and saliva samples to measure immune and endocrine outcomes.

This study is designed to examine the impact of hatha yoga on immune and hormonal functioning in healthy individuals.

To determine the safety and efficacy of early corticosteroid discontinuation in liver transplant recipients more than 90 days post transplant, utilizing a combination of two drugs (tacrolimus and mycophenolate mofetil) for maintenance immunosuppression therapy.

To determine the safety and efficacy of early corticosteroid discontinuation in liver transplant recipients more than 90 days post transplant, utilizing a combination of two drugs (tacrolimus and mycophenolate mofetil) for maintenance immunosuppressant therapy.

The purpose of the protocol is to increase the number of living donor transplants by eliminating immune incompatibilities between donors and recipients through paired donation.~To increase the number of patients transplanted by paired donation by establishment of regional paired donation programs.~To develop educational programs for potential living donors and their recipient, as well as the opportunity for transplant professionals to increase acceptance of the PDC to maximize the opportunity for organ donation.~To identify and evaluate ethical and psychological factors that may influence the effects of paired donation on living kidney donation.

The purpose of the protocol is to increase the number of living donor transplants by eliminating immune incompatibilities between donors and recipients through paired donation.

Objectives: Lessertia frutescens (L.) Goldblatt & J.C. Manning (syn. Sutherlandia frutescens (L.) R. Br.), infusions and decoctions are widely used in South Africa as indigenous medicines, to combat cancer, infections and symptoms associated with AIDS. The aim of this study was to evaluate the safety of this phytotherapy in healthy adults.~Design: A randomised, double blind, placebo-controlled trial to evaluate the safety of Lessertia frutescens in healthy adults.~Setting: Karl Bremer Hospital, Bellville, South Africa.~Participants: 25 adults, aged 18 to 45 years, who provided informed consent. They had no significant diseases or clinically abnormal laboratory blood profiles during screening. They had no history of allergic conditions and were not on regular medical treatment.~Intervention: 12 healthy participants were randomized to a treatment arm where they received 400mg L. frutescens leaf powder capsules twice daily (800mg/day), available as a product called Sutherlandia. 13 healthy participants were randomized to the control arm, where they received an identical placebo capsule. The trial lasted 3 months.~Outcome Measures: The primary endpoint was frequency of adverse events and the secondary endpoint, changes in physical, vital, blood and biomarker indices.~Results: There were no significant differences in general adverse events, cardiovascular, CNS, GIT, infection, allergy, malaise, most physical, haematological, biochemical or physiological parameters, between the treatment and the placebo groups (P>0.05). However, subjects consuming L. frutescens mostly reported improved appetite compared to those in the placebo group (P<0.01). Although the treatment group exhibited a lower respiration rate (P<0.04), higher platelet count (P<0.03), MCH (P<0.01), MCHC (P<0.02), total protein (P<0.03) and albumin levels (P<0.03), than the placebo group, these differences remained within the normal physiological range, and were not clinically relevant. The L. frutescens biomarker, Canavanine, was undetectable in subject plasma.~Conclusion: Overall, consumption of 800mg/day L. frutescens leaf powder capsules, was well tolerated by healthy adults.

Lessertia frutescens (L.) Goldblatt & J.C. Manning (syn. Sutherlandia frutescens (L.) R. Br.), infusions and decoctions are widely used in South Africa as indigenous medicines, to combat cancer, infections and symptoms associated with AIDS. The aim of this study was to evaluate the safety of this phytotherapy in healthy adults.

The purpose of this study is to measure the amount of radiation over a specific period of time that Orthopaedic Surgeons are exposed to while using the mini c-arm fluoroscopy machine. The amount of radiation that the Surgeons will be exposed to will be recorded by a ring dosimeter located on the Surgeons' hand, and two badge dosimeters (one above the scrub collar, and one underneath a lead gown at waist level).

The purpose of this study is to measure the amount of radiation over a specific period of time that Orthopaedic Surgeons are exposed to while using the mini c-arm fluoroscopy machine.

Following screening to determine eligibility (normal medical history, physical examination including vital signs, laboratory findings, negative test for active H. pylori infection, and a negative pregnancy test if applicable) and subsequent enrolment, patients will have a baseline 24-hour intragastric pH recording. Patients will receive either oral rabeprazole 20mg or intravenous pantoprazole 40mg daily for 3 consecutive days. For blinding purposes, patients will also receive either a placebo oral tablet or placebo intravenous solution (double-dummy design). A 24-hour intragastric pH recording will be completed on Day 1 and Day 3 of the drug administration period. This will be followed by a 14-day washout period before the second 3-day drug administration period during which the patient will receive the crossover drug regimen, and will again have 24-hour intragastric pH recordings completed on the first and third days of this second drug administration period.Thirty-seven patients with a negative test for active H. pylori infection test will be randomised into the study. The primary hypothesis is that oral rabeprazole produces equivalent acid suppression to intravenous pantoprazole as indicated by the time during which intragastric pH is greater than 4 on Day 1 of drug administration. Eligible patients will be randomly assigned to 1 of the 2 treatment groups and will first receive either oral rabeprazole 20mg plus placebo intravenous solution or intravenous pantoprazole 40mg plus a placebo oral tablet daily for 3 consecutive days. After a 14-day washout, patients will receive the crossover drug regimen.~Rabeprazole: supplied as 20mg tablets (and matching placebo tablets). Pantoprazole: supplied as 12-mL vials of lyophilized powder containing pantoprazole 40mg (pantoprazole

The purpose of the study is to demonstrate in patients that oral rabeprazole produces equivalent acid suppression to intravenous pantoprazole on Day 1 of drug administration.

Many obesity-related diseases, including diabetes, cancer, and heart disease, occur more frequently in ethnic minorities than in Caucasians. African Americans have an extremely high church attendance rate, making church-based interventions a viable method to reach a wide audience and positively influence health habits and behaviors. The most effective way to prevent or reverse the effects of obesity is through weight loss, which can be accomplished by increasing physical activity and following a low fat and low sodium diet that emphasizes fruits, vegetables, and whole grains. Few programs have been developed that have specifically examined the effects of a church-based physical activity and dietary intervention. This study will encourage church leaders to assist in the development of a health promotion program that will incorporate the church's social, cultural, and policy influences. The purpose of the study is to evaluate the effectiveness of the intervention on increasing physical activity, improving blood pressure levels, and promoting healthy dietary habits among church members. The importance of pastor support and participation will be evaluated, and the results from this study may be used to develop additional church-based interventions across a larger geographic area.~In Year 1 of this 5-year study, representatives from the Palmetto Conference of the African Methodist Episcopal (AME) Church and three state universities in South Carolina will participate in monthly planning sessions to develop the intervention. Local health committees and church pastors and cooks will be trained to implement the program. The 18-month intervention will occur in three waves; where at least 60 churches will be randomly assigned to participate in either the immediate intervention or delayed intervention. The program will emphasize increased physical activity and the adaptation of a healthy diet that includes low fat and low sodium foods, fruits, vegetables, and whole grains. At baseline and Month 18, blood pressure will be measured, and physical activity levels and fruit and vegetable intake will be assessed for some church members. Additionally, throughout the study, some participants will wear an accelerometer, which is a small device that measures physical activity levels.

Obese African Americans are at risk for diseases such as diabetes, cancer, and heart disease. Church-based interventions have the potential to positively influence the health habits and behaviors of a large percentage of African Americans. The purpose of this study is to evaluate the effectiveness of a church-based program that emphasizes increased physical activity and healthy dietary habits among members of predominately African American churches in South Carolina.

This study is an open-label extension study for subjects who have completed 14 days of treatment in protocol ACH443-014A and meet all inclusion and exclusion criteria. Elvucitabine treatment (10mg) will begin on Day 1 (Day 15 following completion of protocol ACH443-014A) for all consented subjects in combination with background ART as determined by the principal investigator. Subjects will have clinical and laboratory assessments every 2 weeks for the first 8 weeks and then every 4 weeks to week 48.

To assess the safety of 48 weeks of treatment with 10 mg of elvucitabine in combination with background ART in subjects who completed protocol ACH443-014A and meet the inclusion and exclusion criteria.

Calcification is an essential part of all atherosclerotic plaques. Its extent increases with the progression of atherosclerotic disease. Heavily calcified lesions form a particular threat to DES; both damage to the polymer coating during vigorous advancement and inadequate diffusion of the drug to the subintima through extensive calcium arcs could contribute to the ineffectiveness of DES when implanted into such lesions, or may lead to primary stent delivery or expansion failure. Rotational atherectomy can effectively ablate calcified plaques. In the DES era, data concerning rotational atherectomy are scarce. DES implantation following rotablation seems a rational combination, but is only poorly supported by controlled studies. In the present study, we are using the polymer-based slow-release paclitaxel-eluting stent (TAXUS; Boston Scientific), with or without prior rotablation, in an angiographically well defined group of patients with complex calcified coronary lesions. This prospective, randomized, controlled study aims at evaluating the long term effects of both strategies in this complex cohort of patients.

The primary purpose of this study is to evaluate the long term effects of the polymer-based slow-release paclitaxel-eluting stent (TAXUS; Boston Scientific), with or without prior rotablation, in an angiographically well defined group of patients with complex calcified coronary lesions.

A cluster-randomized controlled trial was conducted at 7 intervention and 8 control hospitals to evaluate the effect of teamwork training on the occurrence of adverse outcomes and processes of care in labor and delivery. The intervention, called the Labor & Delivery Team Coordination Course, was a standardized teamwork training curriculum based on crew resource management that emphasized communication and team structure. The primary outcome was the proportion of deliveries at greater than or equal to 20 weeks gestation in which one or more adverse maternal and/or neonatal outcomes occurred (Adverse Outcome Index, AOI). Additional outcomes included 11 clinical process measures.

A cluster-randomized controlled trial was conducted at 7 intervention and 8 control hospitals to evaluate the effect of teamwork training on the occurrence of adverse outcomes and processes of care in labor and delivery.

Context: Nursing home patients admitted to the hospital pose a significant challenge for health care providers. Geriatric age, frailty, multiple readmissions, prolonged length of stay, and high mortality are just a few attributes of nursing home patients in the hospital. Geriatric teaching pays particular attention to these challenging problems. However, it is yet to be proven, whether geriatric training helps to overcome any of these issues in a better way than through non-geriatric education.~Objective: To test the hypothesis that geriatric care provides advantages over non-geriatric training in caring for nursing home patients admitted to the hospital in regards to length of stay, rate of expirations and rate of readmissions. The secondary objective is to compare expirations and readmissions among patients cared for by geriatricians and non-geriatricians.~Design, Setting, and Participants: Retrospective cohort study of patients admitted from Metropolitan Jewish Geriatric Nursing Home (MJGNH) to Maimonides Medical Center (MMC) over a certain period of time and under the care of geriatricians, non-geriatric internists, and surgeons. Comparison of the three study groups by age, sex, expiration rate, length of hospital stay (LOS) and readmission rate. Comparison of expired patients by age, sex and average LOS. Comparison of readmissions, expiration rate, by preservation of continuity of care, and by emergency room visits without admission.

Nursing home patients admitted to the hospital pose a significant challenge for health care providers. Geriatric teaching pays particular attention to these admissions and related problems. However, it is yet to be proven, whether geriatric training helps to overcome any of these issues in a better way than through non-geriatric education. The study aims to prove that geriatric training provides advantages over non-geriatric training in caring for nursing home patients admitted to the hospital.

Advances in antiretroviral therapy (ART) have dramatically reduced mortality and morbidity rates for HIV infected people. However, HIV infection is a costly disease to treat. With improvement in survival, quality of life and the long-term cost of HIV treatment have become increasingly important to the majority of individuals infected with HIV. Different HIV treatment regimens may lead to variations in quality of life and health care costs over the course of treatment. In the SMART study, participants were randomly assigned to one of two treatment groups:~Group 1 participants followed a drug conservation (DC) regimen in which ART was stopped or deferred until CD4 cell count dropped below 250 cells/mm3, initiated until CD4 cell count was at least 350 cells/mm3, and then followed by episodic ART based on CD4 cell count.~Group 2 participants followed a viral suppression (VS) regimen in which ART was continued to keep viral loads as low as possible, regardless of CD4 cell count.~The purpose of this study is to compare how the DC and VS regimens affect quality of life, symptom severity, health care utilization, and resulting costs among SMART study participants.~At baseline, participants will complete questionnaires regarding quality of life, symptoms, health care utilization, current insurance, and socioeconomic status. Body appearance and signs of HIV disease progression will also be assessed at this time. Follow-up evaluations on quality of life and symptoms will be repeated at Months 4, 8, and 12 and annually thereafter. Follow-up evaluations of all other baseline measures will occur once a year.

The purpose of this study is to compare the effects of two different anti-HIV drug regimens on quality of life and health care utilization among SMART study participants.

Study Description: Transabdominal surgery might be associated with incisional pain, fear of rupture, inhibited mobilisation and risk of incisional herniation. An abdominal binder was developed for postoperative support of abdominal incisions. The abdominal binder provides a pressure of 10-15 mmHg.~Worlds Society on Abdominal Compartment Syndrome (WSACS) defines that Normal Intra-Abdominal Pressure (IAP) is approximately 5-7 mmHg in critically ill adults, and that Intra-Abdominal Hypertension (IAH) is a sustained or repeated pathologic elevation of IAP >12 mmHg. This safety study was carried out to investigate to what extent the use of the abdominal binder influences IAP. The study was designed as a comparative cross-over study measuring bladder pressure (Foley manometer, Holtec Medical, Copenhagen) in 11 healthy volunteers with and without wearing the abdominal binder.~Results IAP measurements without wearing the abdominal binder were found to be surprisingly high with a range between 8,0 and 16,7 mmHg. (mean 10,5 mmHg.). This finding is explained by the fact that the subjects were not under relaxation and the fact that half of the subjects according to their BMI were categorised as being overweight or fat. Other investigations have demonstrated that relaxation decreases IAP and that BMI is positively related to IAP.~We found that wearing the abdominal binder did increase IAP with a mean of 4,0 mmHg. (+/-1,4) or 39,3% (+/-14,61%).~In conclusion Relating our results to the WSACS guidelines regarding IAP and IAH it is not likely that the use of the abdominal binder will increase IAP to a clinically critical extent in patients with normal IAP. It must though be assessed from case to case, whether the use of the abdominal binder is appropriate.

This safety study was carried out to investigate to what extent the use of an abdominal binder influences IAP. The study was designed as a comparative cross-over study measuring bladder pressure.

Medical doctors, nurses, dentists, and dental hygienists have been shown to be effective in helping their patients quit tobacco. However, Doctors of Chiropractic (DCs) have not been utilized in this role. DCs can provide a unique channel for the conduct of tobacco interventions, but they currently receive little to no training in these techniques (Hawk & Evans, 2005). Doctors of Chiropractic are increasingly concerned with patients' use of cigarettes and smokeless tobacco. The chiropractic team provides educational and preventive services to patients, and the office visit can provide an extended opportunity to talk to patients about their tobacco use (Hawk, Long, Perillo, & Boulanger, 2004; Rupert, 2000). Given the health effects associated with chronic tobacco use, the chiropractic visit provides a teachable moment during which the DC can relate current health problems to tobacco use and provide brief counseling to patients who use tobacco (Gordon & Severson, 2001; Vogt, Lichtenstein, Ary, et al., 1989).~In the proposed developmental study, eight chiropractic clinics will participate in the design, implementation, and evaluation of an office-based tobacco cessation intervention. Adapted from previous office-based intervention protocols, the intervention will be based on Cognitive Learning Theory (Bandura, 1997) and the Clinical Practice Guidelines (Fiore, Bailey, Cohen, et al., 2000) and will also incorporate Motivational Interviewing techniques (Miller & Rollnick, 1991). Finally, using the RE-AIM framework (Glasgow, Vogt & Boles, 1999), we will assess individual-, clinic-, and organization-level variables that may affect the delivery of treatment for tobacco dependence, the implementation and maintenance of the intervention.

The purpose of the study is to develop an office-based tobacco intervention for chiropractic patients.

Main: To demonstrate the bioequivalence of the new buprenorphine transdermal patch T2rev formulation containing 13 mg buprenorphine (Test) as compared to Transtec(R) PRO 70 µg/h patch transdermal patch containing 40 mg buprenorphine as reference after multiple patch application. Pharmacokinetic target parameters are AUCss,Tau and Css,max.~Further: To assess the safety, tolerability, skin tolerability and adhesiveness of the patch applications. To evaluate the following further Pharmacokinetic parameters: Css,min, Css,ave, PTF, Swing, tss,max, and t1/2,z

The purpose of this study is to determine whether Transtec(R) PRO 70 µg/h and a new buprenorphine patch formulation lead to same plasma levels of buprenorphine after multiple dose application.

Composite resins are presently among the most popular esthetic restorative materials in dentistry. These materials offer excellent esthetic appearance, allow for conservative cavity preparation and are now becoming widely accepted for clinical use in primary molars 1-23. Despite the improvement of their properties, achieved with better materials and incremental placing techniques, composite resin restorations appear to have still several drawbacks: although similar to amalgam in short terms studies, they have a high long term failure rate, mainly due to discoloration, loss of retention and secondary caries3,11,19, are time-consuming and technique sensitive, lack anti-cariogenic potential and can be amenable to secondary caries at the cervical dentin margins 1, 2.~Continued interest in providing advance in restorative esthetic materials led to the development of new generations of composites. Among the newest material developed is the use of minute amount of nanoparticles which convert composites to possess permanent antibacterial properties.~It is of great interest to observe the clinical behavior of this new material when utilized in clinical practice. Thus the aims of the present in-vivo study are:~To evaluate the clinical and radiographic performance of the New Restorative System when placed with adhesive systems in class II restorations of primary molars.~To assess, by SEM, the micromorphology of the cervical, buccal and lingual margins of the proximal surfaces of the restored teeth retrieved after exfoliation or extraction.~To asses, by means of polarized light microscopy, the integrity of the cervical margins of the same retrieved teeth.~STUDY DESIGN The study will be performed at the Post Graduate Clinic of the Pediatric Dentistry Department of the Hadassah School of Dental Medicine in Jerusalem. The project will have to be approved by the Human Ethical Committee (Helsinki), at the Hadassah Hospital and by the Israeli Ministry of Health.~The study will be double blind, randomized, two-cell, split mouth, design.~The following clinical treating procedures will be tested:~Fissure sealants in permanent teeth~Class II restorations of primary molars.~A. SUBJECT SELECTION To be eligible to participate in the study the children will have to be between 5 to 10 years old, and present at least two primary molars with a small to moderate proximal carious lesion. These should be in proximal contact with an adjacent tooth and with an antagonist. The children will have to be available for recall appointments every six months until exfoliation of the teeth, and have parental consent to participate in this study.~Following medical history and clinical examination, bilateral bite-wing radiographs will be taken, for diagnosis of caries that need to be restored after assessment of the patient's caries risk 24.~The teeth suitable for the study will be randomly assigned to be restored with one of the two groups:~- restoring with commercial composite - hereafter control group~- restoring with commercial composite supplemented to which~B. CLINICAL PROCEDURE After local anesthesia, the teeth will be isolated with a rubber dam, and tooth preparation will be made using a #330 carbide bur under water coolant spray, having their cervical margins placed on enamel. Cavity design will be limited to caries removal without an occlusal lock, but grooves will be placed on the occlusal buccal and palatal surfaces. Line and point angles will be rounded (Fig. 1).~Fig 1: demonstrates first and second maxillary primary molars preparations before the insertion of the restorative material.~. Restorative steps~Placement of a T-band metal matrix and inserting a wedge firmly, burnishing the matrix band to establish proximal contour and contact area;~Acid etching of enamel and dentin for 15 seconds and rinsing;~Removal of excess water leaving the surface moist;~Appling two layers of Single Bond adhesive to enamel and dentin using a brush saturated with adhesive, and gently drying for 2-5 seconds;~Light curing for 10 seconds;~Applying the Restorative System incrementally.~Curing each increment for 40 seconds;~Removal of the band and curing for another 20 seconds from buccal and lingual at the cervical area.~h. Finishing and polishing the restorations using 3M™ ESPE™ Sof-Lex™ Finishing and polishing System.~Placement of a T-band metal matrix and inserting a wedge firmly, burnishing the matrix band to establish proximal contour and contact area;~Applying Adper Prompt L-Pop to the entire surface of the cavity and rubbing for 15 seconds.~Blow dry, light curing for 10 seconds.~Applying Filtek™ Supreme Universal Restorative System incrementally.~Curing each increment for 40 seconds;~Removal of the band and curing for another 20 seconds from buccal and lingual at the cervical area.~Finishing and polishing the restorations using 3M™ ESPE™ Sof-Lex™ Finishing and polishing System.~C. EVALUATION~CLINICAL The restorations will be evaluated at baseline- immediately after completion, at six months and yearly thereafter for at least three years, or until tooth exfoliation or patient drop out. The following parameters will be examined: surface appearance, color match, marginal adaptation, marginal discoloration, anatomic form and secondary caries, using the criteria described by Cvar and Ryge (1971)25 -see attached evaluation sheet.~30 restorations of each group will be randomly selected and photographed with a digital camera at baseline and after each follow up examination. The stored photographs will be assessed using the same parameters as for the clinical evaluation.~CONTACT AREA~As part of the clinical evaluation, the quality of the contact area will be assessed with waxed dental floss and classified as follows3:~A. Excellent: resistance was met while passing the dental floss; B. Fair: the contact was present, but the dental floss passed without resistance; C. Poor: No contact existed with the adjacent tooth.~RADIOGRAPHIC EVALUATION Bitewing radiographs will be taken at one-year recall intervals, and will be examined for the presence of radiolucent defects at the cervical margins, and bubbles in the body of the restoration.~POST EXFOLIATION EXAMINATION The patients will be encouraged to bring the teeth to the dental clinic after exfoliation, and they will be promised a financial reward (10.00 ₪-ten Israeli shekels = US$.2.00 approximately). They will be instructed to keep the exfoliated tooth in tap water, and small plastic vials will be provided at the recall examination closest to shedding time. The proximal margins of the retrieved teeth will be evaluated for defects and discoloration using a dental explorer.~SEM EVALUATION OF THE MARGINS~The retrieved teeth will be kept in a humid environment until the time of sectioning. Impressions (Aquasil-Dentsply DeTrey GmbH) will be taken, and epoxy replicas (Epokwick resin, Lake Bluff, IL 60044) of the proximal surfaces will be prepared and gold plated. The micromorphology of the margins will be evaluated by SEM (Jeol JSM 35), and defects at the tooth-restoration interface will be assessed at the cervical proximal margins (buccal and lingual). These defects will be classified according to the fraction of margin length showing gaps wider than 10 microns, as described by Fuks & others 26:~No gaps present at the tooth restoration margins;~Gaps present at less than 1/3 of the margin;~Gaps present at less than 2/3 of the margin;~Gaps present along the entire margin.~POLARIZED LIGHT MICROSCOPY The teeth will be embedded in acrylic resin and sectioned following the mesiodistal axis of the tooth, using the Vari/Cut VC-50 sectioning machine (Leco Corp, St. Joseph, MO 49085-2396).~One or two sections of each restoration will be sanded to become thin enough for polarized light examination. The specimens will be examined in water imbibition medium using a polarized light stereomicroscope at X20 magnification. Wall lesions and demineralization areas adjacent to the gingival margins of each restoration will be measured at an enamel distance of 100 microns, a standard distance for most recurrent caries studies27.~D. DATA COLLECTION AND ANALYSIS The restorations, contact areas, radiographs, SEM and polarized microscopy will be evaluated by at least two evaluators. In case of disagreement, the teeth will be reevaluated and the case will be discussed to reach consensus.~The results obtained will be analyzed for statistical differences between the groups.~Table I: Experimental Design: Distribution of the restored teeth.~Group Number of teeth Type of restoration~60 Filtek Supreme + Single Bond Adhesive System~60 Filtek Supreme + Adper Prompt L- Pop

Composite resins are presently among the most popular esthetic restorative materials in dentistry. These materials offer excellent esthetic appearance, allow for conservative cavity preparation and are now becoming widely accepted for clinical use in primary molars 1-23. Despite the improvement of their properties, achieved with better materials and incremental placing techniques, composite resin restorations appear to have still several drawbacks: although similar to amalgam in short terms studies, they have a high long term failure rate, mainly due to discoloration, loss of retention and secondary caries3,11,19, are time-consuming and technique sensitive, lack anti-cariogenic potential and can be amenable to secondary caries at the cervical dentin margins 1, 2.~Continued interest in providing advance in restorative esthetic materials led to the development of new generations of composites. Among the newest material developed is the use of minute amount of nanoparticles which convert composites to possess permanent antibacterial properties.~It is of great interest to observe the clinical behavior of this new material when utilized in clinical practice. Thus the aims of the present in-vivo study are:~To evaluate the clinical and radiographic performance of the New Restorative System when placed with adhesive systems in class II restorations of primary molars.~To assess, by SEM, the micromorphology of the cervical, buccal and lingual margins of the proximal surfaces of the restored teeth retrieved after exfoliation or extraction.~To asses, by means of polarized light microscopy, the integrity of the cervical margins of the same retrieved teeth.

Childhood vaccination is one of the most effective public health measures worldwide, with few serious adverse effects reported. However, pain on vaccination continues to be a frequent occurrence and is the most common cause of childhood iatrogenic pain. In a recent study of paediatricians in the USA, more than ninety percent reported at least one parental vaccine refusal in the past year. The most common concerns cited by parents were short-term reactions and pain from multiple injections.~One of the factors responsible for vaccination pain is the vaccine material itself. Even the same vaccine, when made by different pharmaceutical companies may produce different pain responses. Anecdotal reports from doctors and nurses indicate that Pentacel (DPTaP+Hib) is a relatively painless vaccine to administer whereas Prevnar (conjugated pneumococcal vaccine) causes significant pain on injection and severe distress to the infant being vaccinated. For this reason, many vaccinators administer Pentacel [DPT] prior to Prevnar [PCV] when providing both vaccines in one visit. However, the difference in infant pain responses has not been documented. Although it has been shown that very early pain events affect infants' later experience of pain, it has not been demonstrated that the sequence in which vaccines are administered affects pain response. This study will assess whether there should be a predetermined sequence recommended for administering these two vaccines, with the less painful vaccine (Pentacel) being given first.

The objective of this study is to determine whether there should be a predetermined sequence recommended for administering these two vaccines, with the less painful vaccine being given first.

Once pregnancy is recognized, most women seek prompt prenatal care and try to stop risk behaviors. Unfortunately, women with unintended pregnancies do not recognize their pregnancies promptly, and inadvertently continue risk behaviors into the vulnerable early pregnancy weeks. Home pregnancy testing is a rapid and inexpensive means of pregnancy diagnosis. The objective of this study is to determine whether women in a Medicaid population at risk for unintended pregnancy will keep a home pregnancy test on hand and (if necessary) use it appropriately

The objective of this study is to determine whether women in a Medicaid population at risk for unintended pregnancy will keep a home pregnancy test on hand and (if necessary) use it appropriately.

Peristomal skin complications are thought to be common but the exact frequency and cause of these complications are unknown. We have sought to document the incidence of cutaneous peristomal problems and to find risk factors that might contribute to peristomal complications.~A cross sectional study was conducted from September 2003 to January 2005. The study population included all persons with an ostomy living in Roskilde County, Denmark. We have attempted to include all persons with an ostomy by contacting the local municipalities administering individual aid. Danish law (law of social service section 4 chapter 19 § 97) states that every person with a chronic disease is entitled to reimbursement for any aid needed. For ostomy patients this means that they are entitled to free stoma care products from selected merchants and without restriction to type or manufacturer of ostomy product. All ostomy patients are automatically enrolled in the database at the local municipality in order to received reimbursement for product cost. It was therefore assumed that all ostomy patients were registered, as the law provides benefits without restrictions, and self-payment for alternative purchases would involve substantial additional and unnecessary private expenditure for the individual ostomy patient.~A letter was sent to every ostomy patient by the municipalities, inviting them to participate. The ostomy patients willing to participate would then return the stamped and addressed envelope with their reply. For all patients who accepted the invitation, a physical examination was scheduled.~At the time of the examination a detailed registration form was filled out to provide standardised records of known risk factors and other data of possible pertinence to the investigation.~A careful physical examination was performed by a dermatologist, a stoma care nurse specialist and a resident. The majority of ostomy patients were seen at the dermatological department Roskilde University Hospital, but a few were seen at their homes due to advanced age or physical impairment. Personal details, medical histories, stoma appliances and daily stoma care routines were recorded along with a thorough examination of the peristomal area in regards to ostomy placemant, skin retraction, hernia, stoma height and width. A general skin examination was also undertaken. Each variable was recorded and further documented by colour photographs. To ensure that the participating patients correlated to the general population, a national computer based register of all ostomy patients in Denmark were compared to our patients in regards to ostomy type, sex, age and geographical location. Patients with a peristomal skin problem and a control (person without a skin problem) were selected from the cross-sectional study and invited for further examination. At this examination several non invasive test were conducted. These non invasive test included: D-squame tapes, Capacitans measurements , TEWL(transepidermal water loss) measurements , Tape stripping, Mecanical measurements of the skin and pH measurements.

Peristomal skin complications are thought to be common but the exact frequency and cause of these complications are unknown. We have sought to document the incidence of cutaneous peristomal problems and to find risk factors that might contribute to peristomal complications.

Currently there is no standard treatment to promote wound healing for split thickness skin graft donor sites and healing is determined based on clinical observation of the graft donor site and clinical judgement. Here we propose to use two instruments commonly used in skin research to measure wound healing. This study will validate the use of these two instruments, one that measures transepidermal water loss and the other that measures skin pigmentation to determine healing. To further validate the use of these instruments we will determine if these instruments can detect differences between two different wound dressing products that have been previously reported to heal skin graft donor sites at different rates.

The purpose of this research study is to discover whether instruments widely used in skin research can be used to measure wound healing in split thickness skin graft donor sites and whether these instruments can detect differences in healing when two different dressing products are used.

The Bispectral Index (BIS) is an electroencephalogram-derived measure of anesthetic depth. A closed-loop anesthesia system can be built using BIS as the control variable, two proportional-integral-differential control algorithms, a propofol and a remifentanil target-controlled infusion systems as the control actuators. Preliminary results show that this system can be used during surgery. We propose a prospective randomized study to evaluate the effectiveness of such a closed-loop anesthesia system during the postoperative period. Two groups of patients are compared: one in which propofol and remifentanil are administered by the anesthesiologist using target-controlled infusion systems, and one in which propofol and remifentanil are administered automatically by the combined closed-loop anesthesia system. In both groups, the goal is to maintain BIS between 40 and 60, the recommended range during anesthesia by the manufacturer. We expect the combined closed-loop system group to do similar or better.

This prospective randomized study evaluates the effectiveness of a closed-loop anesthesia system during the postoperative period.

The purpose of this research is to: (1) examine the secrection of risperidone (RIS) (Risperdal) and its metabolite, 9-OH-RIS, in saliva, (2) determine the concentration ratio of RIS and 9-OH-RIS between plasma and saliva, and (3) compare the rate of decline in concentration of RIS and 9-OH-RIS in saliva and plasma by measurements at timed intervals during a single dosing interval.~RIS is a new atypical neuroleptic agent widely used in treatment of schizophrenia and related disorders. It is sometimes used in serious childhood disorders as well, such as autistic disorder. It has a beneficial effect on both positive and negative symptoms of schizophrenia, accompanied by a much lower incidence of adverse effects (e.g. parkinsonism, tardive dyskinesia, dystonias, neuroleptic malignant syndrome). RIS is also used as a treatment of children with pervasive developmental disorders (PDD). RIS is metabolized to 9-OH-RIS by hepatic CYP2D6 which exhibits genetic polymorphism. Since RIS and 9-OH-RIS are equally potent, the clinical significance of CYP 2D6 status is negligible. However, in extensive metabolizers (EM) the T(1/2) or RIS is about 3 hrs and taht of 9-OH-RIS is approximately 20 hrs. In poor metabolizers (PM) the half life of RIS is about 17 hrs and that of 9-OH-RIS 23 hrs.~Since compliance is a major problem in the management of schizophrenia, we are developing a rapid simplified test to measure RIS and 9-OH-RIS in salive and compare the concentration in samples of plasma collected concurrently. In this study, 12 adult patients (18 years and above) or minors (aged 5 to 17 years) already taking risperidone for clinical reasons will take their usual morning dose. Risperidone is usually administered once or twice a day.~At various intervals thereafter, a 1 to 2-milliliter specimen of saliva will be removed from the oral cavity by means of a syringe; in some cases it is more convenient to ask volunteers to expel saliva into a plastic cup. We will try to cover an 18-hour interval following dosing for the entire group (samples will be collected at 1/4, 1/2, 1, 2, 4, 8, 12, and 18 hours after taking the medicine. However, only some of the samples (2 or maximum of 3) will be gathered from any single patient. Following collection of saliva, a sample of 2 to 4 ml of blood will be withdrawn, and plasma will be separated and frozen. Saliva and plasma samples will gathered where the patient's drug concentrations would ordinarily be collected (e.g., Inpatient or Outpatient clinics, or phlebotomy laboratory). RIS concentrations will be measured by high pressure liquid chromatography (HPLC).

The purpose of this research is to: (1) examine the secrection of risperidone (RIS) (Risperdal) and its metabolite, 9-OH-RIS, in saliva, (2) determine the concentration ratio of RIS and 9-OH-RIS between plasma and saliva, and (3) compare the rate of decline in concentration of RIS and 9-OH-RIS in saliva and plasma by measurements at timed intervals during a single dosing interval.

This is a Phase 2, multicenter, prospective, open-label study. Once 70 patients have enrolled, subsequent patients enrolled should have a diagnosis of lymphoma. Patients who would benefit from an autologous stem cell transplant, who have failed previous collections or collection attempts with a mobilization regimen of granulocyte colony-stimulating factor (G-CSF) alone, chemotherapy and G-CSF, or any other conventional therapy including cytokines, chemotherapy and cytokines and bone marrow harvests, and who meet the inclusion/exclusion criteria are eligible to receive plerixafor as outlined in this protocol. The only change to standard of care of a mobilization regimen that includes G-CSF is the addition of a dose of plerixafor on the evening prior to each day of apheresis.~Patients will undergo mobilization with G-CSF (10 µg/kg) for 4 days. On Day 4, plerixafor (240 µg/kg) will be administered in the evening prior to the first apheresis and each subsequent evening prior to apheresis thereafter, such that there is a 10 to 11 hour interval between dosing and the initiation of apheresis. Patients will continue to receive G-CSF on each day of apheresis. Patients will undergo a minimum of 2 and a maximum of 7 aphereses or until ≥2*10^6 CD34+ cells/kg are collected, whichever occurs first. In addition, the mobilization of NHL tumor cells and the pharmacokinetics of repeat doses of plerixafor will be examined.~After the last apheresis has been completed, or after the patient has collected ≥2*10^6 CD34+ cells/kg, he/she will be treated with high-dose chemotherapy in preparation for transplantation. Patients will be transplanted with cells obtained from the G-CSF with plerixafor mobilization regimen. In the event that the minimum number of ≥2*10^6 cells for transplantation are not obtained from the first mobilization with plerixafor, cells may be retained and pooled for transplantation with those from a second mobilization with plerixafor (or from prior mobilization with other agents), at the investigator's discretion. If a second mobilization with plerixafor is attempted, a minimum rest interval of one week should be allowed between the last apheresis of the first regimen and the first dose of G-CSF of the second. The number of CD34+ cells mobilized in the peripheral blood (PB), collected in the apheresis product, and the number of apheresis sessions performed will be measured. Success of the transplantation will be evaluated by the time to engraftment of polymorphonuclear leukocytes (PMN) and platelets (PLT). Participants will be assessed for durability of their transplant for 12 months after transplantation.~This study was previously posted by AnorMED, Inc. In November 2006, AnorMED, Inc. was acquired by Genzyme Corporation. Genzyme Corporation is the sponsor of the trial.

This study evaluates the safety, efficacy, and pharmacokinetics (PK) of plerixafor given in addition to granulocyte-colony stimulating factor (G-CSF) for collection of peripheral blood stem cells (PBSCs) for autologous transplantation in patients who would benefit from an autologous stem cell transplant but have failed previous collections or collection attempts with a mobilization regimen of G-CSF alone, chemotherapy and G-CSF, or any other conventional therapy including cytokines, chemotherapy and cytokines and bone marrow harvests.~The only change to standard of care of a mobilization regimen that includes G-CSF is the addition of a dose of AMD3100 (plerixafor) on the evening prior to each day of apheresis.~Efficacy outcomes include quantification of CD34+ cells in the apheresis product and assessment of successful polymorphonuclear leukocyte (PMN) and platelet (PLT) engraftment after transplantation. PK outcomes include analysis of repeated doses of plerixafor.

This study will be carried out in a double-blinded fashion, so neither the subject nor the investigator will be aware of treatment assignment during the study. This protocol is designed to address the hypothesis that oral testosterone enanthate plus dutasteride can suppress the secretion of LH and FSH after four weeks of administration. In addition, we will compare the gonadotropin suppression mediated by a dose of testosterone enanthate (400 mg twice daily) that would be expected to maintain the serum testosterone in the normal range throughout the day, with the same dose (800 mg once daily) administered once daily. This larger once-daily dose is expected to result in a higher peak and lower trough by the end of the dosing interval. Secondary endpoints in this study include the ability of oral testosterone enanthate plus dutasteride to maintain short-term androgen-mediated endpoints such as mood and sexual function over the 4-week treatment period as well as weekly measures of safety, including blood counts, PSA and liver and kidney function.

The protocol was designed to address the hypothesis that oral testosterone enanthate plus dutasteride can suppress the secretion of LH and FSH after four weeks of administration. In addition, we will compare the gonadotropin suppression mediated by a dose of testosterone enanthate (400 mg twice daily) that would be expected to maintain the serum testosterone in the normal range throughout the day, with the same dose (800 mg once daily) administered once daily. This larger once-daily dose is expected to result in a higher peak and lower trough by the end of the dosing interval

The study is meant to give a better understanding of the basic mechanisms behind migraine, and a better understanding of the effects of sumatriptan on the trigemino vascular system.~The endpoints are changes in the plasma values of the neuropeptides vasoactive intestinal polypeptide (VIP), calcitonin gene-related peptide (CGRP) and pituitary adenylate cyclase activating peptide (PACAP) and the prostanoids 6-keto-PGF1α, and PGE2, PGD2 og PGF2α.

The study aim at examining whether Sumatriptan changes the plasma values of the neuropeptides vasoactive intestinal polypeptide (VIP), calcitonin gene-related peptide (CGRP) and pituitary adenylate cyclase activating peptide (PACAP) and the prostanoids 6-keto-PGF1α, and PGE2, PGD2 og PGF2α.

Walking to school is associated with higher levels of physical activity, which is an objective of Healthy People 2010. However, parents' concerns about safety have been identified as a barrier that prevents their children from walking to school. A walking school bus (WSB) addresses these concerns by providing a supervised period of physical activity on the way to school. A WSB is a group of children led to and from school by responsible adults who walk together along a set route. The peer-reviewed literature on active travel to school is sparse. We evaluated a WSB program, to test the hypothesis that it would increase the proportion of children walking and decrease the proportion of children driven by car to school.~Comparison: We conducted an 18-month controlled, quasi-experimental trial at three public elementary schools in Seattle, Washington. The intervention school was assigned a WSB coordinator who dedicated 10-15 hours/week establishing WSB routes and implementing school activities on pedestrian safety. Each bus had its own set route to school from different locations in the surrounding neighborhoods and was staffed by several parent leaders. The two control schools received standard Seattle Public Schools resources on walking to school including Safe Route Maps, a traffic and safety committee, and school safety patrols. The primary outcomes were the proportions of children who walked with and without an adult or were driven by car to school. We used the test for independent proportions to compare the proportion of children transported to school at the intervention versus control schools.

The purpose of this study is to determine whether a walking school bus program can increase the number of children walking to school and decrease the number of children driven by car to school.

Tobacco use is the single most preventable cause of death in the United States, with cigarette smoking accounting for nearly one-third of all cancer deaths each year. While a number of inexpensive and effective smoking cessation methods exist, including the nicotine patch and nicotine gum, smoking rates have not declined in the past few years. Individuals who engage in regular exercise, in addition to participating in a smoking cessation program, are often successful at quitting smoking and reducing post-cessation weight gain. However, past studies on this topic have consisted of highly structured, supervised physical activity, which made study recruitment and long-term adherence difficult. Additionally, these studies generally have had low long-term quit rates, which may be attributed to the lack of a nicotine replacement component. The purpose of this study is to evaluate the effectiveness of a community-based physical activity intervention, in combination with a behavioral smoking cessation program and nicotine replacement, at increasing smoking cessation rates among sedentary adult smokers.~This 7-week study will enroll sedentary or minimally active cigarette smokers. All participants will take part in a behavioral smoking cessation program and will wear a nicotine patch. In addition, they will be randomly assigned to take part in either a community-based physical activity intervention or a wellness control group intervention. All participants will attend sixteen 60- to 90-minute face-to-face counseling sessions and twelve 20-minute telephone counseling sessions. They will also receive twelve informational mailings. Participants in the physical activity intervention will focus on increasing physical activity; the general wellness control group will receive information on general health topics. Outcome measures, including smoking status, physical activity levels, and body mass index, will be assessed at the end of the intervention and at 6- and 12-month follow-up visits.

Cigarette smoking is the most common risk factor for lung cancer, and it increases the risk of developing other cancers, chronic lung disease, and heart disease. A smoking cessation program that incorporates physical activity may be beneficial in improving long-term smoking cessation rates. This study will evaluate the effectiveness of a community-based physical activity program, in combination with nicotine replacement therapy and a behavioral smoking cessation program, at improving cessation rates among sedentary smokers.

Long-term care (LTC) can be defined as the range of institutional and home and community-based services that support individuals needing chronic care. The defining values of LTC in the VA include caring for patients in the least restrictive environment consistent with meeting a patient's needs. VA faces an increasing demand for these services with the number of veterans 85 years and older, those most in need of LTC. Yet in fiscal year 2007, 87% of the 3.5 billion total VA dollars spent on LTC went to institutional care rather than the less restrictive HCBS. VA Central Office has formally committed to tripling the proportion of LTC that is HCBS between 1999 and 2011.~Findings from our team's study, Assessing Practice Variation in LTC Referrals (IIR 02-228, 2006), evaluated the LTC referral process from the perspective of the referring staff, administrators, and veterans and their families. We found that the referral process is frequently unstandardized, inefficient, and not supportive of referrals to home and community-based services. VAMCs across the country have varying ways of providing LTC referrals and some look promising. Measures of the outcomes for evaluating these systems are available with the exception of two important outcomes, satisfaction with the referral and its process and cost. The goal of this study is to develop the cost and process and satisfaction measures so that such an evaluation can be conducted.~Study Objectives: (1) Develop and test measures of patient/caregiver and provider satisfaction. (2) Develop and test measures of process and cost of the referrals. The long term objective of our research is to identify and implement models of LTC referral with the best outcomes.~Methods: Three VAMCs in VISN 11 with 3 different methods of LTC referral are the study setting. This study was conducted from October 2007-June 2010 and utilized a variety of data sources throughout this timeframe. Data sources include: the Geriatric Extended Care (GEC) form, telephone and in-person interviews, online and paper surveys, Extended Care Screening Committee meeting minutes, and technical reports from the Health Economics Resource Center (HERC). The GEC forms provided recruitment information for Veterans, caregivers, social workers and nurses in both the cost and satisfaction portions of the study and were randomly pulled by the Clinical Application Coordinators at each site. Recruitment information for VA and non-VA long term care (LTC) coordinators was supplied by Site Investigators. The cost portion of the study also utilized the Extended Care Screening Committee meeting minutes and salary information for VHA employees from the HERC technical report.~Site Investigators facilitated completion of the paper surveys by attending department meetings, and coordinated in-person interviews with providers interested in participating in the study. For all telephone interviews, participants received an introduction to the study through the mail or email. Veterans and caregivers were mailed information while VA social workers, nurses, physicians and LTC coordinators were contacted via email. Potential participants then received a telephone call from a Research Assistant who further explained the study and inquired about his/her interest in participation. For the satisfaction online survey, providers were able to complete the survey after receiving the email introduction.~Status: Complete.

Long-term care (LTC) can be defined as the range of institutional and home and community-based services that support individuals needing chronic care. The defining values of LTC in the VA include caring for patients in the least restrictive environment consistent with meeting a patient's needs. VA faces an increasing demand for these services with the growing number of veterans 85 years and older, those most in need of LTC. Yet in fiscal year 2007, 87% of the 3.5 billion total VA dollars spent on LTC went to institutional care rather than the less restrictive Home and Community Based Services (HCBS). VA Central Office has formally committed to tripling the proportion of LTC that is HCBS between 1999 and 2011.~Study Objectives: (1) Develop and test measures of patient/caregiver and provider satisfaction. (2) Develop and test measures of process and cost of the LTC referrals.~Methods: Three VAMCs in VISN 11 are the study setting. This study was conducted from October 2007-June 2010 and utilized a variety of data sources throughout this timeframe. Data sources included: the Geriatric Extended Care form, telephone and in-person interviews, online and paper surveys, Extended Care Screening Committee meeting minutes, and technical reports from the Health Economics Resource Center.~Status: Complete.

In a previous study pre-treatment with intravenous MgSO4 60 mg kg-1 was not shown to have any impact on the onset of action of rocuronium [Kussmann et al, 1997]. Yet, in that study, MgSO4 was injected as a bolus after induction of anaesthesia, one minute only before the injection of the neuromuscular blocking agent. We suppose that magnesium needs some time to penetrate the neuromuscular endplate and to shift the Mg/Ca ratio in favor of magnesium. Thus, the particular design of the previous study may explain why magnesium had no scope to enhance the speed of onset of action of rocuronium.~The aim of our study is to investigate whether an optimised pre-treatment with magnesium (short infusion rather than bolus injection; reasonable delay between administration of magnesium and subsequent injection of the neuromuscular blocking agent) enhances the speed of onset of a standard intubation dose of rocuronium.~Preanaesthetic preparation~Solid food and liquid intake will not be allowed for a minimum of six hours before induction~Patients will be premedicated with 7.5 mg oral midazolam 45 min prior to induction~Standard monitoring will consist of: ECG, SaO2, ETCO2, non-invasive blood pressure, rectal or oesophageal T°~Study drug administration~Intravenous infusion of the study solution, 1 ml per kg bodyweight, corresponding to MgSO4 60 mg kg-1 in the magnesium group. The infusion will be given with an Infusomat during 15 minutes.~Induction and maintenance of anaesthesia~At the end of the study drug infusion, and after a preoxygenation period of three minutes, anaesthesia will be induced with sufentanil 0.2µg kg-1 and propofol, using a Target Controlled Infusion (TCI) system (Base Primea, Fresenius-Vial, Brezins, France) and the pharmacokinetic model of Schnider et al [Schnider et al, 1999]. The initial effect site concentration will be 4 µg ml-1.~Maintenance of anaesthesia will be with a propofol effect site~Neuromuscular monitoring~Neuromuscular function will be monitored using the TOF Watch® SX (NV Organon) and TOF nerve stimulation. The guidelines for good clinical research practice in pharmacodynamic studies of NMBAs will be followed.~The ulnar nerve is stimulated through surface electrodes, and the adductor pollicis muscle response is measured.~After the stabilisation period, rocuronium 0.6 mg kg-1 (2 x ED95) will be injected intravenously during 5 seconds.~The trachea will be intubated after a 95% depression of the first twitch~5.1. Neuromuscular measurements~Onset time = time from beginning of injection of rocuronium until a 95% depression of the first twitch (T1).~Duration 25% = time from beginning of injection of rocuronium until 25% T1 recovery.~Recovery index T25-75 = time between 25% T1 recovery and 75% T1 recovery.~Clinical recovery T25 - 0.9 = time between 25% T1 recovery and TOF ratio (T1/T4) of 0.9 (corresponding to safe extubation condition).~5.2. Haemodynamics~Blood pressure~Heart rate These measurements will be done before (baseline), and at 5-minute intervals during the study drug infusion. Before and immediately after tracheal intubation, haemodynamic measurements will be repeated.~5.3. Adverse events, safety~Any minor adverse event (no need for intervention) or major adverse events will be recorded.

The aim of this study is to investigate whether an optimized pre-treatment with intravenous magnesium enhances the speed of onset of a standard intubation dose of rocuronium.

The purpose of this study is to evaluate the effect on epithelial barrier function of three emarketed multi-purpose solution applied to the human eye with hydrogel lenses as during normal regimen use.

The purpose of this study is to evaluate the effect on epithelial barrier function of three emarketed multi-purpose solution applied to the human eye with hydrogel lenses as during normal regimen use.

The goal of epidural analgesia during labour is to obtain an analgesia with a minimum of motor block. Absence of motor block at the time of the childbirth allows to decrease the rate of instrumentation (forceps, vacuum extractor). When the parturient approach complete cervical dilatation (8-10 cm), the anaesthetist must perform a last epidural injection for perineal analgesia. Generally a local anaesthetic is used (ex : Ropivacaine). Adjuvant can be associated to local anaesthetic (Sufentanil, Clonidine and more recently Neostigmine) to maximize local anaesthetic without increasing motor block.~Neostigmine, a cholinesterase inhibitor, increase concentration of acetylcholine on synaptic level and stimulate analgesic mechanisms mediated by this acetylcholine on dorsal horn of spinal cord.~Perineal pain after childbirth appears in most of the women with or without episiotomy. (Mac Arthur Am J Obst. Gynecol. 2004). This perineal pain can become source of chronic pain in 9%-12% of the cases. Neostigmine, a cholinesterase inhibitor at the dose of 500µg, combined with Sufentanil or Ropivacaine (=local anaesthetic) has an analgesic effect.~The goal of this study is to examine the effect of epidural Neostigmine for perineal analgesia at the end of the labour and on the development of chronic pain post-partum.~Inclusion criteria : any parturient of 18-45 years, normal pregnancy, at full term and having an effective epidural anaesthesia during labour.~Exclusion criteria : multiple pregnancy, obstetric pathology, refusal of participation.~Randomisation : 2 groups of 30 patients~Method :~Installation of the epidural catheter :~- Injection of Ropivacaïne + Sufentanil~Perineal analgesia :~Ropi Group : epidural injection of Ropivacaine~Neostigmine Group : epidural injection of Ropivacaine and Neostigmine~Evaluation of VAS, vital signs of parturient and fetal heart rate, instrumentation rate.~Evaluation of immediate post-partum pain (48hours) and use of analgesic medication in the ward.~Evaluation of chronic pain after 10 days and 1 month.

Perineal pain after childbirth occurs in the majority of women (with or without episiotomy). Perineal pain can become source of chronic pain in 9%-12% of the cases. Neostigmine a cholinesterase inhibitor at a dose of 500µg combined with Sufentanil or Ropivacaine (=local anaesthetic) is an analgesic. The goal of this study is to examine the effect of the use of epidural Neostigmine for perineal analgesia at the end of the labor on acute pain and on the development of chronic pain post partum.

The aim of this study is to verify whether dietary manipulations in lactating women allow increasing the fat and caloric content of human milk. specifically, we will test the following hypotheses:1) at constant caloric intake, 2 high fat (40% fat, 45% CHO) diets ( margarine e nriched versus butter enriched) lead to higher fat and caloric content of human milk than the low fat diet (5% fat, 80% CHO); and 2) All 3 groups will have strikingly different milk fatty acid profiles (mirroring the dietary fatty acid profile).

The aim of this study is to verify whether dietary manipulations in lactating women allow increasing the fat and caloric content of human milk.

The recently completed trial by the National Institute of Child Health and Human Development (NICHD)-sponsored Maternal-Fetal Medicine Units (MFMU) Network has demonstrated that intramuscular 17-alpha-hydroxyprogesterone caproate (17-OHPC) substantially reduces the rate of preterm birth in women at high risk for preterm delivery because of a prior spontaneous preterm birth. No other strategy or treatment for prevention of preterm birth has proven to be effective. Consequently, the American College of Obstetricians and Gynecologists has cautiously supported this treatment but points out that much more information about this therapy and alternative therapies is required. Although a large body of evidence exists about the safety of this treatment, almost nothing is known about the pharmacology of this agent, especially in pregnancy. The purpose of this study is to define the pharmacology of 17-hydroxyprogesterone caproate in pregnancy. This protocol will focus on pharmacokinetics and placental transport and provide preliminary data on the pharmacoepidemiology of 17-OHPC. The primary research question of this study is: Do the pharmacokinetics of 17-OHPC as represented by area under the concentration vs. time curve after IM injection of 250 mg 17-OHPC differ between the second and third trimesters of pregnancy? We will obtain blood samples prior to and daily for one week after injection of 17-OHPC (8 samples total) for each of two parts of the study, with an optional third part for eligible subjects. Additionally, blood samples will be collected prior to each weekly injection of the study drug and at time of delivery. Approximately 60 subjects (ages 18-45) will be accrued at one of the Obstetrical Fetal Pharmacology Research Units (OPRU) Network sites, with 15 at Magee-Womens Hospital of the University of Pittsburgh Medical Center. Study treatment will be administered until delivery. The total duration of this multi-center study is 2-3 years.

We are examining the pharmacology of 17-OHPC in pregnancy, specifically between the second and third trimesters.

Hyoscine butyl bromide has been used to shorten the duration of labor in several hospitals here in Jamaica, as it has elsewhere in the world. Thus, it represents a new addition to the armamentarium of active management. The mechanism by which it acts in the context of labor has not yet been elucidated, and the evidence for its efficacy was previously largely anecdotal. The specific objectives of this project are to assess whether hyoscine butyl bromide (in the form of Buscopan®) is effective in hastening cervical effacement and dilatation, thus shortening the duration of the first stage of labor. We also intend to determine whether the use of hyoscine butyl bromide in the first stage of labor has any associated increase in complications, such as an increase in blood loss or rate of Caesarean deliveries, or a decrease in neonatal APGAR scores.~The study was designed as a double blind, randomized, controlled, clinical trial comparing two groups of patients matched for age and parity. One group of patients received the 20 mg(1 ml)of hyoscine butyl bromide, while the other (control) group received 1 ml of normal saline (placebo).

To determine whether hyoscine butyl bromide is effective in shortening the first stage of labor, with no increase in maternal or neonatal complications.

This was a Phase 3, multicenter, open-label, extension study to characterize the safety and tolerability of long-term, repeated dosing of OROS hydromorphone in patients with chronic cancer or chronic non-malignant pain. Patients with chronic cancer or chronic non-malignant pain had completed an OROS hydromorphone short-term study (DO-104, DO-105, DO-119) of approximately 4 weeks duration. During this study, patients continued to receive the dose of OROS hydromorphone that they had been receiving in the short-term study, with dose adjustments as needed to control pain and adverse events. Patients were treated on an outpatient basis. The study was extended from 1 year to up to 2 years in duration. Monthly evaluations of patients treated with OROS hydromorphone for chronic pain were performed to identify adverse events, construct a safety and tolerability profile, and assess efficacy. Dose adjustments were permitted to provide for disease progression, pain control, and adverse events. Quarterly physical examinations were performed to detect significant changes in the underlying condition of patients or changes that may have been associated with long-term opioid therapy. OROS hydromorphone 24 hour controlled release tablets in 8, 16, 32 and 64 mg were ingested orally daily up to 1 year with dose adjustments as needed to control pain and adverse events.

The purpose of study was to characterize the safety and tolerability of long-term repeated dosing of OROS hydromorphone controlled release tablets (8,16,32, and 64 mg) in patients with chronic cancer pain or chronic non-malignant pain.

CONTEXT: No pharmacotherapies have been shown to increase long-term (&#8805; 6 month) tobacco abstinence rates among smokeless tobacco (ST) users, although bupropion SR has demonstrated potential efficacy in pilot studies.~OBJECTIVE: To determine the efficacy and safety of bupropion SR for tobacco abstinence among ST users compared with placebo.~DESIGN, SETTING, AND PARTICIPANTS: A randomized, double-blind, placebo-controlled trial conducted between August 2003 to May 2005 at two research centers with a 12-week treatment period and follow-up of smoking status to week 52.~INTERVENTION: Bupropion SR titrated to 150 mg twice daily or placebo for 12 weeks plus weekly behavioral interventions.~Main Outcome Measures: The primary endpoint was 7-day point-prevalence tobacco abstinence rate at week 12. Secondary outcomes included the prolonged and continuous tobacco abstinence rates at weeks 12, 24, and 52.

To determine the efficacy and safety of bupropion SR for quitting tobacco in smokeless tobacco users.

Skeletal metastases are the most common cause of morbidity and mortality in patients with malignancy, especially in patients with breast cancer, lung cancer, prostate cancer and head & neck cancer. In patients with lung cancer, bone metastases are present in 20-30% of patient at initial diagnosis (1-2). Accuracy staging bone metastases can lead to modification of following treatment and evaluation of prognosis.~The planar whole-body 99mTc-methylene diphosphonate (MDP) radionuclide bone scintigraphy is the most widely used technique in detecting metastatic bone lesions at present. Abnormal tracer accumulation may occur at any skeletal site with an elevated rate of bone turnover. However, conventional planar bone scintigraphy was reported to be less sensitive than MRI in detecting spinal metastases (3-7).~18F ion is a positron emitting bone radiopharmaceuticals. The skeletal uptake of 18F relies on the exchange of hydroxyl ions in the hydroxyapatit crystal which is an indicator of bone metabolic activity (8). It has good soft tissue clearance and high affinity of to the bone matrix. It is able to perform a highly sensitive whole-body screening for bone metastases using a high resolution PET scanner.~To the best of our knowledge, there are only limited studies evaluating the clinical utilization of 18F-NaF PET for detection of bone metastases (10-12). Therefore, we would like to conduct a prospective study to evaluate the accuracy and clinical value of 18F PET in staging bone metastases by~Comparing the sensitivity of 18F-NaF PET with that of 99mTc-MDP scintigraphy;~Determining the clinical impact of PET results on subsequent patient management.~99mTc-MDP scintigraphy and 18F PET will be performed in 2 weeks for all patients. Interpretation of 99mTc-MDP scintigraphy and 18F PET will be performed following the criteria described by Crasnow et all (13). The accuracy of 99mTc-MDP scintigraphy and 18F PET detection of bone metastases for each patient will be determined by the histopathological results, MRI results, or other clinical evidences afterward.

18F ion is a positron emitting bone radiopharmaceuticals. The skeletal uptake of 18F relies on the exchange of hydroxyl ions in the hydroxyapatit crystal which is an indicator of bone metabolic activity (8). It has good soft tissue clearance and high affinity of to the bone matrix. It is able to perform a highly sensitive whole-body screening for bone metastases using a high resolution PET scanner. Therefore, we conduct a prospective study to evaluate the accuracy and clinical value of 18F PET in staging bone metastases by~Comparing the sensitivity of 18F-NaF PET with that of 99mTc-MDP scintigraphy;~Determining the clinical impact of PET results on subsequent patient management.

This is a multicenter, open-label, randomized, Phase 1B study evaluating liver transplant recipients receiving rhMBL (2 cohorts) or without rhMBL (1 cohort).~Patients will have received an orthotopic liver transplant (OLT) or a living related donor (LRD) liver transplant. Patients in all cohorts are to receive immunosuppressant therapy and anti-infectious prophylactic supportive therapy according to institutional standards.~The donor's mannose-binding lectin (MBL) genotype will be evaluated to determine the liver transplant recipient's study eligibility. For recipients receiving an OLT, a sample of liver tissue or lymph nodes will be collected from the donor liver at the time of organ harvest for MBL genotyping. For recipients receiving a LRD transplant, the MBL genotype of the LRD will be determined in a companion protocol, Screening Protocol to Evaluate Mannose-Binding Lectin (MBL) Genotype in Living Related Donors for Liver Transplant Recipients. A recipient whose donor has an A/O or O/O MBL genotype will be eligible to participate in this study.~Patients will be randomized in a 2:2:1 ratio to receive up to 8 intravenous (i.v.) infusions of rhMBL at a dose of 0.5 or 1.0 mg/kg, or to receive no rhMBL, respectively. Approximately 20 patients will be treated in each of the 2 rhMBL arms, and approximately 10 patients will be treated with standard immunosuppressive agents and anti-infectious prophylaxis but not with rhMBL.~Cohort 1~Number of Patients 20~rhMBL (mg/kg) 0.5~Cohort 2~Number of Patients 20~rhMBL (mg/kg) 1.0~Cohort 3~Number of Patients 10~rhMBL (mg/kg) None

This is a multicenter, open-label, randomized, Phase 1B study evaluating liver transplant recipients receiving rhMBL (2 cohorts) or without rhMBL (1 cohort).