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The postpartum period is a window of opportunity to promote behaviors that reduce the risk of chronic disease and benefit reproductive health. The Expanded Food and Nutrition Education Program (EFNEP) is an educational program delivered by community-based paraprofessional's that aims to improve dietary and activity patterns among low income, multi-ethnic women during the postpartum period. This study will evaluate the efficacy of the EFNEP to impact the diet and activity patterns of women.~Women were recruited through the Special Supplemental Food Program for Women, Infants, and Children (WIC) and randomized to either the EFNEP group or a usual care group. Women in both groups will receive standard WIC care consisting of nutrition-risk and breastfeeding educational messages at postpartum and follow-up visits. Women in the EFNEP group participated in an additional two component intervention that included five home visits and motivational telephone calls from project staff.~Primary study outcomes were assessed at Months 1 and 12. Primary outcomes included fruit and vegetable intake, saturated fat intake, and physical activity. Secondary outcomes will include Body Mass Index and indicators of fat mass and distribution. The study will also analyze mediating and modifying factors, including social support and norms, perceived health status, smoking, television viewing, food insecurity, food and activity access, and utilization of federal programs and health care.

This study will evaluate a community-based program to improve diet and physical activity in women during the first 12 months following the birth of a child. The program is designed to complement existing federal programs for low-income families and is directed toward low-income, postpartum, multi-ethnic women.

OBJECTIVES:~Determine the safety and dose-limiting toxicity of biologically active doses of interleukin-7 in patients with refractory solid tumors.~Determine a range of biologically active doses of this drug in these patients.~Determine the biological effects of this drug in these patients.~Determine the pharmacokinetics and pharmacodynamics of this drug in these patients.~Determine the antitumor effects of this drug in these patients.~OUTLINE: This is a multicenter, dose-escalation study.~Patients receive interleukin-7 (IL-7) subcutaneously on days 0, 2, 4, 6, 8, 10, 12, and 14 (for a total of 8 doses) in the absence of disease progression or unacceptable toxicity.~Cohorts of 3-6 patients receive escalating doses of IL-7 until the maximum tolerated dose (MTD) and biologically active dose (BAD) are determined. The MTD is defined as the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. The BAD is defined as the dose that produces a sustained 50% increase in CD3+ count over the patient's baseline without unacceptable toxicity.~Patients are followed at 1, 3, and 6 months and at 1 year after study completion.~PROJECTED ACCRUAL: A total of 15-30 patients will be accrued for this study within 3.75-10 months.

RATIONALE: Interleukin-7 may stimulate a person's white blood cells to kill tumor cells.~PURPOSE: This phase I trial is studying the side effects and best dose of interleukin-7 in treating patients with refractory solid tumors.

Motor vehicle crashes are the major cause of death and disability among adolescents from 16 through 20 years of age. While adolescents between the ages of 16 and 19 years constitute only 5% of all licensed drivers, they are involved in 15% of the crashes in which they or other occupants are killed. In fact, 16-year-old drivers are more than 20 times as likely to have a crash as the general population of drivers and 17-year-olds are more than 6 times as likely. In addition, for each adolescent motor vehicle fatality, approximately 100 nonfatal injuries occur, making crashes the leading cause of disability due to head and spinal cord injuries in adolescents.~Parents can have a huge impact on adolescent behavior. However, the impact of parenting practices on adolescent driving behavior has not yet been examined. This study aims to determine the efficacy of an intervention designed to increase parents' involvement in, and parental restrictions on, their teens' early driving experiences in order to reduce the number of tickets and crashes among teen drivers. The intervention provides educational materials to parents and adolescents from the time the adolescent gets a learner's permit through the first 6 months of licensure. These persuasive communications are tailored to adolescents' level of driving experience. The intervention materials make explicit the increased risk associated with adolescent driving and methods for reducing risk through increased parental involvement in and restriction of driving.~Participants were recruited in the Connecticut Department of Motor Vehicle offices as adolescents applied for their learner's permits. Participants were randomized to either the intervention group or the control group. The control group received standard information about driving not related to the specific teen risks focused on in the intervention group materials. All participants completed interviews at study entry, licensure, 3 months after licensure, 6 months after licensure, and 12 months after licensure. Parents were asked about their expectations and parenting practices regarding their adolescents' driving behaviors. Adolescents were asked about their driving practices and their parents' rules and restrictions regarding driving. The driving records for each adolescent were obtained from the state motor vehicle administration and examined 18 months after licensure.

The purpose of this study is to evaluate the effectiveness of a program designed to reduce teen crashes and risky driving by increasing parental monitoring and restriction of their adolescents' driving practices during the first year of licensed driving.

Vitamin A and its derivative retinoic acid (RA) have been recognized as important factors in potentiating the immune response and protecting against infection. In developing nations, Vitamin A deficiency is associated with infectious gastroenteritis and increased susceptibility to a number of infections, such as measles. RA is an important regulator of cell growth and differentiation and can augment IgM production from core blood mononuclear cells in response to a polyclonal B-cell activator. This augmentation in immunoglobulin secretion is mediated by the effects of RA on both T and B cells, in part through the production of certain cytokines (e.g., IL-6 and IL-10) important in the terminal differentiation of B-cells to plasma cells. In animal models, correction of Vitamin A deficiency improves immune response to vaccination.~Infants with extremely low birth weight have low plasma and tissue concentrations of Vitamin A. Vitamin A supplementation of pre-term infants reduces chronic lung disease and the risk of sepsis. Because the immune system of the pre-term infant is immature, the response of pre-term infants to Hepatitis B vaccine is diminished compared to full-term babies. This study will determine whether Vitamin A supplementation of pre-term infants will enhance the response of these infants to immunization with Hepatitis B vaccine. The study will also evaluate the effect of Vitamin A supplementation on survival, chronic lung disease, and infection rate.~Low birth weight pre-term infants will be randomized to receive either Vitamin A supplementation or placebo. The Vitamin A treatment group will receive 5,000 IU of Vitamin A (retinyl palmitate) by intramuscular injection 3 times weekly for 28 days starting on postnatal day 2. To avoid pain and discomfort, the placebo group will receive a sham procedure rather than a placebo saline injection. The staff of the neonatal intensive care unit will retain the responsibility for decisions regarding the use of other therapies, such as parental fluids, mechanical ventilation, glucocorticoids, hyperalimentation, and blood replacement. All infants will be assessed for potential Vitamin A toxicity. While in the neonatal intensive care unit, infants will have blood tests at Days 0, 14, 30, and 60. After discharge from the neonatal intensive care unit, patients return for clinic assessment and blood samples at Months 4, 6, and 9. Infants will be given Hepatitis B vaccine at 2, 4, and 6 months chronological age. Primary outcome measures will include Hepatitis B antibody levels, chronic lung disease, rate of infection while in the neonatal intensive care unit, and the incidence and severity of infections during the first 9 months of life.

Extremely low birth weight infants have decreased blood levels of Vitamin A. This Vitamin A deficiency may increase the risk of infections and chronic lung disease in these infants. This study will examine the effects of Vitamin A supplementation in premature babies born weighing less than 1500 grams (3.3 lbs).

This was a 3 arm randomized, open-label, comparative, multi-center study in de novo kidney transplant recipients at 60 centers in the U.S., Canada and Brazil.~The study consisted of a 1-year post-transplant efficacy and safety study with a clinical continuation phase of a minimum of 2 years or until commercial availability of tacrolimus modified release, unless the Data Safety Monitoring Board or sponsor specified otherwise.

The purpose of this study is to compare the safety and efficacy of tacrolimus/mycophenolate mofetil (MMF), cyclosporine/MMF and tacrolimus modified release/MMF in de novo kidney transplant recipients.

Unintended pregnancy is associated with significant public health problems, including inadequate prenatal care, low birth weight infants, infant mortality, and maternal morbidity and mortality. Children born as a result of unplanned pregnancies are at greater risk for poor outcomes such as poor mental health and developmental disabilities. This research project will determine whether providing contraception in the home can reduce the incidence of unintended pregnancy in low income and minority women. The project will also determine whether delaying a pelvic exam encourages or discourages the utilization of clinic-based preventive services to screen for sexually transmitted diseases (STDs) and cervical cancer.~Participants will be randomized to either an experimental group or a comparison group. Each participant will receive family planning counseling during a home visit by a community health nurse. Participants in the experimental group will be offered a three-month supply of oral contraceptives or a depo-provera shot; both forms of contraceptives will be delivered during home visits. Each participant will complete a survey during the initial visit and during a 1-year follow-up. The study will last approximately three years.

This study will evaluate a program that provides birth control to low income and minority women through home visits by a community health nurse. The goal of the program is to reduce unwanted pregnancies.

As per Brief Summary

A series of clinical studies will be conducted in normal, healthy adult volunteers to evaluate the potential for alterations in the pharmacokinetics of anti HIV drugs when botanicals/nutriceuticals are given concurrently via the oral route. Both the drugs and botanicals are known to rely upon or to modulate, respectively, metabolism via glucuronidation.

Vaginal acidity is thought to be one means by which the vagina prevents overgrowth or colonization by harmful microbial flora. Sperm and many STD pathogens, including HSV-1 and HSV-2, Neisseria gonorrhoeae, Treponema pallidum, Haemophilus ducreyi, and a variety of bacterial vaginosis-associated bacteria, are inactivated at pH less than 5 in vitro. BufferGel, a vaginal spermicide and microbicide, is an acidic buffer that maintains the vagina at or near its natural state of mild acidity. Formulated at vaginal pH (pH 3.9), BufferGel prevents or limits the semen-induced rise in vaginal pH. Carbopol 974P, the buffering agent in BufferGel, is a high molecular weight, cross-linked, polyacrylic acid used as a gelling or tableting agent in many pharmaceuticals; it has a well-documented record of mucosal safety in animals and humans. This study will determine the safety and contraceptive efficacy of BufferGel spermicide used with a diaphragm compared to Gynol II spermicide used with a diaphragm. The study will also measure the frequency of bacterial vaginosis, urinary tract infections, and cervical lesions in women using BufferGel compared with Gynol II.~Participants in this study will be fitted for a diaphragm and randomized to receive either BufferGel or Gynol II. All participants will be instructed on the use of the test product with the diaphragm. Participants will be followed through 6 menstrual cycles (approximately 7 months) and will have 4 study visits and one study phone call. Some participants may enroll in an extended version of the study and be followed for an additional 6 cycles and 2 additional study visits. Study visits will include a gynecologic exam, Pap smear, and blood and urine tests. Participants will be asked to keep a diary to record information on product use. Some participants may also be asked to enroll in a colposcopy substudy. These participants will undergo colposcopy at study entry and after cycles 1, 3 and 6.

BufferGel is a new contraceptive gel designed to be used with a diaphragm. In addition to preventing pregnancy, BufferGel may also prevent some types of sexually transmitted diseases (STDs). This study will compare BufferGel to Gynol II, a currently available contraceptive gel.

The Institute of Medicine's Committee on Unintended Pregnancy urges increasing access to contraception through broadening the range of health professionals that provide birth control. Evidence-based family planning practice no longer requires a physical examination before prescribing hormonal contraceptives to women. Community pharmacists efficiently provide emergency contraceptive pills (ECP) and women report satisfaction with the direct access. These women, as well as many women purchasing less effective over-the-counter (OTC) contraceptive methods, could benefit from more pharmacist-dispensed birth control choices, such as hormonal methods. The Direct Access Study will assess the feasibility of pharmacists, under Collaborative Drug Therapy Agreements with independent prescribers, providing hormonal contraceptives in community pharmacies. Specifically, the study will evaluate the impact upon hormonal contraception initiation and continuation rates when women's care is managed by pharmacists.~Using Collaborative Drug Therapy Agreements jointly developed with licensed prescribers (physicians and nurse practitioners), pharmacists in four Fred Meyer pharmacies will identify women who are at risk of unintended pregnancy and will offer to evaluate them for their suitability to safely use oral contraceptives, contraceptive patches, or the contraceptive vaginal ring. Through self-administered medical and contraceptive history questionnaires, interested women will select the most suitable contraceptive methods. Pharmacists will then complete the screening process and prescribe hormonal contraceptives according to the protocol guidelines.~Pharmacists will encourage women to follow up with a primary care practitioner or family planning clinic for cervical exams and reproductive tract infection screening as indicated. Pharmacists will have authority to provide an initial 3-month prescription and an additional 9-month prescription if blood pressure is normal at a three-month revisit. Effectiveness of pharmacists' interventions will be measured by initiation and continuation of hormonal methods by women to whom pharmacists have offered them. Feasibility will be determined by measurement of both acceptability and sustainability. Acceptability will be measured by surveys of women, pharmacists, and prescribers. Sustainability will be measured by economic and work-flow outcomes for the pharmacies, including evidence that women, private third-party payers, and public payers are willing to pay for the services. If safety is documented after preliminary analysis, injectable contraceptive methods will be added to the study.

Hormonal birth control methods include birth control pills, patches, and vaginal rings; they are normally available only with a doctor's prescription. This study will evaluate a program designed to increase the availability of birth control by allowing pharmacists to give women hormonal birth control without a doctor's prescription. Under this program, pharmacists will evaluate women who want to use birth control according to specific guidelines created by doctors. If a woman meets the criteria in the guidelines, a pharmacist could then give her the appropriate form of hormonal birth control.

Amniocentesis is generally performed at 105 to 125 days post last menstrual period (LMP) and TA CVS at 63 to 76 days post LMP. This study will compare the safety and accuracy of transabdominal amniocentesis and TA CVS, each performed during the same modified gestational age window of 77 to 104 days post LMP.~Healthy, pregnant women at 77 to 104 days gestation, whose only indication for prenatal diagnosis is advanced maternal age of at least 34 years at enrollment, will be randomized to receive either TA CVS or amniocentesis following a baseline ultrasound. Eligible women who refuse randomization or for whom a procedure cannot be scheduled by 104 days will also be followed. Primary outcomes include fetal loss or preterm delivery before 196 days gestation as well as total fetal loss, amniotic fluid loss, gestational age at delivery, perinatal morbidity, neonatal morbidity, and congenital abnormalities, including limb reduction defects. Success in obtaining a diagnosis from the two procedures will be compared. One ancillary study will evaluate the feasibility and accuracy of fluorescence in situ hybridization (FISH) as a rapid diagnostic method for certain cytogenetic abnormalities; another will collect data on amniotic fluid alphafetoprotein and acetylcholinesterase for the diagnosis of neural tube defects.

Prenatal diagnosis can provide information to parents about specific fetal disorders. However, invasive prenatal diagnostic procedures are associated with risks to the fetus. This study will compare the safety and effectiveness of two methods of invasive prenatal diagnosis: amniocentesis and transabdominal chorionic villus sampling (TA CVS).

This project utilizes 30 subjects in a prospective, randomly assigned clinical study that uses a four-period, six sequence, three treatment crossover design to test the hypothesis that defined outcomes of variable implant overdenture treatments are equivalent. The project tests three overdenture treatment modalities, (1) four-implant, bar/clip-attached treatment, (2) two-implant, bar/clip-attached treatment, and (3) two-implant independently attached (O-ring) treatment. Each subject has four dental implants placed into the anterior mandible and new dentures are fabricated. After successful implant integration, subjects are randomly assigned to one of six sequences of treatment. Each treatment is followed for data collection for at least twelve months before the mandibular denture is modified to incorporate the next treatment in the sequence. Equivalence is measured in terms of prosthesis retention, stability, supporting and peri-implant tissue response, patient satisfaction/preference and treatment complications/failures.~Information from this study will assist dental practitioners during treatment planning in selecting appropriate and cost effective treatment choices. There is an inverse relationship between edentulism in the U.S. population and socioeconomic status. If less costly and simplified treatment methods are shown to provide an equivalent treatment outcome to more costly/complex methods, these simplified treatments can be used to treat a larger percentage of the edentulous population.

The purpose of this study is to compare the effectiveness of three variable dental implant attachment methodologies in conjunction with lower dental-implant retained/supported complete overdenture treatment. These three methods are all presently used by dental practitioners, but vary significantly in terms of added treatment cost and complexity. The study tests the hypothesis that the least complex and costly method provides an equivalent treatment outcome to other more complex and costly methods.

Phosphorus and phosphate ions play an important role in cellular metabolism as well as bone structure. Scientific evidence suggests that, in addition to Vitamin D and PTH systems, novel factors, such as Fibroblast Growth Factor 23 (FGF-23) and Matrix extracellular phosphoglycoprotein (MEPE), may play an important role in phosphorus regulation. These factors have been best studied in rare genetic and acquired phosphate wasting disorders such as tumor induced osteomalacia (TIO), X linked hypophosphatemia (XLH) and autosomal dominant hypophosphatemic rickets (ADHR). Patients with other abnormal phosphate regulating states such as hyperparathyroidism and hypoparathyroidism, pseudohypoparathyroidism etc. undergoing phosphorus-altering interventions may provide important insight into the role of these hormones.~We are proposing an observational study with collection of blood and urine samples to study both established (e.g. mineral ions, bone markers, PTH-Vit D system, TMP-GFR) and novel (e.g. FGF-23 and MEPE) constituents of the phosphorus metabolism pathway. Patients with abnormal phosphorus regulating states will be enrolled and we will study the natural history of their disease and the effects of specific interventions that are likely to change phosphorus balance.~The outcome will potentially aid understanding of this new field of mineral regulating hormones and generate both interest and research in phosphorus metabolism. It is hoped that this will also encourage clinical trials in treatment of phosphate wasting disorders.

Phosphorus and phosphate irons play critical roles in bone structure and essential cellular functions.~The purpose of this study is to learn more about the factors and hormones that regulate phosphorus in the body by collecting blood and urine samples from patients with disorders of phosphate control.~Both children and adults will be enrolled in this study. Researchers will collect blood and urine samples from participants on multiple occasions (2 to 6 times). Some blood specimens will be taken after an overnight fast and participants may be asked to collect all their urine during a 24-hour period. Researchers will analyze these blood and urine samples to better understanding how the body handles phosphorus.

OBJECTIVES:~I. Determine the maximum tolerated dose and recommended phase II dose of oxaliplatin and bortezomib in patients with advanced malignancy.~II. Determine the dose-limiting toxicity of this regimen in these patients. III. Determine the toxicity profile of this regimen in these patients. IV. Determine the antitumor activity of this regimen in these patients. V. Determine the pattern of neurotoxicity and its reversibility in patients responding to prolonged administration of this treatment regimen.~VI. Determine whether the pharmacokinetics and pharmacodynamics of oxaliplatin or bortezomib are altered by the administration of the other agent in these patients.~OUTLINE: This is a dose-escalation study.~Patients receive oxaliplatin IV over 2 hours on days 1 and 15 and bortezomib IV over 3-5 seconds on days 1, 4, 15, and 18. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.~Cohorts of 3-6 patients receive escalating doses of oxaliplatin and bortezomib until the maximum tolerated doses (MTDs) are determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.~Patients are followed for at least 3 months.~PROJECTED ACCRUAL: A total of 15-30 patients will be accrued for this study within 4-15 months.

Phase I trial to study the effect on the body of combining oxaliplatin with bortezomib in treating patients who have metastatic or unresectable cancer. Drugs used in chemotherapy such as oxaliplatin use different ways to stop cancer cells from dividing so they stop growing or die. Bortezomib may stop the growth of cancer cells by blocking the enzymes necessary for tumor cell growth. Combining oxaliplatin with bortezomib may kill more cancer cells

We will be investigating the fractional disappearance rate of tocopherols in cigarette smokers compared to nonsmokers. This will be accomplished by supplementing individuals with deuterium labeled alpha- and gamma-tocopherols. Quantification of plasma tocopherols as well as urinary metabolites, alpha- and gamma-carboxy ethyl hydroxychromanol, will be determined using liquid chromatography/mass spectrometry analysis. In addition, the role of vitamin C as it pertains to its influence on the fraction disappearance rate of vitamin E will also be evaluated.

The purpose of this study is to determine if oxidative stress derived from cigarette smoking increases vitamin E requirements. The study will also assess the role of vitamin C in modulating vitamin E requirements. Vitamin E requirements will be assessed by measuring vitamin E in plasma as well as by measuring the excreted vitamin E metabolite in the urine.

Despite the effectiveness of oral contraceptives, pregnancy rates are high among women who choose this method of birth control. These pregnancies occur due to incorrect use, premature discontinuation, and failure to begin taking oral contraceptives after they have been prescribed. As many as 25% of adolescents who seek oral contraceptives from family planning clinics never take the first pill. Failure to begin oral contraceptives may occur due to ambivalence, confusion about starting instructions, or intervening pregnancy. Conventional starting instructions for oral contraceptives require waiting until the next menstrual period; this may leave the woman at high risk of pregnancy. This trial will evaluate a quick start approach in which the woman swallows the first pill during the clinic visit under direct observation and then continues daily pill use without waiting for her next menses. The trial will determine whether immediate oral contraceptive initiation offers benefits compared to conventional starting approaches.~Participants in this study will be randomized to receive either the quick start or the standard starting approach. Participants will complete a questionnaire at study entry and Months 3 and 6. The main outcomes are 6-month oral contraceptive continuation rates and pregnancy rates.

Women who choose to take birth control pills are currently instructed to begin taking the pills at the end of a menstrual cycle. This creates a window of time between when the woman is given the pills and when she begins taking them. Some women fail to begin taking the pills, placing them at increased risk of pregnancy. This study will evaluate a new approach to beginning birth control pills. Women will take the first pill in the doctor's office rather than waiting until the next menstrual cycle.

SLE is the most common autoimmune connective tissue disease of childhood, affecting 5,000 to 10,000 children; the prevalence is higher among African American children and approximately 80% of sufferers are female. SLE is multisystemic in onset and has no known cure. Children with chronic illness have at least a two-fold increased risk for adjustment problems relative to their healthy peers. This risk is heightened among adolescents, who are at greater risk for psychopathology than are younger children. The diagnosis of a chronic medical condition during adolescence presents unique stressors, particularly for adolescents with lupus, who must endure bodily changes, including dermatological problems, hair loss, and changes in appearance due to medical therapies. Psychosocial processes, including methods of coping, expectations, and family functioning, are believed to mediate the influence of disease severity. This study will evaluate the effectiveness of a cognitive-based intervention to improve the quality of life of adolescents with SLE.~Participants in this study will be randomly assigned to either the cognitive-based intervention, a lupus education program, or a control group. Participants in the intervention group will have five study visits over 5 months. The first three visits are biweekly, 45-minute sessions during which the adolescent will be taught coping skills and cognitive restructuring techniques. The coping skills training will include training in relaxation, distraction, and problem-solving skills. The cognitive restructuring techniques will assist adolescents in using more accurate and adaptive cognitive responses. Caregivers will join the adolescent at the end of each training session to gain familiarity with the content reviewed in each session. The remaining two study visits are booster sessions during which the intervention material will be reviewed.~Participants in the education program will also have five study visits. Study visits will include disease-appropriate education materials. Caregivers will not be included in the education program. Participants will be assessed at study entry and Months 6, 9, and 12. Assessments will include questionnaires designed to measure disease severity, pain intensity, methods of coping, expectations of efficacy, social support, and adjustment.

This study will evaluate a program designed to help African American adolescents with lupus (systemic lupus erythematosus or SLE) cope with the disease.

Approximately 12% of children under 18 years of age in the United States suffer from a mental disorder; estimates for socioeconomically disadvantaged children are 20% or higher. Unfortunately, these at-risk children often do not receive the needed mental health services either because of a lack of accessible services or because their families lack the motivation or resources to obtain services. In many instances, it is difficult or impossible to involve parents in their children's services. Increased access to services for socioeconomically disadvantaged children is critical. However, increased access alone is not sufficient to meet this population's mental health needs. Effective services must be provided. This study will increase the accessibility of mental health services by providing them in the children's schools and will determine whether teachers can be effective substitutes for parents as the therapeutic change agent. The study will accomplish these objectives through implementation and evaluation of the Reaching Educators, Children, and Parents (RECAP) program.~The RECAP program involves individual and small group sessions with children, classroom groups with the child's broader peer groups, and instruction for classroom teachers and parents. The specific techniques are selected to target the areas thought to be responsible for perpetuating the children's problems. The child component, for example, focuses on: 1) social skills (e.g., how to resolve conflicts non-aggressively; use of humor to deflect teasing); 2) communication skills; 3) improving self-monitoring and self-control; 4) reattribution training (for both hostile attributions and negative self-attributions); 5) setting short- and long-term goals and relating behavior to long-term goals; and 6) relaxation. The program also focuses on motivational issues and helping children understand what is in their best long-term self-interest.~Children in need of but not currently receiving mental health services will be selected from six schools serving high-risk neighborhoods in the Metro Nashville School System. Children will be chosen based on severity of psychopathology. Children will be randomly assigned to receive either: 1) mental health services containing a parent-training component; 2) mental health services containing a teacher-training component; or 3) a no-services control group. All children and their classroom peers will be assessed for behavioral, emotional, and social functioning.

Children from low socioeconomic levels are more likely to have a mental disorder. However, they are less likely to receive appropriate treatment for that disorder than are children at higher socioeconomic levels. This study will evaluate a program designed to improve mental health services for these children through public school systems.

The characterization of glucose levels in healthy children during day and nighttime is critical to the interpretation of glucose levels in diseases such as diabetes. This study was conducted by the DirecNet Study Group to determine whether two FDA-approved continuous glucose monitors are sufficiently accurate.~The study was conducted at five clinical centers and enrolled approximately 20 healthy children (ages 7 to 17 years old) who did not have Type 1 or Type 2 diabetes nor a history of the disease in their immediate families. Each participant was hospitalized for approximately 26 hours to assess the accuracy of the continuous glucose monitors compared with serum glucose determinations.

Continuous glucose monitors may be useful in the treatment of children with Type 1 diabetes mellitus. The purpose of this study was to determine whether two FDA-approved continuous glucose monitors, the Continuous Glucose Monitoring System (CGMS) and the GlucoWatch G2TM Biographer (GW2B), are sufficiently accurate to use in future studies to characterize glucose levels in children.

Mucositis is a common side effect to chemotherapy and radiotherapy involving the formation of erythema and ulcerative lesions in the mouth. Mucositis can be serious, resulting in pain requiring interventions such as analgesic medications and the use of parenteral feedings. Currently, no standard therapy is available to prevent or treat mucositis.

Open label palifermin will be administered to subjects who are at a risk of developing mucositis after radiotherapy and chemotherapy followed by blood stem cell support. The amount of palifermin in the blood following administration will be evaluated. The safety of palifermin administration and its effect on reducing mucositis will also be evaluated.

In Latin American countries certain procedures commonly used in obstetrical care (e.g. episiotomy) have been shown to be ineffective or harmful. This study hypothesizes that obstetrical procedures can be changed and new guidelines implemented via peer opinion leader training. It tests an intervention designed to motivate and facilitate health care professionals' development through the implementation and maintenance of simple evidence-based guidelines to increase the use of evidence-based practices by birth attendants at the hospital level in Argentina and Uruguay. The primary outcomes are the use of episiotomies and of oxytocin during the third stage of labor; secondary outcomes include perineal sutures; postpartum hemorrhages; birth attendants' readiness to change status. The sample size was based upon a 10% frequency of oxytocin use and 20% use of episiotomies in the control group. The study hypothesizes a 40% absolute increase in oxytocin use in the intervention group; a 20% absolute reduction in use of episiotomies in the intervention group, calculated at a 0.05 significance level with 80% power.~Following baseline data collections in 24 hospitals, 19 hospitals met inclusion criteria in three urban districts of Argentina and Uruguay and were randomly assigned to an intervention or control group. Baseline data collection has been completed with a total of 6597 single vaginal spontaneous births. The 19 hospitals met inclusion criteria with a rate of active management of third stage of labor under 25% and an episiotomy rate in spontaneous vaginal deliveries above 20%. Opinion leaders in the intervention hospitals have been identified and trained to develop evidence-based guidelines that will be diffused by a multifaceted approach including seminars, academic detailing, reminders, and feedback on utilization rates. The hospitals in the nonintervention group will continue with their standard in-service training activities.

Many obstetrical interventions used in Latin America, as in other parts of the world, have been shown to be ineffective or harmful, while effective interventions remain underutilized. This study will develop and evaluate an intervention intended to implement two evidence-based practices among birth attendants in Latin America, the selective use of episiotomies and active management of the third stage of labor.

To date, treatment interventions for domestic abuse perpetrators have been conducted almost exclusively in groups. However, the efficacy of such treatments relative to no treatment has not been thoroughly evaluated. Evidence suggests that individual treatments may be more effective than group treatments. This study will combine motivational enhancement therapy with cognitive and behavior change techniques to treat men who abuse their partners.~This study will be conducted in two phases. In Phase 1, an individual cognitive behavior therapy (ICBT) manual will be constructed. During Phase 2, participants will be randomly assigned to receive either 16 sessions of ICBT or 16 sessions of standard group therapy. Data on abusive behavior outcomes and secondary treatment targets will be collected from participants and their partners every 3 months for 1 year after the study.

This study will develop an individual behavior therapy for men who are violent toward their partners and will compare the therapy to standard group treatment.

ECT is a safe and effective modern treatment for severe depression and other psychiatric conditions. An estimated 100,000 treatments occur per year in the United States. ECT's most bothersome adverse effect is memory loss, with all patients receiving ECT experiencing some degree of short-term cognitive impairment. At present there are no known effective pharmacologic treatments to prevent or improve ECT-induced cognitive dysfunction. Preliminary research has shown the herbal preparation GB aids cognitive function and memory in both patients with dementia and in normal volunteers. This study will investigate the utility and safety of GB to minimize the cognitive impairment typically associated with ECT.~Participants in this study will be randomly assigned to receive either twice-daily GB or placebo. Participants will begin taking GB or placebo as soon as consent is obtained and baseline testing is completed in order to reach steady-state plasma levels of GB prior to ECT. Patients will undergo cognitive testing at specified intervals following ECT. The final study visit will occur one week after a participant's final ECT treatment.

Electroconvulsive therapy (ECT) is an effective treatment for severe or medication-resistant depression and other psychiatric disorders. A common side effect of ECT is problems with short-term memory during treatment. This study will test whether taking ginkgo biloba (GB) prior to and during the course of ECT will lessen the effects of ECT on short-term memory.

A large percentage of the practice and use of complementary and alternative medicine (CAM) in the United States is focused on cancer. Whether the CAM use is aimed at reducing one's risk of developing cancer or improving the quality of life of a cancer patient during treatment or at the end of life, the public focus on CAM and cancer has created a driving force for cancer centers to address the efficacy and science of these methods.~Currently, the majority of cancer patients do not receive adequate palliative care. Acupuncture has been shown to be effective in the treatment of pain and nausea and has also been shown to improve one's general well-being. Acupuncture also has some effectiveness in relieving symptoms of anxiety and depression. This study will evaluate the efficacy of acupuncture by Traditional Chinese Medicine clinicians to address the quality of life and symptoms of patients with incurable cancer.~Women with recurrent metastatic ovarian cancer and similar patients with advanced cancer who are ambulatory and receiving conventional palliative care will be enrolled in this study. Patients will continue to receive high-quality, conventional clinical interventions, including chemotherapy and pain and symptom reduction programs. Patients will also receive 8 weeks of acupuncture. Evaluation tools such as Satisfaction with Life Domains Scale for Cancer (SLDS-C), Brief Pain Inventory, and Rotterdam Symptom Check List will be used to assess the acupuncture intervention.

This study will test the feasibility of acupuncture as a complementary therapy for advanced cancer by comparing symptoms and quality of life before and after 8 weeks of acupuncture treatments.

OBJECTIVES:~Primary~Determine the maximum tolerated dose and dose-limiting toxicity of anakinra in patients with metastatic cancer expressing the interleukin-1 gene.~Determine the steady state pharmacokinetics of this drug in these patients.~Secondary~Determine the antitumor efficacy of this drug in these patients.~Determine gene expression changes in tumor biopsies and circulating leukocyte and cytokine levels in these patients before and after treatment with this drug.~OUTLINE: This is a dose-escalation study.~Patients receive anakinra subcutaneously 1-3 times daily on days 1-28. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.~Cohorts of 3-6 patients receive escalating doses of anakinra until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Once the MTD is determined, an additional 6 patients are treated at that dose.~PROJECTED ACCRUAL: A total of 3-24 patients will be accrued for this study within 1-2 years.

RATIONALE: Biological therapies, such as anakinra, may interfere with the growth of the tumor cells and slow the growth of metastatic tumors that express the interleukin-1 gene.~PURPOSE: This phase I trial is studying the side effects and best dose of anakinra in treating patients with metastatic cancer that expresses the interleukin-1 gene.

Child sexual abuse is a serious public health problem that places children at high risk for developing anxiety, mood, conduct, sexual, and substance abuse disorders. It also increases their likelihood of experiencing further victimization. It is imperative that abused children are provided with effective interventions to minimize their risk of developing problems that can be disruptive to their psychosocial development. Evidence suggests that cognitive behavioral therapy (CBT) can effectively ameliorate many abuse-related symptoms exhibited by sexually abused children and their parents. However, it is unknown whether CBT treatment should include gradual exposure (GE), an intervention that involves the gradual confrontation of abuse-related thoughts and memories with therapist feedback to assist the child in effectively processing the abusive experience. Because this component of CBT may be more difficult for children and their parents, it is important to determine if and when GE is essential for optimal recovery in abused children.~Children and their parents will be randomly assigned to receive one of four treatments: brief abuse-focused treatment, brief coping skills treatment, extended abuse-focused treatment, and extended coping skills treatment. Assessments will be conducted before, during, and after treatment and at 6- and 12-month follow-up visits. Standardized evaluations will be conducted to assess parents' distress and support levels; parent reports of children's behavior patterns, sexualized behaviors, and post-traumatic stress disorder (PTSD) symptoms; and children's self-reports of PTSD, depression and anxiety symptoms, body safety skills, and victimization experiences.

This study will determine the necessity of including abuse-focused interventions in the treatment of sexually abused children.

OBJECTIVES:~Primary~Determine the maximum tolerated dose of BCX-1777 in patients with refractory T-cell or non-T-cell malignancies.~Determine the safety and dose-limiting toxicity of this drug in these patients.~Secondary~Determine the pharmacokinetics of single oral and single and multiple IV doses of this drug in these patients.~Determine the oral bioavailability of this drug in these patients.~Determine, preliminarily, the antitumor activity of this drug in these patients.~OUTLINE: This is an open-label, nonrandomized, dose-escalation, multicenter study.~Courses 1 and 2: Patients receive oral BCX-1777 on days 1 and 15* and BCX-1777 IV over 30 minutes on days 8* and 22*.~Course 3: Beginning approximately 6 days* after the completion of courses 1 and 2, patients receive BCX-1777 IV over 30 minutes once daily on days 1-5 and 8-12 (total of 10 doses).~NOTE: *+/- 1 day~Patients with stable disease or better and no dose-limiting toxicity (DLT) may receive an additional 10-dose treatment course (as in course 3) after a 10- to 16-day drug-free interval.~Treatment continues in the absence of disease progression or unacceptable toxicity.~Cohorts of 3-6 patients receive escalating doses of BCX-1777 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience DLT.~Patients are followed at 14 and 30 days.~PROJECTED ACCRUAL: A total of 3-24 patients will be accrued for this study.

RATIONALE: BCX-1777 may stop the growth of cancer cells by blocking the enzymes necessary for their growth.~PURPOSE: Phase I trial to study the effectiveness of BCX-1777 in treating patients who have refractory cancer.

OBJECTIVES:~Primary~Determine the efficacy of low-dose testosterone, in terms of average intra-patient change in libido, in postmenopausal female cancer survivors with a decreased libido.~Secondary~Determine the toxic effects of this drug in these patients.~Determine the levels of estrogen and testosterone and SGOT in patients reporting a decreased libido before and after treatment with this drug.~Determine whether increasing libido significantly positively affects pleasure from sexual activity in patients treated with this drug.~Determine the effect of this drug on vitality, general quality of life, and overall mood in these patients.~OUTLINE: This is a double-blind, placebo-controlled, randomized, crossover, multicenter study. Patients are stratified according to antidepressant medication use (yes vs no), age (under 50 vs 50 to 60 vs 61 to 70 vs over 70), tamoxifen or other selective estrogen receptor modulator use (yes vs no), and ovarian status (in place [natural menopause or hysterectomy] vs not in place [bilateral oophorectomy]). Patients are randomized to 1 of 2 treatment arms.~Arm I: Patients receive topical testosterone once daily for 4 weeks.~Arm II: Patients receive a topical placebo once daily for 4 weeks. After 4 weeks, patients cross over to the other treatment arm.~Changes in sexual functioning, mood states, and medical outcome vitality are assessed at baseline and then at the end of weeks 4 and 8.~Patients who continue or restart testosterone cream after the 8-week study period are followed at 6 months.

RATIONALE: The hormone testosterone may improve the libido (sex drive) in women. It is not yet known whether testosterone is effective in improving libido in female cancer survivors.~PURPOSE: This randomized phase III trial is studying how well low-dose testosterone works to improve libido in postmenopausal cancer survivors.

Abnormal facial sensation has a negative impact on patients' oral behaviors and may adversely affect a patient's quality of life if the altered sensation persists. Many patients with abnormal sensations retain some sensory function and do not develop chronic pain, and for those individuals there are currently no evidence-based noninvasive therapies. The goal of this project is to evaluate sensory re-training, a rehabilitative therapy that offers significant potential for patients who experience impaired sensory function regardless of the cause. This behavioral therapy approach has been used with substantial clinical success with hand injury patients since the 1970s. Re-training appears to enhance central reorganization of impulses from an injured sensory nerve to the cerebral cortex so that the altered sensory signals can be interpreted and translated into functionally meaningful motor functions.~Sensory re-training will be compared to a placebo jaw-opening exercise in a single blind, randomized two-arm parallel group stratified block clinical trial, using orthognathic surgery patients as subjects. Orthognathic surgery patients offer an uncompromised model for the evaluation of new rehabilitative therapies. These healthy individuals, treated to correct dentofacial deformity, present for surgery with no neurosensory impairment, but yet routinely experience substantial alterations in facial sensation following the surgical procedure. The effects of sensory re-training will be evaluated using three types of outcomes: patient-centered measures to assess the magnitude of the negative effect of altered sensation after surgery and the recovery time needed to reach little or no negative effect; neurosensory behavior measures to assess the patient's ability to learn alternate cues for touch perception and discrimination; and a conventional neurosensory contact threshold measure to assess the actual deficit. Our primary focus will be on the patient's perception of the negative impact of altered sensation on daily life.

The purpose of this study is to determine whether facial exercises in conjunction with opening exercises routinely provided after facial surgery to correct a facial skeletal disharmony will shorten the time until a patient receives no unpleasant or negative facial sensation.

PRIMARY OBJECTIVES:~I. To find the maximal tolerated dose for the combination of doxorubicin and Triapine® in patients with refractory solid tumors.~SECONDARY OBJECTIVES:~I. To find the severity and frequency of toxicity associated with this combination and to observe for and record any antitumor activity.~TERTIARY OBJECTIVES:~I. To evaluate the effect of Triapine®/doxorubicin on the ribonucleotide reductase tyrosyl radical in vivo by EPR spectroscopy in buccal mucosal cells, peripheral blood lymphocytes and in tumor biopsies. Formation of low molecular weight iron-Triapine® chelates will also be assessed by EPR.~II. To evaluate the effect of Triapine®/doxorubicin on cell cycle in vivo by measuring S-phase arrest in buccal mucosal cells.~III. To evaluate the effect of Triapine®/doxorubicin on MDR gene expression and polymorphisms in blood.~IV. To evaluate the effect of Triapine®/doxorubicin on ribonucleotide reductase R2 mRNA and immunohistochemistry.~V. To evaluate the pharmacokinetic profile of the combination. VI. To measure the formulation of circulating isoprostanes as an indicator of oxidative stress with this combination.~OUTLINE: This is a dose-escalation study of 3-AP (Triapine^®).~Patients receive doxorubicin IV over 15 minutes on day 1 and 3-AP (Triapine®) IV over 2 hours on days 1-4. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.~Cohorts of 3-6 patients receive escalating doses of 3-AP (Triapine®) until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Once the MTD is determined, an additional 6 patients are treated at that dose level.~Patients are followed until disease progression.

This phase I trial is studying the side effects and best dose of 3-AP and doxorubicin in treating patients with metastatic or refractory solid tumors. Drugs used in chemotherapy, such as doxorubicin, work in different ways to stop tumor cells from dividing so they stop growing or die. 3-AP may stop the growth of tumor cells by blocking the enzymes necessary for tumor cell growth and may help doxorubicin kill more cancer cells by making them more sensitive to the drug.

OBJECTIVES:~Compare the safety and tolerability of voriconazole vs itraconazole for the prevention of fungal infections in patients undergoing allogeneic hematopoietic stem cell transplantation.~OUTLINE: This is a randomized study. Patients are stratified according to donor type (related vs unrelated). Patients are randomized to 1 of 2 treatment arms.~Arm I: Beginning after allogeneic hematopoietic stem cell transplantation (AHSCT), patients receive voriconazole IV twice daily on days 1-14 and then orally* twice daily on days 15-100.~Arm II: Beginning after AHSCT, patients receive itraconazole IV twice daily on days 1-2, once daily on days 3-14, and then orally* twice daily on days 15-100.~NOTE: *Patients unable to tolerate oral medication may continue IV medication beyond day 14.~In both arms, treatment continues in the absence of unacceptable toxicity or an invasive fungal infection. Patients requiring corticosteroid therapy for graft-versus-host disease continue to receive voriconazole or itraconazole beyond day 100.~Patients are followed until day 180 post-transplantation.~PROJECTED ACCRUAL: A total of 150 patients (75 per treatment arm) will be accrued for this study.

RATIONALE: Antifungals, such as voriconazole and itraconazole, may be effective in preventing fungal infections in patients who are undergoing allogeneic stem cell transplantation.~PURPOSE: This randomized clinical trial is studying voriconazole to see how well it works compared to itraconazole in preventing fungal infections in patients who are undergoing allogeneic hematopoietic stem cell transplantation.

PRIMARY OBJECTIVES:~I. Determine the maximum tolerated dose and recommended phase II dose of flavopiridol in combination with gemcitabine and irinotecan in patients with unresectable or metastatic solid tumors.~II. Determine the toxicity profile of this regimen in these patients.~OUTLINE: This is a dose-escalation study of flavopiridol.~Patients receive gemcitabine IV over 30 minutes followed by irinotecan IV over 30 minutes on days 1 and 15. Patients also receive flavopiridol IV over 60 minutes on days 2 and 16. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of flavopiridol until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

This phase I trial is studying the side effects and best dose of flavopiridol when given together with gemcitabine and irinotecan in treating patients with unresectable or metastatic solid tumors. Drugs used in chemotherapy, such as flavopiridol, gemcitabine, and irinotecan, work in different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells

OBJECTIVES:~Primary~Compare the feasibility of a multi-component smoking cessation intervention comprising bupropion and counseling with or without contingency management (cash reward) for cancer survivors who continue to smoke.~Compare 7-day point-prevalence abstinence rates in patients treated with these smoking cessation interventions.~Secondary~Determine the characteristics of these patients that predict success at quitting smoking.~OUTLINE: This is a randomized, multicenter study. Patients are randomized to 1 of 2 smoking cessation intervention arms.~Arm I: Patients receive oral bupropion twice daily on weeks 1-12 and brief practical counseling (i.e., problem-solving strategies, stimulus control, stress management, and social support) on weeks 1-6.~Arm II: Patients receive treatment as in arm I and contingency management (i.e., monetary reinforcement for not smoking) on weeks 1-6.~In both arms, treatment continues in the absence of unacceptable toxicity.~Patients are followed at 12 and 24 weeks after the completion of the smoking cessation interventions.~PROJECTED ACCRUAL: A total of 100 patients (50 per intervention arm) will be accrued for this study within 8 months.

RATIONALE: Contingency management is a behavioral treatment approach that provides immediate rewards for positive change in behavior such as quitting smoking. In this protocol, contingency management will be in the form of a cash reward. A smoking cessation (stop-smoking) program that combines contingency management with bupropion and counseling may be effective in helping cancer survivors stop smoking.~PURPOSE: Randomized clinical trial to compare the effectiveness of bupropion and counseling with or without contingency management in helping cancer survivors stop smoking.

Despite the considerable mass appeal of popular diet books, such diet approaches lack data to support their efficacy and safety. Despite its widespread use for more than 30 years, the Atkins diet has never been evaluated in a large, randomized, controlled trial. This study will assess the short-term and long-term clinical effects of a low-carbohydrate diet and a high-carbohydrate diet in overweight and obese men and women.~Participants in this study will be randomly assigned to the Atkins diet (low-carbohydrate, unlimited fat and protein) or a conventional USDA diet (high-carbohydrate, low-fat). The study will evaluate the effects of each dietary approach on changes in: 1) weight and body composition; 2) metabolic and organ function; and 3) exercise tolerance. Each participant will be enrolled in the study for 2 years.

This study will compare the safety and the effectiveness of a low carbohydrate diet (Atkins diet) with a high carbohydrate diet (conventional USDA diet).

Acupuncture is emerging as an important procedure in complementary medicine. Its mechanism of action remains unclear, but research suggests that its effects are mediated through a widely connected network that is involved in the regulation of mood, behavior, and function of physiological systems. This study will use functional magnetic resonance imaging (fMRI) to monitor the effects of manual acupuncture on the brain function of study participants.~Participants in this study will undergo acupuncture one needle at a time. Researchers will then ask participants questions about how they feel and will compare the sensations reported by participants to their images of brain response.

The purpose of this study is to use brain imaging technology to examine the way acupuncture affects brain function.

Meditation and relaxation-based interventions are becoming more widely accepted in clinical settings because of their low cost, low risk, and proven effectiveness as a complementary intervention in a wide range of diseases. Despite the success and growing use of relaxation-based treatments, few studies have addressed the basic mechanism by which these treatments work. This study will use functional magnetic resonance imaging (fMRI) to define the brain mechanisms underlying the meditative state, to differentiate this state from other states, and to determine how meditation-induced brain changes affect autonomic function.~Participants in this study will have an fMRI brain scan. Brain activity, breathing rate, and heart rate will be measured while the participant engages in three different activities: lying quietly, meditating, and mentally generating numbers.

The purpose of this study is to use brain imaging technology to identify the parts of the brain that are activated during meditation and to compare these parts to those activated during other activities. This study will also determine the effects of meditation on involuntary functions, such as breathing.

OBJECTIVES:~Determine whether the effects of massage therapy in patients with cancer pain are sufficiently promising to warrant a definitive trial.~Determine the feasibility of a definitive trial.~OUTLINE: This is a randomized, controlled, pilot study. Patients are stratified according to in-patient status (yes vs no) and first baseline pain score ≥ 7 (yes vs no). Patients are randomized to 1 of 3 treatment arms.~Arm I (massage therapy): Patients receive a light touch (Reiki) massage over 45 minutes.~Arm II (volunteer visit control): Patients receive a 45-minute visit from a trained volunteer who will be available to sit quietly or talk with the patient to discuss issues of concern, as desired by the patient. Volunteers will not touch the patient except to pat their shoulder or briefly hold their hand.~Arm III (quiet time control): Patients receive 45 minutes of quiet time. Pain and mood are assessed at baseline, immediately after treatment, at 6 hours and 24 hours after treatment, and then daily for the next 5 days after treatment.~PROJECTED ACCRUAL: A total of 60 patients will be accrued for this study.

RATIONALE: Massage therapy may help lessen pain caused by cancer.~PURPOSE: This randomized phase II trial is studying how well massage therapy works in treating patients with cancer pain.

Primary Objective of Phase I~To determine the maximal and Phase II dose of inhaled doxorubicin HCl when given in combination with IV docetaxel and cisplatin in patients with locally advanced or metastatic unresectable NSCLC who have not been previously treated with chemotherapy.~Primary Objective of Phase II~To obtain preliminary evidence of therapeutic activity using imaging studies in patients with measurable or evaluable lung lesions and serial measurements of disease-related pulmonary symptoms and pulmonary function.~Secondary Objective~To define the nature of the toxic effects of inhaled doxorubicin when given in combination with IV docetaxel and cisplatin.

This study is intended to show whether inhaled chemotherapy can be added to a standard IV chemotherapy regime, to investigate the additional toxicities and to show initial evidence of efficacy of the combination.

The proposed trial is intended to test the effectiveness of a proven, manual driven, five-session safer sexual skills building group (SSB) intervention (Schilling et al., 1991; El Bassel and Schilling, 1992) for female patients in MMTP or in drug-free outpatient treatment. The effects of SSB will be compared to a standard group HIV education session (HE).~This study uses a 2-group, randomized, parallel-group design to compare a five-session safer sexual skills building group to a single 60-min HIV education session (control condition). The control condition is designed to standardize and simulate the usual care at community clinics.

The purpose of this study is to look at a program for women in drug abuse treatment designed to reduce Human Immunodeficiency Virus/Sexually Transmitted Disease (HIV/STD) risk behaviors and reduce unprotected sexual risk behavior.

PRIMARY OBJECTIVES:~I. To find the maximal tolerated dose for the combination of irinotecan and Triapine® in patients with refractory solid tumors.~SECONDARY OBJECTIVES:~I. To find the severity and frequency of toxicity associated with this combination and to observe for and record any antitumor activity.~TERTIARY OBJECTIVES:~I. To evaluate the effect of Triapine®/irinotecan on the ribonucleotide reductase tyrosyl radical in vivo by Electron Paramagnetic Spectroscopy (EPR) in buccal mucosal cells, peripheral blood lymphocytes and in tumor biopsies. Formation of low molecular weight iron-Triapine® chelates will also be assessed by EPR.~II. To evaluate the effect of Triapine® /irinotecan on cell cycle in vivo by measuring S-phase arrest in buccal mucosal cells.~III. To evaluate the effect of Triapine® /irinotecan on MDR gene expression and polymorphisms in blood.~IV. To evaluate the effect of Triapine® /irinotecan on ribonucleotide reductase R2 mRNA and Immunohistochemistry.~V. To evaluate the pharmacokinetic profile of the combination.~OUTLINE: This is a dose-escalation study.~Patients receive irinotecan IV over 1 hour on day 1 and 3-AP (Triapine®) IV over 2 hours on days 1-3. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.~Cohorts of 3-6 patients receive escalating doses of irinotecan and 3-AP (Triapine®) until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Once the MTD is determined, 6 additional patients are treated at that dose.~Patients are followed until disease progression.

This phase I trial is studying the side effects and best dose of irinotecan and 3-AP in treating patients with metastatic or unresectable solid tumors. Drugs used in chemotherapy such as irinotecan work in different ways to stop tumor cells from dividing so they stop growing or die. 3-AP may stop the growth of tumor cells by blocking the enzymes necessary for their growth and may help irinotecan kill more tumor cells by making them more sensitive to the drug.

PRIMARY OBJECTIVES:~I. To determine the maximal tolerated dose of R115777 (tipifarnib) in combination with OSI-774 (erlotinib hydrochloride).~II. To describe the toxicity profile of this combination. III. To evaluate the effect of OSI-774 on the disposition of R115777. IV. To evaluate in vitro markers of farnesyl transferase (FT) inhibition and epidermal growth factor receptor (EGFR) inhibition.~OUTLINE: This is a dose-escalation study.~Patients receive erlotinib hydrochloride orally (PO) once daily (QD) on days 1-28 (days 8-28 of course 1 as of 11/4/2013) and tipifarnib PO twice daily (BID) on days 1-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. (Closed to accrual as of 2/2/06)~After completion of study treatment, patients are followed up at 3 months.

This phase I trial studies the side effects and best dose of tipifarnib and erlotinib hydrochloride in treating patients with solid tumors that have spread to other places in the body. Tipifarnib and erlotinib hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

OBJECTIVES:~Determine the antitumor activity of cetuximab and carboplatin in patients with recurrent platinum-sensitive ovarian epithelial or primary peritoneal cancer.~Determine the nature and degree of toxicity of this regimen in these patients.~OUTLINE: This is a multicenter study.~Patients receive cetuximab IV over 1 hour (over 2 hours on day 1 of course 1 only) on days 1, 8 , and 15. Patients also receive carboplatin IV after cetuximab administration on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.~Patients are followed every 3 months for 2 years and then every 6 months for 3 years.~PROJECTED ACCRUAL: A total of 20-65 patients will be accrued for this study.

RATIONALE: Monoclonal antibodies such as cetuximab can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. Drugs used in chemotherapy such as carboplatin work in different ways to stop tumor cells from dividing so they stop growing or die. Combining cetuximab with carboplatin may kill more tumor cells.~PURPOSE: This phase II trial is studying how well giving cetuximab together with carboplatin works in treating patients with recurrent ovarian epithelial cancer or primary peritoneal cancer.

OBJECTIVES:~Determine the antitumor activity of pemetrexed disodium in patients with recurrent or persistent platinum-resistant ovarian epithelial or primary peritoneal cancer that failed higher priority treatment protocols.~Determine the nature and degree of toxicity of this drug in these patients.~OUTLINE: This is a multicenter study.~Patients receive pemetrexed disodium IV over 10 minutes on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.~Beginning 7 days before and continuing until 3 weeks after the last dose of pemetrexed disodium, patients also receive oral folic acid daily and cyanocobalamin (vitamin B_12) intramuscularly every 9 weeks.~Patients are followed every 3 months for 2 years and then every 6 months for 3 years.~PROJECTED ACCRUAL: A total of 19-51 patients will be accrued for this study within 11-22 months.

RATIONALE: Drugs used in chemotherapy, such as pemetrexed disodium, work in different ways to stop tumor cells from dividing so they stop growing or die.~PURPOSE: This phase II trial is studying how well pemetrexed disodium works in treating patients with recurrent or persistent ovarian epithelial cancer or primary peritoneal cancer.

The use of CAM is common among patients with cancer. However, there may be differences in participation, treatment preferences, and quality of life that are influenced by socioeconomic factors and ethnicity. This study will compare two distinct socioeconomic groups to determine differences in CAM use.~Participants in this study will complete a questionnaire regarding demographics, socioeconomic status, disease specifics, and facilitators and barriers to CAM use. Participation in an introductory seminar and in various CAM programs will be monitored. Participants will also complete a quality of life scale that will provide insight into the way different populations perceive and use CAM and will identify potential obstacles to integrating CAM into other cancer treatment programs.

The purpose of this study is to determine whether differences in the use of complementary and alternative medicine (CAM) are influenced by the socioeconomic status and ethnicity of cancer patients.

The primary objectives of this study are 1) to evaluate the safety of a short intravenous infusion of PT-523 when administered on days 1, 8, and 15 of a 28-day cycle to patients with solid tumors who have failed curative or survival prolonging therapy or for whom no such therapies exist; and 2) to establish the maximum tolerated dose (MTD) and identify the dose limiting toxicities (DLT) of PT-523.~The secondary objectives of this study are to determine the pharmacokinetics and to evaluate preliminary efficacy of PT-523.

The purpose of this study is to determine the safety of a short intravenous infusion of PT-523 to patients with solid tumors who have failed curative or survival prolonging therapy or for whom no such therapies exist.

PRIMARY OBJECTIVES:~I. To determine the maximum tolerated dose of single agent decitabine and its toxicity using this schedule in this population of patients with solid tumors or lymphomas.~II. Definition of the dose at which tumor DNA demethylation is optimum. III. Definition of the dose at which peripheral blood mononuclear cell (PBMN) demethylation is optimal.~IV. Definition of decitabine pharmacokinetics and correlation of plasma concentrations with hypomethylation effects.~SECONDARY OBJECTIVES:~I. Preliminary assessment of decitabine efficacy (objective response).~OUTLINE: This is a dose-escalation study.~Patients receive decitabine IV over 1 hour on days 1-5 or on days 1-5 and 8-12. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.~Cohorts of 6 patients receive escalating doses of decitabine until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity.

This phase I trial is studying the side effects and best dose of decitabine in treating patients with metastatic or unresectable refractory solid tumors or lymphomas. Drugs used in chemotherapy, such as decitabine, work in different ways to stop cancer cells from dividing so they stop growing or die

This protocol is designed to provide blood, urine, sputum, stool, cerebrospinal fluid, skin biopsy and bone marrow aspirate samples from paid, volunteer donors for use in in vitro studies of eosinophilia and parasitic diseases. Donors meeting standard normal donor eligibility criteria will be recruited to donate blood, urine, sputum, stool, cerebrospinal fluid, skin biopsy and/or bone marrow using conventional techniques. The investigational nature of the studies in which their samples will be used, as well as the risks and benefits of the donation process will be explained to all donors, and a signed informed consent document will be obtained. Donors will be compensated according to an established schedule based on the duration and discomfort of the donation. Samples provided through this protocol will be used solely for in vitro research. Blood, urine, sputum, stool, cerebrospinal fluid, skin biopsy and bone marrow samples will be assigned a unique product number, and the study investigators listed on this protocol will serve as the custodians of the code that links the product with a donor s identity. The nature of the in vitro studies in which the specimens collected in this study will be used is not the subject of this protocol and will be described in general terms only, since it involves several IRB-approved LPD protocols. Because some of these protocols require normal controls without a history of asthma or allergic disease, all subjects will undergo a standardized allergy/asthma history at enrollment. Serum immunoglobulin levels and a basic RAST panel may be performed on sera from some normal donors, and some normal donors may be asked to undergo pulmonary function testing. This protocol is designed to assure adequate and complete informed consent, counseling, and protection of the study subjects according to IRB, OHSR, OPRR and other applicable Federal regulatory standards.

Increased numbers of white blood cells called eosinophils can cause disease. To investigate this disease, researchers need blood, urine, sputum, stool, cerebrospinal fluid, skin and/or bone marrow samples to compare to samples from patients with this problem. Some of the samples will be used for genetic testing or future research.~This study will last for about 10 years and will include a maximum of 50 paid volunteers ages 18 to 65.

OBJECTIVES:~Determine the safety of contrast-enhanced high-dose radiotherapy administered with sargramostim (GM-CSF) in patients with advanced solid malignancies.~Determine immune response in patients treated with this regimen.~Determine tumor response in patients treated with this regimen.~OUTLINE: Patients are stratified according to prior therapy (biopsy or simple surgery vs radical surgery, chemotherapy, or radiotherapy).~Patients receive a contrast agent intratumorally followed by a single fraction of kilovoltage radiotherapy. Beginning 24 hours after radiotherapy, patients receive sargramostim (GM-CSF) intratumorally continuously for 1 week and then subcutaneously for 2 weeks. Patients with lung tumors receive GM-CSF by inhalation twice daily for 1 week and then every other week for a total of 3 weeks of drug treatment.~Treatment may repeat in several weeks in the absence of disease progression or unacceptable toxicity.~Patients are followed every 8 weeks.~PROJECTED ACCRUAL: A total of 47 patients (12 for phase I and 35 for phase II) will be accrued for this study.

RATIONALE: Colony-stimulating factors such as sargramostim increase the number of immune cells found in bone marrow or peripheral blood. Radiation therapy uses high-energy x-rays to damage tumor cells. Combining radiation therapy with sargramostim may kill more tumor cells.~PURPOSE: This phase I/II trial is studying the side effects of giving radiation therapy together with sargramostim and to see how well it works in treating patients with advanced solid tumors.

OBJECTIVES:~Determine the safety and immunogenicity of adjuvant vaccine comprising ovarian cancer synthetic peptides, tetanus toxoid helper peptide, and sargramostim (GM-CSF) emulsified in Montanide ISA-51 in patients with previously treated ovarian epithelial or primary peritoneal cancer.~OUTLINE: This is an open-label study.~Patients receive vaccine comprising ovarian cancer synthetic peptides, tetanus toxoid helper peptide, sargramostim (GM-CSF), and Montanide ISA-51 subcutaneously and intradermally to 2 different sites on days 1, 8, and 15. On day 22, patients undergo removal of the lymph node draining the vaccination site to determine whether the immune system is responding to the vaccine. Patients then receive additional vaccine as above only to the primary vaccination site on days 29, 36, and 43.~After completion of study treatment, patients are followed at 1 week, 1 month, every 3 months for 9 months, every 6 months for 1 year, and then annually thereafter.~PROJECTED ACCRUAL: A maximum of 9 patients will be accrued for this study.

RATIONALE: Vaccines made from peptides may make the body build an immune response to kill tumor cells.~PURPOSE: This phase I trial is studying the side effects of vaccine therapy in treating patients with ovarian epithelial or primary peritoneal cancer.

OBJECTIVES:~Primary~Determine the acute and chronic changes in INR in patients with advanced solid tumors treated with low-dose warfarin and vatalanib.~Secondary~Determine the steady-state pharmacokinetics of this regimen in these patients.~Determine the safety and tolerability of this regimen in these patients.~OUTLINE: This is a nonrandomized, open-label, multicenter study.~Pharmacokinetic (PK) phase: Patients receive oral low-dose warfarin once daily on days 1-14 and oral vatalanib once daily, 1 hour before warfarin administration, on days 2-14 in the absence of disease progression or unacceptable toxicity.~Continuation phase: Patients not experiencing a drug interaction in the PK phase continue to receive oral vatalanib and oral low-dose warfarin once daily. Patients experiencing a drug interaction (INR > 2.0) in the PK phase receive oral vatalanib alone once daily. Continuation therapy continues indefinitely in the absence of disease progression or unacceptable toxicity.~PROJECTED ACCRUAL: A total of 30 patients will be accrued for this study.

RATIONALE: Vatalanib may stop the growth of tumor cells by stopping blood flow to the tumor. Warfarin may be effective in preventing the formation of blood clots in patients who are undergoing treatment for advanced solid tumors.~PURPOSE: This phase I trial is studying how well giving warfarin together with vatalanib works in treating patients with advanced solid tumors.

OBJECTIVES:~Primary~Determine the effect of green tea extract (Polyphenon E) on cytochrome P450 enzyme activities and glutathione S-transferase activities and levels in healthy participants.~Secondary~Determine the safety and tolerability of this drug in these participants.~OUTLINE: This is an open-label study.~Participants receive oral green tea extract (Polyphenon E) once daily for 4 weeks in the absence of unacceptable toxicity.~Participants are followed for 2 weeks.~PROJECTED ACCRUAL: A total of 44 participants will be accrued for this study.

RATIONALE: Green tea extract (Polyphenon E) contains ingredients that may prevent the development of cancer.~PURPOSE: This phase I trial is studying how well green tea extract works in preventing cancer in healthy participants.

Other objectives of this study include measuring pharmacokinetics (how long the drug can be measured in the blood) and determining the dose and dose schedule for the next phase of studies with SNS-595.

The purpose of this study is to determine whether SNS-595 given intravenously once every 3 weeks is safe.

OBJECTIVES:~Primary~Determine the maximum tolerated dose, biologically active dose, and recommended phase II dose(s) of BMS-599626 in patients with metastatic HER2/neu-overexpressing primary solid tumors.~Secondary~Determine the safety and tolerability of this drug in these patients.~Determine the pharmacokinetics of this drug in these patients.~Determine the effect of this drug on biomarkers and predictive markers of HER1 and HER2 in skin and tumor in these patients.~Evaluate tumor metabolic activity in response to this drug in these patients.~Determine, preliminarily, evidence of anti-tumor activity of this drug in these patients.~OUTLINE: This is an open-label, dose-escalation, multicenter study.~Patients receive oral BMS-599626 once daily on days 1-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.~Cohorts of 3-6 patients receive escalating doses of BMS-599626 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity. Once the MTD is determined, 20 patients are treated at that dose level.~PROJECTED ACCRUAL: Approximately 3-60 patients will be accrued for this study within 1 year.

RATIONALE: BMS-599626 may stop the growth of tumor cells by blocking the enzymes necessary for their growth.~PURPOSE: This phase I trial is studying the side effects and best dose of BMS-599626 in treating patients with metastatic solid tumors.

The goal of the study is to pin down the causal effect of improvements in health on the economic and social prosperity of individuals and their families. Particular attention will be paid to the dynamics underlying the effect of health on labor outcomes; older adults are more likely to experience transitions in health and economic status and so will be emphasized.~Beginning in 2002, about 4,000 households will be interviewed every four months for about 3 years. The first two waves of the survey will serve as baselines. After the second wave, households will be randomly assigned to one of two groups. Iron supplements will be provided to all members of households assigned to one of those groups. Household members in the 2nd group will receive an identical-looking placebo. Participants will take the supplements (or placebo) on a weekly basis for a year. The study will measure the effect of supplementation on the well-being of individuals and their families.~Data will be collected at the individual, household and community level. Individual level data will cover time allocation including work and participation in community activities, earnings, self-reported and physical health and cognition. All adult household members will be interviewed; questions about children will be answered by a caretaker. Data on wealth and consumption will be collected at the household level. Community resources, services and infrastructure information will be gathered along with detailed price data.

This project seeks to understand how changes in the health of an individual affects the economic and social prosperity of the individual, family and community. The study involves providing iron supplements to a sample of participants in Central Java Indonesia and following those respondents for three years. They are compared with a control group who do not receive the supplement.

Other objectives of this study include measuring pharmacokinetics (how long the drug can be measured in the blood) and determining the dose and dose schedule for the next phase of studies with SNS-595.

The purpose of this study is to determine whether SNS-595 given intravenously weekly for 3 weeks is safe.

Volunteer participants will be randomly assigned to experimental (memory training) and comparison (health promotion) groups. Both groups will learn strategies for successful aging. Participants will be in the study for 27 months and will be interviewed on five occasions for 3 hours per interview. The classroom-based intervention is an 8-session, 1 1/2 hour course designed to teach older adults the use of strategies to improve everyday memory. Strategically-placed booster sessions will be provided to subjects within 3 months following the last class session.

The purpose of this study is to determine whether classes on memory training will help older adults to improve or maintain their daily activities.

OBJECTIVES:~Primary~Determine the effect of ketoconazole on the pharmacokinetics of ixabepilone in patients with advanced solid tumors.~Secondary~Determine the safety of ixabepilone when administered alone and in combination with ketoconazole in these patients.~Determine, preliminarily, the antitumor activity of this regimen in these patients.~OUTLINE: This is an open-label, dose-escalation study of ixabepilone.~During course 1, patients receive oral ketoconazole on days 0-5 and ixabepilone IV over 3 hours on day 1. During course 2 and subsequent courses, patients receive only ixabepilone IV over 3 hours on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.~Cohorts of at least 3 patients receive escalating doses of ixabepilone during course 1 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 patients experience dose-limiting toxicity. At least 12 patients are treated at the MTD.~PROJECTED ACCRUAL: A total of 3-35 patients will be accrued for this study.

RATIONALE: Drugs used in chemotherapy, such as ixabepilone and ketoconazole, work in different ways to stop tumor cells from dividing so they stop growing or die. Giving ixabepilone with ketoconazole may kill more tumor cells.~PURPOSE: This phase I/II trial is studying the side effects and best dose of giving ixabepilone together with ketoconazole and to see how well they work in treating patients with advanced solid tumors.

2-deoxy-D-glucose (2DG) is a synthetic glucose analog under development by Threshold Pharmaceuticals, Inc. that exploits the differences in metabolism between normal and malignant cells. Malignant cells utilize glucose at a much higher rate than normal cells and are therefore more dependent on aerobic and anaerobic glycolysis. If glycolysis could be blocked preferentially in malignant cells, 2DG would have potential for anti-tumor therapy. Hypoxic cells are especially dependent on anaerobic glycolysis and are generally resistant to anti-tumor therapies such as chemotherapy and radiotherapy. Therefore, combining 2DG with chemotherapy may be a way to simultaneously target both hypoxic and aerobic cells in tumors.~Four factors may play a role in the preferential toxicity of 2DG in malignant cells: (1) increased uptake and retention of glucose analogs by malignant cells; (2) relative hypoxia of tumor cells relative to normal cells; (3) malignant cells may be more sensitive to glucose deprivation than normal cells; and (4) inhibition of glycolysis may increase sensitivity to some cytotoxic agents. Preliminary data in human tumor xenografts support this hypothesis.~Because 2DG is most likely to be effective in combination with chemotherapy, this trial was designed to evaluate the maximum tolerated dose (MTD) of 2DG both alone and in combination with chemotherapy. Docetaxel was chosen because there is evidence in human tumor xenografts of delayed tumor growth for 2DG in combination with paclitaxel compared to paclitaxel alone and it has been reported that taxanes may enhance uptake of 2DG into malignant cells. Patients with advanced solid tumors were chosen because they are appropriate candidates for a Phase I clinical trial and because their tumors are likely to have areas of hypoxia.

The objectives of this study are to evaluate the safety, tolerability, pharmacokinetics, and biologic effect (FDG PET, preliminary efficacy) of daily oral doses of 2DG with and without weekly docetaxel in subjects with advanced solid tumors.

Unnecessary delays in removing patients from mechanical ventilation increase morbidity, mortality, and cost. According to recently published guidelines, the current standard of care for weaning involves the daily assessment of patients while they are breathing spontaneously, also known as spontaneous breathing trials (SBT). While there are important data to support a daily cessation of sedatives and analgesics to the point of patient awakening, the benefit of combining such a daily spontaneous awakening trial (SAT) and an SBT is not known.~This multi-center, randomized controlled trial will test whether a 2-step process of weaning that combines a daily awakening trial (achieved by stopping all sedatives and narcotics every morning) with a daily spontaneous breathing trial is superior to the current standard of care.~The number of days the patient is able to live off the ventilator is the primary question being studied. The secondary questions include the number of days the patient is in Intensive Care Unit (ICU) and the hospital, the complications associated with being on the ventilator (such as the duration and severity of delirium and coma), and in-hospital and one-year mortality. Also, cognitive, psychological, and functional/quality of life outcomes will be measured at discharge and 3 and 12 months later.~In addition, the study will measure plasma drug levels twice daily on five sequential days within 30 minutes of testing with highly reliable and well validated instruments to measure sedation level (i.e., RASS) and delirium (i.e. CAM-ICU).

The purpose of this study is to determine the impact of a new RN/RRT (Registered Nurse/Registered Respiratory Therapist) directed 2-step protocol to wean patients off of a ventilator. This protocol involves daily attempts to halt sedation (spontaneous awakening trials) combined with daily assessments of patients while they are breathing on their own (spontaneous breathing trials).

The study recruited 273 participants from a community-based HMO for whom computerized health service utilization and cost data were already available, as well as cognitive, functional, and health status measures. The participants were randomly placed into one of four treatment groups: exercise, health promotion, combination exercise and health promotion, and routine medical care. Assessments for physical performance, emotional well-being, and physical and emotional health status were conducted at screening, baseline, after 3 months (post-treatment), and at 6, 12, and 18-month follow-up by interviewers blind to treatment assignment.

The purpose of this study is to examine the relative and combined efficacy of a physical activity and health promotion program to help sedentary adults over age 70 maintain an independent life style.

Menopause affects every woman as she ages, yet every woman's experience is different. We are seeking to enroll 720 women from the University of Pittsburgh's Division of General Internal Medicine Outpatient practice (GIMO) at all stages of menopause (pre-, peri-, and post-menopausal), between 40 and 65 years old. They will be followed for 5 years as they progress through menopause.~Women will complete yearly questionnaires during their usual doctor's visit (or by phone or online if necessary) regarding general health, menopause and menopausal symptoms, health related quality of life, traditional and alternative therapy use, social support, and attitudes towards menopause and aging.~We will combine this information with information from women's medical charts to look at how menopause and health related quality of life impact the use of health care resources. Additionally, some women may be asked about the use of health care resources, such as doctor's visits, hospitalizations and lab tests.

The purpose of this study is to follow a woman's progression through menopause in order to examine the effects on health related quality of life and use of health care resources, and to understand how women are using alternative therapies.

The Phase 1 clinical trial is designed as a single-center, open-label, non-randomized study to evaluate the safety, tolerability and immunogenicity of a two-dose schedule of rBV A/B in healthy volunteers at three ascending dosage levels, 5 ug, 10 ug and 20 ug serotype-specific antigen (10 ug, 20 ug and 40 ug total immunizing protein) in three dosing cohorts and a two-dose regimen (Day 0 and Day 28) of a formulation containing only antigens at the 40 ug total immunizing protein dosage level. Approximately 44 volunteers (11 per cohort) are expected to be enrolled. Cohorts will enroll consecutively beginning with the lowest dosage level. Volunteers in each cohort will receive a two injection series at the assigned dosage level given as a 0.5 mL intramuscular (i.m.) injection on Day 0 and Day 28. Potential volunteers for study participation will undergo qualification screening for this study during the 21 days prior to the date scheduled for vaccination. After successful completion of the informed consent process and all screening assessments, volunteers will be scheduled for vaccination. Volunteers will report acute adverse events daily for 28 days after each vaccination and return to the clinic at regular intervals according to the Schedule of Study Assessments with the last scheduled follow-up 168 days (± 7 days) after the initial vaccination (Day 0).

The purpose of this trial is to evaluate the safety and tolerability of a two-dose regimen (Day 0 and Day 28) of recombinant Botulinum Vaccine (rBV) A/B in healthy volunteers when given intramuscularly at three ascending dosage levels by cohort and a two-dose regimen (Day 0 and Day 28) of a formulation containing only antigens at the 40 ug total immunizing protein dosage level.

Poor mineral nutrition, especially deficiencies of iron and zinc, is a major cause of maternal and, especially, infant morbidity/mortality in developing world countries. The objectives of this study are to determine whether: a) linear growth velocity between 6 and 12 months in infants receiving a 5mg Zn supplement will be greater than that for infants receiving placebo; b) linear growth velocity will be greater for infants receiving complementary foods containing low phytate maize than for the infants fed wild-type control maize. In addition, Zn metabolic studies will be performed. The objective of the metabolic studies are to measure key variables of Zn homeostasis in maternal participants during changes in the reproductive cycle and in infants during a time when they are most vulnerable to Zn deficiency.~The primary outcome measurement is linear growth velocity between 6 and 12 months. Secondary outcomes are weight gain, diarrheal incidence/prevalence and infant neurodevelopmental measures. Optional maternal and infant biochemical data will be collected from a convenience sample comprised of willing participants.~One additional component to this study is to collect information on the nutritional status of the women receiving low-phytate vs. control maize and the infants enrolled in this study.~The current protocol for infants in this study specifies measurements of exchangeable zinc pool (EZP) at 6 and 12 months of age; in order to lessen the burden of study participation we plan to conduct the metabolic studies in infants at only nine months of age. In addition to decreasing the number of infant studies, this change will enable families who are only participating in the metabolic studies (not simultaneously enrolled in the sibling cohort) to cease all study demands at the end of the nine month measurement (an overall decrease of three months in study participation).~The primary outcome measure for this study is the quantity of zinc absorbed (mg/day)from complementary foods and a Zn supplement at age 9 months. The rationale for measures of zinc absorption in infants is that the low phytate complementary feeding is expected to have a beneficial public health effect only if it results in enhanced mineral, especially zinc, absorption. Therefore, confirmation of increased zinc absorption can be regarded as the first logical stage of any efficacy study.~The sample size of 420 is required in order to observe a 6% increase in growth rates for Zn supplemented infants compared to placebo treated infants within each maize group with 80% power.

Malnutrition is a serious health problem in the developing world. This study looks at the effects of changing the type of basic food staple (corn) used in Guatemala and infant zinc supplementation on infants' growth, development, and illnesses from infectious diseases.

Information on fetal well-being during labor is of great importance to the managing physician. The current use of the fetal heart rate monitor provides some information on fetal condition, and is the primary tool used to determine if immediate operative delivery is required. The fetal pulse oximeter can provide additional information regarding fetal oxygen saturation.~Intervention: A fetal oxygen saturation sensor is placed in the uterus, between the fetal cheek or forehead and the uterine wall. In half of the patients, the managing physician will have access to fetal oxygen saturation and fetal heart rate monitoring. In the other half of the patients, labor will be monitored by fetal heart rate alone.~Study hypothesis: The additional information provided by the use of the fetal pulse oximeter will reduce the chances of a cesarean delivery. The primary outcome is cesarean section for any indication and secondary outcomes are cesarean delivery for non-reassuring fetal heart rate or dystocia, and neonatal morbidity.

The purpose of this study is to determine if the information provided to the physician by a fetal pulse oximeter during labor will reduce the chances of a cesarean delivery.

OBJECTIVES:~Determine the concentration of resveratrol and its metabolites in the plasma, urine, and feces of healthy participants.~Correlate dose with systemic concentration of this drug and its metabolites in these participants.~Determine the safety of this drug in these participants.~OUTLINE: This is an open-label, dose-escalation, multicenter study.~Beginning 5 days before study drug administration, participants are put on a controlled diet (avoiding all resveratrol-containing food or drink) for washout. Participants receive oral resveratrol once on day 1.~Cohorts of 10 participants receive escalating doses of resveratrol until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 10 participants experience dose-limiting toxicity. A total of 16 participants are treated at the MTD.~Participants are followed at 2 and 7 days.~PROJECTED ACCRUAL: A total of 10-40 participants will be accrued for this study within 6 months.

RATIONALE: Chemoprevention is the use of certain drugs to keep cancer from forming, growing, or coming back. The use of resveratrol may prevent cancer.~PURPOSE: This phase I trial is studying the side effects and best dose of resveratrol in preventing cancer in healthy participants.

Researchers at the Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University are enrolling overweight men and women aged 20-42 in a 1-year study to develop an effective calorie restricted regimen that minimizes hunger and prevents weight regain. The study also examines the effects of weight loss on body composition, metabolism and aging. Two different diets containing usual foods and a healthy balance of nutrients will be tested at 2 levels of caloric restriction, 10% and 30% (in other words, 90% or 70% of what one would normally eat). Weight loss is expected for most volunteers participating in this study, but cannot be guaranteed.

This study is one of three CALERIE trials that test the hypothesis that a reduced calorie, nutritionally sound diet increases the length of life and prevents some age-related chronic diseases such as cancer, diabetes, and cardiovascular disease. The three sites that are participating in the CALERIE trial represent a diversity of subject populations and interventional strategies.

Animal studies suggest that caloric restriction (CR), or consuming fewer calories, increases life span, and also protects against some aging-related disease processes such as artherosclerosis and type II diabetes. However, it appears that simply burning more calories through physical activity does not increase life span by itself. It is not known how CR affects humans, but based on this evidence it appears that the reduced total intake and metabolism of food is the main factor, rather than increased exercise alone.~To test this, volunteers will be placed on a program of either 20% caloric restriction or 20% increase of energy expenditure by exercise, or in a control group to be instructed in healthy living. All will be evaluated on a number of potential markers of aging, on body composition, and on risk factors for artherosclerosis and diabetes.~Participation in the study will last for 12 months. The Diet group will receive individual instruction from a registered dietician. The Exercise group will be given an individualized exercise program created by a personal trainer. The Healthy Lifestyle group will be given information on how to make healthier choices; both diet and activity will be discussed. All participants will be measured every two weeks, and will keep daily food and activity logs. All will be seen by a physician and will have lab tests done before beginning the study, at 1 month, and then 3 month intervals.

This study is one of three CALERIE trials that test the hypothesis that a reduced calorie, nutritionally sound diet increases the length of life and prevents some age-related chronic diseases such as cancer, diabetes, and cardiovascular disease. The three sites that are participating in the CALERIE trial represent a diversity of subject populations and interventional strategies.

Educational programs to promote the adoption of healthy behaviors and to decrease the onset of risky behaviors in pre-adolescents are far more likely to be successful than attempts to alter established patterns of high-risk behaviors. The project involves an evaluation of a comprehensive 4-year elementary school prevention initiative starting in 3rd grade. The prevention initiative, grounded in social cognitive, influence, and development theories is embedded within a pre-existing comprehensive elementary school social development program and will employ an evidence-based social skills curriculum (PATHS) in selected schools. The aim of the program is to teach children to use problem-solving and communication skills to negotiate and prevent high-risk behaviors.~Students attending schools that will receive the enhanced social development program will be compared to students attending schools that will receive the current, standard social development curriculum. The study hypothesizes that students who participate in the 4-year enhanced social development program will self-report fewer risk behaviors when surveyed by the school system in grades 6-8.

This project will evaluate the benefit of an enhanced social development program in grades 3-6 to decrease the onset of risky behaviors in pre-adolescents.

OBJECTIVES:~Primary~Determine the maximum tolerated dose of indole-3-carbinol in healthy participants.~Determine the safety and tolerability of this drug in these participants.~Determine the pharmacokinetics of this drug in these participants.~Secondary~Determine the effects of this drug on selected markers of sexual function in these participants.~Determine the effects of this drug on markers of susceptibility to cancer in these participants.~OUTLINE: This is a randomized, double-blind, placebo-controlled, dose-escalation study. Participants at each dose level are randomized to 1 of 2 treatment arms.~Arm I: Participants receive a single dose of oral indole-3-carbinol on day 1.~Arm II: Participants receive a single dose of oral placebo on day 1. Cohorts of 3 participants receive escalating doses of indole-3-carbinol until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 1 of 3 participants experiences dose-limiting toxicity. An additional cohort of 3 participants is treated at the MTD.~Participants are followed on days 2, 3, and 6.~PROJECTED ACCRUAL: A total of 24 participants (18 in arm I and 6 in arm II) will be accrued for this study.

RATIONALE: Chemoprevention is the use of certain drugs to keep cancer from forming, growing, or coming back. The use of indole-3-carbinol may prevent cancer.~PURPOSE: This randomized phase I trial is studying the side effects and best dose of indole-3-carbinol and to see how well it works compared to placebo in preventing cancer in healthy participants.

For the past 20 years, Japanese women have reported fewer menopausal symptoms than their North American counterparts. One explanation for the disparity is the differences in diet. Evidence suggests that Japanese women consume large amounts of soy, a phytoestrogen that is structurally similar to the hormone estrogen. However, there is a lack of menopause-related research data from non-Western populations. This study will be a long-term observation of the effects of soy consumption in menopausal Japanese women.~This study will last 6 months. Participants will complete a dietary log and a menopausal symptom checklist daily. There will be three or four study visits. During these visits, participants will complete a diet questionnaire, have a blood sample collected, and be interviewed about their menopausal symptoms. Six months after study completion, participants will be sent a questionnaire about any recent menopausal symptoms they may have experienced.

The purpose of this study is to examine the way soy consumption affects menopausal symptoms in middle-aged Japanese women.

Our prior work shows that d-amphetamine and the dopamine precursor levodopa markedly improve word learning success in healthy subjects. In this randomized, placebo-controlled, double-blind clinical trial, we probe whether a mixed d1/d2 dopamine agonist (pergolid) or cholinergic neuromodulation (rivastigmine) or a general centrally arousing substance (modafinil) will yield a learning enhancement comparable to using levodopa in healthy subjects.~Our results show that the dopamine agonist pergolide impaired learning in healthy subjects compared to placebo, whereas cholinergic neuromodulation had no effect.

The purpose of this study is to determine whether levodopa, pergolid, rivastigmine, or modafinil are effective in boosting semantic language acquisition in healthy subjects.

The purposes of this study are:~To evaluate the tolerability of two cangrelor regimens of bolus plus infusion (A and B).~To characterize the pharmacokinetics of Cangrelor (A and B).~To compare the pharmacodynamics of cangrelor regimens with that of an oral 600 mg dose of clopidogrel (A, B, C and D).~To determine the effect of prior cangrelor treatment on the pharmacodynamics of clopidogrel (C and D).~To determine the effect of prior clopidogrel treatment on the pharmacodynamics of cangrelor (Group D).~To determine the effects of concomitant clopidogrel and cangrelor exposure on the pharmacodynamics of clopidogrel (Group D).

The purposes of this study are to:~Evaluate the tolerability of two cangrelor regimens.~Compare the PD of cangrelor regimens with oral clopidogrel.

Our prior work shows that d-amphetamine and the dopamine precursor levodopa markedly improve word learning success in healthy subjects. In this randomized, placebo-controlled, double-blind clinical trial, we probe whether a selective d2/d3 dopamine agonist (pramipexole) or cholinergic neuromodulation (rivastigmine), after a titration period of five days, will yield a learning enhancement comparable to using levodopa in healthy subjects. The expected scientific results will strengthen the basis for transferring neuromodulatory interventions from the laboratory to stroke patients with language dysfunctions.

The purpose of this study is to determine whether rivastigmine or pramipexol are effective in boosting semantic language acquisition in healthy subjects.

Our prior work using a between-subject design shows that daily administration of d-amphetamine or the dopamine precursor levodopa over the course of five days markedly improves word learning success in healthy subjects. In this randomized, placebo-controlled, double-blind clinical trial, we probe whether the effect can be replicated using a within-subject design, with administration of levodopa and placebo on alternate days for a total period of 10 days.~The expected scientific results will strengthen the basis for transferring neuromodulatory interventions from the laboratory to stroke patients with language dysfunctions. Because of the heterogeneity of stroke patients, only a within-subject design can be used to probe the effects of pharmacological adjuncts to language therapy.

The purpose of this study is to determine whether the non-daily administration of levodopa is effective in boosting semantic language acquisition in healthy subjects.

Music therapy involves the use of music to promote, maintain, and restore physical and mental health. Music analgesia is one aspect of music therapy focused on the reduction of pain through the use of musical activities. This study will build upon music analgesia data in the development of a new concept called music engagement. This concept is based on constructivist theory, which presumes that the brain continuously constructs and revises a model of reality. Pain is a constructed reality that may be prevented from being felt if a person is actively engaged in constructing another perceptual experience. Music listening is an activity that requires activation and integration of many complex cognitive and emotional processes; therefore, being actively engaged in music listening can impede the construction of pain if the listener can fully construct and sustain the music experience. This study will determine whether engagement in and construction of a music listening experience can reduce perceptions of pain.~This trial will comprise two studies and will require two days of participation. At study start, participants will have electrodes placed on a finger on their non-dominant hand and on other body parts to record skin conductance and electrical brain activity. Participants will also wear a headset to have their pupil movement measured. Tone synthesis software will be used to generate different tones. In Study 1, a familiar tune, selected by the participant, will be played against a background of varying tones. Occasionally, notes of the tune will be missing or displaced. Participants will be asked to identify the deviant notes while receiving painful fingertip shocks; they will be instructed to focus on the task and ignore the shocks. Study 1 will consist of three different conditions (easy, hard, and no condition). In the easy condition, the background tones occur far from the pitch range of the tune, making missing or displaced notes easy to detect. In the hard condition, the pitch range of the background tones will be adjacent to that of the tune, making the tune difficult to discern from the background tones. In the no task condition, participants will hear the familiar tune with random background tones, but they will be instructed to pay no attention to the tune or the tones.~Participants will report their pain experiences in both a retrospective report and a concurrent report. For the retrospective report, participants will report the highest, lowest, and average levels of pain experienced during the preceding block of trials. For the concurrent report, participants will give both a report of the level of pain experienced immediately following each shock episode. At each of the two sessions participants take part in, there will be two sets of trial blocks, one with pain reports and one without. There will be two blocks for each of the three music task conditions for a total of twelve blocks per session. Within each block, sixteen 7- to 11-second shocks will be given.~In Study 2, participants will take part in two types of listening tasks, one with only tones and one with both a tune and background tones. There will be three tasks in the tone condition (no task, easy task, and hard task). In the no task condition, participants will hear repeated tones; they will be instructed to pay no attention to the tones. In the easy condition, the deviant tones will be easily detectable; in the hard condition, they will be less detectable. During each condition, participants will receive painful fingertip shocks.~The second task condition is similar to Study 1; participants will listen to a familiar tune with various tones in the background. Participants will be given fingertip shocks and will be asked to identify deviant notes for both the easy and hard conditions. For the no task condition, participants will be instructed to pay no attention to the tune or background tones. Participants will not be required to report pain in this part of the study. Participants will receive two blocks of trials for each of the six task conditions. Fingertip shocks will vary in intensity with the interval between shocks varying between 7 and 11 seconds.~Pain self-reports (Study 1), deviant note detections, skin conductance, pupil dilation, and electroencephalogram changes following stimulations will be used to assess participants.

The purpose of this study is to determine whether engaging in music listening tasks can reduce the perception of pain and provide nondrug pain relief.~Study hypotheses: 1) Performing a highly engaging listening task reduces psychophysiological arousal to painful stimuli. 2) Psychophysiological arousal to painful stimuli is a function of the complexity of the auditory signal. 3) Signal complexity and task difficulty interact to produce the greatest engagement and maximum reduction in psychophysiological arousal to painful stimuli.

The comparison condition is the same length as the cognitive behavior therapy condition but omits the cognitive restructuring component. In both conditions, smokers prepare for a quit date by using scheduled reduced smoking, which involves smoking on a set schedule that gradually reduces the number of cigarettes smoked. Post-treatment assessments occur one week after the end of treatment, and at 3-month followup.~Pre- and post-treatment assessments include measures of coping skills and emotional acceptance, as well as smoking rate.

The purpose of this study is to evaluate the effectiveness of group therapy for cigarette smoking cessation. The group meets for 8 sessions and includes education and group discussion about the effects of smoking and ways to cope with withdrawal symptoms and other challenges to maintaining abstinence. In one condition, the groups also learn techniques based on cognitive therapy, to help cope with negative feelings.

Background:~This study of the FairCare Program (FC) is designed to address end of life (EOL) care delivery issues by reducing barriers to effective EOL care among health care providers, family members, surrogates, and Chronic Heart Failure (CHF) patients using a comprehensive, multi-pronged approach delivered by a care coordinator and supported by an interdisciplinary team.~Objectives:~Evaluate the impact of FC on: 1) improving the quality of life (QOL) and health care delivery for CHF patients with advanced illness, (i.e. ejection fractions of 35% or less, or assessed as level III or IV on the NYS Heart Association Classification System); 2) addressing their fears about dying; 3) increasing their use of Advance Directives (ADs); and 4) improving provider compliance with ADs. Also, describe trends that may occur in disease-specific QOL, survival, and health care use and cost.~Methods:~The study employs a randomized control group design. There are two treatment arms, the FC treatment condition, and the usual care (UC) control condition. Assessments for improving quality of life (QOL), and quality of care delivery are taken at baseline, and at three and six months. Assessments of AD use, i.e. frequency of formulation and documentation of ADs, are taken at baseline, three and six months at one year and 18 months. Because data about compliance with ADs and utilization and cost may not be fully comprehensive until patients' deaths, to maximize the sample size for these variables, and hence the power of the study to detect difference in these outcomes, data on compliance with ADs will be collected in the final year of the study, and data on utilization and cost will be aggregated in monthly intervals and collected from baseline to 18 months. One year of VA pre-intervention health care utilization and cost data will also be collected to assess baseline utilization and to control for any pre-existing differences in the propensity of patients to use health care services. Also, an intention to treat methodology will be used during data analyses.~Status:~The study ends 9-30-04, data for VA cost, Medicare cost, consistency of medical care with patient preferences, and survival, are being collected and analyzed for the final report.

This study of the FairCare Program (FC) is designed to address end of life (EOL) care delivery issues by reducing barriers to effective EOL care among health care providers, family members, surrogates, and Chronic Heart Failure (CHF) patients using a comprehensive, multi-pronged approach delivered by a care coordinator and supported by an interdisciplinary team.

We are testing a coping and communication support (CCS) intervention for advanced stage cancer patients and their family caregivers over the period when goals of care may shift, i.e. beginning shortly after diagnosis. This randomized clinical trial is being conducted in two urban tertiary cancer clinics that reach patients and families in low income and diverse underserved populations: the Louis Stokes Cleveland VAMC and MetroHealth Medical Center. Recruitment and randomization are based on patient's diagnosis and age. The patient had to have been diagnosed with a stage IV cancer within a year of enrollment and they must fall into one of two age groups: middle-aged (ages 40-60); or older (61 and older). Patients are stratified by age group and then randomized to usual care or CCS intervention. Family care-givers are randomized along with the patient. Trained clinical nurse specialists with advanced training in mental health serve as CCS practitioners. They are available to patients and family caregivers on a 24/7 basis to assist with coping and communication challenges as they may arise. The primary goal of this project is to examine main effects of the intervention and patient age group interaction effects of the CCS intervention on perspectives and well-being of family caregivers during advanced cancer care and in bereavement.

The diagnosis of advanced, incurable cancer at different stages of the adult life span holds a variety of meanings for family members who often must play critical roles in patient care and decision-making. Family caregivers are greatly affected by the diagnosis and treatment of late-stage cancer in a loved one and may find it difficult to meet the demands of taking care of their loved one through end-of-life care and taking care of their own well-being. This grant provides funding to examine processes and outcomes of the intervention for family caregivers of advanced cancer patients.

NY-ESO-1 was isolated by serological analysis of recombinant cDNA expression libraries (SEREX), using tumor mRNA and autologous serum from an esophageal cancer patient. Reverse transcription-polymerase chain reaction (RT-PCR) analysis showed that NY-ESO-1 displayed the typical expression pattern of CT antigens. NY-ESO-1 mRNA was expressed only in testis of normal tissues tested and in various types of cancer, including lung cancer, breast cancer, malignant melanoma and bladder cancer. LAGE-1 was identified by the representational difference analysis and revealed to display 84% amino acid homology with NY-ESO-1. In most cases, expression of LAGE-1 parallels the expression of NY-ESO-1. Since testis is an immune privileged organ where HLA molecules are not expressed, these antigens can be considered tumor-specific.~Because of frequent NY-ESO-1 mRNA expression and high immunogenicity in advanced cancer, NY-ESO-1 is an attractive target molecule for a cancer vaccine. Current therapies against advanced cancer have limited effectiveness. The idea of vaccination with NY-ESO-1 protein in cancer patients with tumors expressing NY-ESO-1 mRNA is based on two findings: 1) the number of CD8+ T cell epitopes identified in NY-ESO-1 molecule are limited to those binding to HLA-A0201, A31, Cw3 and Cw6. These HLA subtypes are carried by a minor Japanese population; 2) CD8+ T cell responses specific to NY-ESO-1 are polyclonal. Protein vaccination may induce immune response more effectively against tumors expressing NY-ESO-1 than peptide immunization.

The purpose of this study is to assess the safety of repeated doses of cholesterol-bearing hydrophobized pullulan (CHP) and NY-ESO-1 protein (CHP-NY-ESO-1) and describe the NY-ESO-1 specific-humoral and cellular immune response to immunization with CHP-NY-ESO-1 in patients with cancer expressing NY-ESO-1.

The practice of dermatology is seeing a rise in the number of surgical and laser procedures as technological advances have expanded the number of conditions amenable to these evolving therapies. Skin biopsies, shave excisions, deep excisions, electro-surgical procedures, intralesional injections, and laser surgery are frequently performed by dermatologists on a daily basis. Some pain accompanies almost all of these procedures, and a local anesthetic is commonly used. Traditionally, intracutaneous injection of lidocaine (with or without epinephrine) has been the anesthetic of choice. However, patients undergoing these procedures are often afraid of needles and syringes and the pain associated with injections. As a result, topical anesthetic agents have been explored and developed as painless alternatives to injected anesthesia.~S-Caine™ Peel (lidocaine 7% and tetracaine 7% cream) consists of a new eutectic formulation of lidocaine and tetracaine. S-Caine Peel is a topical local anesthetic cream that forms a pliable peel on the skin when exposed to air. S-Caine Peel is not occluded during application.~The pain associated with medical procedures is often under-treated in children. Children often undergo painful procedures with little or no anesthetic, even when effective therapy is available. Reasons for not providing available therapy in children include concerns over adverse side effects, as well as the length of time necessary to provide adequate anesthesia. Recent guidelines strongly advocate for the proactive treatment of pain in children, including the pain associated with medical procedures.

The purpose of this study is to evaluate the safety of one treatment of S-Caine™ Peel (skin numbing cream) applied on healthy skin before a painful dermatologic procedure in children. This study will also evaluate how well the S-Caine™ Peel eases the pain of the procedure.

The practice of dermatology is seeing a rise in the number of surgical and laser procedures as technological advances have expanded the number of conditions amenable to these evolving therapies. Skin biopsies, shave excisions, deep excisions, electro-surgical procedures, intralesional injections, and laser surgery are frequently performed by dermatologists on a daily basis. Some pain accompanies almost all of these procedures, and a local anesthetic is commonly used. Traditionally, intracutaneous injection of lidocaine (with or without epinephrine) has been the anesthetic of choice. However, patients undergoing these procedures are often afraid of needles and syringes and the pain associated with injections. As a result, topical anesthetic agents have been explored and developed as painless alternatives to injected anesthesia.~S-Caine™ Peel (lidocaine 7% and tetracaine 7% cream) consists of a new eutectic formulation of lidocaine and tetracaine. S-Caine Peel is a topical local anesthetic cream that forms a pliable peel on the skin when exposed to air. S-Caine Peel is not occluded during application.~The purpose of this study is to gain additional safety information for S-Caine Peel when used in minor and major dermal procedures in adults.

The purpose of this study is to evaluate the safety of one treatment of S-Caine™ Peel (skin numbing cream) applied on healthy skin before a painful dermatologic procedure in adults. This study will also evaluate how well the S-Caine™ Peel eases the pain of the procedure.

The study was designed to compare sampling of several nicotine replacement treatments (NRTs) in contrast to a computer learning control. The NRTs include: 2 dosages of nicotine gum, 2 dosages of nicotine lozenges and 2 dosages of oral nicotine inhalers. In the sampling group, each participant tries each of the 6 NRTs for 3 minutes. In the control, the individuals read about the treatments. Dependent measures include: quit attempts, use of NRTs, preferences among NRTs, and learning and motivation.

The purpose of this study is to determine whether sampling nicotine replacement treatments (NRTs) is superior to learning about them by computer. Testing also covers preferences among the treatments. Subjects will be enrolled veterans who smoke.~Hypothesis: Direct experience (sampling) of NRTs will increase knowledge about NRTs, motivation/confidence, use of NRTs and quit attempts in contrast to learning about NRTs by computer.

13C is a stable (i.e., non-radioactive) isotope of carbon with a natural abundance of ~1%. Following infusion of [13C]glucose and/or [13C]acetate, in vivo MRS (magnetic resonance spectroscopy) can monitor the rate of flux of the 13C atom from glucose and/or acetate to glutamate to glutamine. Thus, this procedure can provide measure of glutamate (GLU) and glutamine (GLN) turnover in brain. We have established parameters to obtain these measurements in nonhuman primate brain. The current protocol seeks approval to optimize MRS parameters and to develop new MRS techniques for human brain using the GE 3T, the Siemens 3T, and the Siemens 7T device.~Study population: All subjects will be aged 18 65 years, without serious medical illnesses and meet criteria listed in Section VI A.~Design: Subjects will receive either oral administration of [13C]glucose or an intravenous infusion of [13C]glucose and/or [13C]acetate to approximately double their plasma glucose levels. The plasma acetate level will remain within the physiological range observed in humans (Lebon et al, 2002). While lying in the 3T or 7T device, serial data acquisitions will be obtained over ~2 h to optimize the experimental conditions so as to measure the 13C signals from GLU, GLN and other metabolisms in brain.~Outcome measures: The primary goal of this study is to measure GLU/GLN turnover in brain. With no additional data acquisition, we can also obtain information on the synthesis of GABA, the major inhibitory neurotransmitter in brain. GLU is converted to GABA via the enzyme glutamic acid decarboxylase (GAD). While monitoring the transfer of 13C signal from GLU to GLN, we can simultaneously measure the transfer of 13C signal from GLU to GABA and thereby measure the activity of GAD (Li et al 2005). In addition to directly measure 13C signals, 13C labeling to brain metabolites can also be measured indirectly by detecting proton MRS during infusion of [13C]glucose and/or [13C]acetate.

This study will use magnetic resonance spectroscopy (MRS) to measure in the brain the transfer of [13]C as it is naturally metabolized from glucose to specific chemical transmitters. From this method, we can measure the rate of production of an important excitatory neurotransmitter (glutamate) as well as an inhibitory neurotransmitter (GABA).

Mortality rates among preschool age children in Nepal and many other developing countries remain high despite significant progress made over the past 20 years. There remain significant nutritional deficiencies in these populations, especially important are vitamin and mineral deficiencies.~Comparisons: In this study, we are comparing the morbidity and mortality experience for children 1-36 months of age randomized to one of four daily supplementation regimens: placebo, zinc alone, iron-folic acid alone, zinc + iron-folic acid.

The purpose of this study is to determine whether daily supplementation of young children in Nepal with either zinc, iron-folic acid, or both can reduce mortality and morbidity. Young children in Nepal have numerous nutritional deficiencies and high rates of morbidity and mortality. Zinc and/or iron supplementation may be a cost-effective method for reducing these risks.

While significant progress has been made in reducing preschool child mortality in developing countries over the past 20 years, much less progress has been made in reducing neonatal mortality and morbidity. Neonatal mortality rates are high in Nepal; a significant proportion of which are due to sepsis. In addition, the vast majority of women deliver babies at home without a skilled birth attendant and early neonatal care is routinely used in rural areas. Previous hospital-based research in Malawi suggested that newborn cleansing with a dilute chlorhexidine solution could reduce early infant mortality. This project evaluates the use of a simple intervention at the community level and the impact on neonatal mortality.~Comparisons: Two nested community-based randomized trials are being conducted. The first compares the neonatal mortality rates between newborn infants randomized to receive a whole body skin cleansing soon after birth with baby wipes impregnated with 0.25% chlorhexidine compared with newborns cleaned with baby wipes with a placebo solution. The second trial compares the rates of umbilical cord infections among children assigned to three groups:~education of the mother on clean cord care alone;~education of the mother plus routine washing of the cord and stump with soap and water solution for the first 10 days of life; -OR-~education of the mother plus routine washing of the cord and stump with a 4% chlorhexidine solution.~Enrolled infants are visited on a regular basis during the first month of life to record vital status and grade the cord for signs of infection.

Neonatal mortality and morbidity is common in Nepal and the vast majority of women deliver babies at home without a skilled birth attendant.~The purpose of this project is two-fold: 1) to evaluate whether washing a newborn child with a dilute antiseptic solution soon after birth can reduce mortality in the first 4 weeks of life and 2) to evaluate whether cleaning the umbilical cord and stump with either soap and water or an antiseptic solution for the first few days of life can reduce umbilical cord infections.

This investigation is a multicenter, randomized, placebo and active controlled, double-blind, double-dummy, parallel-group study to evaluate the safety and efficacy of two doses of QVAR-BOI in adolescents and adults.

QVAR in a standard press and breath inhaler (QVAR-MDI) has been approved by the Food and Drug Administration (FDA) for use in the United States. The purpose of this study is to determine the level of asthma control when comparing the safety and effectiveness of QVAR in two different devices, a metered dose inhaler (MDI) and a breath operated inhaler (BOI).

This was a single center, randomized, double-blind, placebo controlled, paired study that evaluated the duration of anesthetic effect produced by S-Caine Peel when applied for 30 or 60 minutes in 40 adult volunteers. A pinprick test was used to determine duration of anesthetic effect.~At the procedure visit, subjects were to be assigned the lowest available sequential subject number. Treatment was randomized according to a computer-generated randomization schedule provided by the sponsor. The randomization to application time of 30 or 60 minutes was to be 1:1 and un-blinded. The randomization of study drug to treatment area (concurrent applications of either S Caine Peel applied to the anterior surface of the right thigh with placebo applied to the anterior surface of the left thigh, or placebo applied to the anterior surface of the right thigh and S-Caine Peel applied to the anterior surface of the left thigh) was 1:1 and double-blind. Instructions for implementing the randomization (ie, the correct application time and treatment area) appeared on the study drug labels assigned to each subject number.~Subjects were administered both S-Caine Peel and placebo on separate thighs for either 30 or 60 minutes. The study drugs were applied concurrently to the anterior surfaces of the right and left thigh (one application per thigh, with study drug applied to the right thigh first, followed immediately by application of the alternate study drug to the left thigh). Each study drug was dispensed to cover a 200 cm² treatment area with a uniform thickness of approximately 1 mm

S-Caine™ Peel (lidocaine 7% and tetracaine 7% cream) is a new skin numbing cream made of lidocaine and tetracaine. The purpose of this study is to evaluate and measure the length of time the S-Caine Peel numbs the skin, when applied for 30 and 60 minutes.

This was a multi-center (5 centers), double-blind, placebo-controlled, parallel study that included 80 adults who met all the eligibility criteria and who were undergoing PDL therapy for the treatment of vascular lesions on the face.~During the screening visit, the study, including potential risks and benefits, was clearly explained to each patient, and written informed consent was obtained from each patient. The screening visit also included: evaluating eligibility criteria, obtaining a medical history (including skin type, demographic data, and concomitant medications), a brief physical examination, and a urine pregnancy test (for women of childbearing potential). The screening visit could be completed on the same day as the procedure visit.~At the procedure visit, eligible patients were assigned the next available sequential patient number. By having a patient number assigned to them, patients were randomized to receive S-Caine Peel or placebo on the facial treatment area.~The surface area of the intended treatment area was determined (up to 200 cm2). A thin layer (approximately 1 mm or the thickness of a dime) of the study drug was applied evenly across the area to be treated. The study drug was applied for 20 minutes (±2 minutes).~Immediately following removal of the study drug, the investigator performed an evaluation of skin reactions, assessing the treatment area for erythema, edema and blanching or any other adverse skin reaction.

Pulsed dye laser (PDL) on the face is painful. For this reason, local anesthesia is commonly used to eliminate or minimize the pain. S-Caine™ Peel (lidocaine 7% and tetracaine 7% cream) is a eutectic formulation of lidocaine and tetracaine. The purpose of this study is to evaluate the efficacy of S-Caine Peel for induction of local dermal anesthesia for PDL therapy in adults.

Finger-stick based self-testing (SBGM), as well as diagnostic continuous glucose monitoring (CGMS®) allow diabetic patients to find a balance between the two hyper- and hypoglycemic extremes. Nevertheless, there are still patients who fail to achieve good control due to fear of hypoglycemia, or who underestimate post-prandial hyperglycemias.~The Guardian® RT Telemetered Glucose Monitoring System is indicated for continuous or periodic monitoring of real-time interstitial blood glucose values and low/high blood glucose alarms (when pre-set levels are reached) in persons with diabetes mellitus. The glucose values calculated by the device will be used to trigger hypo- and hyperglycemia alerts and will be displayed every 5 minutes. The Guardian® RT stores up to 21 days of data.~The overall primary objective of the study is to determine whether patients with poor glycemic control as evidenced by HbA1c > 8.1% can achieve improved metabolic control using the real-time values of the Guardian® RT compared to conventional self-monitoring blood glucose finger-sticks (control group) after 12 weeks of continuous use.

The objective of the study is to determine whether patients with poor glycemic control can improve metabolic control using the real-time values of the Guardian® RT compared to conventional self-monitoring blood glucose finger-sticks.

Microdermabrasion is rapidly becoming one of the most popular cosmetic procedures performed by dermatologists and plastic surgeons. Microdermabrasion is a process that uses a high-pressure stream of aluminum oxide crystals and negative pressure to superficially peel the upper layer of the skin. Its purported benefits include improvement of photoaged skin, acne, and facial scarring.~The appeal of microdermabrasion is its effectiveness, simplicity, low patient and operator risk, and rapid recovery. Clinically, studies have illustrated beneficial effects on photodamaged skin.~Histologically, microdermabrasion has reproducible effects on the epidermis and dermis. Studies have shown a consistent increase in epidermal thickness as well as changes in the elastin content of the dermis while changes in collagen content have not been observed.~The reported clinical and histologic changes seen in previous studies suggest that alterations in the dermis precipitated by epidermal injury may be responsible for the beneficial effects of microdermabrasion on photoaging and scarring. In fact, others have reported that skin fibroblasts under tension may increase collagen synthesis.~Disruption of the epidermal barrier initiates a repair process that restores barrier function within hours to days, depending on the severity of the damage. This repair process involves increased synthesis of barrier lipids, followed by formation of new corneocytes. Elevated lipid synthesis largely occurs as a result of increased gene expression of the major enzymes responsible for lipid biosynthesis.~In this study, subjects will be assigned to one of two treatment groups. Patients in the first group will have their hip/buttock or forearm treated with the microdermabrasion machine. There may be only one treatment or as many as 6 on the same area, spaced up to two weeks apart. The treated area will be on either the right or left buttock and/or forearm and/or underarm. An area of approximately 10x10 cm (4x4 inches) will be treated. Skin biopsies will be performed on up to nine different times, up to six months following dermabrasion, on treated and/or untreated skin from the buttocks, forearm and/or underarm. Therefore, a total of (up to) nine biopsies will be taken from subjects in this group. The biopsies will be 4 mm or smaller in size, or about the size of a pencil eraser. Subjects can expect to make six visits to the hospital over a 3-4 week period of time.~Subjects assigned to the second group will have their face treated with microdermabrasion at a weekly to biweekly interval for a total of six treatments. One pair of biopsies will be taken prior to the first treatment, and the 2nd and 3rd pair will be taken on two different occasions no later than 3 months following the final treatment. Thus, the maximum number of biopsies in group II is six. The biopsies will be 2mm punch, cookie-cutter, biopsies and will be taken from in front of the ear. Subjects can expect to make 8-10 visits to the hospital over a 2-3 month period of time.

This research project aims to study the effects of microdermabrasion, a technique causing minimal injury used to improve the appearance of fine lines, wrinkles, and scars. Subjects will undergo microdermabrasion, which is a gentle sand-blasting of the skin. We are interested in determining how this procedure works at rebuilding the skin following microdermabrasion.

The central hypothesis of this study is that restoring circulating levels of the adrenal hormone dehydroepiandrosterone (DHEA) in older people with low levels to more youthful levels will be associated with beneficial changes in lean mass, fat mass and bone mass.~This will be a randomized, placebo-controlled, double-blinded study. Seventy-two men and 72 women, over 60 years old, who are healthy, will be randomized to receive either a replacement dose of DHEA or placebo for 1 year. The replacement dose of DHEA will bring circulating DHEA sulfate (DHEAS) levels into the range of normal in healthy 20-30 year-old women (approximately 8 micromoles per liter [μM] or 295 micrograms per deciliter [µg/dL]) and men (approximately 10 micromoles per liter [μM] or 368 micrograms per deciliter [µg/dL]).~Fat mass and fat-free body mass will be evaluated by dual energy x-ray absorptiometry (DXA), and intra-abdominal fat volume and thigh muscle area will be measured by computed tomography (CT). Bone mineral density (BMD) of the total body, lumbar spine, and proximal femur will be measured by DXA and biochemical markers of bone resorption and formation. Glucose tolerance and insulin response will be evaluated using an oral glucose tolerance test.~If this study confirms the results of a previous preliminary study, the current study is likely to impact future scientific study regarding the role of DHEA deficiency in the biology of aging and its role as a therapeutic agent for the prevention of sarcopenia.

The purpose of the study is to examine whether DHEA replacement therapy is associated with beneficial changes in body composition (i.e., increases in lean mass and bone mass, and decreases in fat mass).

This study is a randomized, double-blind Phase 1 study of FluMist vs. placebo in mild to moderately immunocompromised children 5 to 17 years of age with cancer. The primary objective of this study is to describe the safety of FluMist compared with placebo in mild to moderately immunocompromised children with cancer. The secondary objectives of this study are to describe the immune responses following vaccination with FluMist and to determine the incidence and duration of viral replication following vaccination with FluMist.~The standard 0.5 mL dose of vaccine or placebo was administered intranasally. Patients were evaluated at four visits scheduled between days 3-5, days 7-10, days 14-28, and days 35-42 for viral shedding via nasal swabs. Safety outcomes were collected at study clinic visits or by telephone contact through 42 days post dose. Serious adverse events and significant new medical conditions were collected through 180 days after receipt of investigational product.~Immune responses were measured by detection of influenza-specific antibodies as measured by the standard hemagglutination inhibition (HAI) assay. Influenza-specific serum antibody isotype levels were determined and nasal swab specimens were analyzed for the expression of influenza-specific immunoglobulin A (IgA). Serum was analyzed for its ability to neutralize viral particles from infecting Madin-Darby canine kidney cells (microneutralization). Baseline immunosuppression as measured by expression of T- and B-lymphocyte subsets was compared to immunosuppression at time points after vaccination. The duration of viral replication and the titers of live-attenuated influenza virus shed was evaluated from nasal swab specimens collected at scheduled time points after administration of FluMist.

The main purpose of this study is to get information about the safety of a flu vaccine spray, called FluMist, in children with cancer. The study is also being done to find out how much and how long the vaccine spray can be found in the nose.

Studies suggest that testosterone (T) replacement in healthy elderly men has beneficial effects on body composition, muscle, bone, memory, and behavior, but the risks of chronic treatment, especially on the prostate, heart, and sleep quality, are not entirely clear. Therefore, it is most desirable to supplement into the lowest effective range in elderly men. However, the effects of lower than usual replacement T doses have not been well studied. Furthermore, the possible important interaction of exercise to enhance the positive effects of T supplementation, yet mitigate the possible side effects, has not been studied in older men.~This one-year study will enroll 150 men with low-normal to slightly below normal serum total T levels. Participants will be randomized into one of 6 treatment groups to receive T supplementation (AndroGel) of 25mg/day, 50 mg/day or a placebo crossed with progressive resistance training (PRT) exercise 3 times a week versus none. At the end of the study, participants in the exercise-control group will be offered PRT.~Please see link below for updated version of full protocol.

The purpose of this study is to evaluate the effects of testosterone supplementation (AndroGel) on body composition, strength, endurance, cognition, and function in older men.

A 2 arm (1 Active, 1 Active Control) study is to compare the safety and efficacy of different induction agents (alemtuzumab, basiliximab or rabbit anti-thymocyte globulin) in renal transplant recipients treated with tacrolimus, MMF and a rapid steroid withdrawal.

The purpose of this study is to compare the safety and efficacy of different induction agents (alemtuzumab, basiliximab or rabbit anti-thymocyte globulin) in renal transplant recipients treated with tacrolimus, mycophenolate mofetil (MMF) and a rapid steroid withdrawal.

Statins inhibit the synthesis of cholesterol by inhibiting the enzyme HMG-CoA reductase. The reduction of intracellular cholesterol leads to an increase in the number of LDL-receptors, and subsequent increased uptake and metabolism of LDL in the liver. Several large clinical trials have shown that the use of statins decreases morbidity and mortality in patients with risk factors for atherosclerotic disease. Unfortunately, 5% of statin users experience adverse events (mainly gastrointestinal [GI] and muscular).~Statins inhibit not only cholesterol synthesis, but also synthesis of other substances in the mevalonate pathway. Among these other substances are Q10 and selenoproteins.~It is well known that serum Q10 levels decrease during statin therapy, and that Q10 supplement inhibits this decrease. One study has shown reduction of Q10 in blood-platelets during statin therapy. Q10 is an important element in the mitochondrial respiratory chain. Depletion of Q10 leads to a reduction of high energy phosphates, anaerobe metabolism and mitochondrial dysfunction. This is suggested to be the cause of muscular adverse events in statin therapy. There are several reports of individuals relieved from muscular adverse effects after Q10 supplement, but no randomized, placebo controlled studies have been conducted.~Symptoms of selenoprotein deficiency are very similar to adverse events seen in statin therapy, but no clinical trials have been conducted to evaluate the effect of selen supplement on adverse effects of statin therapy.

The purpose of this study is to determine whether supplements of Q10 and Selen are effective in reducing muscular adverse events (AE) in statin therapy.

This was a Phase 1/2, randomized, double-blind study in which motavizumab (MEDI-524) or palivizumab was administered to children who previously participated in MI-CP104. Children who received at least 3 doses of motavizumab in MI-CP104 were eligible for enrollment. Subjects were randomized 1:1 to receive motavizumab or palivizumab at 15 mg/kg by IM injection every 30 days for a total of 4-5 injections during the 2004-05 RSV season subsequent to the season in which they were participants of MI-CP104. All subjects were evaluated prior to and 30 minutes after each injection of study drug with 2 follow-up evaluations, one at 30 days and the other at 90-120 days after the last dose.

The primary objective of this study was to determine the effect on immune reactivity to motavizumab (MEDI-524) of monthly intramuscular (IM) doses of motavizumab (MEDI-524) administered for a second season in children.

The primary objective of this study was to assess the safety of FluMist vaccination by comparing the rates of medically attended events (MAEs) (including serious adverse events [SAEs], anaphylaxis, urticaria, asthma, wheezing, pre-specified grouped diagnoses, and rare events potentially related to wild-type influenza) in FluMist recipients to rates in multiple non-randomized control groups.

The purpose of this study was to expand the data describing the safety profile of FluMist in the indicated populations (5-8, 9-17, and 18-49 years of age) and to assess the safety of annual revaccination in those who received FluMist in 2 or more consecutive years.

Numerous studies have shown that many surgical site infections (SSI) are preventable with appropriately timed antimicrobial prophylaxis. Patients receiving prophylaxis either well-before or well after surgery are up to 5 times more likely to develop an SSI than those receiving appropriate therapy (Classen et al, 1992). Unfortunately, errors in antimicrobial prophylaxis timing are extremely common with error rates typically reported to be between 35 and 40%. Given that errors in antimicrobial prophylaxis are common and the consequences of error so grave, identifying methods to assist hospitals in improving prophylaxis must be a high priority. TRAPE will evaluate a multifaceted, theory-based intervention to assist hospitals in progressing through stages of organizational change to improve the prophylaxis process. We will test the impact of the intervention using a rigorous group-randomized, nested, pretest-posttest design (Murray, 1998).~Our specific aims over the 4 year project period are:~determine the incidence of medication errors related to antimicrobial prophylaxis for cardiovascular surgery, joint replacement surgery, and hysterectomies in 44 hospitals recruited to participate in the study;~identify organizational and system factors associated with error rates;~randomize the 44 hospitals to evaluate the effectiveness of a multifaceted intervention.~The interventions consist of: a) the promotion of specific process changes likely to reduce error rates, b) a site-visit, c) customized process feedback, d) facilitated benchmarking, and e) peer consultation. The 22 intervention hospitals will be compared to 22 hospitals that receive written feedback of their error rates only. The study has 80% power to detect a 12-15% improvement in the timing of prophylaxis in the full intervention group compared to the written feedback only group. Data collection will be done at each participating hospital, and the medical records of 100 surgical patients before and after the intervention will be abstracted at each hospital to establish performance rates. Changes in the processes of care, and the evolution through stages of organizational change will also be assessed.

The specific aims are to determine the incidence of medication errors related to antimicrobial prophylaxis for cardiovascular surgery, joint replacement surgery, and hysterectomies across a heterogeneous sample of hospitals; identify organizational and practitioner factors associated with error rates, and evaluate the effectiveness of a multifaceted intervention in reducing prophylaxis error rates compared to written feedback alone in a sample of 44 hospitals enrolled in the study using a rigorous group-randomized design.

In this protocol, men age 60-75 will be randomized to one of 6 groups. Groups 1-5 will receive goserelin acetate (Zoladex) plus 0 (placebo gel), 1.25, 2.5, 5, or 10* g/day of testosterone gel (Androgel). Group 6 will receive placebos for both goserelin acetate and testosterone gel. (*Note that the 10 g/day dose was reduced to 7.5 g/day part-way through the trial due to reports of possible increased risk of cardiovascular events with testosterone administration).~Subjects will be blinded with respect to group assignment. Dietary calcium intake will be assessed by a research dietitian and adjustments made through diet or supplements so that calcium intake is between 1000 and 1200 mg/day.~Subjects will be seen on the Clinical Research Center at 4 week intervals for 16 weeks (0, 4, 8, 12, and 16 weeks). At each visit, compliance with Androgel will be assessed by reviewing a medication diary. A standardized series of questions will be posed to each subject to assess potential side effects of the study drugs. Subjects receiving Androgel' will be given a new 4 week supply of medication (except at week 16). A fasting blood and second voided urine sample will be collected. After the blood and urine samples have been obtained, subjects will be given their goserelin injection. The blood and urine tests listed below as well as anthropometric measures, and questionnaires will be performed at each visit. Dual-energy x-ray absorptiometry (DXA), quantitate computed tomography (QCT) scans, and strength assessments will be performed at 0 and 16 weeks only. Subjects who discontinue participation at or after week 8 will be asked if they are willing to have an early discontinuation visit in which all procedures normally done at week 16 will be performed.~The following measures will be assessed:~Routine chemistries and prostate specific antigen, PSA (for safety assessment)~Bone turnover using blood and urine tests~Hormones~Lipids~Body composition~Strength~Sexual desire and erectile function~Bone mineral density and bone microarchitecture

The purpose of this study is to determine the levels of testosterone and/or estradiol at which changes in bone turnover, body composition, strength, sexual function etc. begin to occur in older men. This information may help determine when to intervene with hormone replacement therapy in aging men.

During the transplantation process, the kidney graft is exposed to numerous events which may in turn lead to function deteriorations. In particular, factors related with brain death, like hemodynamic instability and systemic release of cytokines, cold preservation upon harvesting, and reperfusion injury accumulate in harm conveying a pro-inflammatory state to the graft before transplantation. Early graft dysfunction has long-term consequences. Renal transplants with delayed graft function and acute rejection have a greater incidence of chronic dysfunction. Allorecognition is induced when the host immune system detects alloantigens in the context of danger signals. Reducing danger signals through medical donor management may therefore have a considerable impact on the transplantation outcomes.~In a case control study from the Transplantation Center of Mannheim, Germany, donor use of both dopamine and noradrenaline during intensive care before organ retrieval was associated with less acute rejection episodes after transplantation and resulted in superior long-term graft survival. Donor employment of catecholamines remained predictive of an improved graft survival probability even after controlling for various confounding factors like age, gender, cold ischemia, HLA matching and immunosuppressive medication. This observation has been confirmed by a larger retrospective cohort study based on the Eurotransplant registry, including 2404 kidney transplants performed at 47 renal transplantation centers in 1993. The salutary effect on the graft function rate at 4 years exhibited a dose-response relationship and compared in quantitative terms with prospective HLA matching on class I or II antigens. Besides these long-term benefits, donor preconditioning with dopamine is associated with improvements of immediate graft function after kidney transplantation. Donor dopamine was associated with less requirement of hemodialysis and more rapid recovery of graft function posttransplant in a single centre study involving 254 consecutive renal transplant recipients.~Implementing dopamine as a therapeutic tool in the management of cadaver kidney donors may have a major impact on both immediate graft function and long-term graft survival without adverse side effects for the recipients.

Donor pre-treatment with dopamine reduces injury to the kidney graft with consequences on the clinical performance immediately after transplantation: Donor dopamine reduces the requirement of dialysis post transplant, and results in renal function improvements.~The purpose of the study is to investigate the potentially therapeutic impact of donor preconditioning with low dose dopamine in human renal transplant recipients from a brain dead donor.

The multi-component translational intervention that we plan to test includes medical record audits with feedback and benchmarking, academic detailing by an opinion leader including information from literature review plus the advice of local exemplars, a practice facilitator, who will work with the practices over a six-month period, and an IT application that provides decision-support, prompts, and reminders to office staff and patients.~The proposed project will be a randomized controlled trial of a multi-component strategy designed to facilitate the incorporation into primary care practices of three office management components known to increase preventive service delivery rates: 1) nurse standing orders; 2) special immunization/ preventive services clinics; and 3) recall and reminder systems. Twenty-four practices, all members of a primary care practice-based research network, will be enrolled and randomized to receive the complete intervention or performance feedback with benchmarking only. The primary outcomes will be number of management components implemented. Characteristics of clinicians and practices that are associated with greater or lesser success in implementing the three strategies and barriers encountered will also be examined, and we will measure and compare rates of selected immunizations and preventive services delivered.~The specific aims for this project are to:~Determine the effectiveness of a multi-component translational intervention on adoption of three strategies known to increase delivery of preventive services: nurse standing orders, a reminder/recall system (preferably PSRS), and special immunization and/or preventive services clinics. The intervention will include: a) performance feedback and benchmarking; b) training of clinicians and office staff in principles of effective preventive services (enhanced academic detailing by a physician opinion leader); c) practice enhancement assistants to facilitate office system changes; and d) an IT application that provides prompts and reminders to office staff, clinicians, and patients.~Document contextual factors and barriers to the adoption of the three strategies and their impact on the intervention.~Measure the impact of the intervention on rates of delivery of the following preventive services: DtaP#4, MMR#1, and HepB#3 in 2-3 year olds, and pneumococcal immunization, colorectal cancer screening, and mammography in adults 50 - 75 years of age.

The major goal of this project is to determine the effectiveness of a multi-component intervention designed to help primary care practices implement three office system strategies known to increase delivery of immunizations and other preventive services. This two-year study will contribute to our understanding of multi-component translational interventions in primary care, and particularly within practice-based research networks.