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In the last decade, St. John's wort has become one of the most commonly used botanicals. Levonorgestrel is a form of progesterone, a female hormone involved in conception. It can be given as both a pill and an injection and is used for contraception and for the treatment of endometriosis. However, evidence suggests that St. John's wort may reduce the effectiveness of the contraceptive hormone levonorgestrel. This study will determine whether interactions between St. John's wort and levonorgestrel reduce the effectiveness of the hormone. This study will also determine whether a higher dose of levonorgestrel will override the effects of St. John's wort.~All participants will receive a single dose of levonorgestrel between Days 9 and 12 of their first menstrual cycle after entering this study. Blood and urine collection will occur immediately after the levonorgestrel is given and every week until participants' next menstrual cycle to determine the levels of reproductive hormones in participants' bodies.~At the beginning of participants' next menstrual cycle, they will be randomly assigned to one of four groups and receive either St. John's wort or placebo for 6 weeks. Group 1 will receive a placebo; Groups 2 and 3 will receive a standard dose of St. John's wort (900 mg per day); and Group 4 will receive an increased dose of St. John's wort (1500 mg per day). After 6 weeks, Groups 1, 2, and 4 will receive 150 mcg levonorgestrel; and Group 3 will receive 225 mcg levonorgestrel. Blood and urine collection will occur immediately after levonorgestrel is given and every week until participants' next menstrual cycle.

This study will determine the effects of St. John's wort, a common herbal remedy, on metabolism of the female contraceptive hormone levonorgestrel.

The purpose of this study is to investigate if topically applied constituents of green tea [caffeine or (-) - epigallocatechin gallate; EGCG] have a protective effect on skin exposed to ultraviolet light (UV). In the double-blinded study all subjects will receive 311 nanometer UVB light at a dose that is 0.5-1.5X their individual minimal erythema dose (MED). One part of the experiment will involve applying a topical natural product (caffeine or EGCG) and placebo to bilateral symmetric sites. The natural product and the placebo will be applied immediately after and at 1/2 hour, 1 hour, 2 hours, 4 hours, 6 hours, 8 hours, 24 hours, 25 hours, and 27 hours after exposure to a 0.5-1.5 MED dose of UV light. Another part of the study involves performing skin biopsies. One will be done prior to UVB exposure, 2 will be done at 24 hours and 2 more will be done at 48 hours.

The purpose of this study is to investigate whether topically applied constituents of green tea [caffeine or (-)-epigallocatechin gallate; EGCG] have a protective effect on skin exposed to ultraviolet light (UV).

Complete fasting until resumed bowel function after upper abdominal surgery is not beneficial. Enteral feeding has been claimed to be the preferred way of delivering nutritional support postoperatively. Increasing evidence suggests that letting patients eat (voluntary oral feeding or oral intake at will) from the day after the operation is safe. No prospective randomised trial has been undertaken to compare these two regimens. In this study, we will randomise 444 patients, subject to major upper abdominal surgery, into receiving either continuous enteral feeding by needle catheter jejunostomy until resumed bowel function, or to oral intake at will from postoperative day 1. The main endpoints are the incidence rate of major complications and death, as well as a Quality of Life assessment.~Null-Hypothesis:~Routine postoperative feeding by needle catheter jejunostomy after major, upper abdominal surgery has no clinically relevant advantages over early oral intake at will.

Complete fasting until resumed bowel function after upper abdominal surgery is not beneficial. Enteral feeding has been claimed to be the preferred way of delivering nutritional support postoperatively. Increasing evidence suggests that letting patients eat (voluntary oral feeding or oral intake at will) from the day after the operation is safe. No prospective randomised trial has been undertaken to compare these two regimens. In this study, the investigators will randomise 444 patients, subject to major upper abdominal surgery, into receiving either continuous enteral feeding by needle catheter jejunostomy until resumed bowel function, or to oral intake at will from postoperative day 1. The main endpoints are the incidence rate of major complications and death, as well as a Quality of Life assessment.~Null-Hypothesis:~Routine postoperative feeding by needle catheter jejunostomy after major, upper abdominal surgery has no clinically relevant advantages over early oral intake at will.

Participants fill out a questionnaire on libido and their possible partner relationship on the website http://www.onderzoek-libido.be.~A blood sample is taken for sex steroid analysis. The relation will be investigated between testosterone, free testosterone, sex hormone binding globulin, estradiol, DHEA and androstenedione and scores on relational and sexual satisfaction and sexual desire.

Participants fill out a questionnaire on libido and their possible partner relationship.~A blood sample is taken for sex steroid analysis.

The investigators' long-term goal is to improve the quality of services targeting the prevention of secondhand smoke (SHS). Their specific aims are to:~refine components of office systems and counseling interventions for parental tobacco control in pediatric outpatient settings; and~pilot test the feasibility and efficacy of a parental tobacco control randomized controlled trial in pediatric office settings using 5 intervention and 5 comparison pediatric practice sites.~The investigators hypothesize that:~clinicians in intervention practices (compared to those in control practices) will more often implement successful office systems, screen for parental smoking, advise parents to quit and to prohibit smoking and SHS exposure at home, recommend pharmacotherapy, provide adjuncts, and refer parents to cessation programs; and~parents who smoke in intervention practices (measured by 3-month follow-up telephone surveys) will be more likely than those in control practices to have received cessation services, use pharmacotherapy, make lasting quit attempts, and institute rules to prohibit smoking and limit SHS exposure at home.

The investigators' long-term goal is to improve the quality of services targeting the prevention of secondhand smoke (SHS). Their specific aims are to:~refine components of office systems and counseling interventions for parental tobacco control in pediatric outpatient settings; and~pilot test the feasibility and efficacy of a parental tobacco control randomized controlled trial in pediatric office settings using 5 intervention and 5 comparison pediatric practice sites.~The investigators hypothesize that:~clinicians in intervention practices (compared to those in control practices) will more often implement successful office systems, screen for parental smoking, advise parents to quit and to prohibit smoking and SHS exposure at home, recommend pharmacotherapy, provide adjuncts, and refer parents to cessation programs; and~parents who smoke in intervention practices (measured by 3-month follow-up telephone surveys) will be more likely than those in control practices to have received cessation services, use pharmacotherapy, make lasting quit attempts, and institute rules to prohibit smoking and limit SHS exposure at home.

This is a pilot study addressing office systems and clinician behavior change surrounding smoking cessation interventions for teens. The investigators' long-term goal is to improve the quality of clinical preventive services in practice-based research network settings. Their specific aims are to:~a) pilot procedures for recruitment and randomization of PROS practices; and b) field trial/pilot PROS practitioner cessation counseling and practices' enrollment of adolescent patients; and~assess the feasibility of pediatric clinician referral of adolescent patients to internet-based adjuncts for smoking cessation.~The investigators will evaluate a pilot round of recruitment and randomization, and smoking cessation training and delivery in 10 PROS practice sites; and assess the acceptability of study procedures and on-line internet counseling adjunct referral feasibility within PROS practice sites. Up to 1000 adolescents presenting for well visits will complete a short baseline survey prior to their well-visit. A sample of them will be surveyed by phone at 4-6 weeks to provide preliminary estimates of cessation counseling for future studies. The investigators will field test measures, describe the patterns of smoking among youth, and explore how much receiving interventions affects motivation, quitting, abstinence/relapse attitudes, attitudes towards internet-based outreach strategies, and behaviors for 100 smokers.

This is a pilot study addressing office systems and clinician behavior change surrounding smoking cessation interventions for teens. The investigators' long-term goal is to improve the quality of clinical preventive services in practice-based research network settings. Their specific aims are to:~a) pilot procedures for recruitment and randomization of PROS practices; and b) field trial/pilot PROS practitioner cessation counseling and practices' enrollment of adolescent patients; and~assess the feasibility of pediatric clinician referral of adolescent patients to internet-based adjuncts for smoking cessation.~The investigators will evaluate a pilot round of recruitment and randomization, and smoking cessation training and delivery in 10 PROS practice sites; and assess the acceptability of study procedures and on-line internet counseling adjunct referral feasibility within PROS practice sites. Up to 1000 adolescents presenting for well visits will complete a short baseline survey prior to their well-visit. A sample of them will be surveyed by phone at 4-6 weeks to provide preliminary estimates of cessation counseling effectiveness for future studies. The investigators will field test measures, describe the patterns of smoking among youth, and explore how much receiving interventions affects motivation, quitting, abstinence/relapse attitudes, attitudes towards internet-based outreach strategies, and behaviors for 100 smokers.~**we have completed recruitment of providers; we are recruiting teens ONLY at this point**

Methamphetamine is a drug that causes excess amounts of the neurotransmitters dopamine and norepinephrine to be released into the brain. This overload produces unusual alertness and feelings of elation. When the body undergoes methamphetamine withdrawal, it experiences a reduction in dopamine and norepinephrine. Bupropion is an antidepressant used for the treatment of depression and smoking cessation. Because it functions by increasing the release of dopamine and norepinephrine in the brain, bupropion is likely to decrease the negative effects of methamphetamine withdrawal. The purpose of this study is to evaluate the efficacy of bupropion combined with contingency management (CM) and cognitive behavioral counseling (CBT) as a means of treating methamphetamine dependence.~An initial 2-week screening process will involve participants providing urine samples and completing physical and psychological assessments. If deemed eligible for the remainder of this double-blind study, participants will be randomly assigned to receive either bupropion or placebo over the course of 12 weeks. Participants in both the bupropion and placebo groups will receive contingency management and cognitive behavioral counseling. Participants will report to one of two clinical research sites three times per week. At each visit, participants will be examined by the study staff, provide a urine sample, and receive individual cognitive behavioral counseling sessions. At the end of 12 weeks, treatment will be stopped. Participants will return to the study site 30 days later for evaluation and to be assessed for any possible lingering side effects.

Methamphetamine is an addictive stimulant drug that strongly activates certain parts of the brain. The purpose of this study is to determine the effectiveness of bupropion in combination with behavioral therapy for the treatment of methamphetamine addiction.

BACKGROUND / RATIONALE:~Studies have shown that people with poor health literacy skills have significantly worse health status, greater risk for hospitalization, less knowledge about their health conditions, and are less likely to use preventative services. Little is known about the prevalence of low health literacy skills among veterans who use the VHA or the effect poor health literacy skills may have on complex preventative behaviors, such as screening for colorectal cancer (CRC). Understanding the distribution of health literacy skills among veterans and their effect on preventive behavior is critical for improving patient education, reducing health disparities, and promoting patient-centered care.~OBJECTIVE(S):~The primary objectives for this study are to develop an estimate of the prevalence of health literacy at four geographically diverse VAMCs (Minneapolis, Portland, Durham, and West LA), and for specific groups based on age, race, education, and geographic location. The secondary objectives are to link health literacy estimates for those 50 to 75 years old to CRC screening data, examine variation in guideline concordant screening rates by health literacy levels, and identify the mechanisms that may mediate or moderate the effect of health literacy on screening.~METHODS:~This observational study uses a time-sequential randomized design of 1440 veterans, stratified by age (<50, 50-75, >75), who have upcoming appointments in primary care clinics at the 4 study sites. Patients who are eligible (i.e., have at least 20/50 vision and are not demented) are asked to participate in a face-to-face structured survey with a study interviewer. The survey includes demographic data, functional status, social support, measures of attitudes and beliefs about health care providers, health insurers, medical care and the Short-Test of Functional Health Literacy in Adults (S-TOFHLA). For those between ages 50-75, knowledge of and attitudes towards CRC screening are also measured. Survey data are then matched to data from the CRC QUERI screening assessment and surveillance data system (CRS 02-162-1) to evaluate screening adherence.~STATUS:~Project work is ongoing.~IMPACT:~Findings from this study are expected to have a number of broad implications for research and practice within the VHA. This project will inform organizational changes aimed to improve the efficacy and efficiency of communication strategies and identify areas where interventions or system-level changes could be most effective; inform improvements in informed consent procedures, patient education, discharge summaries and prescription instructions; inform and improve the effectiveness of interventions and the Quality Enhancement and Research Initiative (QUERI) translation efforts; provide the basis for future longitudinal investigations into how health literacy changes over time; and, contribute to our understanding and amelioration of factors associated with health disparities.

The primary objectives for this study are to develop an estimate of the prevalence of health literacy at four geographically diverse Veterans Affairs Medical Centers (Minneapolis, Portland, Durham, and West Los Angeles), and for specific groups based on age, race, education, and geographic location. The investigators' secondary objectives are to illustrate the potential significance of poor health literacy by linking estimates for those over 50 years old to colorectal cancer (CRC) screening data and examining variation in screening rates by health literacy levels. The investigators expect that people with lower health literacy skills will be less adherent to CRC screening guidelines.

Primary Objective To compare renal function (51Cr-EDTA clearance) 12 months posttransplant, in primary renal allograft recipients (from cadaveric donor) at low immunogenic risk, 0 DR mis-match, receiving immunosuppressive therapy with A) Zenapax® (5 doses), CellCept® (1.5 g bid., aiming for TDM for total trough concentrations of 2-6 mg/L) and prednisolone or B) Sandimmun Neoral® (full dose), CellCept® (1.0 g bid.) and prednisolone.~Secondary Objectives To compare the two treatment groups with regard to: patient and graft survival (12 months), biopsy-proven and presumptive rejection episodes (3 and 12 months), posttransplant (12 months) incidence and severity of hypertension, hyperlipidemia, glucose intolerance, incidence of infection and tolerability and success rate of TDM guided CellCept® dosing in a calcineurin inhibitor-free immunosuppressive protocol over 12 months.

To compare renal function (51Cr-EDTA clearance) 12 months posttransplant, in primary renal allograft recipients (from cadaveric donor) at low immunogenic risk, 0 DR mis-match, receiving immunosuppressive therapy with A) Zenapax® (5 doses), CellCept® (1.5 g bid., aiming for TDM for total trough concentrations of 2-6 mg/L) and prednisolone or B) Sandimmun Neoral® (full dose), CellCept® (1.0 g bid.) and prednisolone.

The primary objective is to investigate intralymphocyte concentrations of CsA in renal and heart transplant recipients to elucidate the association between the intracellular concentration and efficacy (rejection episodes and histology) in transplanted patients on CsA based immunosuppressive therapy.~Secondary objectives are to investigate associations between intralymphocyte concentrations and whole-blood concentrations of CsA, renal tissue concentrations and nephrotoxicity, heart tissue concentrations and cardiotoxicity with CsA based immunosuppressive therapy in transplanted patients. In addition, this study aims to validate the use of quinine as a probe for determination of CYP3A4 activity in transplanted patients as well as proteomic-based urine analyses as a screening tool for acute rejection episodes in transplanted patients.

The primary objective is to investigate intralymphocyte concentrations of CsA in renal and heart transplant recipients to elucidate the association between the intracellular concentration and efficacy (rejection episodes and histology) in transplanted patients on CsA based immunosuppressive therapy.

The Telephone Outreach for Therapy Trial was designed to test an intervention to assist new mothers or caregivers of HIV-exposed children with administering medication for the first 6 weeks of life to prevent mother-to-child HIV infection in the infants. To be eligible, mothers of infants were identified as HIV-infected in the Mother-Infant Rapid Intervention at Delivery Study. Mothers or caregivers of infants were randomized into two groups: the intervention group received a cellular phone and scheduled twice daily calls to assure infant medications were given, and the other group received the current standard of care. Enrollment into the study was completed and analysis of the study data is underway.

The Telephone Outreach for Therapy Trial was designed to test an intervention to assist new mothers or caregivers of HIV-exposed children with administering medication for the first 6 weeks of life to prevent mother-to-child HIV infection in the infants. To be eligible, mothers of infants were identified as HIV-infected in the Mother-Infant Rapid Intervention at Delivery Study. Mothers or caregivers of infants were randomized into two groups: the intervention group received a cellular phone and scheduled twice daily calls to assure infant medications were given, and the other group received the current standard of care. Enrollment into the study was completed and analysis of the study data is underway.

A randomized controlled trial to assess the effectiveness of a comprehensive approach to preventing falls among adults 65 years and older at high risk for falls. This intervention includes a comprehensive health assessment in each participant's home combined with tailored risk reduction strategies such as individualized strength and balance exercises. The study is also conducting a community-based program to engage and educate physicians about fall prevention.~The goal of the study is to demonstrate a 40% decrease in fall rates. Other expected outcomes include decreased hospital and nursing home stays, improved physical function, and a decreased fear of falling.

A randomized controlled trial to assess the effectiveness of an at-home comprehensive approach to preventing falls among adults 65 years and older at high risk for falls.

The study is a randomized trial to compare ART delivery through two different models: a) ART delivered through health facilities by clinically qualified staff and b) home-based care in which lay workers, i.e. non-medically qualified people, play a major role in the ART delivery and clients are followed up at health facilities less frequently. The primary objective is to measure the effects of these strategies on plasma HIV viral load. We will also examine the effects on treatment failure, disease progression, survival, adherence, family member HIV testing, sexual behavior, and cost-effectiveness.~The trial is conducted with The AIDS Support Organization (TASO) clinic in Jinja, Uganda. Randomization is conducted through geographic clusters, defined using sub-counties in the district, and stratified by distance from fixed health facilities, and urban/rural. Just over 800 participants, living in 40 clusters, will be recruited over a period of 3-6 months and followed-up over a period of 3 years.

The study is a 3-year, randomized trial to compare ART delivery through two different models: a) ART delivered through health facilities by clinically qualified staff and b) home-based care in which lay workers, i.e. non-medically qualified people, play a major role in the ART delivery and clients are followed up at health facilities less frequently. The primary objective is to measure the effects of these strategies on HIV viral load. We will also examine the effects on treatment failure, disease progression, survival, adherence, family member HIV testing, sexual behavior, and cost-effectiveness.

BACKGROUND GID is a psychic disorder in which an otherwise normal person feels like he/she is a member of the opposite sex to which she/he belongs biologically. These patients require hormonal treatment to suppress the somatic characteristics of their own sex and to develop the somatic characteristics of the other sex. After psychotherapy and a period of hormonal treatment, they undergo surgical sex reassignment which, in the case of FtM subjects, consists of hystero-adnexectomy, reductive mastoplasty and possibly penile reconstruction. Thereafter, and for their entire life, they must be treated with testosterone (T) to maintain androgen-dependent physiological functions.~RATIONALE After sex-reassignment surgery, FtM subjects must be treated with T for their entire life in order to maintain androgen-estrogen dependent physiological functions.~These subjects represent an interesting model for the study of the effects of testosterone and its metabolites on different physiological functions. As of now, there is no information that the androgen receptors differ in males and females. Therefore, induction of the androgen effects in the FtM subjects can be considered similar to those in hypogonadal men and FtM subjects can serve as a model of the hypogonadal male.~Therefore, the aim of this trial is to evaluate the effects of selective steroid replacement on different physiological functions. In particular in this study we will evaluate the relative role of testosterone, DHT and estradiol on the different physiological functions. For these purposes, we will administer testosterone undecanoate alone (Group A) or in combination with letrozole, an aromatase inhibitor (Group B). A third group of FtM subjects will be treated with TU plus dutasteride (Group C).~In view of the development of selective androgen receptor modulators, the understanding of the relative role of each steroid on different physiological functions will provide useful information for future therapeutic indications. The information collected in this study will greatly help to optimize the long-term treatment of FtM subjects.~In particular, in this study, we will test the following questions:~what is the role of testosterone vs. DHT on the physiological functions evaluated in this study i.e. bone metabolism, body composition, insulin resistance and lipid profile (Group B vs. Group C)~what is the role of testosterone and DHT vs estradiol on the physiological functions evaluated in this study i.e. bone metabolism, body composition, insulin resistance and lipid profile (Group C vs. Group A)~DESIGN~For this purpose, in this study we will treat FtM castrated, subjects for 54 weeks with:~testosterone undecanoate 1000 mg 6-12 weeks (injection at week 0, 6, 18, 30, 42 and 54)(n=5) (Group A)~testosterone undecanoate 1000 mg 6-12 weeks (injection at week 0, 6, 18, 30, 42 and 54) mg/day plus letrozole 2.5 mg/day (n=5) (Group B)~testosterone undecanoate 1000 mg 6-12 weeks (injection at week 0, 6, 18, 30, 42 and 54) plus dutasteride 0.5 mg/day (n=5) (Group C)~Overall study design and plan-description Prospective, phase III, randomized study design will be used. The study consists of a control phase lasting 3 weeks and a 54-week treatment period.~Control phase: (will last 3 weeks: In this period, subjects will provide three fasting (at least 10 hours) blood samples and one urine sample. Subjects will undergo 2 visits to ensure fulfillment of inclusion criteria and, absence of exclusion criteria, to determine state of health and to be informed about the purposes of the study. During the two visits, they will undergo:~blood drawings for measurements of: LH, FSH, estradiol, testosterone DHEAS, total cholesterol, HDL cholesterol, triglycerides, insulin, glucose, leptin, adiponectin, uric acid, urea, creatinine, Na, K, Ca, P, Mg, Cl, total protein, bone alkaline phosphate, PTH, osteocalcin, crosslaps, 25(OH) vit D, H RANKL, osteoprotegerin.~anthropometry: weight, measures~DEXA for bone mass determination and body composition~physical examination~a sexual and behavioral questionnaire~a pain questionnaire~Treatment phase All injections will be administered by the investigator or co-investigators for the entire study. Fasting (10 hours) blood samples will be taken (immediately before giving the injections) every time subjects come for injections (week 0, 6, 18, 30 and 42) and at the end of the treatment phase. On these occasions, a physical examination including weight, blood pressure and pulse rate checks will be performed. Volunteers will be asked to complete a sexual and behavioral questionnaire and a pain questionnaire during these visits.~At week 6, 18, 30 and 42 the following tests will be performed:~blood drawings for measurements of: LH, FSH, estradiol, testosterone, DHT, total cholesterol, HDL cholesterol, triglycerides, insulin, glucose, leptin, adiponectin, uric acid, urea, creatinine, Na, K, Ca, P, Mg, Cl, total protein.~anthropometry: weight, measures~physical examination~sexual and behavioral questionnaire~pain questionnaire~At week 54 the following tests will be performed:~blood drawings for measurements of: LH, FSH, estradiol, testosterone, DHT, DHEAS, total cholesterol, HDL cholesterol, triglycerides, insulin, glucose, leptin, adiponectin, uric acid, urea, creatinine, Na, K, Ca, P, Mg, Cl, total protein, bone alkaline phosphate, PTH, osteocalcin, crosslaps, 25(OH) vit D, H RANKL, osteoprotegerin.~anthropometry: weight, measures~DEXA for bone mass determination and body composition~physical examination~sexual and behavioral questionnaire~pain questionnaire~Measurements:~Blood samples(10 hours from last food intake). Blood collections will be carried out by venipuncture. After resting at room temperature for 30 min, the sample will be centrifuged at 3000 rpm for 10 min. Serum samples (about 10 ml) from each blood sample will be stored at -20°C for analysis.~Physical examinations:~They will include inspection of external genitalia (clitorides) and a visit to detect appearance of acne and gynecomastia.~Sexual function and behavior questionnaire:~In the sexual and behavior questionnaire the subjects will judge their sexual activity and behavior in the period between visits. The subjects have the possibility to making additional comments about important events and disturbances.~SELECTION OF STUDY POPULATION:~Healthy female FtM subjects, who have undergone SR surgery (hystero-adnexectomy) will be recruited to participate in this study. Healthy female subjects between 18 to 45 years of age will be enrolled in the study according to Inclusion/Exclusion Criteria listed below. They will be informed about the nature, aim and objectives of the study and will be required to give their written consent to participate in the study. The presence of the inclusion criteria and the absence of the exclusion criteria will be documented in the Case Report Forms (CRF).

The purposes of this study are:~to determine the role of testosterone versus dihydrotestosterone with respect to the following physiological functions: bone metabolism, body composition, insulin resistance and lipid profile~to determine the role of testosterone and dihydrotestosterone versus estradiol with respect to the following physiological functions: bone metabolism, body composition, insulin resistance and lipid profile

Pain management due to minor procedures such as venipuncture or peripheral venous canulation still represents an unmet medical need, especially in pediatric setting. Current therapeutic products have a relatively delayed onset of analgesia of at least 10 minutes; moreover the most used products require application with at least 30-60 minutes prior to procedure. Development of ALGRX 3268 is aimed at addressing this unmet need in management of pain associated with needlestick procedures.~ALGRX 3268 (Previously known as PowderJect(R) Dermal Lidocaine) is used for local anesthesia within 3 minutes to provide painless needle or cathether insertion for blood drawing. ALGRX 3268 is a single-use disposable system, incorporating a drug cassette and cylinder into a single hand held device, with a button to actuate the system.~The purpose of this phase III, multicenter, prospective, randomized, double-blind, placebo-controlled study is to investigate the efficacy, safety and tolerability of ALGRX 3268 versus placebo in pediatric patients 3 to 18 years of age, who undergo venipuncture or peripheral venous canulation procedures. The trial will enroll approximate 504 evaluable subjects at centers located in the US.~Three age groups are enrolled: 3-7 years, 8-12 years, 13-18 years. Within each age group subjects are randomized to receive ALGRX 3268 0.5 mg/20 bar or pressure matched placebo. One to 3 minutes after administration of study treatment at the back of the hand or antecubital fosa, venipuncture is performed with a needle/Vacutainer, needle/syringe or butterfly, at the discretion of the investigator.~Subjects 3-18 years are asked to assess pain on venipuncture using Wong-Baker FACES pain rating scale, anchored at 0 for no hurt and 5 for hurts worst.~Children in the middle (8-12) and older (13-18) age groups will additionally rate pain at the ACF and BOH using a 100 mm VAS anchored at 0 for no pain and at 100 for extreme pain. Parent/legal guardian will evaluate child's level of pain on a 100 mm VAS anchored at 0, for no pain, and at 100 for extreme pain.~Safety ratings of skin are completed immediately prior, after, at 15 and 30 minutes following the procedure. All AEs/SAEs will be monitored.

Minor needlestick procedures often cause significant pain and distress in pediatric patients yet interventions to reduce pain are used infrequently. ALGRX 3268 is a novel, single-use, prefilled, needle-free product that immediately delivers powdered lidocaine into the epidermis and provides local analgesia in 2-3 minutes. The purpose of this phase III, prospective, randomized, double-blind, placebo-controlled study is to investigate the efficacy, safety and tolerability of ALGRX 3268 versus placebo in pediatric patients aged 3 to 18 years undergoing venipuncture or peripheral venous canulation procedures. The trial will enroll approximate 504 evaluable subjects at centers located in the US.

The transfer of care at hospital discharge is complex and requires the transmission of large amounts of data between inpatient physicians (hospitalists) and outpatient physicians (PCPs), including information about pending tests. Frequently, laboratory and radiology tests are not finalized until after a patient is discharged, and when the responsibility for these pending results is not clearly defined, they can be missed. Our project aims to define the problem of these post-discharge results and to study the implementation of an EMR-based system (Hospitalist Results Manager, HRM) for tracking these results on the hospitalist services at Brigham and Women's Hospital (BWH) and Massachusetts General Hospital (MGH). The project consists of two phases: a cross-sectional study before intervention to define the epidemiology of post-discharge results, and a randomized trial of HRM to determine its effect on physician awareness of these results.

This project aims to define the problem of results that return after patient discharge and to study the implementation of an Electronic Medical Record (EMR)-based system for tracking these results.

INSPIRE is a four-site (Baltimore, Miami, New York and San Francisco) randomized control trial to develop and evaluate the efficacy of a ten-session intervention for HIV-positive injection drug users. The primary goals of the intervention are to:~decrease sex and injection risk behaviors that put others at risk for HIV infection,~increase access to or utilization of HIV primary health care, and~increase adherence to HIV medications.~The intervention arm consists of 7 group sessions, 2 individual sessions, and one community experience. The control arm consists of 8 group sessions, aiming at controlling for demand (1st session) and attention (8 group sessions). Behavioral assessments and blood draws (for viral load and CD4 testing) occur at baseline, 6, and 12 month follow-up; a 3 month assessment involves behavioral assessment only. 1161 participants took baseline. Of these, 966 were randomized into the study, and 840, 807, and 821 participants took 3, 6, and 12 month follow-up assessments, respectively.

The purpose of this study is to test whether a ten-session behavioral intervention for HIV-infected injection drug users is effective in reducing sex and injection risk behaviors that put others at risk for HIV infection, increasing access to or utilization of HIV primary health care, and increasing adherence to HIV medications.

COPD is characterised by persisting airway inflammation which leads to a progressive and irreversible deterioration in lung function with the eventual development of respiratory symptoms which may become disabling. Periodic episodes of worsening symptoms or exacerbations are a major cause of additional morbidity, mortality and health care utilization. Currently available therapies have limited efficacy in reducing airway inflammation or preventing exacerbations.~Macrolides such as erythromycin have been shown to have potent anti-inflammatory effects in in vitro experiments and in other lung conditions such as cystic fibrosis and bronchiectasis as well as in open label studies in COPD. We hypothesised that long term therapy with oral erythromycin would reduce airway inflammation and reduce the frequency of exacerbations in patients with COPD. If these properties are demonstrated this therapy can have potentially important benefits if effective in this condition.

The purpose of this study is to determine whether long term treatment with oral erythromycin is effective in the treatment of subjects with Chronic Obstructive Pulmonary Disease (COPD) by reducing the number of exacerbations and the degree of airway inflammation.

This study is an evaluation of the survival of the implants and bridges, quality of prosthetic work and patient satisfaction after immediate loading of the implants in a totally edentate upper and lower jaw.

This study is an evaluation of the survival of the implants and bridges, quality of prosthetic work and patient satisfaction after immediate loading of the implants in a totally edentate upper and lower jaw.

To compare the change in renal function between CsA or MMF withdrawal from before to 12 months after drug withdrawal in renal transplant recipients on triple immunosuppressive therapy.~Secondly to examine safety following withdrawal of CsA or MMF, respectively, by the following parameters:~Biopsy verified acute rejection episodes, time to first rejection and number of steroid resistant rejection episodes within 12 months.~Hematology (Hb, WBC, platelets) abnormalities within 12 months.~Graft and patient survival at 12 months and 5 years. Absolute difference in renal function between withdrawal groups at 12 months. Three monthly changes in renal function from drug withdrawal to 12 months. Change in dyslipidemia frequency from drug withdrawal to 12 months. Change in hypertension frequency from drug withdrawal to 12 months. Change in glucose tolerance from drug withdrawal to 12 months. Cumulative incidence of clinical infections resulting in hospitalization within 12 months.~Sub protocols will also examine the following aspects:~Cardiovascular: Homocysteine. Lipid peroxidation. Microvascular function and vasoactive parameters Quality of life (QoL): ESRD SCL-TM, SF-36 (short version) and EQ-5D (GI-checklist extended) questionnaires will be used.~Pharmacoeconomical evaluation.

To compare the change in renal function between CsA or MMF withdrawal from before to 12 months after drug withdrawal in renal transplant recipients on triple immunosuppressive therapy

Compare lumbar plexus block (randomized)~ropivacaine 0.475%, 0.4 ml/kg~saline 0.4 ml/kg . Each group includes 30 patients.~Block performed preoperatively.~Surgery under general anesthesia (sufentanil, propofol, atracurium ; maintenance : sevoflurane and nitrous oxide in O2. Sufentanil added peroperatively as clinically needed.~Postoperative evaluation of pain (VAS, by an independant blind observer) as first endpoint, and also morphine consumption via PCA device.~Adverse effects (nausea, vomiting, etc) recorded~Follow-up : 24h. Expectation : sizeable reduction of pain with block, of duration.

Compare lumbar plexus block with ropivacaine 0.475%, 0.4 ml/kg to saline. Each group randomized, includes 30 patients. block performed preoperatively Surgery under general anesthesia. Postoperative evaluation of pain (VAS) as first endpoint, and also morphine consumption via PCA device. Follow-up : 24h.~Expectation : sizeable reduction of pain with block, of duration.

The objective of this study is to determine the long-term safety of asoprisnil 10 mg (2-5mg tablets) when taken with Premarin® 0.625 mg, by postmenopausal women, for 6 months after an initial 12 weeks in Study M00-198. Pharmacodynamic effects to be assessed include uterine bleeding pattern, endometrial biopsy results, and endometrial thickness. Safety assessments will include clinical laboratory results, physical examination with vital signs, pelvic and breast examinations, ultrasound results, and adverse events.

The objective of this study is to determine the long-term safety of asoprisnil 10 mg when administered to postmenopausal women with Premarin® 0.625 mg

OBJECTIVE: Responses to 23-valent polysaccharide pneumococcal vaccine (PPV23) are poor in organ transplant recipients. We have recently shown that the conjugate pneumococcal vaccine (PCV7) is immunogenic in this population but responses remain suboptimal. This is a clinical study designed to assess the immunogenicity of a novel pneumococcal vaccination strategy in a cohort of adult liver transplant recipients. The trial will compare a group of patients primed with the pneumococcal conjugate vaccine plus polysaccharide boost with a group primed with placebo plus the standard 23-valent polysaccharide vaccine.~Specific objectives of this study are:~To determine the quantitative antibody response using both vaccine strategies~To determine the functional antibody response by the opsonophagocytic assay. This assay has the advantage of assessing if patient antibody responses represent truly functional antibodies that display opsonic activity against pneumococcus and is likely better correlated with protective efficacy.~To determine the durability of response over two years In addition, the safety of the conjugate vaccine and a determination of whether time from transplant affects response to vaccination will be made.~HYPOTHESIS: It is hypothesized that the PCV7 priming will provide an enhanced response in these immunosuppressed individuals who may respond poorly to standard vaccination.~RESEARCH PLAN: We will enroll 130 liver transplant recipients from the out-patient transplant clinics at Toronto General Hospital, Toronto, Ontario. Recipients who have had pneumococcal vaccination in the past 5 years will be excluded. Upon enrolment, patients will be randomized to receive either placebo or PCV7 in a blinded fashion. Eight weeks later, all subjects will receive PPV23. Serum will be obtained at baseline, 8 weeks, 16 weeks, 6, 12, 18, and 24 months. Sera will be used to perform antibody testing to seven pneumococcal serotypes (4, 6B, 9V, 14, 18C, 19F, 23F). The baseline, 8, and 16 week sera will be used for opsonophagocytic assay to the above seven serotypes. A baseline nasopharyngeal swab will also be obtained to look for colonization with Streptococcus pneumoniae. Patient recruitment is expected to take two years and follow-up of all patients should be complete by year 3. An additional 4 months will be needed to complete all laboratory testing. The primary outcome will be anticapsular antibody concentration at 16 weeks. A serotype response will be defined as a 2-fold or greater rise in titer from the 8 week concentration. A vaccine response will be defined as response to at least one serotype of the seven measured.~FUTURE DIRECTIONS: Results of this trial will help to develop a rational and optimal pneumococcal vaccination strategy that would prevent significant morbidity in organ transplant recipients. We are currently studying the impact of pneumococcal disease in transplantation by: (i) a review of invasive pneumococcal disease in transplant recipients in Toronto-Peel region to determine incidence and predominating serotypes; (ii) a Canadian survey of vaccination practices in transplantation; (iii) a 3-year follow-up study to determine the sustainability of immune response to pneumococcal vaccine in renal transplant patients previously enrolled in a vaccine trial. We hope that these studies will form the basis of pneumococcal vaccination recommendations for organ transplant recipients.

The trial will compare a group of patients whose immune system is primed with the pneumococcal conjugate vaccine and then given a boost with polysaccharide vaccine (prime-boost strategy) vs. a group vaccinated with the standard 23-valent polysaccharide vaccine alone. It is hypothesized that the conjugate vaccine priming will provide an enhanced response in these immunosuppressed individuals who may respond poorly to standard vaccination.

Background: Dexamethasone improves control of acute nausea and vomiting when given prior to chemotherapy, and continued administration of dexamethasone improves nausea and vomiting after highly emetogenic chemotherapy. There is no consensus about the optimal regimen for control of delayed emesis after moderately emetogenic chemotherapy but most patients receive oral dexamethasone. Many patients complain of insomnia, anxiety/agitation and indigestion whilst they are on dexamethasone, and fatigue and depressed mood after stopping it. The impact of these symptoms on patients has not been studied systematically. While patients with less vomiting and nausea are expected to have better quality of life (QOL), the QOL of patients with minimal nausea or vomiting might be more affected by the side effects of antiemetic treatment.~Hypothesis: Dexamethasone given as an antiemetic for delayed nausea and vomiting after moderately emetogenic chemotherapy reduces overall quality of life.~Research Question: Does the use of dexamethasone as a prophylactic antiemetic for delayed nausea and vomiting following moderately emetogenic chemotherapy decrease overall quality of life, as evaluated by the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ C-30).~Study Design: Using a double-blind randomised cross-over design, we will determine:~(i) the effect of oral dexamethasone (4mg PO bid after chemotherapy) versus an identical appearing placebo on QOL of patients that receive moderately emetogenic chemotherapy, and~(ii) patient preference for dexamethasone or placebo.~We will evaluate control of nausea and vomiting and the impact of both the side effects of dexamethasone and of nausea and vomiting on QOL. Therapy for acute emesis will be standardised (single dose intravenous granisetron and dexamethasone) and all patients will receive granisetron for delayed emetic control. Each patient will be randomly allocated to receive either dexamethasone or placebo after the first cycle of chemotherapy, and crossed over to the other arm for the second cycle. Patients will complete questionnaires that evaluate QOL, symptoms associated with dexamethasone, and nausea and vomiting at baseline and one week after their intravenous chemotherapy; they will also record symptoms in a daily diary.~The primary outcome measures are patient preference and overall QOL. The secondary objectives are: (1) to compare complete protection from delayed vomiting and severity of nausea between those receiving dexamethasone and those receiving placebo; (2) to compare differences in the impact of nausea and vomiting on QOL in those receiving dexamethasone and those receiving placebo, and (3) to compare differences in symptoms that have been associated with dexamethasone (insomnia, anxiety, agitation, mood, etc.) between patients receiving dexamethasone and those receiving placebo.~Significance: Our study will evaluate whether the benefits of dexamethasone for delayed emetic control outweigh potential side effects in patients receiving moderately emetogenic chemotherapy. It addresses a problem that is important to the majority of patients receiving anticancer chemotherapy. If overall QOL is improved on dexamethasone, then it should be prescribed routinely. If QOL is reduced on dexamethasone, and patients prefer the placebo, then its use as an antiemetic after moderately emetogenic chemotherapy should be limited to patients who initially have poor control of emesis.

Background: Dexamethasone is a steroid, which is often given into the vein before chemotherapy to help control acute nausea and vomiting. It can also be given as an oral tablet for patients to take for the two days following chemotherapy to help minimise delayed nausea and vomiting. In chemotherapy regimens that cause high rates of nausea and vomiting, the use of dexamethasone is well proven. However, in chemotherapy regimens that generally cause only minimal to moderate rates of nausea and vomiting, the value of oral dexamethasone in the 48-hour period after chemotherapy is not well proven, although it is often prescribed. While dexamethasone does decrease nausea, it causes additional side-effects such as insomnia, indigestion, anxiety and mood changes. While patients with less vomiting and nausea are expected to have better quality of life (QOL), for patients with minimal nausea or vomiting, their QOL might be more affected by the side effects of the dexamethasone treatment than by the nausea.~Study Design: The study will be performed in patients who will be receiving first line chemotherapy treatment with a moderate risk of nausea/vomiting. Anti-nausea therapy for acute nausea/vomiting will be standardised and all patients will receive non-steroidal medication for delayed nausea control. Each patient will be randomly allocated to receive either oral dexamethasone or an identical appearing placebo tablet for two days after chemotherapy for the first cycle of chemotherapy, and then crossed over to the other treatment for the second cycle. Patients will complete QOL assessments, dexamethasone symptom and nausea and vomiting questionnaires, as well as nausea/vomiting diaries. This will enable the researchers to determine the effect of dexamethasone on nausea and vomiting and the impact of both the side effects of dexamethasone, and of nausea and vomiting, on QOL.~Objectives: The primary objectives are to determine patient preference for dexamethasone or placebo, and to compare changes in QOL after chemotherapy in patients who receive dexamethasone with those who receive placebo. The secondary objectives are: (1) to compare complete protection from delayed vomiting and severity of nausea; (2) to compare differences in the impact of nausea and vomiting on QOL, and (3) to compare differences in symptoms that have been associated with dexamethasone (insomnia, anxiety, agitation, mood, etc.) between patients receiving dexamethasone and those receiving placebo.~Significance: This study will provide data to evaluate whether the benefits of dexamethasone for delayed nausea and vomiting outweigh potential side effects in patients receiving chemotherapy with a moderate risk of causing nausea and vomiting. This addresses a problem that is important to a majority of patients receiving anticancer chemotherapy. If overall QOL is improved on dexamethasone, then it should be prescribed more frequently, but if QOL is reduced on dexamethasone, and patients prefer the placebo, then its use as an anti-nausea medication for delayed nausea after moderately nauseating chemotherapy should be limited to patients with poor initial control of nausea/vomiting.

To provide low-income, under- or uninsured 40- to 64-year-old women with the knowledge, skills, and opportunities to improve diet, physical activity, and other lifestyle behaviors to prevent, delay and control cardiovascular and other chronic diseases.

To provide low-income, under- or uninsured 40- to 64-year-old women with the knowledge, skills, and opportunities to improve diet, physical activity, and other lifestyle behaviors to prevent, delay and control cardiovascular and other chronic diseases.

Evidence is accumulating that homelessness and housing may be important factors that influence human immunodeficiency virus (HIV) sex and drug risk behaviors. Despite this apparent connection, few studies have investigated whether homelessness or unstable housing, compared with stable and adequate housing, is linked with HIV risk behaviors, and whether change in housing status is associated with change in risk behaviors.~The Housing and Health Study is a multi-site, multi-agency research collaboration. This project is a unique collaboration between federal agencies (the Department of Housing and Urban Development and the Centers for Disease Control and Prevention), local government agencies, universities, and private not-for-profit organizations.~The goal of the project is to examine the impact of providing housing for people living with HIV who are homeless or at imminent risk of homelessness on their disease progression, their risks of transmitting HIV, and medical care access and utilization. A total of 630 people living with HIV from three study sites complete the baseline study sessions. Half the participants (n=315) are randomly assigned to each of the two study groups. Treatment group participants receive Housing and Health Study housing rental assistance, and comparison group participants receive assistance finding housing according to local standard practice.~At baseline, 6, 12, and 18 months after baseline, participants complete study questionnaires and provide blood specimens to test for CD4 and viral load. In addition, the cost effectiveness of the study will be investigated by examining the HIV-related costs averted by providing housing to persons at high risk for transmitting HIV.

The goal of the project is to examine the impact of providing housing for people living with HIV who are homeless or at imminent risk of homelessness on their HIV disease progression, risks of transmitting HIV, and medical care access and utilization.

Participants will be randomized to 1 of 3 groups: vitamin with omega-3, vitamin w/o omega-3, or omega-3 alone. They will take the vitamin 12 weeks, after which time they will return for all laboratory tests. Persons who are currently taking a supplement must undergo a 2-week washout period before beginning the study. Participants taking the Cooper Complete one-a-day vitamin plus omega-3 fatty acid will have greater improvement in homocysteine, LDL cholesterol, and C-reactive protein than those taking the other supplements.

The goal of the study is to evaluate the effectiveness of a new one-a-day Cooper complete vitamin supplement with or without a combined omega-3 fatty acid supplement on selected clinical risk factor measures. Participants taking the Cooper Complete one-a-day vitamin plus omega-3 fatty acid will have greater improvement in homocysteine, LDL cholesterol, and C-reactive protein than those taking the other supplements.

Anemia associated with lung cancer and chemotherapy is an important factor effecting patient symptoms, functional status, and overall quality of life (Groopman and Itri 1999; Langer, Choy et al. 2002). Darbepoetin alfa (Aranesp®) has demonstrated a significant effect upon ameliorating chemotherapy-induced anemia in lung cancer (Vansteenkiste, Pirker et al. 2002; Vansteenkiste, Poulsen et al. 2002). This trial is designed to evaluate the association between the treatment of anemia with darbepoetin alfa and direct electronic capture of clinical benefits in cancer-related symptoms, functional status and overall quality of life. This trial uses a secure web-based design to capture the patient-associated symptoms, functional status and quality of life. This novel secure web-based system was selected to improve the efficiency and quality of clinical data capture. If our hypothesis is correct, treatment with darbepoetin alfa will be associated with improved palliation of cancer-related symptoms, improved functional status, and result in overall benefits to the patient's health-related quality of life. The development of a web-based system to directly capture patient-related symptoms, functional status and quality of life will permit us in the future to conduct a national or international trial addressing the effects of darbepoetin alfa on these factors. If our hypothesis is incorrect, it may be that these parameters are not affected by the correction of anemia with darbepoetin alfa or the measures are not sensitive enough to detect these differences. A notable finding would be a clearly defined improvement in symptom palliation, functional status, and quality of life associated with darbepoetin alfa therapy.

This is a web-based pilot study to evaluate the association between the treatment of anemia with darbepoetin alfa (aranesp) and the clinical benefits in symptom palliation, improved functional status and quality of life in patients with cancer. The feasibility of web-based assessments and data capture will be evaluated.

Vascular responses to angiotensin II and histamine are compared before and after 30 days of systemic treatment with either irbesartan 150 mg or atorvastatin 20 mg.

Vascular responses to angiotensin II and histamine are compared before and after 30 days of systemic treatment with either irbesartan 150 mg or atorvastatin 20 mg.

This trial is to show the diagnostic efficacy of Gadovist for contrast enhanced Magnetic Resonance Angiography (CE-MRA) of arteries (specified vessel segments) by analyzing the rate of agreement, image quality, and diagnostic confidence between a CE-MRA based diagnosis and the diagnosis achieved from the comparator procedure IA DSA using Ultravist.

This trial is to show the diagnostic efficacy of Gadovist for contrast enhanced magnetic resonance angiography (CE-MRA) of the arteries.

Bone lengthening using distraction osteogenesis has found many clinical applications in the treatment of limb length discrepancies, limb deformities, bone defects and fracture nonunion. Animal studies have shown that mechanical conditions significantly affect the biological process of osteogenesis. Knowledge of the influence of mechanical stimuli on the formation of bone is thus essential for the improvement of the current technique, contributing to the treatment and care of patients receiving bone lengthening. Previous in vivo human studies have approached the problem by measuring the interfragmentary movement of bone fracture and the loading in the limb in terms of the ground reaction forces. The mechanical environment in the callus is not available with these approaches. As the stress and strain behavior of bone is critical to its normal function, the response to bone osteotomy and osteogenesis, a limited number of studies have used simplified FEM technique to examine the strain and stress patterns in the callus in two dimensions during simplified loading conditions. The calculated strain patterns, however, can be far from the real situation in the callus. No data are available for the stress and strain patterns during the process of distraction osteogenesis.~The present study is a further step of our current one-year NSC project, aiming to bridge the above-mentioned gap by continuously monitoring the mechanical stimuli applied to the limb and callus, both through experimental measurements and FEM calculations, and by correlating the observed quantity and quality of the mechanical stimuli with the calculated stress and strain patterns of the callus tissue. Specifically, in this proposed study, 3D finite element models of the osteogenesis at four temporal points during the limb lengthening process for each subject will be developed from CT data of the osteotomy sites. A 3D model of the musculoskeletal model of the lower limb will be used to calculate the forces transmitted by the bone and surrounding tissues, which will be used for subsequent FEM analysis. The purpose of the study is to determine the stress and strain patterns in the callus at different distraction stages and, with the data collected from gait laboratory experiments performed in our current NSC project, to provide a clearer picture of the influence of mechanical stimuli on distraction osteogenesis.~It is hoped that the present study will lead to a better understanding of the mechanisms of osteogenesis, which will be helpful in finding appropriate fixation methods in distraction osteogenesis that optimize the mechanical environment for bone formation.

a further step of our current one-year NSC project, aiming to bridge the above-mentioned gap by continuously monitoring the mechanical stimuli applied to the limb and callus, both through experimental measurements and FEM calculations, and by correlating the observed quantity and quality of the mechanical stimuli with the calculated stress and strain patterns of the callus tissue.

One of the consequences of breast cancer treatment for younger women is the abrupt onset of menopause and its related symptoms. Menopausal symptoms disrupt usual activities, alter sleep patterns and decrease quality of life. In light of the recent findings from the Women's Health Initiative (re:use of exogenous estrogen), the need to investigate non-hormonal approaches (meditation) for short-term menopausal symptom discomfort is high. The purpose of this randomized feasibility pilot study is to examine mindfulness meditation for menopausal symptom management for women who are breast cancer survivors and for women with naturally occurring menopause. The study is designed to: 1. establish the feasibility of a mindfulness meditation program for women who experience menopausal symptoms (e.g. hot flushes). 2. explore the treatment benefit of a mindfulness meditation program for menopausal symptom relief using changes in frequency and severity of hot flushes; frequency of sleep disruption, various aspects of quality of life and physiologic stress response (cortisol) as outcome measures. 3. evaluate whether the treatment benefits of mindfulness meditation differ in menopausal women with naturally occurring menopause versus women with menopause secondary to chemotherapy for breast cancer. A 2x2 factorial repeated design will be used. The four randomized groups will consist of 1) naturally occurring menopause meditation; 2) naturally occurring menopause attention control; 3) breast cancer survivors meditation; 4) breast cancer survivors attention. Participants randomized to the attention control group will be offered meditation training after completion of the intervention and follow up phases. Participants will attend 8 meditation sessions or 8 attention control sessions. Study variables are Menopausal Hot Flushes (self report & skin conductance monitoring), Sleep Disruption (Pgh Sleep Quality Index), Physiologic Stress Response (cortisol), Quality of Life (Menopausal Quality of Life); and Protocol Design (recruitment & retention rates, exit interviews). A convenience sample of 60 women who experience menopausal symptoms will be recruited. Data analysis includes descriptive statistics, repeated measures content analysis. Results from this feasibility pilot study will inform the design of a larger randomized clinical trial to test the effectiveness of mindfulness meditation as a self care intervention for menopausal symptom management and improvement in quality of life.

One of the consequences of breast cancer treatment for younger women is the abrupt onset of menopause and its related symptoms. Menopausal symptoms disrupt usual activities, alter sleep patterns and decrease quality of life. The purpose of this randomized feasibility pilot study is to examine mindfulness meditation for menopausal symptom management for women who are breast cancer survivors and for women with naturally occurring menopause. The study is designed to: 1. establish the feasibility of a mindfulness meditation program for women who experience menopausal symptoms (e.g. hot flushes). 2. explore the treatment benefit of a mindfulness meditation program for menopausal symptom relief using changes in frequency and severity of hot flushes; frequency of sleep disruption, various aspects of quality of life and physiologic stress response (cortisol) as outcome measures. 3. evaluate whether the treatment benefits of mindfulness meditation differ in menopausal women with naturally occurring menopause versus women with menopause secondary to chemotherapy for breast cancer. Participants randomized to the attention control group will be offered meditation training after completion of the intervention and follow up phases. Participants will attend 8 meditation sessions or 8 attention control sessions. Study variables are Menopausal Hot Flushes (self report & skin conductance monitoring), Sleep Disruption (Pgh Sleep Quality Index), Physiologic Stress Response (cortisol), Quality of Life (Menopausal Quality of Life); and Protocol Design (recruitment & retention rates, exit interviews). A convenience sample of 60 women who experience menopausal symptoms will be recruited.

III. Hypothesis: The primary hypothesis of this pilot study is that dependence can be prevented in adolescents who smoke, but who are not yet dependent. With this study, we seek to develop and test the feasibility and provide controlled comparisons of two brief smoking dependence-prevention interventions. Additional analyses will be conducted to determine which, if any, demographic, psychological, personality, behavioral, or family characteristics predict which adolescents respond best to dependence-prevention interventions, though no clear a priori predictions can be made.~IV. Specific Aims: The primary aim of this pilot study is to prevent dependence in adolescent smokers, who are at great risk for nicotine dependence and tobacco-related disease. Nicotine dependence is a disease that begins in children and adolescents: approximately three quarters of adult tobacco users (i.e., cigarette and cigar smokers and users of smokeless tobacco, or SLT) report that their first tobacco use occurred when they were 11-17 years old (USDHHS, 1994a; 1994b; Riley et al., 1996). Moreover, the earlier a person starts smoking, the higher their eventual daily cigarette consumption (Taoli and Wydner, 1991), and the greater their risk of dying from a smoking-related disease (USDHHS, 1989). Because smoking begins in adolescents and because young tobacco users are at the greatest risk for progressing to dependence and dying of smoking-related disease, adolescent smokers would benefit immensely from effective tobacco dependence prevention.~VI. Preliminary Progress/Data Report: This project involves an evaluation phase, including laboratory measurement of tobacco's effects, a dependence-prevention phase, and a follow-up phase. Because the laboratory measurement is critical to the success of all phases (data generated in the laboratory phase are used in the intervention and thus influence the follow-up), this preliminary data section will focus on laboratory research.~The Clinical Behavioral Pharmacology Laboratory (CBPL; T. Eissenberg, Director) has been a site for safe and ethical studies of tobacco use in adults (e.g., Eissenberg et al., 1999; Buchhalter and Eissenberg, 2000; Buchhalter et al., 2001; Breland et al., in press). In addition, Dr. Eissenberg initiated a discussion on how to conduct safe and ethical tobacco research in adolescents: in 2000, he planned and chaired a symposium entitled Ethical and Practical Challenges in Tobacco Research with Children at the 6th Annual Meeting of the Society for Research on Nicotine and Tobacco (Eissenberg, 2000; see also Eissenberg and Balster, 2002). He has also been involved in several laboratory studies involving young adults (e.g., Gire and Eissenberg, 2001) and adolescents (Zack et al., 2001; Corrigall et al., 2000).~Progress on the current project has included the establishment and maintenance of an adolescent clinical lab facility for direct observation of young smokers and for testing brief-intervention strategies in a controlled setting; recruitment of scientific and clinical staff; development of subject recruitment procedures; engagement of local school personnel in the recruiting process, utilization of advertising on city buses to aid recruitment, development and pilot testing of the brief interventions; successful completion of 17 subject baseline lab sessions and 8 telephone follow-at 1 month, 3 at 3 month, 1 visit at 6 months, 1 phone contact at 9 month, and 1 visit at 12 month. Four participants have been lost to follow-up.~VII. Research Method and Design: This pilot protocol includes several integrated components: recruitment, telephone or in-person screening and Parental Information Sheet and assent, a psychosocial assessment, a laboratory assessment, two different dependence-prevention interventions, and a follow-up component. The evaluation and dependence-prevention phases will occur during a single 3- to 4-hour session, and the 30-45 minute follow-up sessions will take place approximately one month, three months, six months, and one year after the completion of the evaluation and dependence prevention phases. Each phase is outlined below.~Recruitment phase. Potential participants will be recruited through print ads, attached to this protocol for IRB review, some of which may be distributed through schools with school permission. Along with the ads, each student will receive the parental information and assent procedures, therefore parents will be informed about the study directly by the adolescent. The parental information sheet would explain that their teenager is interested in being part of a study on the prevention of tobacco dependence. It gives a brief description of the study. Parent signatures indicate they have received the information. For those adolescents that find out about the study by fliers or word of mouth, the parental information sheet will be sent by mail. Flyers may also be distributed by willing adolescents. Interested peers may then call to see if they are eligible, and if they qualify and come to the baseline phase we will send a referral fee of five dollars to the original participant for each referral that does so. Even if the original participant receives the referral fee, the name of the other participant will not be divulged.~Screening, consent, and assent phase. Potential participants will be initially screened using the screening interview. Screenings might occur via telephone or in person, depending upon individual preference. The sole purpose of the screening interview is to determine if interested adolescents meet the study inclusion/exclusion criteria (see below). The screening interview collects the minimum amount of information needed to determine eligibility and maintains the potential participant's anonymity. This same information is collected again (as background data, below) to determine reliability of reporting. Individuals who are unable to report their own smoking history reliably are ineligible for further participation.~Following the initial screening process, potential participants will be told that their parents/legal guardians need to sign and date the parental information and assent procedures. The parental information and assent procedures will explain that their teenager is interested in being part of a study looking at the prevention of becoming an addicted smoker and giving a brief description of the study. Individuals will have as much time as needed to consider their child's participation. The child will bring the parental signed form with the to the first laboratory session. If the parent wants they can bring the adolescent and will still be paid to compensate for their time, however it is not required.~Adolescent assent will be done prior to research collection during the initial study session. A researcher who has completed VCU's Level I IRB training will read the attached assent form to the adolescent and answer any questions that individual may have. Individuals will have as much time as needed to consider their participation. Individuals who are interested in participating will be asked to sign the assent form indicating that they agree to participate and understand that they may stop participating at any time.~Psychosocial Assessment. Adolescent participants will be asked to complete demographic, psychological, personality, behavioral, and family questionnaires. The baseline questionnaires consist of the Child Depression Inventory (Kovacs, 1982), the Revised Children's Manifest Anxiety Scale (Reynolds & Richmond, 1978), the Leyton Obsessional Inventory - Child Version (Berg, Rapoport, & Flament, 1987), Barkley's ADHD Scale (Barkely, 1998), the National Youth Survey of Conduct Scale (Elliot, Huizinga, & Morse, 1988), the Adolescent Life Events Inventory (Compas, et. al., 1987), the Family Assessment Device (Epstein, Baldwin, & Bishop, 1983), the Millon Adolescent Personality Inventory (Millon, Green, & Meagher, 1982), and questions pertaining to body image, substance use, and smoking behavior and attitudes. Each of the questionnaires was developed specifically for use with children and/or adolescents, and most have been standardized and widely used in a general adolescent population. These data will be used to report on participant characteristics and will be especially useful in identifying factors that predict intervention response. We recognize that asking personal questions sometimes makes people feel uncomfortable. Participants will be instructed that is any of the questions are upsetting to them, that they are to tell the researcher. The researcher will then inform a clinician who will evaluate the participant and determine and recommend necessary services.~Laboratory Assessment: The laboratory assessment will be virtually identical to that reported elsewhere (e.g., Corrigall et al., 2001) and will involve an approximately 20 minute rest period, questionnaires related to tobacco withdrawal and tobacco/nicotine effects, ad lib smoking using a mouthpiece that measures puff topography (e.g., puff volume, number, duration, etc), and a variety of physiological measures. Only adolescents who have already been smoking on their own are eligible; therefore, we believe the smoking of a single cigarette in the lab confers no additional risk. During the rest period, participants will complete demographic and background information questionnaires. Participants will then be asked to smoke as they normally would, with no other constraints. Participants will provide their own cigarette (if they have one) or a cigarette will be provided for them. Outcome measures, described below, include physiological data (e.g., heart rate, breath carbon monoxide level, etc), subjective reports of tobacco withdrawal symptoms, and puff topography. Saliva sample will be taken before and after smoking for later measurement of salivary nicotine and cotinine (a nicotine metabolite).~Questionnaires: All questionnaires are computerized. Withdrawal-related questionnaires include the QSU-Brief (Cox et al., 2001) MNWS (Hughes and Hatsukami, 1986). The Fagerstrom Test for Nicotine Dependence will assess dependence levels (FTND; Heatherton, Kozlowski, Frecker, & Fagerstrom, 1991). Subjective effects of smoking will also be assessed.~Physiological Measures. Two physiological measures will be monitored continuously: heart rate (every 20 seconds) and blood pressure (every 3 minutes; Noninvasive Patient Monitor model 507E, Criticare Systems, Waukesha, WI). Expired CO levels will be measured at screening and before and after smoking using a BreathCO monitor (Vitalagraph, Lenaxa, KS). This equipment and these procedures have been used extensively in studies at VCU (e.g., Buchhalter et al., 2001; Breland et al., in press). In addition, salivary nicotine and cotinine will be collected before and after smoking. Participants will be asked to chew a roll of cotton before placing it into a plastic test tube. The test tubes will be stored in a freezer at no warmer than -32 degrees.~Topography measures: Puff topography is a sensitive measure of drug self-administration in cigarette smokers and has been used in previous studies of adolescent smokers (e.g., Corrigall et al., 2001). Cigarettes are smoked through a mouthpiece that is connected to a pressure transducer and inhalation-induced pressure changes are amplified, digitized, and sampled at a rate of 1000 Hz. Software (Plowshare Technologies, Baltimore, MD) converts signals to air flow (ml/sec) and integrates this flow data, producing measures of puff volume, duration, number, and interpuff interval (IPI).~Dependence-Prevention Interventions: After the psychosocial and laboratory components, participants will take a 20-minute break during which snacks and drinks will be provided. Participants will be assigned randomly to one of two possible dependence-prevention groups. The random assignment will occur after the evaluation phase, so as not to bias the experimenters during data collection. One dependence-prevention group involves a brief motivational interview that provides general and personalized feedback about the immediate and long-term consequences of smoking, including feedback about the physiological and psychological impact of tobacco as measured in the evaluation phase. Motivational interviewing is a promising intervention in adolescent smokers (Colby, et. al., 1998; Lawendowski, 1998). The second group will receive brief education-based dependence-prevention interventions. Research indicates that high proportions of adolescents, particularly smokers, are unaware of many of the significant smoking-related health risks, including shortened lifespan and the likelihood of dying a smoking-related death (Romer & Jamieson, 2000). In addition, perceived health risks predicted motivation to quit, suggesting that if adolescents are better informed about smoking-related health problems they may be more motivated to stop smoking (Romer & Jamieson, 2000). The second group will watch a composite of anti-smoking videos, which includes education regarding the immediate and long-term effects of smoking and education regarding tobacco companies and their marketing strategies. All participants will earn a $40 mall gift certificate after the completion of this phase.~Follow-up phase: Brief telephone follow-up sessions will take place approximately one month, three months, six months, and nine months after the completion of the dependence-prevention intervention. The telephone follow-ups will consist of a brief time-line follow-back questionnaire to assess smoking behavior over the past two weeks. Participants will earn $10 mall gift certificates for completion of these telephone follow-ups that will be mailed to them after completion of the follow-up session. In addition, short follow-up check-ups will be performed six months and one year after completion of the dependence-prevention intervention. During these two follow-up check-ups, participants will again complete the time-line follow-back questionnaire, in addition to some questions about their current smoking attitudes. Non-intrusive physiological data will be recorded to validate their reports. Physiological data collection will consist of obtaining salivary nicotine and cotinine and expired CO levels, using the procedures described above. Participants will earn $25 mall gift certificates for completion of each of these follow-up check-up sessions. If the parent / legal guardian does bring the adolescent in, they will be compensated $30 for each follow-up check-up sessions.~VIII. Statistical Analysis:~Data Analysis. Data analysis will include:~Descriptive Statistics. Means, standard deviations, ranges, skewness, and kurtosis of all our measures will be examined to determine outliers and normality in our data. In addition, correlations will be run on all measures to determine what significant relationships exist between questionnaire and physiological data.~Inferential Statistics. Regarding data in our evaluation condition, we will examine relationships between questionnaire data and physiological data. Regarding follow-up data, we will run two-way mixed ANOVAs to examine the effect of the dependence-prevention interventions on smoking at follow-ups. In addition, we will run regressions using questionnaire and physiological data as predictors of smoking behavior at follow-up.~IX. Human Subjects Instructions:~A. Description. A total of 40 adolescent smoking volunteers will be needed to complete this preliminary research protocol. All sessions will take place in the Clinical Behavioral Pharmacology Laboratory on the Virginia Commonwealth University's medical campus.~Inclusion/Exclusion Criteria: Participants must be healthy, between the ages of 12 and 18 years of age, and be current smokers (defined as at least one cigarette in the last week, according to participant self-report). In order to ensure that smokers are not yet dependent, adolescents who have smoked more than 10 cigarettes per day each day of the last week will be excluded. Other exclusionary criteria include: history of or current specific health concerns, including cardiovascular disease, pregnancy or current breast feeding.~C. Recruitment Plan. Participants will be recruited by print advertisements, some of which may be distributed through local schools. Parental information forms will be distributed or mailed upon contact with the adolescent. Participants will then call the CBPL and potential participants will participate in the telephone screening described above. If the participant is eligible for participation, a qualified laboratory staff member who has completed VCU's Level One IRB Training will obtain assent from adolescents at the beginning of the initial session. Potential participants are given the opportunity to ask questions during the assent process and are afforded all the time they need to make an informed decision. Assent forms are attached for IRB review.~G. Compensation Plan. Participants will be compensated for their time with mall gift certificates. All participants who complete the initial session (including the evaluation and intervention components) will receive a $40 mall gift certificate. Participants will receive an additional $20 mall gift certificate each telephone follow-up and $50 for each of the in-person follow-up sessions they attend, with a chance to earn a total of $200 in mall gift certificates. If the participant completes ALL assessments, they will receive a $20 bonus at the 12M follow-up, thereby earning a total of $220 over the year of participation. If the parent brings the child, but not required to, they will be compensated for their time as follows: $60 for the initial session, and $30 for the in person visits, totaling up to. In addition, participants who recruit other adolescents to participate will earn a $5 gift certificate for each enrolled participant they referred.~H. Consent issues. Screening: As stated above, potential participants will be initially screened using the screening interview; screenings might occur via telephone or in person, depending upon individual preference. The sole purpose of the screening interview is to determine if interested adolescents meet the study inclusion/exclusion criteria and to schedule the initial visit. The screening interview collects the minimum amount of information needed to determine eligibility and this same information is collected again (as background data, below) to determine reliability of reporting. Individuals who are unable to report their own smoking history reliably are ineligible for further participation. At the end of the screening interview, the study procedures are described to potential participants, who are then asked whether or not they are still interested in participating. If yes, staff will set up the initial appointment.~Parental Information Sheet: Before any research data are collected, the signed and dated parental information sheet and assent will be collected. The signed Parental Information Sheet indicating that the parent has reviewed information about the study is required for adolescents to participate . Individuals will have as much time as needed to consider their participation. The Parental Information Sheet will be disseminated at with recruitment information or can be mailed if the participant calls in about the study.~Adolescent assent: Adolescent assent will be obtained prior to research collection during the initial study session. A researcher who has completed VCU's Level I IRB training will read the attached assent form to the adolescent and answer any questions that individual may have. Individuals will have as much time as needed to consider their participation. Individuals who are interested in participating will be asked to sign the assent form indicating that they agree to participate and understand that they may stop participating at any time.

The primary hypothesis of this pilot study is that dependence can be prevented in adolescents who smoke, but who are not yet dependent. With this study, we seek to develop and test the feasibility and provide controlled comparisons of two brief smoking dependence-prevention interventions: motivational interviewing with feedback versus a video control. Forty adolescents between the ages of 12 and 18 will be enrolled. The evaluation and dependence-prevention phases will occur during a single 3- to 4-hour session, and the 30-45 minute follow-up sessions will take place approximately one month, three months, six months, and one year after the completion of the evaluation and dependence prevention phases.

Aim-to conduct a randomized clinical intervention study to compare three diets (low-fat, low-carbohydrate and Mediterranean diet) for weight loss

Aim-to conduct a randomized clinical intervention study to compare three diets (low-fat, low-carbohydrate and Mediterranean diet) for weight loss

The purpose of this study is to gather information about total knee replacement surgery using minimally invasive surgical procedures. The MIS™ Minimally Invasive Solutions™ Total Knee Arthroplasty System has been cleared for use by the Food and Drug Administration.~You are invited to participate in this data collection study, comparing the MIS system to standard knee replacement systems. The decision about which system and operation will be best for you has already been made by you and your orthopaedic surgeon.~The information will be used to compare minimally invasive surgery and the standard surgery procedures. The results of this study will provide information that will add to the knowledge base of knee replacement surgery.

The purpose of this study is to gather information about total knee replacement surgery using minimally invasive surgical procedures.

The T-001 study is a placebo-controlled investigation of the effects of injectable testosterone replacement therapy on prostate tissues of aging men with low testosterone levels. The primary objectives of the study are to measure the changes in tissue hormones and other biomarkers in the prostate tissue specimens.

The T-001 study is a placebo-controlled investigation of the effects of injectable testosterone replacement therapy on prostate tissues of aging men with low testosterone levels.

To explore and illuminate the cultural, social, and psychological factors that either facilitate or serve as barriers to behavioral change in angioplasty patients. Through a series of open-ended questions we will explore and build a better understanding of how culturally different patient groups perceive heart disease and the difficulties in changing health behavior. In addition, we hope to better understand and anticipate barriers and issues that participants face in successfully changing their behaviors.~To use the responses obtained in the qualitative interviews to inform how we should operationalize and tailor the positive affect induction and self-affirmation intervention methods in each of the populations under study. Specifically, this involves assessing what small gifts participants prefer to receive and what would be most effective in inducing positive affect.

To explore and illuminate the cultural, social, and psychological factors that either facilitate or serve as barriers to behavioral change in angioplasty patients. Through a series of open-ended questions we will explore and build a better understanding of how culturally different patient groups perceive heart disease and the difficulties in changing health behavior. In addition, we hope to better understand and anticipate barriers and issues that participants face in successfully changing their behaviors.

Pain is difficult to estimate in ICU because most of the patients are sedated. Bispectral index could be helpful in detecting this pain in ICU patients. Remifentanil is a morphinomimetic product with short half life that could be interesting for short nociceptive stimuli, as bronchoalveolar lavage.~The purpose of this study is to evaluate the impact of remifentanil infusion on bispectral index (BIS) variations during bronchoalveolar lavage.~It is a prospective, double blind study, versus placebo on 40 sedated and critically ill patients.~The hypothesis is that BIS can study analgesia in sedated patient.

The aim of this protocol is to study the prophylactic effect of remifentanil on bispectral index variation during a nociceptive stimuli.

Specific Aims~What is the purpose of this study? What question is it designed to answer?~To compare the effect of azithromycin, telithromycin, and levofloxacin on activity of 7 hepatic drug metabolizing enzymes using the Cooperstown 5+1 Cocktail.~Background~Why is this study important?~We have previously shown that a broad drug interaction screening can be performed using enzyme specific probes such as oral caffeine for CYP1A2, N-acetyltrasferase-2 (NAT-2), and xanthine oxidase (XO), warfarin plus vitamin K for CYP2C9, omeprazole for CYP 2C19, dextromethorphan for CYP2D6, and midazolam for CYP3A4/5. This combination of probes has been validated in the Cooperstown 5+1 Cocktail (5+1).1 The use of the 5+1 cocktail provides information on the drug metabolizing enzymes that metabolize 90% of hepatically eliminated drugs for a fraction of the costs of the individual studies. Using a cocktail of biomarkers reduces the overall cost of drug interaction screening. The FDA has indicated that the use of probe drugs can be done in place of specific drug interaction studies.2 This streamlines the detection of drug interactions and reduces costs. However, it is important to control for genetic polymorphism in drug interaction trials so that genetic makeup does not affect the outcome.~Experimental Design and Methods 3) Describe in detail the experimental design and methodology. What information will be collected and how will it be collected? Provide a description of the subject's participation from start to finish.~Prior to any procedure of the study each subject will provide written informed consent. All the subjects will be genotyped for CYP2D6, CYP2C9, and CYP2C19 after obtaining informed consent for pharmacogenomics. This is to distinguish poor metabolizers from extensive metabolizers.~Prestudy screening will be conducted within 4 weeks of the first study phase. Subjects will undergo a complete medical history, social history (including medication, alcohol, and tobacco use), physical examination, standard 12-lead electrocardiogram (ECG), and laboratory screening to assure that inclusion and exclusion criteria are met. The laboratory screening data to be obtained are: complete blood count, prothrombin time (PT), international normalized ratio (INR), macroscopic and microscopic urinalysis, electrolytes, blood urea nitrogen (BUN), serum creatinine, aspartate transaminase (AST), alanine transaminase (ALT), total bilirubin, and serum albumin. Women of childbearing potential (defined as premenopausal with no history of hysterectomy or tubal ligation) will undergo a serum pregnancy test during the screening visit and a urine pregnancy test prior to each phase of the study. Following enrollment, subjects will participate in each of the 4 study phases in a random order.~Study Design and Procedures This will be a randomized, crossover, open-label study. Prestudy screening will be conducted within 4 weeks of the first study phase. Screening visits will involve obtaining informed consent, medical history, social history, physical examination, ECG, and laboratory tests. Following enrollment, subjects will be randomized (and then crossed over) to 4 phases as described in Table 1.~Table 1. Study Design Study Drugs and Procedure Phase 1 (control) Cooperstown 5+1 Cocktail alone. The Cooperstown 5+1 Cocktail consists of the following components:~Caffeine (2 mg/kg orally, rounded to nearest 50 mg) with collection of a 12-hour urine.~Warfarin (10 mg + 10 mg vitamin K orally) with collection of plasma over 96 hours. Plasma collection times are at 0, 3, 6, 12, 24, 36, 48, 72 and 96 hours after dosing. The INR will be checked at 48 hours. If the INR is >1.7, 5 mg of vitamin K will be administered by mouth daily until the INR is 1.2.~Omeprazole (40 mg orally) with collection of a plasma sample 2 hours after dosing.~Dextromethorphan (30 mg orally) with collection of a 12-hour urine.~Midazolam (0.075 mg/kg orally) with collection of 8 plasma samples over 6 hours (only for Phase 1) to determine CYP3A activity (MDZ CL/F mL/min). Samples will be drawn immediately after midazolam administration (0 minute), then at 5 minute, 0.5, 1, 2, 4, 5 and 6 hours. Breathing, heart rate, and oxygen saturation will be monitored via pulse oximetry for the first 90 minutes after midazolam dose.~Phase 2 Azithromycin 500 mg qAM for 3 days on an empty stomach. On day 4, the Cooperstown 5+1 Cocktail will be administered with a fourth dose of azithromycin given 2 hours after 5+1 administration.~Phase 3 Telithromycin 800 mg qAM for 3 days on an empty stomach. On day 4, the Cooperstown 5+1 Cocktail will be administered with a fourth dose of telithromycin given 2 hours after 5+1 administration.~Phase 4 Levofloxacin 750 mg qAM for 3 days on an empty stomach. On day 4, the Cooperstown 5+1 Cocktail will be administered with a fourth dose of levofloxacin given 2 hours after 5+1 administration.~During the azithromycin, telithromycin, and levofloxacin phases, plasma samples for midazolam will be collected at 0.25, 0.75, 1, 1.5, 2, 4, 6, 8, 10, 12, and 24 hours to allow for adequate sampling with drugs that potentially inhibit CYP3A. The 5+1 cocktail will be administered on day 4 after a minimum of 8-hour fasting.~Subjects will not be allowed to eat until 2 hours after administration of study drugs (5+1 cocktail or antibiotic).~Washout periods: One week after each phase except for the azithromycin phase is required to ensure the drug is completely eliminated from the body. Three weeks after the azithromycin phase is required since azithromycin has a longer half-life.~Sample Collection and Analysis • For caffeine phenotyping, subjects will collect all of their urine for 12 hours after receiving the dose to determine CYP1A2 activity [(AFMU+1X+1U)/17U], NAT-2 [AFMU/(AFMU+1X+1U)], and XO [1U/(1X+1U)]. Urine will be acidified with ascorbic acid (in vitro) to prevent AFMU conversion.~• For warfarin phenotyping, blood samples will be obtained at 0, 3, 6, 12, 24, 36, 48, 72 and 96 hours following warfarin plus vitamin K administration to determine CYP2C9 activity (S-warfarin CL/F, mL/min). For the first 12 hours, blood will be obtained through an intravenous (IV) catheter. Thereafter it will be via venipuncture.~• For omeprazole phenotyping, one 15 mL blood sample will be drawn 2 hours after the oral omeprazole dose to determine CYP2C19 activity (OMP/5OH OMP).~• For dextromethorphan phenotyping, subjects will collect all of their urine for 12 hours after receiving the dose to determine CYP2D6 activity (DM/DX).~For midazolam phenotyping, use of oral midazolam gives an assessment of inhibition of both gut and hepatic CYP3A.~For Phase 1 (5+1 cocktail alone), 8 blood samples (10 mL each) will be obtained immediately after midazolam administration (0 minute), then at 5 minutes, 0.5, 1, 2, 4, 5 and 6 hours to determine CYP3A activity (MDZ CL/F, mL/min).~During the azithromycin, telithromycin, and levofloxacin phases, blood samples will be collected at 0.25, 0.75, 1, 1.5, 2, 4, 6, 8, 10, 12, and 24 hours (to allow for adequate sampling with drugs that potentially inhibit CYP3A).~All blood samples (except 15 mL for omeprazole) will be collected in duplicate in 10 mL EDTA-containing test tubes and centrifuged for 15 minutes at 2800 rpm.~Plasma and urine samples will be frozen at -80C until analysis.~Data Analysis • Caffeine phenotyping assay: Urine aliquots will be assayed to determine urinary concentration of 1U, 1X, 17U, and AFMU. Urine aliquots will be analyzed at University of Missouri, Kansas City. Caffeine demethylation ratios will be used to express CYP1A2, NAT-2, and XO activity.~• S- and R-warfarin phenotyping assay: S- and R-warfarin in plasma will be determined utilizing high performance liquid chromatography (HPLC) analysis at the University of North Carolina, Chapel Hill. Warfarin clearance will be determined using non-compartmental analysis. WinNonlin® 3.1 will be used for pharmacokinetic analyses.~• Omeprazole phenotyping assay: Blood samples will be analyzed at the University of North Carolina, Chapel Hill, to determine plasma concentrations of OMP and 5OH OMP. The ratio of OMP and 5OH OMP at 2 hours following the oral dose of omeprazole will be used to describe CYP2C19 activity.~• Dextromethorphan phenotyping assay: Urine aliquots will be analyzed at University of Missouri, Kansas City, to determine urinary concentrations of DM/DX. The dextromethorphan metabolic ratio will be used to describe CYP2D6 activity.~• Midazolam phenotyping assay: Blood samples will be analyzed to determine plasma concentration of midazolam, 1-hydroxymidazolam, and 4-hydroxymidazolam. Analyses will be performed at Oneida Research Services, Inc. using a proprietary LC/MS/MS method. Midazolam clearance will be used to reflect CYP3A activity and clearance will be determined by using non-compartmental analysis of midazolam plasma concentration-time data. WinNonlin® 3.1 will be used for pharmacokinetic analyses.~Statistical Analysis~Sample size: Using =0.05, four treatment phases, and =0.20 (power of 80%), an estimated sample size of sixteen volunteers will detect a 25% difference in metabolism.~Data will be analyzed using the FDA's standard bioequivalency testing.3 If the drug phases fall outside of the 0.8-1.25 range versus the control phase, BE will not be shown.~4) If the research is in part a treatment protocol, identify which parts are routine and which parts are being done solely for research.~This study is for research purposes.

Studies have previously shown that a broad drug interaction screening can be performed using enzyme specific probes such as oral caffeine for CYP1A2, N-acetyltrasferase-2 (NAT-2), and xanthine oxidase (XO), warfarin plus vitamin K for CYP2C9, omeprazole for CYP 2C19, dextromethorphan for CYP2D6, and midazolam for CYP3A4/5. This combination of probes has been validated in the Cooperstown 5+1 Cocktail (5+1).1 The use of the 5+1 cocktail provides information on the drug metabolizing enzymes that metabolize 90% of hepatically eliminated drugs for a fraction of the costs of the individual studies. Using a cocktail of biomarkers reduces the overall cost of drug interaction screening. The purpose of this study is to evaluate the effects of three Food and Drug Administration (FDA) approved oral antibiotics (azithromycin, telithromycin, and levofloxacin) on metabolism of other medications when taken together. This will be determined by the measuring the activity of drug metabolizing enzymes following administration of certain drug probes (caffeine, dextromethorphan, omeprazole, midazolam, and warfarin with vitamin K). A total of 16 subjects will complete four phases of the study: 1) Cooperstown 5+1 alone, 2) Azithromycin plus Cooperstown 5+1, 3) Telithromycin plus Cooperstown 5+1, and 4) Levofloxacin plus Cooperstown 5+1.

Approximately 1.2 million Americans are living with the loss of a limb and the incidence is increasing due to increases in the prevalence of diabetes. Pain, emotional distress, reduced functional abilities are common conditions following limb loss and reduce quality of life. Self-management interventions have been found to be effective in reducing the secondary conditions associated with arthritis and diabetes. Self management uses the principles of cognitive-behavioral therapy including education, self monitoring, problem solving, and skill acquisition.~The goal of the project is to develop and test the efficacy of a community based self management intervention for reducing pain, depression, and improving self efficacy and function in persons with limb loss using a randomized controlled design.~50 groups of 8-10 persons will be randomized to either a control group or a treatment group.

The goal of the project is to develop and test the efficacy of a community-based self-management intervention for reducing pain, depression, and improving self-efficacy and function in person with limb loss

A randomized controlled multi-component fall prevention study for older adults. The study integrates fall prevention into an existing community-based public health program for older adults. The study will evaluate the effectiveness of a fall prevention intervention among 552 seniors attending Preventive Health Care for the Aging (PHCA) clinics in two counties: urban San Diego county and rural Humboldt county. The intervention includes four elements: education about fall risk factors, referrals to community exercise programs to increase strength and balance, medication review, and home modification to reduce home hazards. The goal of the intervention is to reduce incidence of falls requiring hospitalization by 10%. Results of the study, which are expected to be completed by October 2004, will help guide future efforts to develop multifaceted fall prevention programs.

A randomized controlled multi-component fall prevention study for older adults. The study integrates fall prevention into an existing community-based public health program for older adults.

Testing the POWER project: A Neighborhood Intervention Trial PROTOCOL SUMMARY Sheana S. Bull, Ph.D. Principal Investigator Protocol # 02-978~Background The POWER project (Prevention Options for Women Equals Rights) was a social marketing pilot project Targeting African American and Latina women aged 15-25 to promote the mixing of female and male condoms conducted in Denver, Colorado in 2000 and 2001. The results of the project show promise for increasing awareness and use of female condoms and use of male condoms (Bull et al., 2002). Sixty-four percent of the women in the follow-up study were able to identify one or more unique aspects of the POWER campaign. There was a significant increase in awareness and use of female condoms and in use of male condoms from baseline to follow-up. Being exposed to the POWER campaign was significantly correlated with having heard of (r = 0.13) and seen (r = 0.20) the female condom, and with having talked about female condoms more frequently with friends, family and acquaintances (r = 0.15). Chi-square analyses using follow-up study data (n=269) showed that women exposed to the campaign had significantly greater positive outcome expectancies toward female condom use (p<0.10) and talked about female condoms more frequently with more people (p<0.01).~The CDC reports increasing prevalence of Chlamydia among women in Oakland/Alameda County, San Diego, Las Vegas and Los Angeles and increasing rates of gonorrhea in Los Angeles and Las Vegas (Centers for Disease Control and Prevention, 2000, 2002). National data on teen births indicate that while teen births have been declining, the number of births to women aged 20-24 are increasing as are births to unmarried women. With the advent of the female condom as an efficacious female controlled barrier method for STD/HIV and pregnancy prevention in the early 1990's (Bounds, 1997; Farr, Gabelnick, Sturgen, & Dorflinger, 1994; Fontanet et al., 1998; McCabe, Golub S., & Lee, 1997; Soper et al., 1993; Trussell, Sturgen, Strickler, & Dominik, 1994), women at risk for these conditions were given a greater range of choices to control fertility and prevent disease.~Social marketing utilizes marketing and advertising concepts, integrated with social science theory for the development of behavior promotion campaigns targeted to specific subgroups. Such targeting is a key element of the social marketing approach. Social marketing approaches have been shown to be effective for changing blood cholesterol levels (Lefebvre, Lasater, Carleton, & Peterson, 1987), smoking behaviors (Kotler & Roberto, 1989), and women's and children's health (Hornick, 1991; Rasmuson, Seidel, & Smith, 1988).~The intent of this project is to replicate the POWER pilot campaign using a randomized controlled trial with neighborhoods as the unit of randomization and analysis. We plan to rigorously test the effects of the POWER campaign on women's knowledge of, attitudes toward and use of female and male condoms for the prevention of sexually transmitted disease (STD) and unintended pregnancy. We will work in 12 non-contiguous neighborhoods in four southwestern U.S. cities (four each in Oakland/Alameda County and Los Angeles and two each in San Diego and Las Vegas). We will complete a baseline assessment in all 12 neighborhoods to document knowledge of, attitudes toward and use of female and male condoms. We will then randomly assign six neighborhoods to intervention status and six neighborhoods to control status. We will adapt the campaign for each city, and implement it in six intervention neighborhoods for nine months, and will complete a follow-up assessment similar to the baseline assessment, with added questions regarding exposure to the POWER campaign. Study partners include Dr. Sheana Bull and research staff from the Colorado Health Outcomes Program (COHO) of the University of Colorado Health Sciences Center, Educational Message Services (EMS), and Centers for Disease Control and Prevention (CDC).~Methods In order to achieve our objectives, we will utilize a randomized controlled trial, pre-post test design with the neighborhood as the unit of randomization and analysis. To avoid introduction of bias, COHO staff will maintain responsibility for all research and evaluation activities during pre and post test assessment. EMS will implement and maintain the POWER social marketing campaign in six intervention neighborhoods. CDC will serve as technical advisors to the project. COHO will first identify high risk neighborhoods in each study city that have higher than US average rates (as defined by the CDC, 2000) of Chlamydia and Gonorrhea combined with high concentrations of African American and Latina residents aged 15-25. We will then approach contacts in health departments and community organizations in each city and enlist their help in implementing a venue-based method for sampling hard-to-reach populations (more on this process described in the recruiting methods and selection of study population sections below). We will use this method to recruit participants for a cross-sectional, baseline study to document knowledge of, attitudes toward and use of female and male condoms. We will then randomly assign six neighborhoods to intervention status and six neighborhoods to control status. We will adapt the campaign for each city, and implement it in six intervention neighborhoods for nine months, and will complete a follow-up assessment similar to the baseline assessment, with added questions regarding exposure to the POWER campaign.~Recruiting methods Participants will be recruited from the selected study neighborhoods for baseline and follow-up studies using a venue-based application of time-space sampling (Muhib et al., 2001). The method involves first identifying venues, places at which members of the target population may be found, then identifying days and times during which members of the target population are likely to be found at the selected venues. After venue day-time (VDT) units are identified, forming a sampling frame, a random sample of VDTs is selected and eligible members of the target population are systematically sampled within selected VDTs.~Throughout the nine month baseline data collection period we will maintain a sampling frame of VDTs from which to recruit participants. Sampling frames will be updated monthly, with the addition of sporadically occurring VDTs and the removal of VDTs that are no longer viable (have failed to yield sufficient eligible participants or are infeasible due to practical constraints). Each month, after the sampling frame is updated, VDTs will be randomly selected and placed on the sampling event calendar. At the time of each sampling event, trained staff will systematically approach (e.g. every third woman appearing to be 15 years or older) potential participants who enter a predefined sampling area of the venue. Potential participants will be screened to determine eligibility. Members of the target population who meet all of the eligibility criteria and who agree to participate in the study will then complete informed consents prior to enrollment. They will self-administer the study questionnaire, and will be offered an incentive valued at $10 for their time.~This process for venue-based sampling will be repeated for the follow-up data collection process. We will revisit the sampling frame prior to beginning data collection and will remove no longer viable VDTs while adding new VDTs. Subsequent follow-up sampling activities will mirror those conducted at baseline.~Consent procedures Training of staff to explain study process. Participants will self-administer the questionnaire. However, recruitment of participants, explanation of consent process and study protocols, and distribution of incentives will require trained staff. We will have a core recruitment director hired by COHO trained in study protocols and COMIRB 101. Any additional persons hired to assist with data collection will be required to attend an IRB training in their area, and take the IRB 201 test online.~Setting in which consent will be obtained. Consent will be obtained in multiple community settings, e.g. bars, community organizations, community businesses (such as beauty salons, clothing stores, grocery stores), recreation centers. The settings will be selected at random using the procedure described above. Potential participants will be approached and eligibility will be determined by asking potential participants a few short eligibility questions.~Assessment of subject comprehension and autonomy. Staff will ask the participant to explain the study in their own words prior to handing them a questionnaire to complete.~Consent form copies will be made available to the participant. Staff will ask participants to sign two copies of the informed consent. They will offer the participant one copy and will keep one copy. Documentation of the consent process in a medical source document is not applicable for this study, as the study will take place in community rather than medical settings.~Intervention The POWER campaign will be implemented in six neighborhoods chosen at random (see methods section above); two neighborhoods in Oakland/Alameda County, two in Los Angeles and one each in San Diego and Las Vegas. The campaign will last nine months, and will be implemented by EMS. We will have up to 100 display points in 25 sites in each neighborhood. Some settings will be larger than others, and will require many more display points (e.g., 10) while others may be very small and will require fewer display points (e.g., two). Six control neighborhoods (those not chosen at random to be intervention neighborhoods) will be involved in the study. No POWER campaign materials will be placed in these neighborhoods. All study participants at baseline will be asked to complete an assessment to document knowledge of, attitudes toward and use of female and male condoms. All study participants at follow-up will complete an assessment similar to the baseline assessment, with added questions regarding exposure to the POWER campaign. None of these assessments are part of regular clinical care for participants.~Inclusion and exclusion criteria Persons who meet eligibility criteria include women aged 15-25 who speak English. Children recruited for the study include those women aged 15-17. Although women who are pregnant will not be excluded from the research, they are not targeted for recruitment.~We are requesting a waiver of parental permission from COMIRB to include women under age 18 in the study. Per California and Nevada Statutes, minors are allowed to consent for contraceptive services, STD testing and pregnancy testing without parental consent. Detailed justification for this request is included in the full protocol. Minors (15-17 years old-determined at the time of recruitment) will be encouraged to discuss their participation with a parent or guardian prior to enrollment in the study.~Patient accrual We will enroll 300 women in each of the 12 study neighborhoods at the baseline study and 300 women in each of the 12 study neighborhoods at the follow-up study, for a total of 3600 at baseline, 3600 at follow-up and a total of 7200 for the entire study. This number includes the total number of women who will need to sign a consent form in order to reach study end points.~This study will employ the neighborhood as the unit of analysis. Thus, six neighborhoods will be assigned to intervention status. Baseline data will be collected prior to campaign implementation. The POWER campaign will be implemented in these neighborhoods for a nine month period. Follow-up data collection will take place in all 12 study neighborhoods. Thus, individuals per se are not assigned to intervention or control status, rather the neighborhoods where people live will be assigned to intervention or control status.~Estimated duration of the study The baseline data collection will take place over nine months, starting in month six of the project. The campaign will last the subsequent nine months, and the follow-up data collection will take place in the next subsequent nine months, for a total of 27 months.~Persons who enroll in the baseline and/or follow-up studies will spend a total of 20 minutes in completing the consent process, self-administering the questionnaire, and in receiving their incentive.~Study instruments We will ask all participants at baseline to complete a questionnaire to document knowledge of, attitudes toward and use of female and male condoms. Participants in the follow-up study will be asked to complete a questionnaire identical to the baseline assessment, with added questions regarding exposure to the POWER campaign.~Data Safety and Monitoring Plan Analyses for this study will be led by Dr. Sheana Bull, with input from CDC Colleagues Drs. Sam Posner, Lillian Lin and Sherri Varnell. Three analysis strategies will be employed: (a) comparison of neighborhood-level (unadjusted) means, (b) comparison of neighborhood-level adjusted means, and (c) hierarchical modeling.~We anticipate no adverse events associated with participation in this study beyond possible embarrassment and reluctance to answer sensitive questions. That said, any serious and unexpected adverse event will be reported to the IRB immediately. Dr. Sheana Bull will oversee this aspect of the study. The informed consent indicates that should medical care be necessary for any person responding to the questionnaire, we can facilitate access to care by providing referrals. It also indicates that we will not be able to pay for that care. The consent also offers two telephone numbers for persons who wish to obtain more information on the study, referrals or information on their rights as a research subject.~Plans for interim analyses. We regularly monitor recruitment and risk behaviors disclosed by participants on the assessment. Because we will need to continue enrollment up to 7200 persons to determine if the intervention is effective, we do not plan to stop the study prior to achieving this enrollment.~DSMB. Because this is a behavioral study, and offers low risk outside of some embarrassment over answering personal questions, we do not plan to convene a data safety and monitoring board independently of monitoring this work.~Study conduct is monitored each day by Dr. Sheana Bull, who regularly tracks enrollment and recruitment processes. She is responsible for oversight of all protocol implementation for the project. Specific monitoring duties include regular contact with persons recruiting participants to ensure that protocols for recruitment are adhered to.~Procedures for protecting the privacy of subjects and maintaining confidentiality of data. All participants in the study are asked to sign a consent form and a receipt acknowledging they received an incentive for the study. These two forms are the only documents that have any identifiers on them. We will not scan these materials or keep electronic copies of them. We will keep signed consent forms separate from completed questionnaires. Persons collecting data will place signed consent forms and receipts in a separate locked file from completed questionnaires. All questionnaire data will be entered into a computer on the COHO server. This is a COHO dedicated server, with firewall, login and encryption security, none of which are accessible from outside the COHO local area network.~Statistical analyses planned for data include development of a database using ACCESS (Microsoft Corporation, 2002) to store and manage study data, and to import data into SAS (version 8.1) for quantitative analyses. Analyses of data from the baseline and follow-up studies will concentrate on establishing knowledge of, attitudes toward and use of female and male condoms. Analyses of the follow-up study data will also include documentation of exposure to project material, including open-ended questions on the ability to name a relevant feature or message related to the material.~We have planned a nested cross-sectional design with baseline and follow-up observations, implementing a randomized controlled community-level trial with neighborhood as the unit of randomization and analysis. Neighborhoods will be block-randomized within cities to achieve balance between intervention and control conditions on city-level factors. Assuming an intraclass correlation of 0.02 with a sample size of 300 per neighborhood this study will have 80% power to detect a difference in proportions between intervention and control communities of 20% (45% vs. 36%).~Risks-Subjects There are few anticipated risks related to this research. We believe that participants may experience some embarrassment and or psychological discomfort related to the subject content. There are no anticipated physical or legal risks faced by participants.~Investigators/Institutions There are no anticipated risks to investigators and institutions related to this research.~Benefits It is anticipated that any persons enrolled in the study who live in intervention neighborhoods will be exposed to project materials that will contain useful information about how to prevent pregnancy and STD infection. We will make campaign materials available in control neighborhoods after collecting follow-up data, so this information will be available for all study participants. If shown effective, this campaign will be an extremely cost effective way to deliver important information and one that can reach a much larger audience than that typically seen in clinic settings. If the program is shown not to be effective, we will have useful data on the limitations of the POWER campaign for promotion of increased condom use.~Funding All funding for this study is provided by the Association of Teachers of Preventive Medicine through the Centers for Disease Control and Prevention.~Participants in the baseline study will receive $10 for completing a questionnaire. Participants in the follow-up study will receive $10 for completing a questionnaire. These monies will be prorated, and women who partially complete a questionnaire will receive $5.~Special consent issues We seek a waiver of parental consent for those women aged 15-17 participating in the study. Justification for said waiver is included in the section on inclusion and exclusion criteria above.

The intent of this project is to replicate the POWER pilot campaign using a randomized controlled trial with neighborhoods as the unit of randomization and analysis. We plan to rigorously test the effects of the POWER campaign on women's knowledge of, attitudes toward and use of female and male condoms for the prevention of sexually transmitted disease (STD) and unintended pregnancy. We will work in 12 non-contiguous neighborhoods in four southwestern U.S. cities (four each in Oakland/Alameda County and Los Angeles and two each in San Diego and Las Vegas). We will complete a baseline assessment in all 12 neighborhoods to document knowledge of, attitudes toward and use of female and male condoms. We will then randomly assign six neighborhoods to intervention status and six neighborhoods to control status. We will adapt the campaign for each city, and implement it in six intervention neighborhoods for nine months, and will complete a follow-up assessment similar to the baseline assessment, with added questions regarding exposure to the POWER campaign. Study partners include Dr. Sheana Bull and research staff from the Colorado Health Outcomes Program (COHO) of the University of Colorado Health Sciences Center, Educational Message Services (EMS), and Centers for Disease Control and Prevention (CDC).

The dose and pharmacokinetic of an immunosuppressant may differ in different ethnics, and different combinations.~The purpose of this study is to determine the dose-level relationship of sirolimus through pharmacokinetic study. The dose-level relationship of cyclosporine and tacrolimus was also assessed. From clinical outcome and blood level of sirolimus and cyclosporine or tacrolimus, we can design the most appropriate cyclosporine/sirolimus/steroid or tacrolimus/sirolimus/steroid dose regimen for Taiwanese.

The purpose of this study is to understand the pharmacokinetic of sirolimus in different regimens, as well as the dose-level relationship of cyclosporine and tacrolimus, and design the most appropriate cyclosporine/sirolimus/steroid or tacrolimus/sirolimus/steroid dose regimen for Taiwanese.

The controlled clinical trial held in NTUH in 2001 revealed that the bioavailability of tacrolimus when combined with sirolimus is lower than that reported in the literature where tacrolimus was not combined with sirolimus. To determine if the difference was due to the drug interaction between sirolimus and tacrolimus, a controlled clinical trial was proposed.~The purpose of this study is to understand whether the pharmacokinetics of tacrolimus is influenced by the concurrent use of sirolimus.

The purpose of this study is to understand whether the pharmacokinetics of tacrolimus is influenced by the concurrent use of sirolimus.

Sirolimus tablets will be available more than one year after the launch of sirolimus solution. Most patients on sirolimus solution will use sirolimus tablet instead.~The purpose of this study is to understand the pharmacokinetics of sirolimus tablets in different regimens in newly renal transplant patients, and the effect of dosage form conversion on the concentration of sirolimus in stable renal transplant patients. So that we can design a better tacrolimus or cyclosporine/sirolimus/steroid dose regimen for Taiwanese.

The purpose of this study is to understand the pharmacokinetics of sirolimus tablets in different regimens in newly renal transplant patients, and the effect of dosage form conversion on the concentration of sirolimus in stable renal transplant patients. So that we can design a better tacrolimus or cyclosporine/sirolimus/steroid dose regimen for Taiwanese.

All images in this study were acquired on a 1.5 T Sonata whole body scanner (Siemens Medical Inc., Erlangen, Germany) using 2D multi-echo gradient echo/spin echo sequence and 2D single-shot gradient echo-planar imaging sequence plus intravenous magnetic susceptibility contrast medium. The quantitative estimates and mapping of cerebral metabolic rate of oxygen utilization were calculated and plotted in all subjects.

All images in this study were acquired on a 1.5 T Sonata whole body scanner (Siemens Medical Inc., Erlangen, Germany) using 2D multi-echo gradient echo/spin echo sequence and 2D single-shot gradient echo-planar imaging sequence plus intravenous magnetic susceptibility contrast medium. The quantitative estimates and mapping of cerebral metabolic rate of oxygen utilization were calculated and plotted in all subjects.

Volunteers with normal and subnormal semen parameters receive a hormonal male contraceptive in order to investigate whether there are differences between normal and subnormal men in terms of suppressibility, rate of azoospermia and reversibility of suppression of spermatogenesis. Twenty-five men will be recruited for each group. They will be exposed to hormonal male contraception for six months.

Volunteers with normal and subnormal semen parameters receive a hormonal male contraceptive in order to investigate whether there are differences between normal and subnormal men in terms of suppressibility, rate of azoospermia and reversibility of suppression of spermatogenesis.

Successful rehabilitation for the majority of lower extremity amputees includes prosthetic limb fitting and training. Critical to the success of prosthetic fitting is a comfortable, well fitting socket. Accomplishing this remains a clinical challenge with residual limb pain and socket discomfort affecting 20-55% of lower limb amputees. Achieving an acceptable socket fit using conventional prosthetic techniques requires individual custom molding and fabrication in a labor intensive, costly process. Alternative methods of fabricating prosthetic sockets that can improve efficiency in prosthetic provision, enhance comfort and fit, or reduce cost are needed to ensure the continued optimal rehabilitation of the amputee. This project will continue the development of a new promising method of socket fabrication using solid freeform fabrication (SFF) based on selective laser sintering (SLS) technology. SFF allows the direct manufacture of a prosthetic socket without the intermediate molds and laminating process required with conventional techniques.~The overall long-term goal of this project is the development of a clinically practical system for rapid prosthetic limb provision that integrates computer-aided design with solid freeform fabrication techniques. This proposal builds on our previous successful demonstration of the feasibility of SFF socket fabrication and will address several key issues that underlie its clinical viability. The specific objectives of the proposed work are:~To develop improved designs for SFF transtibial prosthetic sockets that allow the use of industry standard pylon mounts and incorporate variable compliance elements.~Determine the clinical effectiveness of variable wall compliance elements in enhancing the comfort and fit of transtibial prosthetic sockets.~Determine the durability and functionality of SFF sockets during extended clinical use.~These objectives will be met over a three-year period. The initial phase of the proposed work will use an iterative engineering design - modeling - evaluation process to develop variable compliance elements and an industry standard pylon mount adapter. During the second phase of the proposed work, clinical evaluations of SFF prosthetic sockets will be studied. The effectiveness of variable compliant elements in enhancing comfort and fit will be determined using a within subject case comparison study of SFF sockets with conventional laminated sockets. Durability of SFF sockets that incorporate an industry standard pylon mounting system will be determined during a 12-month clinical field trial.

The overall long-term goal of this project is the development of a clinically practical system for rapid prosthetic limb provision that integrates computer-aided design with solid freeform fabrication techniques. This proposal builds on our previous successful demonstration of the feasibility of SFF socket fabrication and will address several key issues that underlie its clinical viability. The specific objectives of the proposed work are:~To develop improved designs for SFF transtibial prosthetic sockets that allow the use of industry standard pylon mounts and incorporate variable compliance elements.~Determine the clinical effectiveness of variable wall compliance elements in enhancing the comfort and fit of transtibial prosthetic sockets.~Determine the durability and functionality of SFF sockets during extended clinical use.~These objectives will be met over a three-year period. The initial phase of the proposed work will use an iterative engineering design - modeling - evaluation process to develop variable compliance elements and an industry standard pylon mount adapter. During the second phase of the proposed work, clinical evaluations of SFF prosthetic sockets will be studied. The effectiveness of variable compliant elements in enhancing comfort and fit will be determined using a within subject case comparison study of SFF sockets with conventional laminated sockets. Durability of SFF sockets that incorporate an industry standard pylon mounting system will be determined during a 12-month clinical field trial.

Vitamin A supplementation (VAS) acts as an adjuvant to vaccines, and VAS has been shown to enhance both cellular and humoral immune responses in animals and in humans. Routine childhood vaccinations have recently been shown to have important non-targeted effects on mortality, i.e. effects that cannot be explained merely by the prevention of the targeted disease. We have hypothesized that the improved survival after VAS may depend not only on the prevention of vitamin A deficiency, but also on vitamin A amplifying the non-specific immune modulation induced by routine vaccinations.~In the present study we used information collected in connection with a national vitamin A campaign in Guinea-Bissau during which different doses of VAS was provided together with missing doses of DTP, OPV, and measles vaccines. We aimed to study the potential interactions between VAS and vaccine type.

Vitamin A supplementation (VAS) is important for the immune system and may interact with different childhood vaccinations. We have hypothesized that the improved survival after VAS may depend on vitamin A amplifying the non-specific immune modulation induced by vaccinations.~In the present study we used information collected in connection with a national vitamin A campaign in Guinea-Bissau during which different doses of VAS was provided together with missing doses of DTP, OPV, and measles vaccines. We aimed to study the potential interactions between VAS and vaccine type.

In Guinea-Bissau, a combined OPV and VAS campaign took place in November 2002. Given the uncertainty about the best dose of VAS, we examined whether the half dose compared with the full dose currently recommended by WHO gave an equally good protection against childhood morbidity and mortality. Mortality after supplementation was lower, though not significantly so, for children who had received the half dose. However, there was a highly significant inversion of the effect for boys and girls; while the low dose was clearly better for girls, the full dose might have been slightly better for boys. The girls' responses to the high versus the low dose of vitamin A might have depended on the last vaccine received before the OPV and VAS campaign.~We believe that these findings call for confirmation. In connection with the OPV and VAS campaign in November 2004 in Guinea-Bissau, we intend to examined whether half the dose of the dose currently recommended by WHO as compared to the full dose has a more beneficial effect on mortality and morbidity in girls, and furthermore address the potential effect modification by the last vaccine received before the supplementation.

We previously compared the effect on mortality of the half dose and the full dose currently recommended by WHO. Unexpectedly, the low dose was clearly better for girls, but not for boys. The girls' response might have depended on the last vaccine received before the OPV and VAS campaign. We believe that these findings call for confirmation. In connection with a new campaign, we will examine whether half the dose or the full dose has a more beneficial effect on mortality and morbidity in girls, and furthermore address the potential effect modification by the last vaccine received before the supplementation.

Vitamin A given as treatment and pre-treatment has reduced the severity of symptoms after infusion with endotoxin in several animal models. We intend to examine the effect of vitamin A as pre-treatment on the response to endotoxin in humans. As studies in children in low-income countries have indicated that vitamin A has long-term effects on the immune system, we furthermore wish to examine the long-term effects of vitamin A on the response to endotoxin. This will be done in an established model using infusion with endotoxin to male human volunteers. We hypothesise that vitamin A decreases endotoxin levels and TNF-alfa responses. Furthermore, we hypothesise that it reduces oxidative stress and injury.

Vitamin A given as treatment and pre-treatment has reduced the severity of symptoms after infusion with endotoxin in several animal models. We intend to examine the effect of vitamin A as pre-treatment on the response to endotoxin in humans. We furthermore wish to examine the long-term effects of vitamin A on the response to endotoxin. We hypothesise that vitamin A decreases endotoxin levels and TNF-alfa responses.

The purpose of this study is to determine if there is a perceived benefit from adding a restorative yoga class as a method of stress reduction for the HFA Addiction Medicine Clinic staff. Working in a busy clinic can be very stressful. While it is not always possible to completely eliminate stress from our lives, it is known that stress reduction techniques help to diminish the negative consequences of stress. This study was designed to answer the following question How much change in perceived stress is obtained through weekly Restorative Yoga sessions? Study population were members of the HFA Addiction Medicine Clinic. All staff completed the Spielberger Job Stress Survey and the State-Trait Anxiety Inventory at baseline and at six months following intervention onset. Volunteers from the Addiction Medicine Clinic attended weekly restorative yoga sessions 45 minutes in length held over the noon hour. Serial State-Trait Anxiety Inventory and weekly questionnaire regarding the perceived effects of the restorative yoga on aspects fo patient care were completed by study volunteers.

The study examined Restorative Yoga as a method of stress reduction for the HFA Addiction Medicine Clinic staff volunteers.

Streptococcus pyogenes (GrAS) is a human pathogen that leads to great disease burden throughout the world. In the United States, an estimated 30 million infections occur yearly. Most of these are local infections of the skin or the throat but still lead to considerable use of health-care resources. These common, simple forms of GrAS disease may progress to or be followed by the more serious GrAS-related illnesses acute rheumatic fever, post-streptococcal glomerulonephritis, streptococcal toxic shock syndrome, sepsis, pneumonia, or other invasive illnesses. Outside the U.S., in the developing world, the burden of GrAS-related disease is presumed to be even higher, but is not completely elucidated in many of the poorer regions of the world. It is known, though, that rheumatic heart disease causes more cardiovascular morbidity in the children of the world than any other illness. Although the incidence of rheumatic fever in the U.S. has fallen to levels of approximately 0.5 per 100,000 per year, in some areas, the developing world's children still have rates over 100 per 100,000 per year. The percentage of cardiac admissions attributable to rheumatic heart disease in hospitals located in the developing world remains in the range of 30 to 50%, where it has been studied. GrAS is one of the best characterized human pathogens with regards to its microbiology, its spectrum of diseases, and its ability to lead to serious sequelae such as rheumatic fever and glomerulonephritis. Yet, efforts to control it through the use of antibiotics have been only partially successful in the United States and largely unsuccessful in the developing world. The health impact of uncomplicated streptococcal infections, such as pharyngitis, and the less common but more severe diseases, such as rheumatic heart disease, must be better studied in order to move forward with control measures. In this study, patients aged 3-15 presenting with sore throat, fever and cervical lymphadenopathy will be examined and a throat swab will be submitted to the lab for culture. All of these patients will be treated with either benzathine penicillin or, if they have a history of allergy to penicillin, oral erythromycin. The parent will be given a follow-up appointment to convey the result of the culture and to evaluate the course of the child's illness. Children presenting with sore throat only will be cultured and given a follow-up appointment to return after the result of the culture is known. Antibiotic treatment is given only if the culture is positive for group A streptococci. Within this algorithm is latitude for the physician to treat any patient based on clinical signs and symptoms and the concern that a particular child may not return for treatment if it is delayed based on the culture result. The overriding goal is the prevention of acute rheumatic fever and suppurative complications. The primary objective of this study is to characterize the GrAS isolates genotypically (emm type or sub-type). The secondary objective is to describe the epidemiology of throat isolates of GrAS among 3- to 15- year old children with pharyngitis living in Leon, Nicaragua. Primary endpoint of the study is the frequency and proportion of each emm-type among children with pharyngitis. Secondary Endpoints for the study are as follows: The proportion of children with pharyngitis from whom GrAS is isolated. The minimal incidence of GrAS pharyngitis in children based on annual cases per 100,000 children in the catchment areas. The age, gender, and ethnicity-specific minimal incidence rates of GrAS pharyngitis in children living in the catchment areas.

The purpose of this study is to determine the epidemiology of throat isolates of group A streptococci among 3-15 year-old children with pharyngitis (sore throat) living in Leon, Nicaragua.

A prospective, controlled, randomized, study evaluating the clinical efficacy, including nutritional status, immune function and safety of Omegaven (ω-3 fish oil) supplemented parenteral nutrition in subjects of SICU.~Study patients are the critical ill patients in SICU of NTUH and the enrolled patients will be 30 subjects ,including 15 in each treatment group.~During parenteral nutrition, fat emulsions will be given separately from amino acid and glucose solutions. Infusion pump must be used.The recommended infusion duration of the daily lipid emulsion is 16 hours (0.0625 g fat/kg B.W./hour) from 8:00 am to 12:00 pm.~During the study the assessments of safety and efficacy are to be performed according to case report form. The assessment for safety variables including blood pressure、heat rate 、body temperature、liver function、renal function、coagulation、WBC、lipid profile etc. In addition，the assessments for efficacy variables including lymphocytes、cytokines(IL-1、IL-2、IL-6、IL-8、IL-11、IL-18、OX40 ligand、G-CSF、FN-γ、TGF-β1、TNF-α etc)、incidence of infections、 length of ICU and hospital stay、mortality etc.

A prospective, controlled, randomized, study evaluating the clinical efficacy, including nutritional status, immune function and safety of Omegaven (ω-3 fish oil) supplemented parenteral nutrition in subjects of SICU.~Study patients are the critical ill patients in SICU of NTUH and the enrolled patients will be 30 subjects ,including 15 in each treatment group.~During parenteral nutrition, fat emulsions will be given separately from amino acid and glucose solutions. Infusion pump must be used.The recommended infusion duration of the daily lipid emulsion is 16 hours (0.0625 g fat/kg B.W./hour) from 8:00 am to 12:00 pm.~During the study the assessments of safety and efficacy are to be performed according to case report form. The assessment for safety variables including blood pressure、heat rate 、body temperature、liver function、renal function、coagulation、WBC、lipid profile etc. In addition，the assessments for efficacy variables including lymphocytes、cytokines(IL-1、IL-2、IL-6、IL-8、IL-11、IL-18、OX40 ligand、G-CSF、FN-γ、TGF-β1、TNF-α etc)、incidence of infections、 length of ICU and hospital stay、mortality etc.

Tai Chi, a traditional Chinese martial art that has been practiced for many centuries, has only recently gained the interest of researchers in Western countries as an alternative form of exercise. Tai Chi combines deep diaphragmatic breathing and relaxation with many fundamental postures that flow imperceptibly and smoothly from one to the other through slow, gentle, and graceful movements. Based on the maximum oxygen consumption (VO2max) measured during the practice, Tai Chi is characterized as a low- to moderate-intensity form of exercise. Tai Chi has been applied as a rehabilitation program in patients with heart failure, hypertension, acute myocardial infarction, arthritis, and multiple sclerosis. Improvements in cardiorespiratory function, balance, muscular strength, flexibility in older subjects; preventing falls in the frail elderly; stress reduction, and mood state with Tai Chi practices have been well established. A potential immune response effect of Tai Chi practice is a frequent claim; however, this is an under-researched area. A nonrandomized controlled study of 60 elderly subjects found that the total number of circulating T cells were significantly higher in the Tai Chi group (who regularly practiced Tai Chi for 4 or more years) than in the untrained group. Irwin et al. demonstrated that older adults with no previous Tai Chi experience after practicing for 15 wks (1-3 times/wk), a nearly 50% increase in varicella zoster virus specific, cell-mediated immunity was found. Thus in this proposed study, we will examine the effects of regular Tai Chi practitioners on innate and adaptive immune function.

Tai Chi is a traditional Chinese martial art that has been practiced for many centuries. Improvements in cardiorespiratory function, balance, muscular strength, flexibility in older subjects; preventing falls in the frail elderly; stress reduction, and mood state with Tai Chi practices have been well established. A potential immune response effect of Tai Chi practice is a frequent claim; however, this is an under-researched area. Therefore, in this study, the researchers will examine the effects of Tai Chi on innate and adaptive immune function.

In a randomised, double-blind, placebo-controlled, cross-over study in healthy men we will assess the effect of oral fluvoxamine (50mg qd on day 1-3; 100mg qd on day 4-10) on sildenafil kinetics (single oral 50mg dose on day 11). Sildenafil plasma concentrations will be determined by LC/MS. We will also assess the effect of sildenafil on venodilation induced by a constant dose-rate of the NO-donor sodium nitroprusside (SNP) during preconstriction with phenylephrine (dorsal hand vein compliance technique).

Aim of the study is to assess the interaction between sildenafil and fluvoxamine and its effect on the venous response to sodium nitroprusside.

The purpose of this study is to assess if capnography can be utilized in the process of endotracheal intubation; specifically, in locating the glottic opening. Ultimately this would result in a new use of capnography to aid in securing normal and difficult airways. Currently capnography is only utilized for the confirmation of endotracheal tube placement.~If successful, this study will provide information, and allow for the development of instrumentation that will assist in difficult airway management; specifically, in locating the glottic opening when visualization may be impaired. Ultimately this technique will be useful for routine and emergency airway management.

The purpose of this study is to assess if capnography can be utilized to assist in the process of endotracheal intubation; specifically, in locating the glottic opening. Ultimately this would result in a new use of capnography to aid in securing normal and difficult airways. Currently capnography is only utilized for the confirmation of endotracheal tube placement.~If successful, this study will provide information, and allow for the development of instrumentation that will assist in difficult airway management; specifically, in locating the glottic opening when visualization may be impaired. Ultimately, this technique will be useful for routine and emergency airway management.

This is a phase II study that will investigate weekly dosing of docetaxel in combination with capecitabine in advanced gastric and gastro-esophageal adenocarcinomas. Docetaxel 30mg/m2 will be administered on days 1 and 8 of each cycle and capecitabine 825mg/m2 bid (total daily dose 1650mg/m2) will be administered orally for 14 days (days 1-14) of each cycle. Each cycle is 21 days. Subjects will receive unlimited cycles of docetaxel and capecitabine until there is evidence of disease progression or unacceptable side effects.

This is a phase II study that will investigate weekly dosing of docetaxel in combination with capecitabine in advanced gastric and gastro-esophageal adenocarcinomas.

The purpose of this study is to measure the amount of MMF and tacrolimus concentration in the blood at a given time. Currently MMF is ordered as a set dose and tacrolimus is given based on body weight. While the deceased donor transplant receives the complete liver, in the live donor just over half of the liver is given (about 60%). The way these different types of transplants break down drugs could be different. Measuring the drug levels allows us to know what happens to the medication in between the morning and the evening dose.~12 subjects with live liver donors and 12 subjects with deceased donors will be included in the study.~Each patient will have 12 (twelve) blood samples (half a teaspoon) drawn at 0,1, 2, 3, 4, 4½; 5, 6, 7, 8, 10 and 12 hours from an intravenous line placed during the operation. At the same time, 24-hour urine will be collected to measure your kidney function. After 4 to 6 days post transplant when the will be switched to oral MMF, again 10 (ten) blood samples a half teaspoon each will be drawn at 0, 1, 2, 3, 4, 5, 6, 8, 10, 12 hours. Blood will be drawn with the routine daily blood work for the first 14 days and then at 1 and 3 months after transplant. Total blood drawn over 3 months will be about 7 tablespoons. A 24-hour urine will be collected in a container given to you starting one day before the routine clinic visit (as a standard of care). The 24-hour urine will be collected at 1 and 3 months after transplant as well.~If a woman, who could become pregnant, a pregnancy test will be done before your transplant. They would also have to use birth control during the study period and 6 months after the completion of study.

The purpose of this study is to measure the amount of MMF and tacrolimus concentration in the blood at a given time. Currently MMF is ordered as a set dose and tacrolimus is given based on body weight. While the deceased donor transplant receives the complete liver, in the live donor just over half of the liver is given (about 60%). The way these different types of transplants break down drugs could be different. Measuring the drug levels allows us to know what happens to the medication in between the morning and the evening dose.

Despite improvements made to the traditional laryngoscope blade since its invention, occasionally intubation of the trachea cannot be accomplished with facility, even in patients with anatomy that does not predict difficult intubation. It is estimated that endotracheal intubation is performed on some 8 million patients per year in the United States. Of these endotracheal intubations, approximately 80% are performed by direct laryngoscopy with transoral placement of the endotracheal tube (ET) into the trachea. There is fairly uniform reporting of the incidence of failed intubation in the literature; it occurs in approximately 0.05% or 1:2230 of surgical patients and in approximately 0.13% to 0.35%, or 1:750 to 1:280, of the obstetric patients. The incidence of unsuspected difficult intubation is estimated to be higher at 3%. One factor that contributes to difficult intubation is poor visualization.~The VL is designed to optimize visualization by presenting to the operator an enlarged video image of airway structures. In contrast, using conventional laryngoscopy, anesthesiologists have only a keyhole view of the airway structures; a view that may be further obscured during attempts to pass the ET.~The VL consists of a laryngoscope handle and Macintosh blade that have been modified to provide a video image of airway structures on a screen, which can be conveniently located directly in front of the anesthesiologist. A micro video module is contained in the modified handle. An image/light bundle is introduced into the standard blade. This system has been previously tested in which the consensus was that the device is extremely easy to learn to use because most anesthesiologists are familiar with the use of the Macintosh blade. It has also been useful in the instruction of laryngoscopy by non-anesthesiologists.~There are several potential advantages of a video image in the context of direct laryngoscopy. The system provides high quality video images that are enlarged on the video monitor for easier visualization. If laryngeal manipulation is required to improve visualization of laryngeal structures, the intubator and the person assisting can coordinate movements as they observe, simultaneously, the image on the video monitor. With the video image projected from the distal end of the laryngoscope blade, laryngeal structures are kept in view as the ET is passed through the oropharynx into the trachea.~Comparison: Video Laryngoscope as a conduit for possible difficult intubation compared to the traditional Macintosh blade.

The purpose of this study is to determine if the Video Laryngoscope (VL) is a useful instrument in patients at risk for difficult intubation. We will compare this device to the traditional Macintosh Laryngoscope.

Intercessory prayer is widely believed to influence recovery from illness, but claims of benefits are not supported by well-controlled clinical trials. Prior studies have not addressed whether prayer itself or knowledge/certainty that prayer is being provided may influence outcome. We evaluated whether (1) receiving intercessory prayer or (2) being certain of receiving intercessory prayer was associated with uncomplicated recovery after coronary artery bypass graft (CABG) surgery.

Intercessory prayer is widely believed to influence recovery from illness, but claims of benefits are not supported by well-controlled clinical trials. Prior studies have not addressed whether prayer itself or knowledge/certainty that prayer is being provided may influence outcome. We evaluated whether (1) receiving intercessory prayer or (2) being certain of receiving intercessory prayer was associated with uncomplicated recovery after coronary artery bypass graft (CABG) surgery.

Stress contributes to health and behavioral issues in students, but will not be integrated into schools without evidence of benefit. This study was conducted to determine if a 6-week relaxation response (RR) curriculum improves cognitive performance in ninth grade students.

Stress contributes to health and behavioral issues in students, but will not be integrated into schools without evidence of benefit. This study was conducted to determine if a 6-week relaxation response (RR) curriculum improves cognitive performance in ninth grade students.

Hot flashes occur in 75% of menopausal women and impact quality of life. Interest has arisen in isoflavones, found in rich supply in soy products, as therapy for hot flashes. The effect of a daidzein-rich isoflavone-aglycone supplement from soy germ fermentation with Koji fungus, on the severity and frequency of hot flashes in postmenopausal women is being examined in a randomized, placebo controlled, double-blinded clinical trial. The study is a 13 week trial in which subjects record their hot flash frequency and severity in a diary. Subjects are given 40 mg or 60 mg of isoflavones (or placebo) once a day. This isoflavone-aglycone extract (Agly-Max TM, Nichimo, Shinagawa, Tokyo, Japan) is a product prepared from soybean germ fermentation with Koji fungus (Aspergliius awamori) producing ß-glycosidase efficiency, followed by ethanol and water extraction and purification by using a proprietary extraction procedure. The product is rich in daidzein (70% daidzein, 10% genistein, and 20% glycitein).

Hot flashes occur in three quarters of menopausal women, and can negatively impact quality of life. Interest has arisen in isoflavones, found in rich supply in soy products, as therapy for hot flashes. The study examines the effect of a new soy supplement, as compared to a placebo, in menopausal women on hot flash symptoms.

The purposes of this study are:~To examine molecular and biochemical changes, associated with the relaxation response (RR) that can counteract the effects of stress in healthy adults.~To compare genomic, molecular and biochemical parameters between healthy adults with a long term meditative practice and those with no experience in meditation.~Since stress is a factor in the development of many health conditions, a further understanding of the mechanisms of the RR should be developed. The project is designed to determine how the RR can improve the quality of life that has been adversely affected by stress.

The purposes of this study are:~To examine molecular and biochemical changes, associated with the relaxation response (RR) that can counteract the effects of stress in healthy adults.~To compare genomic, molecular and biochemical parameters between healthy adults with a long term meditative practice and those with no experience in meditation.~Since stress is a factor in the development of many health conditions, a further understanding of the mechanisms of the RR should be developed. The project is designed to determine how the RR can improve the quality of life that has been adversely affected by stress.

Therapies that have brought about sharp decreases in neonatal mortality have not brought about similar decreases in neurodevelopmental morbidity for preterm infants. Developmentally supportive care is NICU care that seeks to optimize the developmental course and outcomes for preterm infants. While other staff training programs for developmentally supportive care exist, it is the Newborn Developmental Care and Assessment Program (NIDCAP) that has been the methodology used in randomly controlled trials that demonstrate positive medical and neurobehavioral outcomes for preterm infants receiving developmentally supportive care. NICUs that care for all out-born or transported infants face unique challenges in balancing developmentally supportive nursing care with the high-technological medical needs of the most critically ill and extremely premature infants. Yet it is these most fragile infants who can most benefit from the positive impact the NIDCAP program can offer. Yet, there are no published studies documenting the impact of the NIDCAP program on neurobehavioral outcomes of these transported preterm infants exclusively.~Objectives: The objective of this project is to study the impact of implementing the NIDCAP program of individualized patient consultation on the neurobehavioral organization of transported preterm infants in the NICU of a major pediatric medical center.~Research Methods: A random sample of approximately 40 preterm infants will be recruited to participate in this descriptive study. In this phase-lag design, 20 infants will participate in the pre-NIDCAP intervention phase and 20 infants will participate in the post-NIDCAP intervention phase. Each infant within each phase will be videotaped during 2 routine nurse-caregiving sessions. The first session will occur within 72 hours of admission to the NICU at Children's Memorial Hospital (CMH). The second session will occur when the infant is 34-36 weeks corrected gestational age. The videotapes will be collected so that observations of the infant's physical environment and caregiving and an assessment of the infant's behavioral function can be scored randomly at the end of the study by an outside consultant without bias as to what phase the infant participated. In addition, demographic data will be collected on the sample infants. Data will be subjected to descriptive statistics, inferential statistics and correlational procedures.

The purpose of this study is to evaluate the impact of the NIDCAP program of individualized patient consultation on the neurobehavioral organization of transported preterm infants in the NICU. Behavioral response to routine caregiving will be compared between infants in the pre-NIDCAP group to infants in the post-NIDCAP group. And it is this behavioral response that will be used to evaluate the effectiveness of the NIDCAP program.

Main Research Question: Does community-based specialist oncology nursing case management improve continuity of cancer care and lead to fewer unmet cancer patient needs?~Why this research is important: This research proposal addresses the issue of gaps in continuity of supportive care for cancer patients during the early phases of the disease trajectory that result in unmet needs and unnecessary morbidity, prior to entry into a formalized cancer care system (e.g., a regional cancer centre or hospital with a cancer treatment program). This initial diagnostic period of cancer is associated with significant stress, anxiety and uncertainty that can impact upon overall quality of life for all types of cancer. These problems are further exacerbated by waiting times of up to 16 weeks between diagnosis and attendance in a formalized cancer treatment system. During this time patients will face a fragmented supportive care service system resulting in a substantial number of patients reporting unmet needs and distress. These care gaps have significant implications considering that 38% of women and 41% of men will develop cancer during their lifetime and that cancer incidence continues to rise with an estimated 139,000 new cases in Canada (over 54,000 of these in Ontario) in 2003. There has been growing interest in nursing models to address these gaps in supportive cancer care but at this time there is not sufficient high quality evidence upon which to base policy decisions to support the widespread introduction of this type of model. The results of this study will be very important for policy development for community cancer care in Ontario and in other provinces in Canada.~What is being studied: We will study the impact of a specialized nursing intervention (Interlink) on patient outcomes early in the disease trajectory. Impact will be assessed directly using validated measures in a randomized controlled trial design. These measures will include: continuity of care, unmet needs, psychological distress, uncertainty in illness, and quality of life.

This research project will address the issue of gaps in continuity of supportive care for cancer patients during the early phases of the disease trajectory that result in unmet needs and unnecessary morbidity. The investigators intend to study the impact of a specialized cancer-nursing program, Interlink Community Cancer Nurses (Interlink) on patient outcomes. Impact will be assessed directly using a validated measure of continuity of care from the patients' perspective and validated measures of key supportive care patient outcomes including unmet needs, distress, uncertainty in illness, and quality of life, in a randomized trial.

Many women are turning to the Internet to meet their health information needs, but the large amount of information available, as well as the unknown reliability and applicability of information can be overwhelming. Studies in specific patient populations have determined that patients given access to personalized, on-line medical information are more satisfied with their care than patients provided generalized information. None of these studies have looked at whether this type of patient education would be helpful for pregnant women. This study is being done to determine whether pregnant women who have access to their own health records and personalized health information over the Internet are more satisfied with their prenatal care, and if they are more compliant with health visits and tests, compared to pregnant women who receive only generic pregnancy information on the Internet and from pamphlets~Women are being randomly assigned to receive secure access to pregnancy health information links chosen by the centre's physicians, or to receive these links with access to their online personal health that includes the antenatal record and a section of their care planner, from the centre's electronic medical record

Many women are turning to the Internet to meet their health information needs, but the large amount of information available, as well as the unknown reliability and applicability of information can be overwhelming. Studies in specific patient populations have determined that patients given access to personalized, on-line medical information are more satisfied with their care than patients provided generalized information. None of these studies have looked at whether this type of patient education would be helpful for pregnant women. This study is being done to determine whether pregnant women who have access to their own health records and personalized health information over the Internet are more satisfied with their prenatal care, and if they are more compliant with health visits and tests, compared to pregnant women who receive only generic pregnancy information on the Internet and from pamphlets

Adolescents and young adults who use drugs are at high risk for infection with HIV, STDs and other diseases with similar transmission dynamics. Although several age-appropriate and effective HIV, STD and disease prevention efforts have been identified for young substance abusers, most interventions have been narrow in focus and are generally not structured to readily address changing patterns of drug use among adolescents that place them at risk for infection with these diseases. In this study, we are developing and evaluating an interactive, computer-assisted HIV, STD and disease prevention program for young substance abusers that incorporates effective components of both prevention science and educational technologies. We plan to develop this program with the input from the target population of adolescents and young adults. We also plan to conduct a randomized, controlled trial to evaluate the benefit of including this program in HIV and disease prevention efforts with youth in substance abuse treatment. In so doing, we will evaluate the ability of the program to promote accurate knowledge about HIV and other diseases, promote self-efficacy to reduce risk behavior and change actual rates of risk behavior among young substance abusers. This computer-based program will be designed to promote the increased adoption of effective HIV and disease prevention science for this population. New information about changing patterns of drug use and HIV risk behaviors can be readily incorporated into the program as it becomes available. The program can be easily exported and able to be applied with fidelity. Importantly, the program will be structured such that a therapist or educator may customize the program content for use by various sub-populations of substance-abusing adolescents and young adults. Thus, the program will be able to address risk factors specific to each young drug user. This program may address many of the challenges associated with the current delivery of evidence-based HIV prevention programs to this population.

In this study, the investigators are developing and evaluating an interactive, computer-assisted HIV, STD and disease prevention program for young substance abusers that incorporates effective components of both prevention science and educational technologies.

The need to obtain human tissue for methods development and disease correlation is frequent in Biomedical Research Center laboratories. This protocol is designed to create the opportunity to obtain such tissue samples including: blood, urine, saliva, sweat, feces, hair and nail clippings, nasal scraping, muscle, fat, skin and taste buds. It may also include samples taken during a surgical procedure, including: fluid from around the spinal column, heart, lungs and abdomen; fat, muscle, connective tissue and organs (liver, bladder, heart, kidney and skin).~Information derived from such studies is for research purposes only and is not provided to the participants or their health care provider. Samples will be coded (no names) and identifying information linking the participant to the sample will be maintained in a secure location by the P.I. and Study Coordinator.~Participants will be 18 years or older and have been identified by the investigator and/or physician to have a condition of interest for exploratory studies related to the participant s illness or other feature that offers the possibility of creating information that leads to scientifically useful and important studies. Participants could also be healthy volunteers, willing to provide their samples. These samples could be requested by an investigator to be used as age, gender, race and/or ethnicity-matched controls or to calibrate or compare and contrast across lab equipment. Participants will be excluded if obtaining the sample would be over and above usual clinical care, would result in excessive blood loss, or the individual is unable to provide informed consent.~The expected outcome is to provide investigators with the opportunity to obtain tissues of interest for laboratory evaluation.

The need to obtain human tissue for methods development and disease correlation is frequent in Biomedical Research Center laboratories. This protocol is designed to create the opportunity to obtain such tissue samples including: blood, urine, saliva, sweat, feces, hair and nail clippings, nasal scraping, muscle, fat, skin and taste buds. It may also include samples taken during a surgical procedure, including: fluid from around the spinal column, heart, lungs and abdomen; fat, muscle, connective tissue and organs (liver, bladder, heart, kidney and skin).~Information derived from such studies is for research purposes only and is not provided to the participants or their health care provider. Samples will be coded (no names) and identifying information linking the participant to the sample will be maintained in a secure location by the P.I. and Study Coordinator.~Participants will be 18 years or older and have been identified by the investigator and/or physician to have a condition of interest for exploratory studies related to the participant s illness or other feature that offers the possibility of creating information that leads to scientifically useful and important studies. Participants could also be healthy volunteers, willing to provide their samples. These samples could be requested by an investigator to be used as age, gender, race and/or ethnicity-matched controls or to calibrate or compare and contrast across lab equipment. Participants will be excluded if obtaining the sample would be over and above usual clinical care, would result in excessive blood loss, or the individual is unable to provide informed consent.~The expected outcome is to provide investigators with the opportunity to obtain tissues of interest for laboratory evaluation.

Regular physical activity contributes to the health and quality of life of older adults, but unfortunately only 20% of men and 25% of women aged 65 years and greater meet the minimal national guidelines for physical activity. Older Latinos have higher rates of diseases that are most likely to benefit from physical activity, but have disproportionately high rates of sedentary lifestyle. To address this major public health problem, this study will implement and evaluate a multifaceted intervention to raise and sustain walking levels among older Latinos.~A total of 600 sedentary older Latinos will be recruited from community-based senior centers in the greater Los Angeles region. The specific aims of the study are to test the effect of the intervention on:~the change in steps per week measured by digital pedometer from baseline to 1, 12, and 24-month follow-up;~self-reported physical activity level and intervening constructs (including expectations regarding aging and self-efficacy expectations for physical activity);~psychosocial health constructs, physical performance measures, and clinical health outcomes.~The core of the intervention consists of a series of 4 weekly 1-hour group discussion sessions that utilize attribution retraining techniques from the field of motivational psychology in combination with behavioral strategies based in social cognitive theory. Discussion sessions will be conducted at senior centers and led by a bilingual health educator; each session will be followed by a 1-hour exercise class aimed at increasing strength, flexibility and endurance. During the discussion sessions, the health educator will administer a structured culturally-tailored curriculum in which participants are taught to raise their expectations for physical activity with aging and not to attribute being sedentary to old age. The 4 weekly sessions will be followed by monthly sessions for 11 months, and sessions every 2 months for the following 12 months (total intervention duration = 24 months). Participants will be randomized to 1 of 2 arms:~intervention arm: receiving the discussion session and the exercise class;~control arm: receiving just the exercise class with the same frequency and duration as the intervention group.

The purpose of this study is to examine the efficacy of a multifaceted behavioral intervention aimed at raising walking levels among sedentary older Latinos.

This study is designed to provide bone marrow cells for other research studies. The research is being done because there are ongoing experiments in a number of National Institute on Aging (NIA) laboratories that require access to normal human bone marrow aspirate for their studies of the immune system. These studies are done to understand how blood cells are formed and how they function. Samples will be used to study problems such as the immune system in bone marrow failure and related conditions. Cells will be used in laboratory research and may be banked for future laboratory studies

The purpose of this study is to collect bone marrow cells for research purposes.

Physical activity and exercise have been shown to prevent falling in older adults, although the exact mechanisms by which exercise prevents falls is unclear. Compensatory stepping and grasping reactions are frequently used to prevent a fall to the ground following a loss of balance. Age-related impairment in these reactions may be related to an increased risk of falling. Therefore, the purpose of this study is to investigate means for reversing age-related impairment in compensatory stepping and grasping reactions. A training program involving perturbation-evoked reactions will be evaluated.~Comparison(s): Balance recovery ability before and after a 6-week training program will be assessed. Performance of the training group will be compared to a control group not receiving stepping and grasping training.

This study aims to investigate the potential to train compensatory stepping and grasping reactions for the prevention of falls.

For twin pregnancies of 32-38 weeks gestation, where twin A is presenting cephalic, does a policy of planned CS decrease the likelihood of perinatal or neonatal mortality or serious neonatal morbidity, during the first 28 days after birth, compared to a policy of planned VB?

For twin pregnancies at 32-38 weeks gestation, where twin A is head down, does a policy of planned caesarean section (CS) lower the likelihood of death or serious illness, during the first 28 days after birth, compared to a plan for vaginal birth (VB)?

Demonstrating the effectiveness of safe and widely available dietary interventions to prevent osteoporosis could have important public health ramifications. Different food sources of dietary protein may have different effects on bone metabolism. Animal foods provide a dietary acid load that may lead to negative calcium balance and increased bone resorption. In contrast, vegetable sources of protein, while providing some acid due to their protein content, provide proportionally more base that counters the dietary acid load. The effect of dairy products, which are rich in animal protein but also contain potential base precursors not found in vegetable foods, has not been established. Finally, soy protein sources may have a dual benefit: soy foods provide base precursors as well as plant estrogens that may have a beneficial effect on bone. We are resubmitting this proposal to randomize postmenopausal women to one of four diets equal in calories, protein, calcium, and sodium. The diets will differ by having 80 percent of the protein from one of four sources: non-dairy animal, vegetable, dairy, or soy foods, resulting in significant differences among the diets in acid, base, and isoflavone content. All food will be prepared and provided by the General Clinical Research Center. The subjects will consume the diets for 6 weeks with measurements of acid-base status, isoflavone excretion, and calcium metabolism. This will be the first intervention study to examine the effect of different sources of dietary protein in whole foods on calcium metabolism. Eventually our findings could have substantial public health implications and provide a widely available and low risk means to help prevent osteoporosis.

Osteoporosis is a major health concern worldwide. While there are drugs available for the treatment and prevention of osteoporosis, they are not practical for population-wide prevention efforts. Demonstrating the effectiveness of safe and widely available dietary interventions to prevent osteoporosis could have important public health ramifications. Different food sources of dietary protein may have different effects on bone metabolism. Animal foods provide a dietary acid load that may lead to negative calcium balance and increased bone resorption. In contrast, vegetable sources of protein, while providing some acid due to their protein content, provide proportionally more base that counters the dietary acid load. The effect of dairy products, which are rich in animal protein but also contain potential base precursors not found in vegetable foods, has not been established. Finally, soy protein sources may have a dual benefit: soy foods provide base precursors as well as plant estrogens that may have a beneficial effect on bone. We are resubmitting this proposal to randomize postmenopausal women to one of four diets equal in calories, protein, calcium, and sodium. The diets will differ by having 80 percent of the protein from one of four sources: non-dairy animal, vegetable, dairy, or soy foods, resulting in significant differences among the diets in acid, base, and isoflavone content. All food will be prepared and provided by the General Clinical Research Center. The subjects will consume the diets for 6 weeks with measurements of acid-base status, isoflavone excretion, and calcium metabolism. This will be the first intervention study to examine the effect of different sources of dietary protein in whole foods on calcium metabolism. Eventually our findings could have substantial public health implications and provide a widely available and low risk means to help prevent osteoporosis.

Among all racial/ethnic groups, African Americans have the greatest risk of becoming ill or dying from tobacco-related diseases. Because of this disproportionate disease burden, it is particularly urgent that researchers focusing on tobacco control partner with African American communities. Intervention strategies which hold the tobacco industry accountable for its behavior are effective in changing views of tobacco use. In earlier work, we found that information from internal tobacco industry documents, when shown to African American smokers, stimulated reflection about quitting and interest in disseminating information about industry targeting behaviors to others. However, to date there have been no attempts to utilize the information in industry documents as part of a smoking cessation intervention. In this project, we will test whether a community co-developed, tailored quit-smoking program featuring exposures to African American-specific tobacco industry documents and media exercises in addition to proven individual quitting strategies can increase the number of people who quit smoking at six months and one year, as compared with usual care.~The specific aims of the project are to:~test, using statistics, how well an innovative community-based, culturally tailored quit-smoking program for African Americans works at 6 and 12 months;~test selected variables for how well they predict who will return to smoking;~use interviews to identify additional individual and/or community factors associated with successful quitting or relapse; and~collect information to evaluate the overall effectiveness of the CARA project collaborative efforts in developing and sustaining the project over time, enhancing community awareness of tobacco issues, and creation or enhancement of community tobacco control resources.

Among all racial/ethnic groups, African Americans have the greatest risk of becoming ill or dying from tobacco-related diseases. Because of this disproportionate disease burden, it is particularly urgent that researchers focusing on tobacco control partner with African American communities. Intervention strategies which hold the tobacco industry accountable for its behavior are effective in changing views of tobacco use. In earlier work, the investigators found that information from internal tobacco industry documents, when shown to African American smokers, stimulated reflection about quitting and interest in disseminating information about industry targeting behaviors to others. However, to date there have been no attempts to utilize the information in industry documents as part of a smoking cessation intervention. In this project, the investigators will test whether a community co-developed, tailored quit-smoking program featuring exposures to African American-specific tobacco industry documents and media exercises in addition to proven individual quitting strategies can increase the number of people who quit smoking at six months and one year, as compared with usual care.~The specific aims of the project are to:~test, using statistics, how well an innovative community-based, culturally tailored quit-smoking program for African Americans works at 6 and 12 months;~test selected variables for how well they predict who will return to smoking;~use interviews to identify additional individual and/or community factors associated with successful quitting or relapse; and~collect information to evaluate the overall effectiveness of the CARA project collaborative efforts in developing and sustaining the project over time, enhancing community awareness of tobacco issues, and creation or enhancement of community tobacco control resources.

Traditionally, clinical pharmacogenetic studies have begun with identifying a known phenotype (e.g., an aberrant response to a drug) followed by isolating the variant protein and gene responsible for that phenotype. With the sequence of most human genes known, it is possible to carry out pharmacogenetic studies in the reverse manner (i.e., genotype to phenotype). Patients with a known variant of a gene can be studied for their response to certain drugs, which can help elucidate the importance of that gene in drug response. In the proposed study, we plan to use a genotype to phenotype strategy to study the role of OAT3 and related variants in drug response.~Renal elimination of anionic drugs occurs by filtration and active secretion. For secretion, the drug is transported from the blood into the renal tubular cell through the basolateral membrane. This transport occurs against both a concentration and electrochemical gradient, and must therefore be mediated by organic anion transporters (OATs). To date, six human OATs have been identified, OAT 1-5, and OAT7. OAT1 and OAT3 are the dominant OATs found on the basolateral aspect of the renal proximal tubular cells and are hence suspected of playing a significant role in renal anionic drug elimination [3, 4].~Active renal tubular secretion of most beta-lactam antibiotics, including cephalosporins, has long been recognized, with OATs likely playing a major role, though the relative role of each is unclear [5]. In vivo studies have demonstrated that the cephalosporin cefotaxime has a ten-fold higher affinity for OAT3 than OAT1 [6]. Thus, patients with OAT3 variants would be expected to exhibit altered renal secretion of cefotaxime.~Cefotaxime is a common cephalosporin used in the treatment of bacterial infections. Dosed up to 1-2 mg every 6-8 hours, it has been shown to be safe in patients with normal renal function. Cefotaxime is given intravenously, and is metabolized to desacetyl cefotaxime (DACM) which retains antibacterial activity. DACM is further metabolized to two inactive metabolites, M2 and M3; all four forms of cefotaxime are renally eliminated, with active secretion representing a significant percentage of total clearance (44% for cefotaxime, 64% for DACM) [7]. The half-life of cefotaxime and DACM are 1 and 1.5 hours, respectively. Patients with poorly functional OAT3 and related variants might be expected to exhibit reduced tubular secretion of both cefotaxime and its metabolites, and result in higher or prolonged blood levels. Because such variants may reduce the amount of cefotaxime that enters the tubular cells, they may also be associated with a reduced incidence of cephalosporin-induced nephrotoxicity.~The PMT group has a collection of 500 DNA samples from young, healthy adults from four major ethnic groups (125 each from Caucasians, African-Americans, Mexicans, and Chinese). This collection (The Pharmacogenetics of Membrane Transporters), is referred to as SOPHIE (Study of Pharmacogenetics in Ethnically-diverse Populations), and includes only volunteers who have consented to be called back for consideration of enrollment in future studies.~In recent studies, we identified nine non-synonymous OAT3 variants among subjects participating in the SOPHIE study. We cloned and introduced each variant into a heterologous expression system and tested the encoded transporters for their ability to transport estrone sulfate (a documented substrate for OAT3). Four variants were identified that resulted in a complete loss of function: F129L (in one Hispanic subject), R149S (in an Caucasian and an African American subject), Q239stop (in the same African American subject), and R277W (in an Asian subject). In the subject with two non-functional variants, it is unknown whether the variants occur on the same chromosome, or if the variants are on different chromosomes. The latter would potentially make the subject completely OAT3 deficient. An additional variant (I305F) which showed reduced transport ability for some, but not all, OAT3 substrates was identified in three Asian and one Hispanic subject. One variant (A310V) which showed increased transport of estrone sulfate compared to the common allele was identified in a single Caucasian subject.~This study will address the following question: Do individuals who carry altered-function in OAT3 and related variants exhibit differences in the pharmacokinetics of cefotaxime in comparison to individuals who carry the common allele?

In the proposed study, we plan to use a genotype to phenotype strategy to study the role of the organic anion transporter, OAT3, in drug response. More specifically we will examine the contribution of OAT3 to the renal clearance of anionic drugs such as cefotaxime by studying individuals with a non-functional (or poorly-functional) variant of OAT3.

In the proposed studies, we will address two questions:~•Do individuals who carry one of OCT1 variants with reduced or no function exhibit differences in the pharmacokinetics of metformin in comparison to individuals who carry the common allele?~Compared to wild type mice, Oct1-/- mice have reduced metformin distribution to the liver and intestine. We expect a similar pattern between persons who carry the variant OCT1 allele and those who carry the common allele. This effect might be reflected by a difference of Tmax or Cmax after oral administration of metformin. Other differences in metformin pharmacokinetic properties such as volume of distribution, half life and clearance may also be evident.~•Do individuals who carry the decreased or non-functional variants exhibit differences in the response to metformin in comparison to individuals who carry the common allele? Specially, we will test the hypothesis that the OCT1-expressing tissues are target organs for metformin, and that individuals with the variant transporters may have reduced metformin uptake into these sites (is this the correct meaning?) and therefore a reduced drug response to metformin.~In this study, we will evaluate metformin pharmacokinetics and glucose metabolic effects in healthy subjects rather than in patients with type 2 diabetes. Our rationale is as follows. The hepatic glucose production in diabetic patients is abnormally increased. Metformin decreases fasting blood glucose concentration by reducing hepatic glucose production and improving glucose utilization. However, the fasting blood glucose concentration is not decreased by metformin in non-diabetics who have a normal hepatic glucose production. It was suggested that the glucose-lowering effect of metformin was difficult to demonstrate in non-diabetics unless glucose concentrations were artificially raised. Although there are studies showing that metformin improves the glucose tolerance both in non-diabetics and diabetics, the results for non-diabetics have been inconsistent, depending on the variable experimental condition. Variation in OCT1 expression and activity may be one of those variables, and the time points for blood sampling after drug and glucose (meal) intakes may also be important to observe the glucose-lowering effect [16]. In this study, we employ a similar study design as that reported [16] to observe the glucose-lowering effect by metformin in healthy subjects. Before and after metformin administration, oral glucose tolerance test (OGTT) will be conducted. We expect a difference of glucose tolerance between different OCT1 genotypes, under the hypothesis that individuals with different OCT1 genotypes have different metformin concentrations in the target tissues, and hence have different glucose uptakes into (and so utilization in) the target tissues (primary muscle and liver).~In non-diabetic healthy subjects, metformin significantly attenuated the rise in immediate postprandial insulin levels. In this study, we will also determine insulin levels after glucose administration. With metformin treatment, we expect to observe significant difference in post-glucose-administration insulin levels between individuals with different OCT1 genotypes.~When mice were given metformin, the blood lactate concentration significantly increased in the wild-type mice, whereas only a slight increase was observed in Oct1-/- mice. This is consistent with our hypothesis that OCT1 is a determinant of metformin effect on glucose utilization. It will be interesting to compare plasma lactate concentrations after metformin treatment between individuals with different OCT1 genotypes.~Metformin can improve lipid metabolism in obese and diabetics patients, which is reflected by the reduced plasma levels of free fatty acid, cholesterol, and triglycerides. However, in this study with a single dose of metformin, it may not be possible to observe those effects in healthy subjects, although the corresponding concentrations will be measured.

Specific Objectives:~To determine if individuals who carry a decreased or non-functional variant of OCT1 exhibit differences in the pharmacokinetics of metformin in comparison to individuals who carry the common allele.~To determine if individuals who carry the decreased or non-functional variants exhibit differences in the response to metformin in comparison to individuals who carry the common allele.

This study examines the efficacy of Child-Parent Psychotherapy (CPP) for the treatment of preschoolers exposed to marital violence. Multi-ethnic preschool-mother dyads from diverse socioeconomic backgrounds were randomly assigned to CPP or to a case management plus community referral for individual treatment comparison group. It was hypothesized the children who received CPP treatment would show significantly greater improvement in general symptomatology and in traumatic stress symptoms than those in the comparison group.~There is growing recognition that, contrary to the long-standing assumption that young children are impervious to environmental stresses, preschoolers exposed to violence show increased rates of disturbances in self-regulation and in emotional, social and cognitive functioning (Osofsky, 2004; Pynoos et al., 1999; van der Kolk, 2003). The present study examines the efficacy of a relationship-based treatment approach involving the child and the mother. Dyads were randomly assigned to either the Child-Parent Psychotherapy (CPP) treatment group or to a comparison group that consisted of monthly case management by an experienced Ph.D.-level clinician plus referrals for individual treatment in the community for mothers and child. We hypothesized that Child-Parent Psychotherapy would be more effective in alleviating children's traumatic stress symptoms and behavior problems because it focuses on improving the quality of the child-mother relationship and engages the mother as the child's ally in coping with the trauma. Treatment was offered for 50 weeks.

This study will examine the efficacy of Child-Parent Psychotherapy (CPP) for the treatment of preschoolers exposed to marital violence.

Twin studies have long been a valuable tool for examining the relative role of environment and heredity in health issues such as disease and drug response. For example, twin studies in the 1960's and 1970's showed for the first time that variability in the elimination of many drugs was largely influenced by heredity. Monozygotic twin pairs showed little variability in the elimination of various drugs while dizygotic twin pairs, sharing only about one half of their genes, showed much greater variability. It is now known that the some of the variability in drug elimination observed in dizygotic twins was due to genetic differences in drug metabolizing enzymes, such as the cytochrome P450's. However, genetic variation in other genes, such as membrane transporters may also contribute to variability in drug response.~Membrane transporters play multiple roles in the body; they help to maintain cellular homeostasis through import and export mechanisms and also play an important role in drug response, affecting both the pharmacokinetics and pharmacodynamics of drugs. Animal studies using mice genetically deficient in drug transporters and reports of drug interaction studies involving transporter substrates have provided convincing evidence that the level of function of several important drug transporters is an important determinant of drug response.~The current study will examine differences in the renal clearance of metformin in monozygotic and dizygotic twin pairs. Metformin is an antidiabetic drug that has no significant hepatic metabolism and is actively secreted by the kidneys. Studies in our lab have shown that metformin is a substrate of the human organic cation transporter, hOCT2, which appears to be a major transporter involved in the renal secretion of cationic drugs. Data in the literature indicate that there is substantial variation in the net secretory clearance of metformin in normal, healthy volunteers. In five healthy volunteers, the ratio of renal clearance to creatinine clearance ranged from 1.5 to 4.2, nearly a 3-fold variation. We hypothesize that genetic variation in secretory transporters in the kidney, like hOCT2, may be responsible for the inter-individual differences in the secretory clearance of metformin and other drugs. Studies examining renal clearance of metformin in monozygotic and dizygotic twins will allow us to better understand the influence of heredity on variation in renal elimination. Furthermore, genotyping monozygotic and dizygotic twin pairs with significant differences in renal clearance of metformin may give us insight into the genes responsible for this variability.

Specific Aims: To compare metformin pharmacokinetics in monozygotic and dizygotic twin pairs. Comparing renal clearance of metformin in monozygotic and dizygotic twins will allow us to better understand the influence of heredity on variation in renal elimination. Furthermore, genotyping renal transporter genes in monozygotic and dizygotic twin pairs with significant differences in renal clearance of metformin may give us insight into the genes responsible for this variability.

To prospectively determine the virologic impact of switching treatment-experienced HIV-infected patients with virologic failure to a salvage regimen with or without a 12 week STI prior to the switch.~Hypothesis: By withdrawing ARV drug pressure, resistant HIV virus will revert to wild-type. In treatment-experienced HIV patients who experience virologic failure, a STI prior to starting a salvage regimen will result in an improved virologic response and more prolonged vral suppression compared to immediate switching to a new regime.~Interventions:~Immediate Switch to Salvage Therapy: Patients randomized to the control arm will be switched immediately to a salvage regimen using the information from the treatment history and genotype results.~Structured Treatment Interruption: Patients randomized to the STI arm will have their present regimen stopped for 12 weeks and will have a genotype repeated in the 12th week. A salvage regimen will be started at week 12 using the information from the treatment history and baseline genotype results.

The purpose of this study is to assess the virologic impact of switching treatment-experienced HIV-infected patients with virologic failure to a salvage regimen with or without a 12 week STI prior to the switch.~Hypothesis: A STI prior to starting a salvage regimen will result in an improved virologic response.

A multicentre, 1:1 randomised, double blind, double dummy, two arm parallel group phase III study comparing a triple modified release tacrolimus FK506E (MR4) / MMF / steroid regimen with a triple standard tacrolimus FK506 / MMF / steroid regimen.

The purpose of this study is to evaluate and to compare the efficacy and safety of a triple modified release tacrolimus FK506E (MR4) / MMF / steroid regimen with a triple standard tacrolimus FK506 / MMF / steroid regimen in patients undergoing kidney transplantation. It shall be demonstrated that FK506E (MR4) is non-inferior to FK506 with regards to the primary endpoint.

Pharmacokinetic/Pharmacodynamic Parameters Associated With the Emergence of Resistance to Ciprofloxacin in Human Commensal Flora Bacterial resistance to antibiotics has been a growing therapeutic problem since the late 1980s. Resistant strains of pathogenic bacteria can arise through initial selection of resistant strains in the commensal flora. The emergence of fluoroquinolone resistance in the commensal flora will be assessed in 48 healthy volunteers receiving variable doses of ciprofloxacin during 14 days. Emergence of resistance will be correlated to pharmacokinetic characteristics of ciprofloxacin.

Bacterial resistance to antibiotics has been a growing therapeutic problem since the late 1980s. Resistant strains of pathogenic bacteria can arise through initial selection of resistant strains in the commensal flora. The emergence of fluoroquinolone resistance in the commensal flora will be assessed in 48 healthy volunteers receiving variable doses of ciprofloxacin during 14 days. Emergence of resistance will be correlated to pharmacokinetic characteristics of ciprofloxacin.

This was a phase II, prospective, open-label, multicenter, outpatient study designed to evaluate the safety, tolerability, and immunogenicity of one or two doses of CAIV-T in children and adolescents between 6 and 17 years of age. Subjects were allocated to one of three study groups according to age at the time of enrollment: study group one consisted of subjects between 6 and 9 years of age, group two of subjects 10 to 12 years of age, and group three of subjects 13 to 17 years of age.~Approximately 450 subjects (ie, 150 subjects per age group) participated in the study and were scheduled to receive two intranasal doses of CAIV-T separated by 35 ± 7 days in an open-label manner.

The study was designed to determine the number of doses of CAIV-T required to effectively immunize children and adolescents in the 6 to 17 year age group.

The primary objective of this Phase I study is to evaluate the safety and tolerability of escalating single IV doses of MEDI-528 administered to healthy adult volunteers.

Phase I study to evaluate the safety and tolerability of escalating single IV doses of MEDI-528.

The objective of this study was to compare the safety and tolerability of one and two doses of influenza virus vaccine, trivalent, types A and B, live cold-adapted liquid (CAIV-T) with placebo when administered intranasally to healthy infants aged 6 < 24 weeks.

Trial to compare the safety and tolerability of one and two doses of influenza virus vaccine.

- A Prospective, Randomized, Double-Blind, Placebo-Controlled, Phase III, Multicenter Trial to Compare the Safety, Tolerability, Immunogenicity and Efficacy of Three Dose Levels of a Liquid Formulation of Influenza Virus Vaccine, Trivalent, Types A & B, Live Cold-Adapted (CAIV-T) in Healthy Children

- Trial to Compare the Safety, Tolerability, Immunogenicity and Efficacy of Three Dose Levels of a Liquid Formulation of(CAIV-T) in Healthy Children.

The HIVNET 012 clinical trial demonstrates a cost effective strategy to prevent maternal fetal transmission of HIV. In this study, a single 200 mg dose of Nevirapine was given to pregnant Ugandan women at the onset of labour and a single 2 mg/kg dose to their infants within 72 hours of birth (1). Given the efficacy, simplicity and low cost of this regime, the World Health Organization recently recommended implementation of this regimen as one of several options for prevention of maternal fetal transmission of HIV in resource limited settings.~Pharmacokinetic studies have demonstrated that 200 mg of Nevirapine given to the mother during labour results in concentrations >100 mg/mL (10 times the in vitro IC50) in the newborn. Nevirapine elimination is prolonged in both mothers and infants with median t½ of 36.8 to 65.7 hours. Administration of 200 mg orally to the mother and a single 2 mg/kg oral dose to the infant at 48-72 hours, maintains serum concentration in the infants >100 mg/ml through 7 days of life (2, 3)~Early studies demonstrated that the use of Nevirapine monotherapy resulted in a rapid selection of Nevirapine resistant mutations (4). This was associated with loss of antiviral activity and return of the viral load to baseline within 12 weeks. It appeared very soon that the non-nucleoside reverse transcriptase inhibitors were drugs with a low genetic barrier and that a single mutation in the reverse transcriptase gene induced a high level of phenotypic resistance (5). Similarly, when Nevirapine was used in combination with a single nucleoside, and there was incomplete suppression of viral replication, resistance emerged to the non-nucleoside reverse transcriptase inhibitor (6).~In contrast, when used as part of triple antiretroviral combination and there was successful inhibition of viral replication to <50 copies/ml, the viral response was maintained in 50% of patients out to 48 weeks (7, 8, 9, 10). However, again when virologic control is lost, resistance to Nevirapine emerges rapidly in 50-100% of patients (11). It is unclear whether or not these mutations developed during the initial suppression of viral load replication or during rebound of viremia with failure.~Given the pharmacokinetics of Nevirapine in pregnant women and infants, concern was raised that mother and child would be exposed to Nevirapine monotherapy for one to several days and that the selection of resistant mutants could arise limiting this strategy over the long term. In fact, a recent sub-analysis of the HIVNET 012 cohort found Nevirapine resistant mutations in 21/111 (19%) of women tested at 6-8 weeks after delivery. The K103N was the most common mutation. Women with the highest baseline viral load developed the mutations more frequently. Nevirapine resistant mutations were also detected in 11/24 or (46%) of infected infants at 6-8 weeks. In contrast to the mothers, the Y181C was the most commonly detected.~Similarly, the K103N resistance mutation was detected 6 weeks after Nevirapine administration in 3/15 (20%) women in the HIVNET006 phase I/II trial. This had the same Nevirapine dosing schedule as HIVNET012 (12).~New information has become available based on recent post-marketing surveillance data clarifying risk factors for severe life threatening and fatal hepatotoxicity with nevirapine. Women with CD4 counts > 250 cellsmm3 at initiation of therapy including pregnant women receiving chronic treatment for HIV infection are at considerably higher risk (12-fold) of hepatotoxicity which in some cases has been fatal. The greatest risk of severe and potentially fatal hepatic events occurs in the first 6 weeks of therapy. However, the risk continues after this time and patients should be closely monitored for the first 18 weeks of therapy. For this reason, women with CD4 > 250/mm3 will not be included in Objective 1 of this study.~Hypothesis~Nevirapine resistance developed in women and infants in the HIVNET 006 and 012 cohorts as a consequence of use of an agent with a long t½ as monotherapy in individuals with high viral loads.~Objective 1 To demonstrate that Nevirapine resistance does not develop in HIV infected patients when used as part of triple antiretroviral combination therapy between the initiation of treatment and suppression of HIV RNA to <1000 copies/ml.~Objective 2 To demonstrate that resistance to nevirapine does not develop when patients with suppressed HIV RNA discontinue combination antiretroviral therapy which contains nevirapine.

Hypothesis~Nevirapine resistance developed in women and infants in the HIVNET 006 and 012 cohorts as a consequence of use of an agent with a long t½ as monotherapy in individuals with high viral loads.~Objective 1 To demonstrate that Nevirapine resistance does not develop in HIV infected patients when used as part of triple antiretroviral combination therapy between the initiation of treatment and suppression of HIV RNA to <1000 copies/ml.~Objective 2 To demonstrate that resistance to nevirapine does not develop when patients with suppressed HIV RNA discontinue combination antiretroviral therapy which contains nevirapine.

The purpose of the study is to use valganciclovir to define the role of antiviral therapy in suppression of HHV-8 shedding in HHV-8 seropositive men. Our hypothesis is that valganciclovir will substantially reduce the frequency of detection and amount of HHV-8 in the mouth. Such reduction will serve to confirm that the mouth is the site of active HHV-8 replication. If valganciclovir is found to be effective, the findings from this proposal would serve as the basis for a clinical trial with valganciclovir for prevention of Kaposi's Sarcoma (KS) in high-risk HHV-8 seropositive persons.~After informed consent, all subjects will undergo medical history, physical examination and screening laboratory examination. Eligible patients will return to clinic for randomization to receiver either valganciclovir 900 mg qd or placebo. Participants will receive a diary for noting adverse events and concurrent medications. The clinician will instruct the participants on collection of mouth swabs and provide Dacron swabs, vials with PCR media and pre-printed labels. Subjects will be asked to obtain a swab of oral mucosa every morning. Clinic visits every other week will serve to review interim medical history and diaries for adverse events, collect PCR swabs, dispense additional medication and draw safety labs. The study uses a double-blind, randomized placebo design. Therefore, participants will not know whether they will be taking a placebo or active medication at any time during the study. Due to the crossover study design, however, all participants will receive the same amount of placebo and study drug over the duration.

The purpose of the study is to use valganciclovir to define the role of antiviral therapy in suppression of HHV-8 shedding in HHV-8 seropositive men. Our hypothesis is that valganciclovir will substantially reduce the frequency of detection and amount of HHV-8 in the mouth.

Background: Obesity and inactivity independently increase risks of chronic disease in adolescence and all-cause mortality in adulthood. In clinical trials, changes in exercise and diet can reduce adiposity and risk of diabetes and other chronic diseases in obese adults and youth. In many school systems, physical education is mandatory in elementary school but not high school, and physical activity often declines during adolescence. Because physical activity habits track from adolescence to adulthood, adolescence may represent a critical period for establishing a physically active lifestyle to prevent diseases associated with inactivity in adulthood. Obesity can make adherence to aerobic activity challenging, but would present less of an obstacle to resistance training. Resistance exercise has shown favorable effects on lean body mass, metabolic rate, insulin resistance, and quality of life in adults, but almost no research has examined effects of resistance training in obese adolescents. Our own survey in a sample of obese, primarily sedentary youth found greater overall interest in resistance exercise than aerobic exercise.~Objectives: The primary objective of this study is to evaluate the effects of resistance training, aerobic training, and combined aerobic and resistance training on percent body fat measured using Magnetic Resonance Imaging (MRI) in sedentary post-pubertal overweight or obese youth aged 14-18 years.~Study Design: Randomized controlled trial conducted at a single site. After a 4-week supervised low-intensity exercise run-in period to test compliance, 292 adolescents with BMI ≥ 85th percentile for age and gender will be randomized in equal numbers to one of 4 arms: Diet + aerobic exercise, diet + resistance exercise, diet + combined aerobic and resistance exercise, or diet-only control. The intervention will last 22 weeks, with a follow-up assessment at 6-months post-treatment (11-months post-randomization).~Hypotheses: Reduction in percent body fat will be larger in diet + aerobic exercise and diet + resistance exercise than diet-only controls at post-treatment, and the combined aerobic and resistance training will be superior to either aerobic or resistance training alone in reducing percent body fat at post-treatment. The combined resistance and aerobic group will show greater improvements in percent body fat, body composition, and physiological and psychosocial function at post-treatment and 12-months follow-up. Groups that include resistance training will produce greater psychosocial changes and better adherence than aerobic training alone at post-treatment and follow-up.~Significance: The global burden of obesity in youth is increasing, and more effective intervention is needed. This study may identify that resistance training is an important component in the treatment of overweight adolescents. As such, findings may influence clinical decision making in the management of juvenile obesity, as well as inform public health exercise guidelines and school-based physical education curricula in attempt to reduce the economic, medical, and psychosocial burden of obesity in youth.

The purpose of this study is to evaluate the effects of resistance training, aerobic training, and combined aerobic and resistance training on percent body fat, measured using Magnetic Resonance Imaging (MRI), in sedentary post-pubertal overweight or obese youth aged 14-18 years.

The goal of this study is to identify infants who are at risk for developing problems related to being breast-fed. A previous study identified items that place an infant at a high risk for developing complications related to being breast-fed. The present study will use the same survey and collect data from more participants. These additional participants are necessary to provide statistical analysis for the survey. The survey being developed will assist health care professionals to identify those infants at risk for developing health problems related to being breast-fed and provide care that will minimize the chances of developing complications.

The goal of this study is to identify infants who are at risk for developing problems related to being breast-fed.

A: Study group~FK506-MMF.~Immunosupression protocol:~Metylprednisolon 10 mg/kg intraoperatively i.v.~FK506 Day 0 or 1 oraly (0,15 mg/kg/D in two doses).~MMF max. dosage 30 mg/kg/D p.o. day 0 through day 90 according to patient condition and therapeutic MMF blood concentration~Tailoring:~Immunosupression protocol will be tailored according to the cause of liver failure: patients with autoimmune liver disease (autoimmune hepatitis, PBC, PSC, overlap syndrome etc) would be maintained on MMF. All other recipients including cryptogenic liver cirrhosis will be gradually (over 1 month) withdrawn from MMF administration 90 days after transplantation if there is:~good kidney function (S-creatinin < 150 umol/l) enabling to achieve and maintain Tacrolimus trough levels above 6 ng/ml and~if there was no more than one episode of acute rejection of the graft which resolved completely.~Targeted Tacrolimus trough levels:~Month 1 - 3 through levels 10-15 ng/ml Month 4-6 10-12 ng/ml Month 7-12 10 - 6 ng/ml~Rejection treatment:~Tacrolimus dose adjustment to upper limit of target level if last Tacrolimus trough level is below the intended limit.~Steroid boluses would be administered Metylprednisolon 10 mg/kg daily 3 consecutive days. No steroid taper. Control biopsy after normalisation of LFTs.~After two attacks of acute rejection before MMF disontinuation Prednison dose would be introduced on at least 0,3 mg/D for 3 months.~After second attack of AR after MMF discontinuation Prednison dose would be introduced on at least 0,3 mg/D for 6 months.~Steroid resistant rejection: biopsy proven rejection persisting after three courses of steroid pulses. Steroid resistant rejection would be treated according to local praxis.~Concomitant drugs:~Antiviral and antibacterial prophylaxis according to current centre praxis. Prophylaxis of cholestasis and prophylaxis/treatment of the bone disease where applicable.~B. Control group~Tacrolimus, steroids.~Immunosupression protocol:~Metylprednisolon 10 mg/kg bm intraoperatively Children < 25kg bm: Metylprednisolon taper from 100 mg/D on day 0 to MP 10 mg on day 7 Children > 25kg bm: Metylprednisolon taper from 200 mg/D on day 0 to MP 20 mg on day 7 Week 2-4 Prednison - 0,5-0,3 mg/kg/D Week 4-12 Prednison -0,3-0,2 mg/kg/D Month 4-6 Prednison 0,2 - 0,1 mg/kg/D Month 7 - Steroid withdrawal~FK506 Day 0 or 1 orally (0,15 mg/kg/D in two doses).~Intended Tacrolimus trough levels:~Month 1 -3 through levels 10-15 ng/ml Month 4-6 10-12 ng/ml Month 7-12 6-10 ng/ml~Rejection treatment:~Tacrolimus dose adjustment to upper limit of target level if last Tacrolimus trough level is below the intended limit.~Steroid boluses would be administered Metylprednisolon 10 mg/kg bm daily 3 consecutive days. No steroid taper, return to previous steroid dose. Control biopsy after normalisation of LFTs.~After two attacks of acute rejection Prednison dose would be maintained on at least 0,3 mg/D for 3 months.~Steroid resistant rejection: biopsy proven rejection persisting after three courses of steroid pulses. Steroid resistant rejection would be treated according to local praxis.~Biopsy: Liver biopsy should be taken in any suspicion of graft rejection or disease recurrence. Protocol biopsy would be taken according to local practice, liver biopsy in one-year after transplantation is mandatory.~Primary end points:~Number of rejections, number of steroid-resistant rejections.~Secondary end points:~Patients and graft survival Dyslipidemia one year after transplantation Hypertension one year after transplantation Hyperglycemia/Diabetes de novo one year after transplantation Renal function before Tx and 1 year after Tx~Inclusion criteria:~Subjects who meet all of the following criteria are eligible for this study:~Male or female patients, not older than 18 years old.~Primary liver transplantation~Patient is capable of understanding the purpose and risks of the study and has been informed both orally and in writing and has given informed consent~Exclusion criteria:~Subjects who meet one or more of the following criteria are not eligible for this study:~Female patients who are pregnant or are breast feeding~Patients > 18 years old~Combined liver-kidney transplantation~Recipient of second liver graft~Patients are allergic, hyper-sensitive or intolerant to HCO-60 or structurally related compounds, macrolide antibiotics or tacrolimus.~Patients with known HIV-anamnesis~Patient requires ongoing dosing with a systemic immunosuppressive drug at study entry for another indication than the prophylaxis of liver graft rejection~Patient has significant, uncontrolled concomitant infections and/or severe diarrhea, vomiting, or active peptic ulcer.~Patient is participating or has participated in another clinical study and/or is taking or has been taking an investigational drug in the past 28 days.~Other reasons which depend on the assessment of the physician (no MMF will be given to patients with severe persistent hypersplenism (WBC < 3.500/ml, platelets < 50.000/ml)~Informed Consent:~Patient, who will give written consent for participation in the study and will fulfil all the inclusion and exclusion criteria, will be included in the study. After inclusion into the study, the patient may withdraw at any time for any reason.~Follow-up: (time of one patient observation ) -12 months~Number of centers: 1 Number of patients: 40 Indication: - Primary Liver transplantation Duration of study: 36 months Enrollment period: 18 months

Open label, randomised, prospective, onecentre Investigator Driven Study:~Comparison of two protocols of immunosuppression after liver Tx in children:~A: Study group - FK506-MMF. Immunosupression protocol: Methylprednisolone 10 mg/kg intraoperatively i.v. FK506 Day 0 or 1 orally (0,15 mg/kg/D in two doses).MMF max. dosage 30 mg/kg/D p.o. day 0 through day 90.~B. Control group - Tacrolimus, steroids. Immunosupression protocol: Methylprednisolone 10 mg/kg bm intraoperatively Children < 25kg bm: Methylprednisolone taper from 100 mg/D on day 0 to MP 10 mg on day 7 Children > 25kg bm: Methylprednisolone taper from 200 mg/D on day 0 to MP 20 mg on day 7 Week 2-4 Prednisone - 0,5-0,3 mg/kg/D; Week 4-12 Prednisone -0,3-0,2 mg/kg/D; Month 4-6 Prednisone 0,2 - 0,1 mg/kg/D Month 7 - Steroid withdrawal FK506 Day 0 or 1 orally (0,15 mg/kg/D in two doses).~Primary end points:~Number of rejections, number of steroid-resistant rejections.~Secondary end points:~Patients and graft survival Dyslipidemia one year after transplantation Hypertension one year after transplantation Hyperglycemia/Diabetes de novo one year after transplantation Renal function before Tx and 1 year after Tx

The purpose of this study is to validate the psychometrics of the Individual Workload Perception Scale (IWPS) designed to measure the perception of individual workloads of inpatient registered nurses.

The purpose of this study is to validate the psychometrics of the Individual Workload Perception Scale (IWPS).

This study is being conducted to evaluate the safety of an extended-regimen oral contraceptive, with ethinyl estradiol supplementation during the usual hormone-free week, for up to an additional three consecutive years. This is an extension of the Seasonique Phase 3 clinical trial to evaluate long-term safety. Only patients enrolled in the earlier trial are eligible for participation.

This study is being conducted to evaluate the safety of ethinyl an extended-regimen oral contraceptive, with ethinyl estradiol supplementation during the usual hormone-free week, for up to an additional three consecutive years.

The purpose of this study is to analyze stored samples and data collected during the conduct of the study A Trial of Vitamins in HIV Progression and Transmission (HD32257). The aims are to examine the effect of vitamin supplementation on HIV infected women during pregnancy

The purpose of this study is to analyze stored samples and data collected during the conduct of the study A Trial of Vitamins in HIV Progression and Transmission (HD32257). The aims are to examine the effect of vitamin supplementation on HIV infected women during pregnancy on a number of parameters in breastmilk.

The aromatase inhibitors are drugs already approved for the treatment of breast cancer in the adjuvant and metastatic setting, and have demonstrated a superiority when compared to other hormone therapy agents as tamoxifen. FRAGRANCE is a trial of neoadjuvant hormone therapy activated in September 2004 at the Jules Bordet Institute. The main objective of this study is to find a genetic signature of de novo resistance to letrozole The standard dose of letrozol, 2,5 mg/day, is given orally during 4 months previous to the definitive breast surgery. The advantages of the neoadjuvant setting are a) the possibility to directly evaluate the response to therapy, which is of great value to decide adjuvant treatment; b) the increase chance of performing breast conserving surgery; c) and, because a tumor sample is obtained before and after treatment, the identification of predictive markers of response or resistance to treatment, including a genetic signature, obtained using the microarray technology. Eligible patients are women with early hormonal receptor positive breast cancer, with any contra-indication or refusal to the administration of chemotherapy The side effects of letrozole are already well known, and include more commonly hot flashes, nausea and vomiting, headache, arthralgia/myalgia, fatigue, and oedema. After surgery, adjuvant treatment will be done according to the standard practice of the Institute, considering the possibility of continuing letrozole for a total of at least 5 years, if a satisfactory response is achieved The first part of this trial will include 49 patients.~This trial will soon become a multicenter, multinational trial of 160 patients.

Find a genetic signature of de novo resistance to letrozole in adjuvant breast cancer;

Hypotension during cesarean section with spinal anesthesia is common. We compare low dose versus standard dose spinal anesthesia with and without intravenous phenylephrine-infusion.

The purpose of this study is to determine the effect of low dose versus standard dose spinal anesthesia with and without intravenous phenylephrine-infusion on blood pressure, cardiac output and systemic vascular resistance.

NY-ESO-1 Plasmid DNA (pPJV7611) Cancer Vaccine was administered by particle-mediated epidermal delivery (PMED) at a pressure of 500 psi using the XR-1 Powderject® delivery device. The 4 microgram dosage of NY-ESO-1 was administered as 4 X 1 microgram PMEDs in close proximity. Similarly, the 8 microgram dosage was administered as 8 X 1 microgram PMEDs. The third cohort of patients received the 8 microgram dosage as a cluster dosage of 4 doses (day 1, 3, 5, 8) as 2 X 1 microgram PMEDs per day.~Blood samples were to be obtained at baseline, 2 weeks after each vaccination, prior to the second and third vaccination, and 4 weeks after the third vaccination for the assessment of clinical hematology, biochemistry measurements and immunology responses. Patients were to be evaluated for toxicity throughout the study.~Delayed-type hypersensitivity (DTH) testing was to be performed at baseline and at the 2-week visit following the first and third vaccinations.~NY-ESO-1 and/or LAGE-1 specific antibodies were to be assessed in all patients by an enzyme-linked immunosorbent assay (ELISA). NY-ESO-1 specific CD4+ and CD8+ T-cells were to be assessed in all patients by tetramer and/or ELISPOT assays.~Disease status was to be assessed at baseline and 4 weeks after the third vaccination in patients with measurable disease.

To evaluate the safety of NY-ESO-1 Plasmid DNA (pPJV7611) Cancer Vaccine given by particle-mediated epidermal delivery (PMED) in patients with tumor types known to express NY-ESO-1 or LAGE-1.

Gastroesophageal reflux disease(GERD) is a common disorder of the esophagus, affecting 7-10% of the U.S. population. Characteristic symptoms include heartburn, chest pain, and indigestion. EER denotes gastroesophageal refluxate that reaches structures above the upper esophageal sphincter. EER has been implicated in the pathogenesis of several otolaryngologic disorders such as chronic posterior laryngitis, laryngeal contact ulcer or granuloma, paroxysmal laryngospasm, vocal cord nodules, Reinke's edema, subglottic or laryngotracheal stenosis, globus pharyngeus,and laryngeal and hypopharyngeal carcinoma. In addition, EER has been associated with disorders of both the lower and upper respiratory tract and with chronic sinonasal inflammation.~Patients with EER rarely complain of the common symptoms of GERD, such as heartburn. Often they present with symptoms involving the larynx and pharynx, including throat-clearing, globus pharyngeus, and postnasal drainage. These symptoms may be present due to direct irritation of the nasal epithelium by gastric refluxate and/or a neurogenic inflammatory process mediated by the autonomic nervous system.~Specific Aims:~Specific Aim 1: To establish the relation ship between EER and PND in patients without sinonasal inflammatory disease.~Hypothesis 1: In patients without radiographic or endoscopic evidence of sinonasal inflammatory disease, PND is a symptom of EER.~Method 1: We will test this hypothesis utilizing a 2-site 24-hour pH probe test in a symptomatic patient group and compare then to a previously tested age and sex-matched control group.~Specific Aim 2: To establish the efficacy of PPI in the management of PND.~Hypothesis 2: Patients with a chief complaint of PND and no sinonasal inflammatory disease will improve with 3-month PPI treatment with Rabeprazole 20 mg twice a day.~Method 2: A group of patients with a chief complaint of postnasal drainage, without radiographic or endoscopic evidence of sinonasal inflammatory disease will be entered into a prospective placebo-controlled trial utilizing BID PPIs over a 3-month period. the primary outcome measures will be: 1) Visual analog Scales, assessing the severity and frequency of PND at days 0 and 90 of treatment and 2)A quantitative color analysis of laryngeal erythema, utilizing videolaryngoscopy at days 0 and 90 of treatment.

Objectives of this study are:~To quantitatively evaluate the relationship between extraesophageal manifestations of gastroesophageal reflux (EER) and postnasal drainage(PND)in a group of patients without radiographic or endoscopic evidence of sinonasal inflammatory disease.~To assess the efficacy of BID proton pump inhibitors (PPI) in the management of patients with symptomatic postnasal drainage.

Scientific research into the basic mechanisms underlying neuromodulation is relatively recent and incomplete. The purpose of the proposed study is to determine how a form of neuromodulation, transcutaneous vagus nerve stimulation, which is non-invasive and non-painful, affects human brain and autonomic activity. We will accomplish this by integrating whole brain functional MRI (fMRI) methodologies with gastric MRI and physiological monitoring.~This study will comprise 2 functional magnetic resonance imaging (fMRI) brain-gut scans and 2 behavioral visits consisting of a nutrient drink test, all while receiving the neuromodulation with varying parameters. Participants will also have their heart rate, breathing, and gastric activity monitored during all visits.

This study will determine how vagus nerve stimulation affects human brain, stomach, and autonomic activity.

In this interventional study we want to evaluate the effect of Variable ventilation (1) in patients with ARDS. Patients will be mechanically ventilated with Variable Ventilation (3 step with increased level of variability) and traditional CMV, for a total of 4 step. Each step lasts in 60 minutes. During this period we will record the gas exchange parameters and the mechanics of the respiratory system.~1. Arold S, Mora R, Lutchen K, et al. Variable ventilation improves lung mechanics and gas exchange in a rodent model of acute lung injury. Am J Resp Crit Care Med 2000; 165: 366-71.

The purpose of this study is to determine the effects of variable ventilation on respiratory system of patients affected by acute respiratory distress syndrome.