A Study to Evaluate the Safety and Efficacy of Single Day or Single Dose Famciclovir for the Treatment of Recurrent Herpes Labialis

Summary: The study is designed to assess the efficacy and safety of patient-initiated therapy with famciclovir 1500 mg o.d. or 750 mg b.i.d. for one day treatment in adult men and women with recurrent herpes labialis
Inclusion criteria: inclusion criteria:

 Patients aged 18 years or older

 A history typical for recurrent herpes labialis. The subject must have experienced three or more episodes of cold sores in the last 12 months, and have a history of prodromal symptoms, as defined by the patient, preceding at least 50% of these cold sores, and must also have a history of vesicular lesions in at least 50% of the recurrent episodes of cold sores.

 General good health, without other serious medical conditions and specifically with normal renal and hepatic function, as determined by the patient's account of his/her medical history

 Women of child bearing potential had to use an accepted method of birth control (surgical sterilization; intra-uterine contraceptive device; oral contraceptives; hormone delivery systems such as Norplant® or Depo-Provera injections; a diaphragm in combination with contraceptive cream, jelly, or foam; or a condom in combination with contraceptive cream, jelly or foam). Patients unable or unwilling to use one of the methods of birth control listed above for the duration of the study could not enter the study.

 For women of child-bearing potential, a negative pregnancy test (urine) at screening was required

 Signature on the informed consent document

Exclusion criteria: :

 Previous herpes vaccination

 Patients using topical immunosuppressive agents (including steroids, tacrolimus and pimecrolimus) on or near the face or systemic immunosuppressive agents (including steroids, tacrolimus and pimecrolimus) within 30 days of screening

 Patients known to be immunosuppressed due to underlying disease (e.g. HIV infection) or concomitant treatment (e.g. cancer chemotherapy)

 Recent history of alcohol or drug abuse, which in the opinion of the investigator, could interfere with that study patient's compliance with study requirements

 Significant skin disease such as atopic dermatitis or eczema that would interfere with the assessment of lesions

 Allergy or hypersensitivity to formulations containing acyclovir, penciclovir, famciclovir, and/or other nucleoside analogues

 Women who were lactating or breast feeding

 Had already been randomized once into the study

 Patients who had received an investigational drug in the past four weeks


Dietary Nitrate in COPD

Summary: The acute consumption of dietary nitrate has been shown to improve exercise capacity in athletes, healthy adults and subjects with peripheral vascular disease. Many COPD patients have reduced exercise capacity, The investigators hypothesized that acute nitrate consumption, in the form of beetroot juice, might increase incremental shuttle walk test (ISWT) distance in COPD subjects.
Inclusion criteria: inclusion criteria:

 Information consenting out-patients with a previous physician diagnosis of COPD

 Clinically stable

 Ambulatory

Exclusion criteria: :

 Subjects who required supplemental oxygen for exercise

 Subjects with pulmonary hypertension and angina

 Intolerant to beetroot

 Insulin dependent diabetes

 Thyroid disease

['Nitrate rich beverage', 'Nitrate free beverage']

Nitrate rich beverage
Nitrate free beverage

['Chronic Obstructive Pulmonary Disease']


Effects of Oral Salt Supplementation on Physical Performance During a Half-ironman

Summary: Background: Ultradistance athletes frequently consume salt supplements during competitions to compensate the loss of electrolytes by sweating. The aim of this study was to investigate the effectiveness of oral salt supplementation to improve exercise performance during a half-ironman triathlon. Methodology: Twenty-six experienced triathletes were matched for age, anthropometric data and training status and randomly placed into the salt group (113 mmol Na+ and 112 mmol Cl-) or the control group (cellulose). The experimental treatments were provided in unidentifiable capsules and were ingested before and during the race. Participants competed in a real half-ironman triathlon and race time was measured by means of chip timing. Pre and post-race, body mass, maximal force during a whole-body isometric strength test, maximal height during a countermovement jump, and blood samples were obtained. Sweat samples were obtained during the running section.
Inclusion criteria: inclusion criteria:

 -Triathletes with previous experience in half-ironman

Exclusion criteria: :

 -Potential participants (triathletes) with a previous history of muscle disorder, cardiac or kidney disease or those taking medicines or supplements during the two prior weeks were discarded.

['Salt administration', 'Placebo administration']

Salt administration
Placebo administration


Spine Quantitative Computed Tomography (QCT) for the Assessment of Osteoporosis on Children

Summary: The purpose of this study is to compare healthy children to children who have systemic lupus erythematosus (SLE). SLE is a childhood disease that has high risk for low bone mass and vertebral compression fractures.
Inclusion criteria: inclusion criteria:

 For SLE subjects: Subjects age 5-21 drawn from rheumatology clinic at Children's Hospital of Philadelphia diagnosed with SLE for at least 1 month. Also subjects with no known vertebral compression fracture of L2.

 For Control subjects: Subjects age 5-21. Controls will be a 50% male/female.

Exclusion criteria: :

 For SLE subjects: Subjects with SLE will be excluded if they have conditions or drug exposure unrelated to SLE and known to impact growth or bone health.

 For Control subjects: Chronic disease or syndrome known to affect growth or bone health, prematurity (<37 weeks gestation), or use of any medication known to affect growth.


Nitric Oxide Inhalation to Treat Sickle Cell Pain Crises

Summary: This study will examine whether nitric oxide (NO) gas can reduce the time it takes for pain to go away in patients who are in sickle cell crisis. NO is important in regulating blood vessel dilation, and consequently, blood flow. The gas is continuously produced by cells that line the blood vessels. It is also transported from the lungs by hemoglobin in red blood cells.~Patients 10 years of age or older with sickle cell disease (known SS, S-beta-thalassemia or other blood problems causing sickle cell disease) may be eligible for this study. Patients whose disease is due to hemoglobin (Hgb) SC are excluded. Candidates are screened with blood tests and a chest x-ray to look at the lungs and heart.~Participants are admitted to the hospital in a pain crisis. They are evaluated and then randomly assigned to receive one of two treatments: 1) standard treatment plus NO, or 2) standard treatment plus placebo. The placebo used in this study is nitrogen, a gas that makes up most of the air we breathe and is not known to help in sickle cell disease.~For the first 8 hours of the study, patients receive placebo or NO through a facemask. The mask may be taken off for 5 minutes every hour and for not more than 20 minutes to eat a meal. After the first 8 hours, the gas is delivered through a nasal cannula (small plastic tubing that rests under the nose) that may be taken off only while showering or using the restroom. Patients are questioned about the severity of their pain when they start the study and then every few hours while they are in the hospital. Their vital signs (temperature, breathing rate, and blood pressure) and medicines are checked. Patients will breathe the gas for a maximum of 3 days, but will stay hospitalized until the patient feels well enough to go home. Patients are followed up about 1 month after starting the study by a return visit to the hospital or by a phone call.
Inclusion criteria: inclusion criteria:

 Each subject must meet all of the following inclusion criteria during the screening process in order to participate in the study:

 Patient must have a diagnosis of SCD (known SS, S-Beta-thalassemia or other hemoglobinopathies causing sickle cell disease). Patients with disease due to Hgb SC are not permitted.

 Must present to the ED/EC or other appropriate unit in VOC.

 Greater than or equal to 10 years old.

 Written informed consent/assent has been obtained.

Exclusion criteria: :

 Subjects meeting any of the following criteria during baseline evaluation will be excluded from entry into the study:

 Exposure to therapeutic nitric oxide within the past 12 hours.

 Patient has received sildenafil or other phosphodiesterase 5 inhibitors, therapeutic L-arginine, nitroprusside or nitroglycerine within the past 12 hours.

 Patient has received previous ED/EC or other appropriate unit treatment for a vaso-occlusive crisis less than 48 hours or hospitalization less than 14 days ago (patients transferred directly from another ED or clinic may be enrolled).

 Patient has visited the ED/EC or other appropriate unit greater than 10 times in the past year having a vaso-occlusive crisis.

 Patients presenting with clinically diagnosed bacterial infection (e.g., osteomyelitis, pneumonia, sepsis or meningitis).

 Patients who are currently enrolled in any other investigational drug study except for hydroxyurea studies.

 Pregnant women (urine HCG + )/ nursing mothers.

 Patients who have received an exchange transfusion (not simple transfusion) in the last 30 days or are on a chronic simple or exchange transfusion program.

 Suspected splenic sequestration.

 Acute chest syndrome or pneumonia: Abnormal new pulmonary infiltrate (alveolar infiltration and not atelectasis) and one or more pulmonary signs and/or symptoms (fever, rales, wheezing, cough, shortness of breath, retractions).

 Previous participation in this study.


Safety Trial of Atrovent® in Pediatric Patients With Rhinorrhea Associated With a Common Cold or Allergy

Summary: Study to determine the safety of Atrovent Nasal Spray 0.06% in pediatric patients (ages 2-5 years) with symptoms of rhinorrhea associated with a naturally occurring common cold or from symptoms of rhinorrhea associated with allergies
Inclusion criteria: inclusion criteria for patients with common cold

 Male or female at least 2 but not older than 5 years of age at screening

 Have a diagnosis of a common cold defined as presence of acute onset of rhinorrhea (within 48 hours of screening visit) and at least 1 of the following:

 Presence of swollen nasal membranes characteristic of a common cold on examination at screening

 Presence of fever up to 102°F (oral or equivalent) within 48 hours of visit (may be taken at home/away from the clinic) or at time of screening

 Capability of parent/legal guardian to read and understand the informed consent, record trial diary information, administer trial drug and read and understand trial assessment questionnaire

 inclusion criteria for patients with allergies

 Male or female at least 2 but not older than 5 year of age

 Have a diagnosis of seasonal or perennial allergic rhinitis defined as having both of the following:

 Positive skin or Radioallergosorbent test (RAST) test to a relevant allergen within 12 months of screening or at the screening visit. For the purpose of this trial a positive skin test is defined as wheal diameter that is at least 3 mm greater than the negative control

 Positive prior history for atopy with nasal symptoms associated with expose to allergens

 Symptoms associated with rhinorrhea for at least 48 hours prior to the screening visit

 Capability of parent/legal guardian to read and understand the informed consent, record trial diary information, administer trial drug and read and understand trial assessment questionnaire

 General
Exclusion criteria:  for both common cold and allergy

 Significant cardiovascular, renal, hepatic, endocrine, metabolic, neurologic or other systemic disease. A significant disease was defined as one which, in the opinion of the Investigator, either put the patient at risk because of participation in the trial or influenced the results of the trial or the patient's ability to participate in the trial

 Presence of rales or rhonchi suggestive of a lower respiratory tract infection

 An oral (or equivalent) temperature higher than 102°F

 Presence of otitis media

 Be initiating or advancing immunotherapy regimen during the course of this trial. Patients receiving a maintenance dose of immunotherapy are eligible

 Known intolerance to anticholinergics of hypersensitivity to benzalkonium chloride

 Excluded medications prior to Visit 1 and during the trial included:

 24 hours before

 Over-the-counter decongestants or nasal/ocular cromolyn

 3 days before:

 Anticholinergics

 Over-the-counter antihistamines

 sympathomimetic decongestants

 5 days before:

 Fexofenadine

 Loratadine

 7 days before:

 Cetirizine

 antihistamines such as Atarax® or doxepin hydrochloride

 Antidepressants

 14 days before:

 Intranasal steroids

 28 days before:

 Steroids (oral and injectable)

 Leukotriene modifiers (e.g. Accolate®, Singulair®)

 Other investigational drugs

 Participation in any trial with an investigational drug within 30 days of the screening visit

 Nasal obstruction greater than 50% that would prevent deposition of trial drug

 The parent/legal guardian has a disability or lives in a geographical location that could impair compliance with the protocol or visits to the trial center


MI Varnish and MI Paste Plus in a Caries Prevention and Remineralization Study

Summary: The objective of this clinical study is to evaluate the efficacy of multiple applications of MI Varnish in combination with MI Paste Plus in caries protection and remineralization in comparison to the use of a control (Crest 1,100ppm Fluoride tooth paste, Fluoride rinse recommendation) in orthodontic patients in a randomized, single blind, prospective, controlled clinical trial over 12 months.~The effect will be measured by white spot lesion regression and prevention as lesion count. Lesions will be scored using the Enamel Decalcification Index (EDI) area evaluation scheme (primary outcome), International Caries Detection and Assessment System (ICDAS), the caries lesion activity criteria (Nyvad criteria; Bente Nyvad, Scandinavian Researcher), and Quantitative Light Fluorescence (QLF, Inspektor Pro, Netherlands)/SOPROLIFE (SOPROLIFE fluorescence camera system, Acteon, France) evaluation in maxillary and mandibular anterior teeth with orthodontic brackets in treatment and control groups.
Inclusion criteria: inclusion criteria:

 age 11 or older,

 good health,

 either gender

 present with at least two active white spot lesions on his/her anterior teeth at the start of the study

 have a moderate or high caries risk according to CAMBRA (Caries Management By Risk Assessment) rules

 require at least 12 additional months of full fixed appliance therapy from the time they are recruited for the study

 able to cooperate for treatment in the dental chair and follow at-home instructions

 have an understanding of the study

 willing to comply with all study procedures and protocols

 patient participant is able to provide written informed consent in English; if the participant is a minor, the parent/guardian is able to provide written informed consent in English and the patient participant is able to provide written assent in English

 patient participant or if a minor, the parent/guardian, is willing to sign the Authorization for Release of Personal Health Information and Use of Personally Unidentified Study Data for Research form; data will only be used for research

 verifiable records of bonding with Transbond Plus Self-Etching Primer (3M Unitek, Monrovia, CA) and Transbond Light Cure Adhesive or similar products

 verifiable records that ProSeal has not been applied at any time during the orthodontic treatment

Exclusion criteria: :

 untreated cavitated lesions

 extensive composite fillings on buccal surfaces of front teeth/first bicuspids or more than one dental crown on front teeth/first bicuspids

 has sealants or fluoride releasing cements on the buccal surface of the anterior teeth

 in-office fluoride treatment in the last three months

 history of using any products containing CCP-ACP (casein phosphopeptides and amorphous calcium phosphate; MI paste, chewing gums or candies, etc.), prescription Fluoride products, and Chlorhexidine use in the last three months

 intrinsic or extremely heavy extrinsic staining

 any signs of fluorosis in the dentition

 any signs of morphologic/anatomical/developmental deviations in the teeth

 previous history of in office bleaching treatment

 subject not willing to stop the use of any other oral hygiene product than those prescribed/suggested

 has underlying systemic disease which could alter enamel composition or formation

 suffering from systemic diseases, significant past or medical history with conditions that may affect oral health or oral flora (i.e. diabetes, HIV, heart conditions that require antibiotic prophylaxis)

 use of medication causing dry mouth (extreme high caries risk)

 subject is pregnant or lactating

 milk protein allergy

 any illness/condition that the investigator feels will affect the study outcome

 will leave the area and will not be available for recall visits

 subjects who are not willing to inform us about prospective visits of other dentist and will not allow us to discuss treatment with those dentist

 subjects who are not willing to refrain from any additional professional tooth cleaning or any additional Fluoride application.

['CPP-ACP 5% sodium fluoride varnish & 900ppm fluoride paste', '1,100pm F-toothpaste and 0.5%NaF rinse']


Phase 1 Study of Preoperative Gemcitabine Plus CP-870, 893 Followed by Addition of CP-870,893 to Standard -Of-care Adjuvant Chemoradiation for Patients With Newly Diagnosed Resectable Pancreatic Carcinoma

Summary: This is a pilot study to evaluate the role of the addition of CP870, 893 to the neoadjuvant and adjuvant setting for patients with resectable pancreatic cancer. Patients will receive standard surgery followed by chemoradiation for their disease, but one dose of gem/cp 870,893 will be pre-op and 3 doses post-op.
Inclusion criteria: inclusion criteria:

 Histological documentation of primary adenocarcinoma of the pancreas

 Surgically eligible for tumor resection with curative intent

 Age> 18 years old

 ECOG PS 0 or 1

 Adequate bone marrow function (WBC>3,000; Hgb>9; Plt>100)

 Adequate renal function (Cr<1.5ULN)

 Adequate hepatic function (total bilirubin WNL unless associated with hepatobiliary metastases or Gilbert syndrome, then total bilirubin <2x ULN; and alanine aminotransferase (ALT) and aspartate aminotransferase (AST) <2.5 x ULN

 Signed, written informed consent

Exclusion criteria: :

 Non ductal adenocarcinomas, neuroendocrine neoplasms, cystic tumors of the pancreas such as cystadenomas, cystadenocarcinomas and solid pseudopapillary neoplasms. In addition adenocarcinomas arising from duodenum, distal bile duct, and ampulla will also be excluded.

 Patients with M1 disease.

 Patients with any type of recurrent pancreatic adenocarcinoma

 Prior therapy such as chemotherapy or radiation therapy for pancreatic cancer

 Patients with a previous history of active malignancy within 5 years prior to study entry, except 1) in situ cervical carcinoma or 2) non-melanoma skin cancer

 Previous treatment with any other compound that targets CD40

 Concurrent treatment with any anticancer agent outside of this protocol.

 Prior allogeneic bone marrow transplant

 History of autoimmune disorder, including type 1 diabetes mellitus, pemphigus vulgaris, systemic mastocytosis, systemic lupus erythromatosis, dermatomyositis/polymyositis, rheumatoid arthritis, systemic sclerosis, Sjorgen's syndrome, vasculitis/arteritis, Behcet's syndrome, autoimmune thyroiditis, multiple sclerosis, or uveitis. Vitiligo is allowed.

 History (within the previous year) of stroke or transient ischemic attack, unstable angina, myocardial infarction, congestive heart failure.

 History of deep venous thrombosis or migratory thrombophlebitis (Trousseau);

 Hereditary or acquired coagulopathies (e.g., hemophilia, von Willebrands's disease, or cancer-associated DIC)

 Prior allergic reactions attributed to other monoclonal antibodies.

 Concurrent or planned concurrent treatment with systemic high dose (immunosuppressive) corticosteroids or treatment with systemic corticosteroids within 4 weeks of baseline.

 Treatment on another therapeutic clinical trial within 4 weeks of enrollment in this trial.

 Concurrent or planned concurrent treatment with anticoagulant such as Coumadin or heparin, except to maintain patency of in-dwelling catheters.

 Ongoing or active infection;treatment with systemic antibiotics or antifungals for ongoing or recurrent infection (topical use of antibiotics or antifungals is allowed)

 Pregnancy or breast-feeding-female patients must be surgically sterile, be post-menopausal, or must agree to use effective contraception during the period of therapy and for 12 months following the last dose of CP-870,893. All female patients with reproductive potential may not participate unless they agree to use an effective contraceptive method.

 Other uncontrolled, concurrent illness that would preclude study participation; or, psychiatric illness or social challenges that would entail unreasonable risk or preclude informed consent or compliance with study procedures.


Next-generation Sequencing (NGS) of Peripheral Blood Immune Repertoire in Graves' Disease

Summary: Graves' disease (MIM 27500) is the leading cause of hyperthyroidism worldwide. The prevalence of Graves' disease is quite high (2.7% in women), and there is solid evidence of genetic predisposition. Despite its clinical and scientific significance, Graves' disease is still mysterious in terms of its susceptibility genes or pathophysiological mechanisms. The immune repertoire, being the sum of T and B lymphocytes in a body at any given time, is both a snapshot and a historical record of a person's immune function. Thanks to the power of next-generation sequencing (NGS), massively parallel sequencing of the B cell and T cell receptors suddenly becomes plausible, and opens a door for many creative approaches to study immune related diseases. The ultimate goal of this project is to use both the NGS deep sequencing and immune repertoire experiment to perform Graves' disease sub-group genetic fine mapping, and to identify Graves' disease-specific T cell and B cell receptors. Furthermore, using the immune repertoire approach, investigators want to study the critical epitopes of thyroid auto-antigens, and to delineate the pathophysiological steps in various disease stages and in various sub-groups. Investigators expect to solve the immune repertoire of Graves' disease of different sub-group presentations and at various disease activity stages.
Inclusion criteria: Patients with Graves disease
Exclusion criteria:


Comparison of the Effects of Aripiprazole and Risperidone on the Pattern of Brain Activation in Schizophrenic Patients

Summary: After an initial screening visit, including an assessment of psychiatric disorders, patients stabilized on antipsychotic medication (aripiprazole or risperidone) for at least 6 weeks and control subjects will undergo an assessment using functional magnetic resonance imaging (fMRI) of the differences of patterns of brain activation during an emotional task
Inclusion criteria: inclusion criteria:

 For patients

 Men and women, right handed, 18 to 45 years;

 Having given their written informed consent;

 Presenting a diagnosis of schizophrenia made by DMS IV, hospitalized or followed regularly in a hospital proper, and whose symptoms are stable for at least 6 weeks, at the discretion of the psychiatrist;

 Receiving antipsychotic treatment (risperidone or aripiprazole) monotherapy stable (treatment and dose) for at least than 6 weeks;

 Showing no contra-indication for fMRI;

 Patients whose physical examination is unremarkable clinically significant;

 Patients without serious somatic pathology;

 Affiliated to a social security system.

 For women of childbearing potential, an appropriate contraception is mandatory and an negative pregnancy test

 For controls

 Men and women, right handed, aged 18 to 45 years of age, sex and socio-educational level comparable to patients included;

 Having given their written informed consent;

 Do not present a diagnosis of schizophrenia according to DSM IV set;

 Do not present psychiatric history, and free of any psychotropic medication;

 Including the physical examination is unremarkable clinically significant;

 Having no professional musical practice;

 Affiliated with a social security system.

Exclusion criteria: :

 For patients

 Patients in menstruation without effective contraception (oral, intramuscular hormonal, intrauterine device, or surgical);

 Patients who are pregnant or breastfeeding;

 Patients not meeting criteria for schizophrenia according to DSM IV criteria or those with resistant schizophrenia (Kane criteria);

 Introducing a somatic disease or serious neurological, particularly Parkinson's disease, epilepsy, tardive dyskinesia and disabling cardiovascular disease, liver or kidney disease;

 Presenting a contra-indication to MRI;

 Having a history of alcoholism or drug addiction during the past year;

 Participating in another clinical trial or are in a period of exclusion from a previous protocol;

 Patients likely to have behavioral self aggression from the trial investigators

 During the study:

 The investigator considers, for safety reasons, it is in the interest of the patient to be excluded from the study (Hospital readmission due to psychotic symptoms, clinical or psychiatric reasons)

 Consentment withdrawal

 The patient does not longer correspond to the inclusion criteria or protocol requirements

 For controls

 Women of childbearing potential without effective contraception (oral, intramuscular hormonal, intrauterine device, or surgical);

 Pregnant or breastfeeding;

 Presenting a somatic, psychiatric or neurological disorder;

 Presenting a history of alcohol or substance abuse during the past year;

 Participating in another clinical trial or are in a period of exclusion from a previous protocol;

 Presenting a contra-indication to MRI.


Diagnosis and Follow-up of Patients With Subclinical Hypothyroidism

Summary: Long term follow-up of the patients with delayed TSH elevation or subclinical hypothyroidism has been seldom reported. The purpose of this study was to explore the diagnostic criteria for subclinical hypothyroidism and the initial dosage of L-thyroxine through long-term follow up for infants with subclinical hypothyroidism ，and evaluate the curative effect.
Inclusion criteria: inclusion criteria:

 The diagnostic standard for manifest hypothyroidism and subclinical hypothyroidism was defined as follows:

 Hypothyroidism - TSH > 40 mU/L and T3 and T4 below the reference range or TSH > 40 mU/L, T3 normal and T4 below the reference range [2]

 Subclinical hypothyroidism - TSH ≥ 20 mU/L, T3 and T4 normal or low-normal or TSH > 5.6 mU/L and < 20 mU/L on initial determination and on follow-up or TSH levels increase on follow-up and/or gradually declining T4 levels.
Exclusion criteria:

['Congenital Hypothyroidism', 'L-Thyroxine', 'Follow-Up']

Congenital Hypothyroidism
L-Thyroxine
Follow-Up


Fibroid Growth Study

Summary: Uterine leiomyomas, commonly called fibroids, are a major health concern for women of reproductive age. The objectives of the study described herein are to investigate the growth dynamics of uterine leiomyomas in a clinically relevant population of women. We will test the hypotheses that uterine leiomyomas are heterogeneous in terms of their growth characteristics and in their clinical symptoms or outcomes, and that differences in leiomyoma growth dynamics can be discriminated by molecular markers and cellular phenotypes. Participants will include 300 premenopausal women (greater than 18 years old) with at least one uterine leiomyoma. The inclusion criteria for patient enrollment is confirmed diagnosis of leiomyoma by ultrasound. At least one leiomyoma must be equal to or greater than 2 cm in diameter and the uterus must be enlarged to the size typical during the eigth week of pregnancy. After enrollment and informed consent, T1- and T2-weighted magnetic resonance image (MRI) scans will be conducted beginning at the first visit and then at 3, 6, and 12 months. Each patient will have a physical exam, provide urine and blood samples at each MRI visit, and respond to an initial extensive telephone-administered questionnaire followed by abbreviated monthly questionnaire updates. A number of the enrolled women will require surgical intervention (hysterectomy/myomectomy) as standard care. If surgery is an outcome for women enrolled in the study, MRI will be conducted before surgery and the surgical pathologist will map uterine leiomyomas for comparison to MRI. Leiomyoma samples will be analyzed for histopathological and molecular changes correlated with growth. Because hysterectomy and myomectomy are common outcomes in women with leiomyomas, we anticipate tissue will be available from at least 100 of the 300 women in the study. For those women who opt for surgery, we will also administer a brief (less than 5 minute) questionnaire clarifying their reason for electing surgery. Upon completion of data collection, we will be able to compare leiomyoma growth as a function of multiplicity and location; examine the relationship between leiomyoma growth and clinical symptoms or outcome; identify molecular, cellular, and pathological characteristics of leiomyomas with differing growth dynamics; and examine endocrinological parameters and lifestyle factors related to differential growth dynamics of uterine leiomyomas. The data may be used to establish a clinical severity scale and establish diagnostic markers currently not available for uterine leiomyomas.
Inclusion criteria: inclusion criteria:

 Women included in the study must be at least 18 years if age, premenopausal, speak English, and have one or more uterine leiomyomas at least 2 cm in diameter and the utuerus must be enlarged to the size typical during the 8th week of pregnancy. Note that while the selcetion criteia are set to recruit women in which surgical intervention is a likely outcome, surgery is not a requirement for study inclusion.

Exclusion criteria: :

 Women will be excluded if they are pregnant because of potential safety concerns associated with imaging and image contrast enhancements. If women become pregnant during the study, they wil have the option to stay in the study, but will have pelvic ultrasound scans in place of MRI scans.

 Women who are taking or likely to start taking GnRH therapy will be excluded because this therapy, which is used as a treatment method for leiomyomas, sometmes induces their regression.

 Women who are greater than 52 inches in circumference or greater than 350 pounds will be excluded because they will be too large to fit in the imaging equipment.

 Women that have an intra-uterine device (IUD) will be excluded because these metal devices create 'shadowing' in MR images, making accurate measurement and interpretation of leiomyomas in the MRIs difficult.

 Women are not excluded if they had a prior myomectomy, or if they are taking oral contraceptives.

 The inclusion of only women of premenopausal age (greater than 18 years old) in this study is dictated by the nature of the condition.


Ultrasound Elasticity Imaging of Venous Thrombi

Summary: The purpose of this study is to see if the investigators can use ultrasound imaging to determine the type of clots in patients to help better manage their care.
Inclusion criteria: inclusion criteria:

 Male or female subjects who have a diagnosis of chronic DVT that is at least 2 weeks old and are free from an acute DVT on top of your chronic DVT.

 Male and female patients who have been diagnosed with an acute blood clot by the Diagnostic Vascular Lab and w/symptoms occurring within the previous 2 weeks.

 Patients under the age of 18 who give assent (permission) and whose parents give consent.

 Adult patients who give consent.

Exclusion criteria: :

 None


PROCHYMAL™ (Human Adult Stem Cells) for the Treatment of Moderate to Severe Chronic Obstructive Pulmonary Disease (COPD)

Summary: The objective of the present study is to establish the safety and efficacy of multiple administrations of Prochymal™(ex-vivo cultured human adult mesenchymal stem cells) in participants with moderate to severe chronic obstructive pulmonary disease (COPD).
Inclusion criteria: inclusion criteria:

 Participant must have a diagnosis of moderate or severe COPD.

 Participant must have a post-bronchodilator FEV1/forced vital capacity (FVC) ratio < 0.7.

 Participant must have a post-bronchodilator FEV1 % predicted value ≥ 30% and < 70%.

 Participant must be between 40 and 80 years of age, of either sex, and of any race.

 Participant must be a current or ex-smoker, with a cigarette smoking history of ≥ 10 years or > 10 pack-years.

Exclusion criteria: :

 Participant has been diagnosed with asthma or other clinically relevant lung disease other than COPD (e.g. restrictive lung diseases, sarcoidosis, tuberculosis, idiopathic pulmonary fibrosis, bronchiectasis, or lung cancer).

 Participant has been diagnosed with α1-antitrypsin deficiency.

 Participant has a body mass greater than 150 kg (330 lb) or less than 40 kg (88 lb).

 Participant has active infection.

 Participant has had a significant exacerbation of COPD or has required mechanical ventilation within 4 weeks of screening.

 The participant with clinically relevant uncontrolled medical condition not associated with COPD.

 Participant has documented history of uncontrolled heart failure.

 Participant has pulmonary hypertension due to left heart condition.

 Participant has atrial fibrillation or significant congenital heart defect/disease.

 Participant has initiated pulmonary rehabilitation within 3 months of screening.

 Participant is allergic to bovine or porcine products.

 Participant has evidence of active malignancy, or prior history of active malignancy that has not been in remission for at least 5 years.

 Participant has a life expectancy of < 6 months.

['Pulmonary Disease, Chronic Obstructive', 'Pulmonary Emphysema', 'Chronic Bronchitis']

Pulmonary Disease
Chronic Obstructive
Pulmonary Emphysema
Chronic Bronchitis


Lidocaine: Effect of Lidocaine in Chronic Cough

Summary: People cough in order to clear their airways. Most coughs are caused by viruses and settle down by themselves, but some people develop persistent coughing which can be anywhere from 8 weeks to several years. This is called chronic cough. People with chronic cough find the symptom distressing and it can have a major impact on their quality of life. Patients with chronic cough often report a sensation at the back of their throat which makes them feel an urge to cough. There is some evidence that Lidocaine (an anaesthetic used during medical procedures) can suppress a person's cough when given to patients via a nebuliser (a machine that turns liquid into a fine mist).~It is currently unknown whether using a local anaesthetic, such as Lidocaine, in the form of a throat spray would successfully suppress a person's cough. A throat spray would be an easier treatment option in chronic cough patients. Thus, the investigators research aims to compare cough rates, severity and urge to cough scores between Lidocaine throat spray and nebulised Lidocaine.
Inclusion criteria: inclusion criteria:

 Male and female subjects, age 18 years and over.

 History of cough for more than 8 weeks.

 Normal chest x ray

 Chronic idiopathic cough or chronic cough resistant to treatment of specific triggers.

Exclusion criteria: :

 Smoking status:

 Current smokers

 Ex smokers with history of smoking > 20 pack years or those who have given up < 6 months ago.

 Prohibited medications:

 Use of medications likely to suppress / affect cough including codeine, morphine, pregabalin, gabapentin, amitriptylline, angiotensin converting enzyme inhibitors (type 1) and baclofen.

 Use of any anti-arrhythmic medication.

 Use of cimetidine, beta blockers, or diuretics.

 Cardiovascular conditions:

 Sinoatrial disease, bradycardia or all types of heart blocks.

 History of ischaemic heart disease or heart failure.

 Clinically significant abnormal electrocardiogram (ECG) at Screening or Baseline.

 History of cardiac surgery

 Respiratory conditions:

 o Asthma.

 Central nervous system / Peripheral nervous system conditions:

 Epilepsy.

 Myasthenia gravis.

 Miscellaneous:

 History of hepatic or renal dysfunction.

 Porphyria

 History of hypersensitivity to Lidocaine or related drugs.

 Pregnancy or breast feeding.

 Participation in another trial within the preceding 6 weeks.

 Trauma or ulceration to oral mucosa.

 History of chest or upper airway infection within the past 6 weeks.

 Conditions which may affect cough response such as stroke, diabetes, Parkinson's Disease.

['10 % Lidocaine', '10 % Lidocaine', '0.9% saline']

10 % Lidocaine
10 % Lidocaine
0.9% saline


Evaluation of Renal Blood Flow Using Contrast Enhanced Ultrasound for Differential Diagnosis of Acute Kidney Injury in Cirrhotic Patients: A Pilot Study

Summary: Hepatorenal syndrome (HRS) is a common cause of acute kidney injury (AKI) in cirrhotic patients and has a one month survival rate of 50% and a 3 month survival rate of 20%. The leading theory behind HRS is selective vasoconstriction of renal vasculature in the setting of decreased systemic vascular resistance. Patients with liver cirrhosis suffer from a large degree of third spacing in the form of peripheral edema and ascites. In addition treatment with multiple drugs, including diuretics puts these patients at higher risks of prerenal AKI and ischemic acute tubular necrosis (ATN). AKI occurring due to HRS, prerenal AKI and ischemic or nephrotoxic ATN have different pathophysiologic mechanisms and are treated differently with significantly different outcomes. While renal perfusion is expected to be reduced in HRS and prerenal AKI, it is normal or increased in ATN. Prerenal AKI has the most favorable prognosis among these pathologies and treatment simply consists of volume expansion with blood, albumin, crystalloids or colloids. In clinical practice vasoactive agents such as midodrine and octreotide are used to increase the tone of splanchnic vessels and to improve renal perfusion. These interventions would not affect renal function in cases with ATN. Unfortunately, the diagnostic criteria proposed by the International Club for Ascites (ICA) for HRS are not specific and do not always exclude patients with other forms of acute kidney injury. Therefore, availability of a simple diagnostic tool for measurement of renal blood flow (RBF) at the bedside would be of great value in management of cases with cirrhosis of the liver presenting with acute reduction in kidney function. However, currently, there are no practical and simple tools available for this purpose.~Contrast enhanced ultrasonography (CEU) involves the intravenous injection of gas-filled microbubbles to enhance the ultrasound image of the organs and mainly to assess tissue vascularity and blood flow. We and others have used CEU to assess changes in RBF in response to physiologic stimuli and therapeutic interventions. Here we propose a prospective, pilot diagnostic study to validate the use of CEU, in assessing RBF in cirrhotic patients with AKI, and to assess the utility of CEU to differentiate between causes of AKI in cirrhotic patients.~Our hypothesis is that CEU will show arteriolar vasoconstriction and decreased blood flow in the renal cortex in patients with HRS which would not change in response to volume expansion. On the contrary, patients with prerenal AKI will have reduced RBF which will increase after volume expansion. Finally, those with ATN will not have a reduced RBF at baseline.~We plan to enroll 25 patients with liver cirrhosis and acute kidney injury who are admitted to the University of Virginia hospital into the study.~CEU will be performed on all subjects to measure baseline RBF. CEU will be repeated in all subjects within 24 hours after volume expansion with at least 1gm/kg of albumin (up to 100 gm/day) to assess a potential change. Hourly urine output and serum creatinine will be monitored for potential renal response to the volume expansion as part of clinical care. For the subgroup of subjects who receive treatment with combination therapy with albumin, midodrine, and octreotide (AMO) RBF assessment with CEU will be repeated after at least 48 hours of receiving this combination. Renal response will be assessed by monitoring urine output and serum creatinine monitored as part of clinical care. All subjects will have measurements of fractional excretion of sodium (FENa) and urea (FEUrea) and urine microscopy as a part of their routine clinical care (work up of AKI). The results of these tests and the response to volume expansion will be used to categorize subjects into three categories of AKI (HRS, prerenal AKI, ATN). Correlations between RBF and its changes between different therapeutic interventions and renal diagnosis will be tested in this study.
Inclusion criteria: inclusion criteria:

 Age >18 years

 Cirrhosis of liver

 Hospitalization at University of Virginia Medical Center

 Diagnosis of acute kidney injury based on AKIN criteria

Exclusion criteria: :

 Known history of a right to left intracardiac shunt

 Known history of pulmonary hypertension, including portopulmonary hypertension

 Pregnancy or lactation

 History of allergies to Definity®

 History of Liver or Kidney Transplant

 Patient on hemodialysis

['Liver Cirrhosis and Acute Kidney Injury']


Combination Chemotherapy and Radiation Therapy in Treating Patients With Cancer of the Esophagus

Summary: RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage tumor cells. Combining radiation therapy with chemotherapy may kill more tumor cells.~PURPOSE: Phase I trial to study the effectiveness of combination chemotherapy and radiation therapy in treating patients with cancer of the esophagus.
Inclusion criteria: DISEASE CHARACTERISTICS: Histologically confirmed epidermoid carcinoma or adenocarcinoma of the esophagus eligible for potentially curative radiotherapy Disease in one of the following categories: Newly diagnosed Locoregional failure after prior resection with curative intent Positive microscopic margin after palliative resection of all gross disease Disease clinically limited to esophagus T 1-4, any N, M0 Gastroesophageal junction tumor allowed No positive pleural, pericardial, or peritoneal cytology No tracheobronchial invasion on bronchoscopy, including tracheoesophageal fistula

 PATIENT CHARACTERISTICS: Age: 18 and over Performance status: Karnofsky 60-100% Hematopoietic: WBC more than 4,000/mm3 Platelet count at least 150,000/mm3 Hepatic: Bilirubin no greater than 1.5 mg/dL Renal: Creatinine no greater than 1.5 mg/dL OR Creatinine clearance at least 65 mL/min per 1.73 square meters Cardiovascular: No NYHA class 3/4 status No cerebral vascular disease No hypertension Other: No severe uncontrolled diabetes No uncontrolled infection No other medical condition that precludes treatment No mental status abnormality that precludes comprehension of or compliance with treatment No active cancer arising at another primary site other than basal cell carcinoma of the skin or in situ cervical carcinoma

 PRIOR CONCURRENT THERAPY: No prior chemotherapy or radiotherapy
Exclusion criteria:

['chemotherapy', 'cisplatin', 'paclitaxel', 'low-LET electron therapy', 'low-LET photon therapy']

chemotherapy
cisplatin
paclitaxel
low-LET electron therapy
low-LET photon therapy


Organized Program To Initiate Lifesaving Treatment In Hospitalized Patients With Heart Failure (OPTIMIZE-HF)

Summary: This program is designed to improve medical care and education of hospitalized patients with heart failure and accelerate the initiation of evidence-based heart failure guideline recommended therapies by administering them before hospital discharge. A registry component focusing on admission to discharge and 60- to 90-day follow-up is designed to evaluate the demographic, pathophysiologic, clinical, treatment, and outcome characteristics of patients hospitalized with heart failure.
Inclusion criteria: inclusion criteria:

 Hospitalized for episode of worsening heart failure as primary cause of admission or significant heart failure symptoms that develop during the hospitalization when the initial reason for admission was not heart failure.

 Systolic dysfunction (LVEF < 40%) or heart failure symptoms in the setting of preserved systolic function (diastolic dysfunction).

Exclusion criteria: :

 This study has no

['Beta-blockers including Carvedilol', 'ACE inhibitors']

Beta-blockers including Carvedilol
ACE inhibitors


Safety and Feasibility of the Injectable BL-1040 Implant

Summary: This is a Phase I, multi-center, open label study designed to assess the safety and feasibility of the injectable BL-1040 implant to provide scaffolding to infarcted myocardial tissue.
Inclusion criteria: inclusion criteria:

 Signed informed consent

 18 to 75 years of age, inclusive

 Male or female

 Negative pregnancy test for women of child-bearing potential, or surgically sterile, or post menopausal

 Acute MI defined as:

 Typical rise and gradual fall (troponin) or more rapid rise and fall (CK-MB) of biochemical markers of myocardial necrosis with at least one of the following:

 Ischemic symptoms;

 Development of pathologic Qwaves on the ECG;

 ECG changes indicative of ischemia (ST segment elevation or depression)

 First anterior or inferolateral STEMI or Qwave MI (QMI Anterior: V1-V3 or V1-V4 or V1-V5 or V1-V6.QMI Inferior: L2, L3, AVF, or L2, L3, AVF+ V5, V6 or L2, L3, AVF+ V6-V9 [posterior leads])

 Regional wall motion score index (at least 4 out of 16 akinetic segments)

 One or more of the following:

 LVEF >20% and <45% measured and calculated by 2-dimensional measurement

 Biomarkers: peak CK > 2000 IU

 Infarct size > 25% as measured by MRI

 Successful revascularization with PCI with 1 stent only, within 7 days of the index MI

 At time of application of study device, patient must have patent infarct related artery (IRA) and TIMI flow grade = 3

Exclusion criteria: :

 History of CHF, Class I to Class IV, as per NYHA criteria

 History of prior LV dysfunction

 At time of application of study device - Killip III-IV (pulmonary edema, cardiogenic shock - hypotension systolic < 90 mmHg and evidence of peripheral hypoperfusion oliguria, cyanosis, sweating) or HR > 100 bpm

 Prior CABG

 Prior MI

 History of stroke

 Significant valvular disease (moderate or severe)

 Patient is a candidate for CABG or PCI on non-IRA

 Patient is being considered for CRT within the next 30 days

 Renal insufficiency (eGFR < 60)

 Chronic liver disease (> 3 times upper limit of normal)

 Life expectancy < 12 months

 Current participant in another clinical trial, or participation in another trial within the last 6 months

 Any contraindication to coronary angiography, MRI or PCI procedures

 Patient taking anti-coagulation medication prior to MI

 Pregnant or lactating women; pregnancy confirmed by urine pregnancy test


Trial of Amoxicillin Compared With Placebo for Pneumonia in Children Aged 2-59 Months

Summary: Many children with non-severe pneumonia (cough and fast breathing) have neither clinical pneumonia as assessed by physicians nor pneumonia on chest radiographs. Inappropriate use of antibiotics for these cases is leading to resistant strains of bacteria in the community. Evidence shows that almost 50% of antibiotic prescription is unnecessary.As over half of antibiotic prescription for ARI are not necessary since most of these infections are viral and do not respond to antibiotic therapy which will be source of resistance in the community.~To address this issue the investigators conducted this randomized, double blind placebo controlled clinical trial of oral Amoxicillin versus placebo in children with non-severe pneumonia taking into account all the necessary safety precautions for their well being.~The study hypothesis was that the clinical outcome of children 2 to 59 months of age with cough and fast breathing (WHO defined non-severe pneumonia) with or without wheezing is equivalent, whether they are treated with amoxicillin or placebo.
Inclusion criteria: inclusion criteria:

 Children aged 2 to 59 months attending the outpatient's clinics of participating sites

 WHO defined non-severe pneumonia

 Accessibility for follow-up

 Written informed consent by a parent or legal guardian

Exclusion criteria: :

 WHO signs of severe pneumonia recognised by lower chest wall retraction. Children who present with wheezing will be evaluated for lower chest wall indrawing after treatments with nebulised salbutamol. WHO signs of very severe disease/pneumonia defined as any of the following:

 Cyanosis

 Inability to drink

 Convulsions

 Abnormally sleepy or difficult to wake

 Severe malnutrition recognised by weight for age less than third percentile by the NCHS (National Child Health Statistics) growth chart and/or oedema (see chart).

 All patients with a previous history of 3 or more episodes of wheeze or diagnosed to have asthma.

 Known or clinically recognisable congenital heart disease with cyanosis or, congestive heart failure or cardiomegaly.

 Known or clinically recognisable acute/chronic organ system disorders including jaundice, nephrotic syndrome, severe anaemia manifested as extreme pallor etc.

 Other infectious conditions requiring antibiotic therapy at the day of contact including meningitis, tuberculosis, dysentery, osteomyelitis, septic arthritis etc.

 Children who have taken the appropriate doses of WHO-recommended dose of anti microbial drug for 48 hours prior to presentation.

 A history of hospitalization in the past 2 weeks

 Measles or a history of measles within the last month: Measles recognized by presence of fever with rash, and conjunctivitis.

 Prior enrolment in the current trial.

 Known penicillin allergy, including a history of rash, urticaria, or anaphylactic symptoms.

 The children living outside the municipal limits of the city who cannot be followed up.

['Acute Respiratory Infections', 'Pneumonia']


Latent Viral Infection of Lymphoid Cells in Idiopathic Nephrotic Syndrome

Summary: The primary purpose of the study is to evaluate the association of a latent infection of lymphoid cells during the first manifestation of steroid sensitive nephrite syndrome. The thirty nine units of general pediatrics and pediatric nephrite covering the parisian area will participate to the study. We speculate that hybridization of the genome, or a part of the genome, of a virus in lymphoid cells is responsible specific changes of genes expression, leading to the development of the disease.
Inclusion criteria: inclusion criteria:

 proteinuria over 0.25 g/mmol of creatinine with hypoalbuminemia below 30g/L for the case

 No history of renal disease

 Normal C3 and negativity for hepatitis B and C

Exclusion criteria: :

 no medical insurance

 inclusion in another study


Substudy : Patients With an Acute Exacerbation of Chronic Obstructive Pulmonary Disease

Summary: Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality worldwide. Its prevalence is in progression and COPD is expected to become the fourth leading cause of death by 2030. COPD is characterized by periods of stability interspersed with acute infectious/inflammatory flare-ups, also called acute exacerbations, during which patients deteriorate, sometimes to the point of requiring immediate medical assistance. Although most patients eventually recover, repeated episodes of exacerbations may accelerate COPD progression. Exacerbations may further compromise the integrity of limb muscles by promoting further loss in muscle mass and strength.~The overall objective of this substudy is to elucidate how an acute COPD exacerbation may affect limb muscles.
Inclusion criteria: inclusion criteria:

 male and female

 COPD with an FEV1 of under 60% of predicted

 non-smoker

 between 50 and 75 years old

 experiencing an acute exacerbation of COPD (24-48 hours, before treatment)

Exclusion criteria: :

 all inflammatory disease (HIV, cancer, renal and cardiac deficiency)

 hormonal dysregulation

 inferior limb pathology

 neuromuscular pathology

 history of tobacco or alcool abuse

 oxygen dependent

['No specific intervention for this study']


Long-term Treatment for Cancer Patients With Deep Venous Thrombosis or Pulmonary Embolism

Summary: Background~Patients with cancer and a first deep venous thrombosis of the leg or pulmonary embolism (venous thromboembolism, VTE) are generally treated with low molecular weight heparin (LMWH)injections for 6 months, since this treatment is associated with a reduced incidence of recurrent VTE compared to vitamin K antagonists (VKA). It is recommended that patients with active malignancy (metastatic cancer and/or ongoing cancer treatment)continue anticoagulant treatment. However, it is unknown whether LMWH is still superior compared to VKA for the long-term anticoagulant treatment.~Aim~The aim of this study is to evaluate whether low-molecular-weight heparin more effectively reduces recurrent VTE compared to vitamin K antagonists in patients with cancer who have already completed 6 to 12 months of anticoagulant treatment because of deep venous thrombosis of the leg or pulmonary embolism.~Hypothesis~The investigators hypothesize that LMWH is more effective compared to VKA in the long-term treatment of VTE in cancer patients who have already been treated for 6-12 months with anticoagulants.~Design~This is a multicenter, multinational, randomized, open label trial.~Patients~Patients with a malignancy (all types, solid and hematological) who have received 6-12 months of anticoagulation for VTE and have an indication for continuing anticoagulation, will be randomly assigned to six additional months of LMWH or VKA. LMWH will be administered in a weight-adjusted scheme, with 65-75% of therapeutic doses. All types of LMWH and VKA are allowed, as long as weight adjusted dosing is possible for LMWH. The target INR will be 2.0-3.0. The primary efficacy outcome is symptomatic recurrent VTE, i.e. deep vein thrombosis and pulmonary embolism. The primary safety outcome is major bleeding.~Sample size~A total of 65 to 87 recurrent VTE events are needed to show a 50% reduction with LMWH as compared to VKA (type I error 0.05, two-sided, power respectively 80 and 90%). To observe 75 events, with a 10% event rate per half year in the VKA arm and 5% in the LMWH arm a total of 1000 patients will need to be included.~Organisation~Outcomes will be adjudicated by a central adjudication committee. A steering committee will be formed, preferably consisting of one member of every participating center. An electronic case report form will be used for data collection. Also, an electronic trial master file will be used.
Inclusion criteria: inclusion criteria:

 Patients with cancer and confirmed pulmonary embolism (PE) or deep vein thrombosis (DVT) of the leg who have been treated for minimally 6 and maximally 12 months with therapeutic doses of anticoagulants, i.e. LMWH or VKA or a new anticoagulant in a trial

 Written informed consent

 Indication for long-term anticoagulant therapy (e.g. because of metastasized disease, chemotherapy)

Exclusion criteria: :

 Legal age limitations (country specific), minimum age at least 18 years

 Indications for anticoagulant therapy other than DVT or PE

 Any contraindication listed in the local labeling of LMWH or VKA

 Childbearing potential without proper contraceptive measures, pregnancy or breastfeeding

 Life expectancy <3 months

['low molecular weight heparin', 'vitamin K antagonists']

low molecular weight heparin
vitamin K antagonists


Zonegran in the Treatment of Binge Eating Disorder Associated With Obesity

Summary: The specific aim of this study is to examine the efficacy and safety of zonisamide compared with placebo in outpatients with binge eating disorder associated with obesity.
Inclusion criteria: inclusion criteria:

 Patients will meet DSM-IV criteria for BED for at least the last 6 months. These criteria are as follows:

 Recurrent episodes of binge eating. An episode of binge eating is characterized by both of the following: (1) eating, in discrete period of time (eg, within any two hour period), an amount of food that is definitely larger than most people would eat in a similar period of time under similar circumstances and (2) a sense of lack of control over eating during the episode (eg, a feeling that one cannot stop eating or control what or how much one is eating)

 The binge eating episodes are associated with at least three of the following:

 Eating much more rapidly than normal

 Eating until uncomfortably full

 Eating large amounts of food when not feeling physically hungry

 Eating alone because of being embarrassed by how much one is eating

 Feeling disgusted with oneself, depressed, or feeling very guilty after overeating

 Marked distress regarding binge eating.

 The binge eating occurs, on average, at least two days a week for six months.

 Does not occur exclusively during the course of bulimia nervosa and anorexia nervosa.

 Obesity as defined by body mass index > 30 kg/m2.

 Men or women, between the ages of 18 and 65. The patient population is expected to be predominantly made up of women based on previous research.

Exclusion criteria: :

 Have current body mass index < 30kg/m2.

 Women who are pregnant or lactating and women of childbearing potential who are not taking adequate contraceptive measures. If there is a possibility a female subject might be pregnant, a pregnancy test will be performed. (All women of childbearing potential will have a negative pregnancy test before entering the study.)

 Subjects who are displaying clinically significant suicidality or homicidality.

 Subjects who are displaying a current clinically unstable depressive disorder (e.g., HAM-D > 21).

 A current or recent (within 6 months of the start of study medication) DSM-IV diagnosis of substance abuse or dependence.

 A lifetime history of a DSM-IV bipolar disorder or dementia.

 History of a personality disorder (eg, schizotypal, borderline, or antisocial) which might interfere with assessment or compliance with study procedures.

 Clinically unstable medical disease, including cardiovascular, hepatic, renal, gastrointestinal, pulmonary, metabolic, endocrine or other systemic disease which could interfere with diagnosis, assessment, or treatment of binge eating disorder. Patients should be biochemically euthyroid prior to entering the study.

 History of seizures, including febrile seizures in childhood

 History of clinically significant nephrolithiasis.

 Subjects requiring treatment with any drug which might interact adversely with or obscure the action of the study medication (e.g. stimulants, sympathomimetics, antidepressants, carbonic anhydrase inhibitors, anti-obesity drugs).

 Subjects who have received psychoactive medication (other than zaleplon [Sonata] or zolpidem [Ambien] -- as needed for restlessness/insomnia) within one week prior to randomization.

 Subjects who have begun and/or are receiving formal psychotherapy (cognitive behavioral therapy, interpersonal therapy, or dietary behavioral therapy) for BED or weight loss within the past 3 months.

 Subjects previously enrolled in this study or have previously been treated with zonisamide.

 Subjects who have received an experimental drug or used an experimental device within 30 days.

['Binge Eating Disorder Associated With Obesity']


Vitamin D Supplementation in Systemic Lupus Erythematosus

Summary: Systemic Lupus Erythematosus (SLE) is a systemic autoimmune disorder. It mainly involves the skin, the joints, the nervous system and the kidney and may be life threatening.~SLE is associated with production of autoantibodies and perturbations in regulatory T cells and T helper lymphocytes producing interleukin (IL)-17 (Th17 cells).~Treatments include corticosteroids, hydroxychloroquine and immunosuppressive agents.~Immunomodulatory effects of vitamin D supplementation in VITRO was recently described, notably the expansion of Treg able to suppress inflammatory responses mediated by CD4+ and CD8+ T cells and the decrease of Th17 cells.
Inclusion criteria: inclusion criteria:

 Systemic lupus erythematosus

 Age > 18 years

 Serum vitamin D levels [25(OH)D] < 30 ng/mL

 Low to moderate active disease without modification of associated treatments

Exclusion criteria: :

 Pregnancy

 Serum 25(OH)D levels > 30 ng/mL

 Flare requiring modification of treatments


Second Generation Drug-Eluting Stents Implantation Followed by Six Versus Twelve-Month - Dual Antiplatelet Therapy

Summary: Prospective, randomized, non-inferiority, multicenter, international study.In total 4000 patients (70 centers in Europe) with de novo lesions in native coronary arteries who meet the eligibility criteria randomized to 6 versus 12 month dual antiplatelet therapies following a second generation DES implantation.~Assuming that the true proportion of thrombotic events is equal to 2.3% for both regimens (6-month and 12-month clopidogrel) 2000 patients for each treatment group are necessary to demonstrate a non-inferiority of the 6-months regimen if the proportion of thrombotic events will be no more than 3.5% with a power of 0.80 and a significance level of 0.05 (one-tail).~If the non-inferiority hypothesis will be rejected, the superiority hypothesis (12-months regimen is superior to the 6-months-regimen) will be tested at a significance level of 0.05 (two-tails).~The maximal not clinically relevant difference for the non-inferiority hypothesis of 1.2 % more thrombotic events has to be considered together with the lower expected number of bleeding events in the 6-months regimen.~All the analysis will be done as intention-to-treat analysis.
Inclusion criteria: inclusion criteria:

 Diagnosis of angina pectoris as defined by Canadian Cardiovascular Society Classification (CCS I,II, III, IV) OR unstable angina pectoris (Braunwald Classification B&C, I-II-III) OR patients with documented silent ischemia, all treated with a second generation drug eluting stent

 Presence of one or more de novo stenosis equal or greater than 70% in a native coronary artery, treated with a Resolute drug eluting stent

 Patient is > 18 years of age (or minimum age as required by local regulations).

 The patient has consented to participate by signing the Patient Informed Consent Form

 The patient is willing and able to cooperate with study procedures and required follow up visits

 Any type of lesion or number of lesion can be included in this trial unless specifically detailed in the
Exclusion criteria: .

 At least one second generation DES implanted in the target lesion in the last 24 hours

 No other DES implanted before the target procedure

 No BMS implanted in the 12 months before the target procedure


Nutrition Study of Effect of High Iron Beans on Iron Status

Summary: The purpose of this study is to determine whether beans bred to have a high iron content are effective in improving the iron status of young women.
Inclusion criteria: inclusion criteria:

 Non-pregnant adolescent subjects of reproductive age with low iron stores with or without mild anemia, who are otherwise healthy, will be enrolled in the study

Exclusion criteria: :

 Pregnant, lactating, severe anemia, low BMI would be excluded


Safety and Effectiveness of Giving CPI-1189 to HIV-Infected Patients With AIDS Dementia

Summary: The purpose of this study is to see if it is safe and effective to give CPI-1189 to patients with AIDS dementia.~Advanced HIV infection can cause AIDS dementia (brain damage due to HIV leading to loss of memory and muscle control). CPI-1189 may be able to postpone AIDS dementia or slow it down.
Inclusion criteria: inclusion criteria

 You may be eligible for this study if you:

 Are HIV-positive.

 Are at least 18 years old.

 Have symptoms of AIDS dementia including forgetfulness, loss of concentration, slow mental processing, or a loss of muscle control.

 Have been on stable anti-HIV drug therapy for the past 6 weeks (if you are taking anti-HIV drugs).

Exclusion criteria:

 You will not be eligible for this study if you:

 Have certain serious medical conditions, such as a mental disorder or an opportunistic (AIDS-related) infection.


Escitalopram as a Mood Stabilizer for Bipolar II Disorder

Summary: This study will investigate the efficacy of Escitalopram, a Selective Serotonin Reuptake Inhibitor (SSRI) antidepressant, in the treatment of Bipolar II Disorder.~The use of antidepressants for those with bipolar disorder appears common in clinical practice but is not countenanced - at least as monotherapy - in formal treatment guidelines. This view reflects concerns about the possibility of antidepressant drugs inducing switching and rapid cycling in those with Bipolar Disorder. Although the effectiveness of treating Bipolar II patients with SSRIs has received very little attention in the literature, observations of Bipolar II patients treated with SSRIs suggest they may have general mood stabilising properties. Many patients have reported improvements not only in their depressed mood, but also a reduction in the severity, duration and frequency of hypomanic episodes.~In this proof of concept study we specifically assess whether a standard dose of an SSRI antidepressant is more effective than placebo in reducing the frequency, severity and duration of both depressive and hypomanic episodes.
Inclusion criteria: inclusion criteria:

 Aged 18-65

 Minimum two year history of depressive and hypomanic episodes

 Mood episodes occuring monthly

 Meet DSM-IV criteria for Bipolar II Disorder (with exception of minimum 4 day period for hypomanic episodes)

Exclusion criteria: :

 Previous treatment with any antidepressant, mood stabilizer or neuroleptic medication

 History of psychotic symptoms during hypomanic or depressive episodes

 Current suicidal behaviours

 Current substantive illicit drug use or alcohol consumption

 Significant personality disorder

 Pregnancy or breastfeeding

 History of heart disease, liver disease, epilepsy or seizures


Problem Adaptation Therapy (PATH) vs. Supportive Therapy in Treating Depressed, Cognitively Impaired Older Adults

Summary: This study will evaluate the efficacy of Problem Adaptation Therapy (PATH) vs. Supportive Therapy for Cognitively Impaired (ST-CI) older adults in reducing depression and disability in treating depressed, cognitively impaired older adults.
Inclusion criteria: inclusion criteria:

 Meets Diagnostic and Statistical Manual for Mental Disorders(DSM)IV criteria for unipolar major depression

 Severity of depression greater than or equal to 17 on MADRS

 Disability as determined by at least 1 impairment in instrumental activities of daily living

 Evidence of executive dysfunction or impairment in at least one of the following cognitive domains of Dementia Rating Scale (DRS): attention, construction, conceptualization, and memory ([scaled score less than 7] adjusted for age and race based on Mayo's older participants normative data)

 Family member or caregiver able and willing to participate in treatment

 Not currently taking antidepressants, cholinesterase inhibitors, or memantine or on a stable dosage for 8 weeks prior to study entry with no medical recommendation for change of these agents in the near future

Exclusion criteria: :

 High suicide risk

 Axis I psychiatric disorder or substance abuse other than unipolar major depression or nonpsychotic depression

 Axis II diagnosis of antisocial personality

 Moderate to severe dementia: DRS total score corresponding to moderate or more severe impairment (scaled score less than or equal to 5)

 Acute or severe medical illness (e.g., delirium; metastatic cancer; decompensated cardiac; liver or kidney failure; major surgery; stroke; myocardial infarction during the 3 months prior to entry)

 Currently taking drugs known to cause depression (e.g., reserpine, alpha-methyl-dopa, steroids)

 Currently receiving psychotherapy

 Aphasia

 Sensory problems

 Inability to speak English


A Comparison of Propofol Based Total Intravenous Anesthesia and Desflurane Based Balanced Anesthesia on Renal Protection During Deceased Brain Dead Donor Kidney Transplantation - A Prospective, Randomized Trial

Summary: Renal ischemia/reperfusion (I/R)-induced injury is known to be associated with immediate and long-term kidney dysfunction after renal transplantation. Protecting the kidney against I/R injury and maintaining renal function during renal transplant surgery is therefore very important in order to improve post-operative outcome. This purpose of this study is to investigate whether propofol anesthesia done in both kidney donors and recipients during deceased brain dead donor kidney transplantation is effective in reducing renal I/R injury via its antioxidant and antiinflammatory properties and improve post-transplant outcome compared to desflurane anesthesia.
Inclusion criteria: inclusion criteria:

 Adult deceased brain dead kidney donors and recipients scheduled for renal transplantation

Exclusion criteria: :

 1. Donor

['Desflurane balanced anesthesia', 'Propofol total intravenous anesthesia']

Desflurane balanced anesthesia
Propofol total intravenous anesthesia


Safety and Feasibility of Endovascular Cooling Device in Patients With Hypothermic Cardiopulmonary Resuscitation

Summary: Hypothermic resuscitation is proven to be benefit to the cardiac origin cardiac arrest patients for it improve brain recovery dramatically. However, traditional cooling devices and methods, most external cooling methods, include ice blanket, cooling helmet, or ice packing lower the body temperature slowly or inefficiently which make many emergency physicians hesitate to perform hypothermic resuscitation. To improve and promote the practice of hypothermia resuscitation, more efficient temperature control method is necessary. We conduct this clinical trial to evaluate the safety and feasibility of internal cooling catheter and temperature regulatory device, which is approved by FDA in neurologic ICU for temperature control, in the cardiac arrest patients.
Inclusion criteria: inclusion criteria:

 Non-traumatic collapsed patients, whose pulsation continues and persists more than 5 minutes after return of spontaneous circulation from cardiopulmonary resuscitation and consciousness level is less than GCS 5 points.

Exclusion criteria: :

 1. Age > 78 y/o or < 18 y/o 2. Core temperature< 34℃or > 38 ℃ after resuscitation 3. Pregnancy 4. Underline terminal malignancy disorder or refuse aggressive treatment cancer patient 5. Massive bleeding, known coagulopathy, or received regular anticoagulant medication 6. Persisted hypotension ( mean arterial BP < 60 mmHg) after resuscitation even under inotropic agents 7. No bed available in ICU


Antibiotics Versus Surgery in Acute Appendicitis

Summary: The acute appendicitis (AA) is a very common disease with a life time risk 7-8% and the highest incidence in the second decades . The aetiology of AA is still poor understood: the commonest hypothesis refers to appendix obstruction followed by impairment of wall appendix barrier and thus wall perforation and/or abscess formation1. However some studies suggest that no-complicate and complicate appendicitis are different entities allowing a different treatment. The study aims to test the no inferiority in terms of efficacy of antibiotic treatment compared to surgery in a population with high probability to suffer of 1st episode of AA.The study aims to test the no inferiority in terms of efficacy of antibiotic treatment compared to surgery in a population with high probability to suffer of 1st episode of AA.
Inclusion criteria: inclusion criteria:

 patients between 18 and 65 years old

 first episode of suspected AA diagnosed by Andersson's score or combination with abdominal ultrasound

Exclusion criteria: :

 patients with any potential immunodeficiency status

 assumption of antibiotics for different infectious disease or surgery in the last 30 days

 allergy to antibiotics established in the study protocol

 no acceptance of study protocol

 pregnancy or delivery in the last 6 months

 ASA IV or V, no Italian or English fluently speakers.

['Acute Appendicitis Without Peritonitis']


WalkMore Walking Interventions for Overweight/Obese Postmenopausal Women

Summary: The WalkMore study will help find out how walking interventions can help overweight/obese postmenopausal women with increased risk of cardiovascular disease lower their blood pressure.
Inclusion criteria: inclusion criteria:

 Woman between 45-74 years of age

 Have not had a menstrual period for at least 12 months

 Are not regularly physically active (self-reported non-exerciser for previous 6 months)

 Have a body mass index (BMI) between 25-45 kg/m2

 Have high normal blood pressure or (systolic pressure of 130-179 mmHg or a diastolic pressure of 85-99 mmHg)

 Not limited in your ability to walk

 Understand these criteria

 Are willing to provide informed consent

 Willing to be randomized to either type of walking intervention or a control group being studied, and are willing to follow the protocol for the group to which they have been assigned

Exclusion criteria: :

 Have a past history and/or physical examination or laboratory findings of a medical condition including (but not limited to):

 Have any medical condition or disease that is life-threatening or that can interfere with or be aggravated by exercise

 Have been diagnosed with diabetes

 Blood pressure is greater than 179 mmHg systolic or 99 mmHg diastolic.

 Participating in another research study which may effect the results of WalkMore

['Basic Intervention', 'Enhanced Pedometry', 'Control Group']

Basic Intervention
Enhanced Pedometry
Control Group

['Postmenopausal Disorder', 'Blood Pressure', 'Over Weight']

Postmenopausal Disorder
Blood Pressure
Over Weight


Bioequivalency Study of 300 mg Lithium Carbonate Under Fed Conditions

Summary: The objective of this study was the bioequivalence of a Roxane lithium carbonate 300 mg extended release tablet formulation compared to Solvay's Lithobid 300 mg extended release tablet under fed conditions using a single-dose, randomized, 2 treatment, 2-period, 2-sequence crossover design.
Inclusion criteria: inclusion criteria:

 No clinically significant abnormal findings on the physical examination, medical history, or clinical laboratory results during screening.

Exclusion criteria: :

 Positive test for HIV, Hepatitis B, or Hepatitis C.

 Treatment with known enzyme altering drugs.

 History of allergic or adverse response to lithium, or any comparable or similar product.


Clinical Evaluation of the Response to Chest Physiotherapy in Children With Acute Bronchiolitis

Summary: The objective of this study is to evaluate the clinical response of children diagnosed with acute bronchiolitis, relative to a chest physiotherapy protocol. Comparing this treatment with standard care of the nursing staff and auxiliaries of infants patients aged 1 month to 2 years.
Inclusion criteria: inclusion criteria:

 Patients admitted to the pediatric intensive care unit or pediatric nursing unit. Which they are diagnostic of acute viral bronchiolitis (AVB).

Exclusion criteria: :

 Presence of cyanotic congenital heart disease no longer for comparing the constants.

 Relative or absolute contraindication CPT techniques included in the protocol.

 Patients diagnosed with moderate or severe gastroesophageal reflux since the PSE gastroesophageal reflux can accentuate a previously exist.

 Patients with laryngeal diseases caused because the cough is a technique that is applied directly to the tracheal wall and can affect the larynx.

 Absence of cough reflects and presence of laryngeal stridor is a contraindication to chest physiotherapy in general.

 Systematic presence of gag reflex as the aspiration of secretions and coughing caused nasobucales stimulate this reflex

['Nebulization of hypertonic saline', 'Prolonged slow expiration technique (PSE)', 'Patient coughing Provocation (TP)', 'inspiratory maneuver to rhinopharyngeal cleaning DRR', 'Aspiration of secretions']


Post Operative Sore Throat and Dexamethasone

Summary: Sore throat is a common postoperative complaint that can lead to morbidity and patient dissatisfaction . The incidence of sore throat has been reported to be between 6% and 90% even under optimal intubating conditions. There are several factors that have been shown to contribute to postoperative sore throat such as patient related factors, type of anesthesia and type of surgery.~Corticosteroids are also commonly used in the perioperative period to potentiate analgesics and as antiemetics. The preoperative administration of dexamethasone can decrease the incidence and severity of postoperative sore throat which is rated by patients as one of the most undesirable outcomes in the postoperative period.
Inclusion criteria: inclusion criteria:

 Female patients undergoing outpatient laparoscopic gynecologic surgery

 ASA PS I and II

 Age between 18 and 64 years

 Fluent in English

Exclusion criteria: :

 History of recent respiratory tract infection

 Pregnancy, breastfeeding

 Current treatment with analgesics

 Current use of corticosteroids

 Anticipated difficult intubation

 Risk factors for post-operative aspiration

['Placebo administration', 'Dexamethasone 0.05mg/kr administration', 'Dexamethasone 0.1mg/kg']

Placebo administration
Dexamethasone 0.05mg/kr administration
Dexamethasone 0.1mg/kg


Home Hypnotherapy for Refractory Functional Chest Pain: A Pilot Study

Summary: The primary aim is to develop and test the feasibility of a standardized digital audio home-hypnotherapy (HHT) program for patients with refractory functional chest pain (FCP).~The secondary aims of this study are:~To obtain pilot data to assess the magnitude of the treatment effect of self-hypnosis in refractory FCP for an anticipated future, larger treatment trial;~To determine the stability of the treatment effect of HHT in refractory FCP;~To assess the relationship between response to HHT and psychological factors; and~To assess the relationship between response to HHT and symptomatic dimensions of chest pain (severity, frequency, and duration).~To assess the difference
Inclusion criteria: inclusion criteria:

 Age 18 to 80, male or female.

 Patients must fulfill the Rome III criteria for Functional Chest Pain of Presumed Esophageal Origin for the previous 3 months (with symptom onset at least 6 months before diagnosis), including all of the following:

 Midline chest pain or discomfort that is not of burning quality

 Absence of evidence that gastroesophageal reflux is the cause of the symptom

 Absence of histopathology-based esophageal motility disorders

 Persistent symptoms despite a trial of antidepressant therapy, as defined by either:

 chest pain despite at least a continuous 4-week trial of at least one antidepressant within the last 6 months; or

 intolerance of at least one antidepressant within the last 6 months.

 Negative cardiac evaluation (negative cardiac stress test or negative coronary angiogram)

 Negative gastrointestinal evaluation for cause of the pain, defined by absence of Los Angeles grade C or D erosive esophagitis on endoscopy, persistent chest pain on PPI therapy, and no association of chest pain with reflux episodes on an ambulatory pH or pH-impedance study, defined as a symptom index <50% or symptom association probability <95% for chest pain .

Exclusion criteria: :

 Severe co-morbid illness (cardiac, pulmonary, renal, hematologic, hepatic)

 Prior treatment with hypnosis/hypnotherapy for a medical condition

 Prior major thoracic surgery

 Prior diagnosis of or treatment for dissociative disorders, post-traumatic stress disorder, borderline personality disorder, or other psychiatric disorders that include psychotic features

 Pregnancy or planned pregnancy within the upcoming 3 months

 Inability or unwillingness to give informed consent


A Phase I Trial of T Cells Expressing an Anti-GD2 Chimeric Antigen Receptor in Children and Young Adults With GD2+ Solid Tumors

Summary: Background~GD2 is a well-characterized tumor antigen in neuroblastoma, which is also expressed on osteosarcomas and some other sarcomas. T cells expressing 1st generation anti-GD2 chimeric antigen receptors (CARs) were safe and mediated modest antitumor activity in some patients with refractory neuroblastoma.~A 3rd generation anti-GD2-CAR (GD2-CAR.OX40.28.z.ICD9) has been produced and holds promise for increased activity compared to the 1st generation GD2-CAR already studied in clinical trials. As an added safety measure, the vector includes a suicide switch comprising a caspase dimerization domain (ICD9) that can be activated by a small molecule to induce death of the genetically engineered cells if they were induce untoward toxicity.~Objectives~Primary:Determine the feasibility of producing anti GD2-CAR cells meeting the established release criteria and to assess the safety of administering escalating doses of anti-GD2-CAR engineered T cells in children and young adults with GD2+ solid tumors, including neuroblastoma, following cyclophosphamide-based lymphodepletion.~Secondary:~Determine if administration anti-GD2-CAR engineered T cells mediate antitumor effects in children and young adults with GD2+ solid tumors;~Measure persistence of adoptively transferred anti-GD2-CAR T cells and correlate this with antitumor effects;~Extend information regarding the prevalence and intensity of GD2 expression in non-neuroblastoma, non-osteosarcoma solid tumors in children and young adults;~If unacceptable toxicity occurs that is possibly, probably or likely related to anti-GD2-CAR T cells, assess the capacity for AP1903, a dimerizing agent, to mediate clearance of the genetically engineered cells and resolve toxicity; and~Assess toxicity of AP1903 if administered to mediate clearance of anti-GD2-CAR T cells.~Eligibility~Patients 1-35 years of age, at least 15 kg, with osteosarcoma or a GD2+ solid tumor (including neuroblastoma) that has recurred after or not responded to standard therapy and is deemed incurable by standard therapy.~Design~After apheresis to collect T cells for transduction, patients receive cyclophosphamide 1800mg/m(2)/d as a lymphodepleting regimen. A phase I cell dose escalation scheme will used at 4 dose levels (1 x 10(5) transduced T cells/kg; 1 x 10(6) transduced T cells/kg; 3 x 10(6) transduced T cells/kg; and 1 x 10(7) transduced T cells/kg), using a standard 3 plus 3 dose escalation design. An expanded group of a total of 12 patients will be treated at the highest dose, comprising at least 6 osteosarcoma patients.~Patients will be monitored for toxicity, antitumor effects and persistence of anti-GD2-CAR T cells.~Patients with a PR, SD may receive a 2nd cycle at the next higher dose level a minimum of 60 days following completion of the first cycle if eligibility criteria are met.~A maximum of 36 patients may be treated on this study. Given that there is likelihood that some patients with non-osteosarcoma will not meet the criteria for GD2 expression to be eligible for enrollment, up to 72 subjects will be screened to enroll a maximum of 36 patients for treatment. Up to 2-3 patients will be accrued per month, and therefore this study may require up to 2-3 years to complete enrollment and treatment.~...
Inclusion criteria: inclusion criteria:

 Diagnosis

 (a) Osteosarcoma, neuroblastoma and melanoma that have been treated with standard frontline therapy and are judged to be incurable with standard therapy, based upon the fact that they are unresectable, metastatic, progressive/persistent or recurrent.

 Evaluable disease must be present.

 i) For all histologies except osteosarcoma and neuroblastoma, pathologic review of frozen tissue must document GD2+ expression. Positive expression is defined as at least 2+ expression (0-4+ scale) in >50 percent of the tumor cells using anti-GD2 mAb 14G2a. If adequate archived frozen tissue is available, this may be utilized, or if not, patients may undergo biopsy following enrollment to obtain tissue to assess GD2 expression, with the following restrictions.

 ii) Patients with histologies other than osteosarcoma or neuroblastoma must have adequate accessible tumor for biopsy (at least 1 cm diameter).

 iii) Procedures employed to acquire biopsies for tumor lysates will be limited to percutaneous needle or core biopsies, thoracoscopic excision or open biopsies of readily accessible lesions. Pulmonary lesions may be biopsied but extensive surgery such as thoracotomy or laparotomy should not be employed.

 iv) Patients who will require biopsy should not be enrolled if in the opinion of the principal investigator, the tumor site places the patient at substantial risk from the biopsy procedure.

 Weight greater than or equal to 15 kg

 Age less than or equal to 35 years old at the time of enrollment.

 Prior Therapy:

 The patient s malignancy must have relapsed after or failed to respond to frontline curative therapy and/or there must not be any curative treatment options available at the time of study entry.

 There is no limit to the number of prior treatment regimens. However, patients must have fully recovered from the acute toxic effects of prior chemotherapy, immunotherapy, or radiotherapy prior to study enrollment. Any grade 3 or 4 non-hematologic toxicity of any previous therapy must have resolved to grade 2 or less.

 Myelosuppressive chemotherapy: Patients must not have received myelosuppressive chemotherapy within 3 weeks of enrollment (6 weeks if prior nitrosourea).

 Hematopoietic growth factors: At least 7 days must have elapsed since the completion of therapy with a growth factor. At least 14 days must have elapsed after receiving pegfilgrastim.

 At least 7 days must have elapsed since the completion of therapy with a biologic agent, targeted agent, tyrosine kinease inhibitor or a metronomic nonmyelosuppressive regimen.

 Monoclonal antibodies: At least 4 weeks must have elapsed since prior therapy that included a monoclonal antibody.

 Radiotherapy: 3 weeks must have elapsed since XRT

 Performance status:

 ECOG 0, 1 or 2, or for children less than or equal to 10 years of age, Lansky greater than or equal to 60.

 Cardiac function:

 Left ventricular ejection fraction greater than or equal to 40 percent or fractional shortening greater than or equal to 28 percent.

 Liver function:

 Serum total bilirubin < 2 mg/dl, serum AST and ALT less than or equal to 3 x upper limit of normal. Patients with Gilbert s syndrome are excluded from the requirement of a normal bilirubin and patients will not be excluded if liver enzyme elevation is due to tumor involvement. (Gilbert s syndrome is found in 3-10% of the general population, and is characterized by mild, chronic unconjugated hyperbilirubinemia in the absence of liver disease or overt hemolysis). NOTE: Adult values will be used for calculating hepatic toxicity and determining eligibility, as is standard on POB phase I trials.

 Renal function:

 Age-adjusted normal serum creatinine according to the following table or a creatinine clearance greater than or equal to 60 ml/min/1.73 m(2).

 Age less than or equal to 5 Maximum serum creatinine (mg/dl) 0.8

 Age greater than 5 and less than or equal to 10 Maximum serum creatinine (mg/dl) 1.0

 Age greater than 10 and less than or equal to 15 Maximum serum creatinine (mg/dl) 1.2

 Age greater than 15 Maximum serum creatinine (mg/dl) 1.5

 Marrow function:

 ANC must be > 750/mm(3), platelet count must be greater than or equal to 75,000/mm(3) (not achieved by transfusion).

 Ability to give informed consent.

 For patients <18 years of age, their legal guardian must give informed consent. Pediatric patients will be included in age-appropriate discussion in order to obtain verbal assent.

 Durable power of attorney form offered (patients (Bullet)18 years of age only).

 Birth Control

 Female and male patients (and when relevant their partners) must be willing to practice birth control (including abstinence) during and for two months after treatment, if of childbearing potential.

Exclusion criteria: :

 Concurrent Illnesses

 Clinically significant systemic illness (e.g. serious active infections or significant cardiac, pulmonary, hepatic or other organ dysfunction), that in the judgment of the PI would compromise the patient s ability to tolerate protocol therapy or significantly increase the risk of complications.

 Peripheral nerve symptoms from prior therapies or from tumor compression > grade 1.

 Untreated CNS metastasis

 Extradural masses that have not invaded the brain parenchyma or parameningeal tumors without evidence for leptomeningeal spread will not render the patient ineligible. Patients with previous CNS tumor involvement that has been treated and is stable for at least 6 weeks following completion of therapy are eligible.

 Prior Therapy

 Previous treatment with genetically engineered GD2-CAR T cells. Previous vaccine therapy, anti-GD2 mAb therapy or therapy with other genetically engineered T cells is not an

['Anti-GD2-CAR engineered T cells', 'AP1903', 'Cyclophosphamide']

Anti-GD2-CAR engineered T cells
AP1903
Cyclophosphamide

['Sarcoma', 'Osteosarcoma', 'Neuroblastoma', 'Melanoma']

Sarcoma Osteosarcoma Neuroblastoma Melanoma


A Randomized Phase II Trial to Compare the Safety and Neutralizing Activity of CL184 in Combination With Rabies Vaccine vs. HRIG or Placebo in Combination With Rabies Vaccine in Healthy Adult Subjects

Summary: The aim of this study is to evaluate the safety of the monoclonal antibody cocktail CL184 in combination with rabies vaccine compared with human rabies immune globulin (HRIG) or placebo in combination with rabies vaccine in healthy adult subjects.
Inclusion criteria: inclusion criteria:

 Subjects free of obvious health-problems or with stable condition

 Male or female subjects aged ≥19 to ≤65 years

 BMI between ≥18 and ≤30 kg/m2

Exclusion criteria: :

 Prior history of active or passive rabies immunization

 Clinically significant acute illness or infection within 2 weeks before first dosing based on the clinical judgment of the investigator

 History and/or family history of clinically significant immunodeficiency or auto-immune disease

 Any clinically significant history of known or suspected anaphylaxis or hypersensitivity reaction

 Chronic administration of immunosuppressants or other immune-modifying drugs within 6 months before the first dose of investigational medicinal product

['CL184', 'HRIG', 'Placebo matching CL184']


Laparoscopic Appendectomy for Chronic Right Lower Abdominal Pain

Summary: It is questionable whether elective appendectomy can effectively reduce pain in persistent or recurrent lower abdominal quadrant pain due to chronic appendicitis.~A single centre randomised double-blind sham surgery controlled clinical trial studied the effects of elective laparoscopic appendectomy on postoperative pain perception in patients with persistent or recurrent lower abdominal quadrant pain on abdominal pain at 6 months postoperatively. Secondary outcome was the relation between clinical response and the appendix' histopathology. The analysis was performed on an intention-to-treat basis. Pain scores were compared using a Fisher's exact test.
Inclusion criteria: inclusion criteria:

 Patients were eligible if they were between 15 and 45 years of age, and if they suffered from chronic or recurrent right lower abdominal quadrant pain for more than three months. They were to experience continuous pain, or should have endured at least one pain attack in the month prior to inclusion.

Exclusion criteria: :

['laparoscopic appendectomy or not (surgery)']


The Functional and Clinicopathological Roles and Therapeutic Implication of Connective Tissue Growth Factor in Peritoneal Metastasis of Gastric Cancer

Summary: For the past 50 years, gastric cancer has been one of the ten most frequent cancers and the second leading cause of cancer-related death in the world. In Taiwan, it is the fifth most common cause of cancer-related deaths, accounting for 6.3% of all cancer deaths. The poor prognosis of gastric cancer is mostly caused by the extensive metastasis to the lymph nodes, liver, and peritoneal dissemination even if curative resection was performed. The main cause of recurrence after curative or noncurative resection of advanced tumors is peritoneal metastasis because of possible direct spillage and dissemination of tumor cells as a result of surgical manipulation, and it is associated with a poor prognosis. As yet, no effective treatment has been developed for this condition. The development of peritoneal metastasis is a multistep process, beginning with attachment to peritoneal mesothelial cells, retraction of the mesothelial cells and exposure of the basement membrane, attachment to the basement membrane, degradation in the extracellular matrix, proliferation by the cancer cells, and angiogenesis, and it is clear that many types of agents are involved at the various stages of this process. Developing a new therapeutic method for this mode of metastasis is very important for improvement of gastric cancer treatment.~CTGF is a secretory protein belonging to the CCN family (one among the three originally discovered members: cysteine-rich61, CTGF, and nephroblastoma-overexpressed gene). It is a multifunctional growth factor involved in wound healing, inflammation, cell adhesion, chemotaxis, apoptosis, tumor growth, and fibrosis. Recent studies showed that overexpression of CTGF in human oral squamous cell carcinoma reduces cell growth and tumorigenecity. Similar tumor growth inhibitory effects were observed in lung cancer cells in which CTGF overexpression was less angiogenic and metastatic due to blocking of the VEGF A signaling pathway. CTGF was also reported to be a key regulator of colorectal cancer invasion and metastasis, and it appears to be a better prognostic factor. These studies suggest that CTGF may involve the processes of peritoneal metastasis which includes cancer cell adhesion in peritoneum, proliferation and angiogenesis. Peritoneal mesothelium is the first surface encountered by disseminated tumor cells and successful adhesion is, therefore, of paramount importance in metastasis formation. Therefore, we hypothesized that CTGF is a potential molecule target, which may be related to cell adhesion to peritoneum, the first step of peritoneal metastasis, and its exact mechanism may includes proliferation and angiogenesis.~In order to answer these important questions, first, we have performed the preliminary studies to prove CTGF did express in different gastric cancer cell lines including AGS, N87, TSGH, and MKN-45 by using RT-PCR and Western blotting, and gastric cancer tissues by using immunohistochemical method. Second, we demonstrated different levels of CTGF expression in different cell lines pose different adhesion ability in in-vitro adhesion assay. Third, we conducted a transient CTGF-overexpressed MKN45 gastric cancer cell line, and CTGF-overexpressed cell line had lower adhesive ability compared to the control.~Next step in this project, we will be studying the roles of CTGF plays in cellular and molecular biology in vitro and in vivo and clinical significance associated with therapeutic potential of peritoneal metastasis from gastric cancer. We will generate stable clones of MKN45 cells harboring CTGF and its control cell line to elucidate the roles of CTGF in cancer cell adhesion, proliferation and angiogenesis in peritoneum.
Inclusion criteria: inclusion criteria:

 Gastric cancer patients who are elegible for curative surgery

 Age 25-90

Exclusion criteria: :

 Gastric cancer patients who are not elegible for curative surgery


Osteoporosis School

Summary: The purpose of this study is to investigate the efficacy of systematic education (osteoporosis school) on fall frequency, compliance and quality of life of a group of patients more than fifty years of age.~Hypothetically, systematic information can increase compliance to the medical treatment, decrease the frequency of falls and increase the quality of life.
Inclusion criteria: inclusion criteria:

 fracture caused by osteoporosis

 fifty years or more of age

 informed consent

Exclusion criteria: :

 - Physically or mental state that does not participation

['Intensive systematic information (osteoporosis school)']