Background: The lymphatic system is a network of vessels that carry a clear fluid called lymph through the body. Problems in the lymphatic system can cause pain, fluid buildup, and issues with immunity. There is much researchers do not understand about lymphatic anomalies. In this natural history study, they will collect data from a lot of people over a long time. Objective: To better understand why lymphatic anomalies develop. The goal is to improve future treatments. Eligibility: People aged 0 days and older with a suspected or confirmed lymphatic anomaly. Their unaffected parents or siblings aged 7 years or older are also needed. Design: Participants may remain in the study indefinitely. Affected participants may be evaluated every 10 months to 2 years. Some participants will be seen over telemedicine. Others will be seen at the NIH Clinical Center for 2-5 days. All participants will have a physical exam. They may provide specimens including blood, saliva, hair follicles, stool, skin, and other tissues. Samples may be used for genetic testing. Participants may undergo other tests depending on their medical conditions. The NIH Clinical Center visit may include: Heart tests include placing stickers on the chest to measure electrical activity and using sound waves to capture pictures of the heart. A lung test measures the muscle strength in the chest. Participants will blow into a tube. Photographs may be taken of participants faces and other features. Imaging scans will take pictures of the inside of the body. One scan will measure bone density. One type of scan tracks how lymph fluid moves through the body. Participants will be under anesthesia, and they will be injected with a dye.

Type: Observational

Start Date: Mar 2023

open study

Background: Fanconi anemia (FA) is an inherited disorder. People with FA are more likely to get certain cancers, especially squamous cell carcinoma (SCC). These cancers usually appear first in the mouth, esophagus, and genital and anal areas. Early detection of SCCs may help improve survival rates for people with FA. Objective: This natural history study will regularly screen people with FA for SCC. Eligibility: People aged 12 years and older with FA or a prior cancer diagnosis. Children aged 8 to 11 years with FA may also be eligible. Design: Participants will receive a comprehensive screening for cancer or early signs of cancer. Participants will have a physical exam. They will provide blood and saliva samples. Cells will be collected by rubbing a swab on the inside of the cheeks. A skin sample may be removed from the back, buttocks, or inside of the upper arm. Participants will have pictures taken of their mouth. Any mouth sores will be mapped. Cells will be collected from the sores with a small brush. Specialists will examine the participant s ears, nose, throat, teeth, and skin. Adult participants may have a gastrointestinal exam or pelvic exam. Participants may have an endoscopy. A long tube with a camera and a light will be inserted through the mouth and down into the stomach. Participants may have a liver ultrasound. A wand will be pressed against their belly to get pictures of the organs inside the body. Participants will have screenings every year for up to 10 years. Each visit will last up to 3 days. They will have remote follow-up visits every 6 - 8 months....

Type: Observational

Start Date: Mar 2023

open study

Background: - Plaquenil (hydroxychloroquine) is an anti-inflammatory drug that is used to treat some autoimmune diseases such as lupus and rheumatoid arthritis. This drug can damage the retina by causing a condition called Plaquenil-induced retinal toxicity, which may lead to vision loss. However, most people taking Plaquenil do not develop this problem. Researchers are interested in studying whether differences in a person's genes explain why some people develop Plaquenil-induced retinal toxicity while others do not. Objectives: - To investigate possible correlations between certain genes or genetic mutations and Plaquenil-induced retinal toxicity. Eligibility: - Individuals at least 18 years of age who have previously used Plaquenil. - History of systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), or Sjogren's syndrome. - Both individuals who have and have not developed Plaquenil-induced retinal toxicity will be eligible for this study. Design: - The study requires five annual outpatient visits to the NIH Clinical Center. - Participants will provide a personal and family medical history, and will have a full eye examination. - Participants will also provide blood samples for genetic analysis, including whole exome and whole genome sequencing. - No treatment will be provided as part of this protocol.

Type: Observational

Start Date: Aug 2010

open study

This study will evaluate subjects with adult- and childhood-onset myositis to learn more about their cause and the immune system changes and medical problems associated with them. Myositis is an inflammatory muscle disease that can damage muscles and other organs, resulting in significant disability. Children or adults with polymyositis or dermatomyositis or a related condition may be evaluated under this study. Healthy children or adults will also be enrolled as "controls," for comparison of test results. All patients will undergo a complete history (including completing some questionnaires) and physical examination, review of medical records, and blood and urine tests. Patients may then choose to participate in an additional 1- to 5-day evaluation, which will include some or all of the following diagnostic, treatment or research procedures: 1. Standardized muscle strength testing, range of motion of joints and walking (gait) analysis by a physiotherapist; completion of a questionnaire regarding ability to perform daily tasks 2. Skin assessment, possibly including photographs of lesions and a skin biopsy (removal of a small skin sample under local anesthetic) 3. Magnetic resonance imaging (scans that use magnetic fields to visualize tissues) of leg muscles 4. Swallowing studies, including a physical examination and questionnaire on swallowing ability, studies of tongue strength, and ultrasound imaging during swallowing, and possibly, a modified barium swallow 5. Voice and speech assessment, possibly including computerized voice analysis and laryngoscopy-analysis of the larynx (voice box) using a small rigid scope with a camera placed in the mouth to view and record vocal cord function 6. Pulmonary function tests (measurement of air moved into and out of the lungs, using a breathing machine) to evaluate lung function and, possibly, chest X-ray 7. Electrocardiogram (measurement of the electrical activity of the heart) and, possibly, echocardiogram (ultrasound imaging of the heart) 8. Endocrine evaluation 9. Eye examination, in patients with vision loss or other eye symptoms 10. Nutrition assessment to evaluate muscle mass and muscle wasting, including tape measurements or bioelectric impedance testing, a painless procedure in which wires are attached to the extremities with a sticky paste. 11. Muscle ultrasound. 12. Electromyography (record of the electrical activity of muscles) 13. Muscle or skin biopsy (removal of a small piece of muscle tissue for microscopic examination) All patients may have only a one-time evaluation or may return for one follow-up evaluations (either the 1-day or 3- to 5-day evaluation) over a 1-year period. Healthy children will undergo a medical history and brief physical examination; blood and urine tests; speech and swallowing studies including questionnaires and physical examination, tongue strength, and ultrasound study; and bioelectric impedance testing. Children 8 to 18 years old may also have exercise testing.

Type: Observational

Start Date: Jun 1995

open study

Background: Lung transplants can save lives, but the procedure has risks. Some people develop donor-specific antibodies (DSA) after the procedure-that is, their bodies create proteins that treat the new lungs as foreign and mount an immune response against them. This is called rejection. But not everyone who has a transplant develops DSA, and not everyone who has DSA develops rejection. Researchers want to understand why. Objective: To collect data to try to find out why some people develop rejection after lung transplants while others do not. Eligibility: People aged 18 to 75 years who have progressive lung disease or undergone or may undergo a lung transplant. Design: Participants will have clinic visits every 3 to 6 months for up to 4 years. Some visits might require an overnight stay. Each visit will include multiple tests and procedures: Physical exam with blood and urine tests. Some blood will be used for genetic testing. Imaging scans. Participants will have 2 types of scan to get images of their lungs. For one, they will have a contrast agent given through a tube inserted into a vein. Six-minute walk test. Participants will walk back and forth in a hallway at their own pace. Researchers will check on how their body responds. Lung function test. Participants will breathe into a tube connected to a machine. Two other tests are optional: Bronchoscopy with washings (lavage). A long tube with a light will be threaded down through the participant s nose or mouth and into their lungs. Endomicroscopy. During the bronchoscopy a tiny camera may be used to take pictures inside the lungs. ...

Type: Observational

Start Date: May 2026

open study

Background: Blood cancers (such as leukemias or lymphomas) often do not respond to standard treatments. A transplant of blood stem cells from a healthy donor can help people with these cancers. Sometimes these transplants cause serious side effects, including a common immunologic problem called graft-versus-host disease. A drug called cyclophosphamide given early after the transplant (post-transplantation cyclophosphamide, PTCy) can reduce these complications. But sometimes this drug has its own negative effects. Furthermore, studies in mice suggest that an intermediate, rather than very high, dose of this drug may best protect against graft-versus-host disease. Objective: To find out if a lower dose of PTCy is more helpful for people who undergo blood stem cell transplants. Eligibility: People aged 18 and older who have a blood cancer and are eligible for a transplant of blood stem cells from another person. Healthy donors are also needed but must be related to the individual needing the transplant. Design: Participants will undergo screening. Transplant recipients will have imaging scans and tests of their heart and lung function. They will be assessed for the status of their cancer, including bone marrow taken from their pelvis and possibly also scans and/or fluid drawn from the spine depending on the disease type. Donors will be screened for general health. They will give several tubes of blood. They will give an oral swab and saliva and stool samples for research. Recipients will be in the hospital at least 4 to 6 weeks. They will have a temporary catheter inserted into a vein in the chest or neck. Medications will be given and blood will be drawn through the catheter. The transplanted stem cells will be given through the catheter. Participants will receive medications both before and after the transplant. Participants will return to the clinic at least once a week for 3 months after leaving the hospital. Follow-up visits will continue periodically for 5 years.

Type: Interventional

Start Date: Nov 2022

open study

Background: Researchers want to learn more about head and neck disorders. Understanding these disorders could help them find better treatments. To do this, they are collecting tissue samples for research. Objective: To create a repository of tissue samples and data to better study conditions of the head and neck. Eligibility: People who had or will have tissue samples taken because of a head or neck disorder. They must be ages 3 and older and not pregnant to join Part 2. Design: Participants will be screened with a questionnaire, medical history, and physical exam. Part 1. Participants will give permission for any of their tissue samples leftover from private care or other research protocols to be used. If participants tissue did not contain normal tissue or if they have a condition that suggests a genetic issue, they will be invited to join Part 2. Part 2: Participants will have additional samples collected. These could be: - Blood: Blood is drawn through a needle in the arm. - Cheek swab or brushing: A cotton swab or small brush is rubbed inside the cheek. - Saliva: They rinse their mouth with water and spit into a tube or cup. - Skin biopsy: They are injected with a numbing drug. A biopsy tool removes a small piece of skin. - Mucosal biopsy: They are injected in the mouth with a numbing medication. A small piece of tissue from the inside of the cheek is removed. Participants samples will be used for future research, including genetic testing.

Type: Observational

Start Date: May 2018

open study

Without an explanation for severe and sometimes life-threatening symptoms, patients and their families are left in a state of unknown. Many individuals find themselves being passed from physician to physician, undergoing countless and often repetitive tests in the hopes of finding answers and insight about what the future may hold. This long and arduous journey to find a diagnosis does not end for many patients- the Office of Rare Diseases Research (ORDR) notes that 6% of individuals seeking their assistance have an undiagnosed disorder. In 2008, the National Institutes of Health (NIH) Undiagnosed Diseases Program (UDP) was established with the goal of providing care and answers for these individuals with mysterious conditions who have long eluded diagnosis. The NIH UDP is a joint venture of the NIH ORDR, the National Human Genome Research Institute Intramural Research Program (NHGRI-IRP), and the NIH Clinical Research Center (CRC) (1-3). The goals of the NIH UDP are to: (1) provide answers for patients with undiagnosed diseases; (2) generate new knowledge about disease mechanisms; (3) assess the application of new approaches to phenotyping and the use of genomic technologies; and (4) identify potential therapeutic targets, if possible. To date, the UDP has evaluated 3300 medical records and admitted 750 individuals with rare and undiagnosed conditions to the NIH Clinical Center. The NIH UDP has identified more than 70 rare disease diagnoses and several new conditions. The success of the NIH UDP prompted the NIH Common Fund to support the establishment of a network of medical research centers, the Undiagnosed Diseases Network (UDN), for fiscal years 2013-2020. The clinical sites will perform extensive phenotyping, genetic analyses, and functional studies of potential disease-causing variants. The testing performed on patients involves medically indicated studies intended to help reach a diagnosis, as well as research investigations that include a skin biopsy, blood draws, and DNA analysis. In addition, the UDN will further the goals of the UDP by permitting the sharing of personally identifiable phenotypic and genotypic information within the network. By sharing participant information and encouraging collaboration, the UDN hopes to improve the understanding of rare conditions and advance the diagnostic process and care for individuals with undiagnosed diseases.

Type: Observational

Start Date: Sep 2015

open study

Human phagocytic cells such as polymorphonuclear leukocytes (PMNs) are readily mobilized to sites of infection and ingest microorganisms by a process known as phagocytosis. The combined effects of reactive oxygen species (ROS) and proteolytic peptides and enzymes released into forming bacterial phagosomes kill most ingested bacteria. However, many human bacterial pathogens have devised means to subvert normal phagocyte responses and the innate immune response and cause severe disease. The overall objective of this study is to elucidate specific features of pathogen-phagocyte interactions that underlie evasion of the innate immune response or contribute to the pathophysiology of disease or inflammatory disorders. Therefore, specific projects will: 1. Identify and characterize specific mechanisms used by pathogenic microorganisms to evade or subvert normal phagocyte responses and therefore cause disease. 2. Investigate phagocyte response mechanisms to specific pathogenic microorganisms. 3. Identify specific bacterial structures and/or (gene) products that dictate differences in phagocyte responses among a range of pathogens so that generalized statements can be made about the pathophysiology of disease states. The studies will be performed using multiple techniques including state-of-the-art equipment for genomics and proteomics strategies to identify target bacterial genes/proteins of interest or those up-regulated in phagocytes. Phagocyte-pathogen interactions will be examined using fluorescence-based real-time assays and video microscopy, confocal and electron microscopy in combination with enzymatic assays for ROS production, routine biochemistry, immunology and cell biology. Implementing these studies will require isolation of phagocytic leukocytes from venous blood of healthy human volunteers. The study population will be all-inclusive except in certain instances where individuals possess genetic defects that impair phagocyte function (e.g., myeloperoxidase-deficiency) or have altered phagocyte function due to outside influences such as recent bacterial or viral infection. The proposed studies will likely provide new information pertinent to understanding host cell-pathogen interactions and the pathophysiology of inflammatory conditions....

Type: Observational

Start Date: Feb 2001

open study

This study will investigate how genetic and environmental factors contribute to the development of melanoma, a type of skin cancer, and related conditions. Individuals >=4 weeks with a personal or family history of melanoma or atypical spitzoid/Spitz tumor may be eligible for this study. Participants will: - Fill out one or two questionnaires about their personal and family medical history. - Provide written consent for researchers to review their medical records and pathology materials related to their care and those of deceased relatives with melanomas, tumors, cancer, or other related illnesses for whom they are the next-of-kin or legally authorized representative. - Donate a blood or cheek cell sample to be used for genetic studies. (The blood sample is collected through a needle in an arm vein. The cheek cell sample is obtained either by gently brushing the inside of the mouth with a soft brush or by swishing a tablespoon of mouthwash and then spitting it into a container.) - Undergo a skin biopsy (removal of a small piece of skin tissue) for genetic study. For this procedure, the area of skin to be removed is numbed with a local anesthetic and a 1/4-inch piece of skin is excised with a cookie cutter-like instrument. The wound is then covered with a band-aid. Participants may be asked to travel to the NIH Clinical Center for evaluation, including a medical history, physical examination, and some of the following procedures: - Full body skin examination to evaluate the type and number of moles and document any evidence of sun damage to the skin. The examination involves all the skin from the scalp to the bottoms of the feet. After the examination, a medical photographer will photograph the skin, with close-ups of skin lesions marked by the examiner. If there are parts of the skin the participant does not want examined or photographed, he or she can tell the examiner. - Blood draw of about 120 milliliters (4 ounces) or less - Skin biopsy - Cheek cell sample - X-rays, ultrasound and magnetic resonance imaging (MRI) studies to detect tumors or changes in tumors or other types of changes in specific tissues. MRI is a diagnostic test that uses strong magnetic fields and radiowaves to examine body tissues. The subject lies on a table that is moved into a large tunnel-like machine (the scanner) for about 45 minutes to 1 hour. When the tests are finished, a doctor will discuss the results with the participant and the need, if any, for clinical follow-up.

Type: Observational

Start Date: Jul 2002

open study

This study will examine rare congenital disorders that involve malformations and abnormal growth. It will focus on patients with Proteus syndrome, whose physical features are characterized by overgrowth, benign tumors of fatty tissue or blood vessels, asymmetric arms or legs, and large feet with very thick soles. The study will explore the genetic and biochemical cause and course of the disease, the changes in symptoms over time, and the effects of the disease on patients. Patients with Proteus syndrome may be eligible for this study. Study candidates will have a medical history and physical examination, including X-rays and possibly other imaging tests, such as computerized tomography (CT), magnetic resonance imaging (MRI) and ultrasound. Other tests and examinations may be done if needed. Those enrolled in the study may be interviewed or complete questionnaires, or both, about how their disease affects them. Patients will provide a small blood sample for research.

Type: Observational

Start Date: Apr 1994

open study

Background: Anxiety disorders are becoming more common among children and teenagers. Anxiety can lead to long-term physical and mental problems, such as depression. Treatments for anxiety disorders include medications as well as cognitive behavioral therapy (CBT); CBT is a form of talking therapy. Both approaches work in only about 50 percent of cases. A new approach, called gaze-contingent music reward therapy (GCMRT), may help. Objective: To find out whether GCMRT combined with CBT is more effective than CBT alone. Eligibility: Children aged 8 to 17 years with separation anxiety disorder; generalized anxiety disorder; or social anxiety disorder. They must be enrolled in protocol 01-M-0192. Design: Participants will come to the clinic once a week for 4 weeks for CBT. Sometimes the participant will meet with the doctor alone; sometimes their parent may be present. They will do some computer-based tasks: They may be asked to push a button when a target appears; they may look at pictures of faces while the computer tracks their eye movements. Participants will take questionnaires each week. They will answer questions about their anxiety symptoms, feelings, and behavior. For the next 8 weeks, participants will participate in both CBT and 1 of 2 types of GCMRT. GCMRT is a computer-based task. Participants will look at pictures with many faces in them; while they do this, pleasant music will play and stop playing over a 12-minute period. Participants will have a final visit in week 13. They will take questionnaires. They will do final research tasks. Each visit lasts about 2 hours.

Type: Interventional

Start Date: Dec 2024

open study

Background: Primary sclerosing cholangitis is a rare chronic liver disease. It affects the bile ducts of the liver. It can result in bile duct infections, cirrhosis, cancer, and end stage liver disease. Researchers want to learn more about this disease. Objective: To understand the biological causes of primary sclerosing cholangitis. Eligibility: Adults age 18 and older who have primary sclerosing cholangitis. Design: Participants will be screened with a medical history, physical exam, and blood tests. Participants will give blood, saliva, urine, and stool samples. They will have nasal swabs. They will complete surveys. Participants will get an intravenous (IV) catheter. A plastic tube is inserted into an arm vein. Participants will have a colonoscopy. A tube with a video camera at the end is inserted into the rectum. Participants will have an upper endoscopy. A scope with a light and camera at its tip is used to look inside the upper digestive tract. Participants will have a liver biopsy, entering through the chest wall or a neck vein. Blood is drawn from a blood vessel that carries blood to the liver. A liver tissue sample is taken. Participants will have magnetic resonance imaging or spectroscopy. They will get a contrast agent through an IV. Participants may have an optional bone marrow aspiration. A large needle is inserted into the hip to withdraw marrow. Participants will have a liver ultrasound. Participants will complete a 3-day food diary. They will have a nutrition assessment. Participants may give contact details for people who live with them, to also take part in this study. Participation will last for 12 months.

Type: Observational

Start Date: Mar 2023

open study

Background: The eyeGENE (Registered Trademark) program is a research resource for inherited eye conditions which includes genotypic and phenotypic data, imaging, and a corresponding biobank of DNA samples from people with a variety of eye diseases. Since 2007 this registry has been helping researchers learn more about the genetic sources for many inherited eye diseases. These findings helped them create better treatments. Now researchers want to expand eyeGENE (Registered Trademark) to include more people for certain eye diseases. Objective: To collect information and DNA samples for the study of eye diseases. - Primary objective --To expand the current eyeGENE (Registered Trademark) data repository with targeted participant accrual - Secondary objectives - To enhance recruitment for clinical trials and investigations in inherited eye diseases - To establish genotype-phenotype correlations for rare eye diseases Eligibility: People of any age with certain eye diseases. These can include aniridia; Best disease; blue-cone monochromacy; corneal dystrophy; and disorders of pigmentation, such as albinism. Relatives unaffected by the eye disease of interest may also be needed. Design: Researchers will select participants based on their diagnosis. The data may include images and test results from eye exams. Participants will provide a sample of saliva. They will receive a kit with written instructions. They will spit in a tube and mail it to the NIH. Participants may be asked to provide a blood sample. The blood may be drawn at the NIH or at a local clinic. The eyeGENE (Registered Trademark) repository will offer researchers data about the participants eye conditions. The data may include pictures of their eyes, results of the genetic testing, and history of other diseases. Researchers will be able to see data such as age and gender, but they will not see names, dates of birth, or contact information.

Type: Observational

Start Date: Jul 2024

open study

Background: - In deep brain stimulation (DBS), a device called a neurostimulator is placed in the chest. It is attached to wires in parts of the brain that affect movement. DBS might help people with movement disorders like Parkinson s disease (PD), dystonia, and essential tremor (ET). Objective: - To provide DBS treatment to people with some movement disorders. Eligibility: - Adults 18 years and older with PD, ET, or certain forms of dystonia. Design: - Participants will be screened with medical history and physical exam. They will have blood and urine tests and: - MRI brain scan. The participant will lie on a table that slides in and out of a metal cylinder with a magnetic field. They will be in the scanner about 60 minutes. They will get earplugs for the loud noises. During part of the MRI, a needle will guide a thin plastic tube into an arm vein and a dye will be injected. - Electrocardiogram. Metal disks or sticky pads will be placed on the chest, arms, and legs. They record heart activity. - Chest X-ray. - Tests of memory, attention, concentration, thinking, and movement. - Eligible participants will have DBS surgery. The surgery and hospital care afterward are NOT part of this protocol. - Study doctors will see participants 3 4 weeks after surgery to turn on the neurostimulator. - Participants will return every month for 3 months, then every 3 months during the first year, and every 6 months during the second year. Each time, participants will be examined and answer questions. DBS placement will be evaluated with MRI. The neurostimulator will be programmed. At two visits, participants will have tests of movements, thinking, and memory.

Type: Interventional

Start Date: Apr 2014

open study

This study will allow National Eye Institute (NEI) doctors the opportunity to examine people with eye disease, whether the diagnosis is known or not, to determine if they are eligible for other NEI research studies. No treatment is offered in this study. People of all ages with various eye conditions, including genetic conditions, eye movement disorders, inflammatory eye diseases, retinal diseases and external eye diseases, may be eligible for this study. Participants undergo various tests and procedures to diagnose or evaluate their eye disease. The procedures may include the following: - Personal and family medical history - Physical examination and blood tests, including genetic testing. - Eye examination with dilation to measure visual acuity and eye pressure and to examine the front and back parts of the eye. - Questionnaire about vision and daily activities. - Conjunctival swab or lacrimal bland biopsy, or both: A sample of cells from the eyes is collected by swabbing the surface of the eye or by surgically removing a small sample of the surface of the eye or tear gland. - Electroretinogram to examine retinal function: The subject sits in the dark with his or her eyes patched for 30 minutes. The patches are removed, the surface of the eyes is numbed, and contact lenses that can sense signals from the retina are placed on the eyes. The subject then watches flashing lights. - Fluorescein angiography to examine the blood vessels in the eye: A dye is injected into a vein in the arm. The dye travels through the veins to the blood vessels in the eyes. A camera takes pictures of the dye as it flows through the blood vessels. - Optical coherence tomography to measure retinal thickness: A machine used to examine the eyes produces cross-sectional pictures of the retina. - Microperimetry to test how sensitive different parts of the retina are to changing levels of light. The subject sits in front of a computer and presses a button when he or she sees a light on the screen. - Oculography to record eye movements: Eye movements are measured by contact lenses or goggles that the subject wears while watching a series of spots on a computer screen.

Type: Observational

Start Date: Aug 2008

open study

Background: - The blood-brain barrier separates the brain from the rest of the body. Epilepsy is a neurological disease that causes seizures. It can affect this barrier. Researchers think a contrast agent called mangafodipir might be better able to show areas of the brain that epilepsy affects. Objective: - To see if mangafodipir is well tolerated and safe. To see if magnetic resonance imaging (MRI) using either mangafodipir or gadolinium can show areas of blood-brain barrier breakdown in people with epilepsy. Eligibility: - People ages 18-60 who: - Have epilepsy not controlled by drugs - Prior or concurrent enrollment in 18-N-0066 is required Design: - Participants will be screened with: - Medical history - Physical exam - Blood and urine tests - Participants will have up to 6 visits in 1-3 months. One visit is an inpatient stay lasting 2-10 days. Visits may include: - Video-EEG monitoring for participants with epilepsy - An IV catheter put in place: a needle guides a thin plastic tube into an arm vein. - Getting mangafodipir through the IV. - Getting gadolinium through the IV. - Up to 6 MRI scans over a 10-day period: a magnetic field and radio waves take pictures of the brain. Participants lie on a table that slides into a metal cylinder. They are in the cylinder for 45-90 minutes, lying still for up to 10 minutes at a time. The scanner makes loud knocking sounds. Participants will get earplugs. - A final MRI at least 2 weeks after receiving mangafodipir.

Type: Interventional

Start Date: Nov 2024

open study

Studies performed under 89-N-0045 are designed to examine the natural history of multiple sclerosis (MS) using MRI and immunological measures. In addition to studying the natural history of untreated patients, the natural history of patients receiving approved disease-modifying therapies of MS will be examined. In both cohorts of patients levels of disease activity on MRI will be compared with immunological characteristics in order to help identify disease mechanism. Patients with either definite MS (based either on clinical or combined clinical and MRI criteria) or with an initial presentation of neurological dysfunction consistent with MS will be studied longitudinally by MRI. Disease activity on MRI will be assessed using several MRI measures of disease activity including the number of contrast enhancing lesions, the overall burden of disease, brain atrophy and measures to assess axonal damage. Patients will be assessed clinically and correlations between immunological and genetic factors and disease activity as seen clinically or by MRI will be studied. A second cohort of patients starting the use of approved therapy will also be examined. Patients referred to NIH prior to beginning approved therapy will be assessed with a series of three monthly MRIs to determine the level of pretreatment disease activity. After beginning approved therapy under the direction of their private physician, patients will be followed similarly to the natural history cohort. Immunological and genetic findings will be accessed before and during therapy in order to help establish the mechanisms of action of the therapies and to identify mechanisms accounting for either a response or lack of response to therapy. Part of the collected samples willl be cryopreserved to provide respository for further studies focusing on detection of biomarkers indicative of disease state, disease stage or repsonse to therapies. Additionally, a cohort of normal volunteers will be studied. The studies in the normal volunteers will be used to establish the most appropriate imaging sequences for studying normal white matter in MS patients using magnetization transfer (MT) imaging sequences for studying normal white matter in MS patients using magnetization transfer (MT) imaging and to provide normative immunological measures.

Type: Observational

Start Date: Jul 1992

open study

Background: All childhood cancers are rare, but some are called very rare. Very rare cancers are diagnosed in 2 or fewer out of 1 million people each year. Researchers want to gather data so they can learn more about these very rare cancers. They hope to use the data to develop future treatments. Objective: To gather data for a registry of very rare cancers found in children, teens, and young adults. Eligibility: People aged 1 month to 39 years newly diagnosed (within the past year) with a very rare cancer. Design: Participation will be by phone or email. No clinic visits are required. Researchers will look at the participant s medical records. They will ask for samples of tumor tissue that were already removed. They will use the samples for genetic testing. The results of these tests will be sent to the participant s own doctors. Some participants will be asked for saliva or cheek swab samples. They will receive a kit in the mail. They will spit into a tube or swab the inside of their cheek. They will mail the sample back to the lab. Participants will fill out questionnaires once a year for 5 years. They will answer questions about: Family history, such as other cancers in the family and their income, work, and education. Demographics, such as their gender, nationality, ethnicity, education, and work history. Symptoms and treatment for their cancer. This may include level of pain, and emotional and physical well-being. Participants data will be added to a secure database for other researchers. Their data will be anonymous.

Type: Observational

Start Date: Jun 2026

open study

Background: Lung cancer is the leading cause of cancer-related death worldwide. Non-small cell lung cancer (NSCLC) is the most common type of lung cancer. Surgery to remove the tumors is the standard treatment for people diagnosed with early stages of NSCLC. Despite complete removal of these tumors, many recur (happen again). An FDA-approved drug combination to treat early-stage NSCLC prior to the surgery is durvalumab plus standard chemotherapy. The FDA approved infusion drug azacytidine [AZA] is used to treat several diseases because it can rapidly kill dividing cells (including cancer cells) but it is not approved for NSCLC. An inhaled (aerosolized) form of AZA is also not approved for NSCLC. However, researchers want to know if an inhaled version of AZA can help improve treatment of people with NSCLC because inhaled AZA goes directly into the lungs with limited absorption into the bloodstream. Objective: To find the safest and most effective dose of inhaled AZA in participants with early-stage non-small cell lung cancer (NSCLC) that can still be removed by surgery. Eligibility: Adults aged 18 and older with operable early-stage NSCLC. Participants will be required to also enroll in NIH protocol 06C0014 which allows for pre- and post-treatment biopsies and bloodwork to be obtained for additional research studies. Design: Participants will be screened. They will have a physical exam with blood tests. Their medical records will be reviewed. They will have imaging scans and tests of their heart and lung functions. Participants will be required to have a tissue sample (biopsy) taken of their tumor prior to receiving study drug and again during surgery after Cycle 3; airway tissue biopsies and collection of collect bronchial (lung) fluid may also be done. Participants will receive the study treatment for 3 cycles. Each cycle is 21 days. They will need to come to the NIH Clinical Center (CC) on days 1-4 of Cycles 1-3. AZA will be given as a drug mist that can be inhaled (like the type of mist in an asthma inhaler) using a nebulizer at the NIH Clinical Center (CC) for 3 days in a row (consecutive days) during the first week of each cycle. The participant will inhale the AZA drug mist for 20 to 30 minutes each time. Participants will also receive durvalumab and a specific 2-drug assigned chemotherapy by intravenous (IV) infusion on day 4 of each cycle. Participants will have a follow-up visit 2 weeks after their last dose of study drugs. Then they will have planned surgery to remove the tumors. Participants will have additional follow-up visits at the NIH CC about 1 and 3 months after the surgery, and then for every 3 months for up to 3 years. ...

Type: Interventional

Start Date: Jun 2026

open study

Background: Medical advances have improved survival rates for many cancers and other illnesses. This means that more people are coping with the long-term effects of these treatments. Some treatments can cause female infertility. Ovarian tissue cryopreservation (OTC) may help. Before undergoing a treatment that may damage their fertility, patients may opt to freeze a sample of ovarian tissue. The tissue contains immature egg cells. When thawed, the tissue can be reimplanted. This procedure can help women become pregnant. Objective: This natural history study will create a databank of ovarian tissue. The NIH will provide OTC as a clinical service. The NIH will also request a portion of the tissue to use for research. Eligibility: Females aged 4 to 35 who opt to have OTC before receiving cancer treatment. Design: Participants will be screened. Their existing medical records will be reviewed. They will be asked if they want to donate a portion of their ovarian tissue for research. No more than 20% of the tissue collected will be taken for research. Some other tissues that would otherwise be discarded will also be kept. Medical data from each participant may also be collected and stored in the database. This data may include results of routine blood tests, imaging tests, and other information. The data will be coded for privacy. Participants will answer a questionnaire. They will be asked about their fertility treatment and general health. The survey takes about 30 minutes. They will repeat the questionnaire once a year for 30 years.

Type: Observational

Start Date: Jul 2022

open study

Background: Multiple sclerosis (MS) is a disease that damages the central nervous system (brain and spinal cord). This leads to increased physical disability over time. The disease is lifelong once it begins. Researchers want to learn more about MS s stages and follow them until a person s death. Objective: To understand how the physical and clinical signs of MS relate to its changes over time. Eligibility: Adults age 18 or older with MS or a disease of the brain and spinal cord that may act like MS. Design: Participants will have a medical history and a complete neurological exam. They may have timed tests of neurological function, such as a 25-foot walk and a 9-hole peg test. Participants will have multi-day visits about once a year. Participants will have blood drawn. Participants may have a brain magnetic resonance imaging (MRI) scan. They may also have an MRI of the spinal cord. They may get a contrast agent (dye) injected into a tube in an arm vein. During the MRI, participants will lie on a table that slides in and out of a metal cylinder. Participants will have the thickness of their retina measured using optical coherence tomography. A camera on top of a table uses lasers. Participants will look through a lens and follow instructions. Eye drops may be used to dilate the pupils. Participants will chew on a piece of sterile cotton for 1 minute to collect saliva. Participants agree to have an autopsy at the time of their death and to donate some of their organs to research, such as the brain and spinal cord.

Type: Observational

Start Date: Apr 2016

open study

Background: - Chromatin is is the structural building block of a chromosome. It is found inside the nucleus of the cell and consists of a complex of DNA and protein. - Cancers of the lung, pleura (lung lining) and esophagus show profound changes in chromatin structure that may affect the course of disease in patients. - A better understanding of these diseases and the genetic changes associated with them may be helpful in developing new treatments for them. Objectives: - To evaluate people with cancer of the lung, pleura or esophagus for participation in NCI clinical trials. - To obtain biopsies (small pieces of tissue) from tumor, normal tissue and blood samples to learn more about the cellular changes in blood and tissue in tumors of the lung, esophagus and pleura and surrounding structures in the chest. Eligibility: Patients 2 years of age and older with cancer of the lung, esophagus, pleura, mediastinum or chest wall, or cancers of other origin that have invaded the lung. Note: Patients >= 2 years of age and under 18 years of age may only participate in research sample collection. Design: - Up to 1310 patients may be included in this study. - Patients undergo standard tests for evaluating the stage of their disease and for determining eligibility for an NCI investigational treatment study. - All patients undergo bronchoscopy and bronchoalveolar lavage ("washing" with salt water) to assess their tumor and collect a sample of normal tissue. Patients whose tumor is located on the outside portion of the lung may also undergo thoracoscopy to obtain a tumor sample. For bronchoscopy and bronchoalveolar lavage a tube with a light is passed through the nose or mouth into the lungs to examine the airways. Salt water is injected through the tube and then withdrawn to obtain cells for laboratory studies. For the thoracoscopy a small tube with a light is put through a small hole in the chest to obtain the tumor sample. Both procedures are usually done under general anesthesia. The tissue is examined to identify cell characteristics of people who respond to certain therapies and to identify markers on the surface of the tissue that may be useful in future research and treatment. - Blood and urine samples are collected from patients. - Patients who are eligible for a treatment study at NCI are offered participation in the study. - Patients for whom standard surgery, radiation or chemotherapy is more appropriate may receive treatment at NCI or with their own physician. - Patients who receive treatment at NCI return for follow-up examinations 4 weeks after discharge and then every 2 to 4 months depending on the nature of their cancer.

Type: Observational

Start Date: Nov 2005

open study

Background: Less toxic and more effective treatments are needed for cancers caused by viruses. These cancers include Hodgkin and non-Hodgkin lymphoma, hepatocellular carcinoma, head and neck cancer, nasopharyngeal carcinoma, gastric cancer, anal cancer, cervical cancer, vaginal cancer, vulvar cancer, penile cancer, Merkel cell carcinoma, Kaposi sarcoma, and leiomyosarcoma. Researchers want to see if a combination of drugs can help. Objective: To find a safe dose of pomalidomide plus nivolumab in people with cancers caused by viruses. Eligibility: Adults ages 18 or older who have cancers caused by Epstein Barr virus (EBV), human herpes virus 8/Kaposi sarcoma herpesvirus (HHV8/KSHV), human papilloma virus (HPV), hepatitis B or C virus (HBV/HCV), and Merkel cell polyomavirus (MCPyV) that have not responded to previous treatments or have relapsed, or in adults who do not want to have surgery because of disfigurement or other risks. Adults who have HIV with any CD4 T cell count are eligible. Design: Participants will be screened with blood and urine tests, scans, and heart tests. They will have a physical exam. Their ability to perform normal daily activities will be assessed. They may have a tumor biopsy. Treatment will be given in 28-day cycles. Participants will take pomalidomide as a tablet by mouth for 21 days of each cycle, for up to 24 cycles. They will get nivolumab by intravenous infusion once each cycle. They will take an aspirin each day until 30 days after their last dose of the study drugs. Participants will keep a pill diary. They will bring it to their study visit at the end of each cycle. At these visits, some screening tests will be repeated. Participants with Kaposi sarcoma will have pictures taken of their lesions. Participants will give blood and saliva samples for research. They may have optional anal and/or cervical swabs. They may have optional biopsies. Participants will have a follow-up visit 30 days after they stop taking the study drugs, then every month for 100 days. Some screening tests will be repeated. Then they may by contacted by phone every 3 months for 9 months, and then every 6 months thereafter.

Type: Interventional

Start Date: Dec 2021

open study

Objective: To screen and create a list of adult volunteers in good health for participation in research studies conducted at the National Institutes of Health (NIH) in Bethesda, Maryland. Develop a normative set of structural and functional brain MRI scans that are linked to healthy research volunteer characteristics. Maximize scientific impact of data from volunteers by broadly sharing with other researchers. Study Population: Adult males and females in general good health who are 18 years of age and older. Design: Adult individuals who are interested in participating in NIMH IRP clinical studies as a healthy research volunteer can directly visit or be directed to visit the study website where they will first consent electronically and then complete a set of online self-report measures. Items may include: demographic information, mental health symptoms, disability status, substance use patterns, handedness and clinical/family history. Individuals who are flagged based on predetermined responses to survey items will be further screened by a member of the study clinical team. If found to be ineligible for the study because of a clinically significant or unstable medical or mental health condition, these individuals will be referred back to the community and/or given information about NIMH clinical studies for which they may be eligible. Respondents with no flags or who pass through additional screening will be scheduled for an in-person assessment. During the outpatient appointment and after in-person informed consent, participants will receive a brief clinical interview to screen for current medical and mental conditions, and risk for self-harm. They will complete assessments of psychological, emotional, physiologic, biological and cognitive functioning. Participants will undergo a physical exam and be asked to provide blood and urine samples for routine clinical labs. Participants can separately consent for an optional baseline brain magnetic resonance imaging (MRI) scan and an optional magnetoencephalography (MEG) exam. All consent forms will explicitly inform participants that if enrolled in the study, their de-identified data will be broadly and publicly shared through NIH-approved data repositories. Participants in this recruitment and characterization study will then be placed on a list of healthy research volunteers from which other NIMH IRP studies may recruit according to the inclusion and exclusion criteria in their respective IRB-approved protocols. Outcome Measures: Outcome measures may include demographic data, mental and medical history and symptoms, results of psychological, emotional, physiologic, biological, and cognitive testing, physical exam and MRI findings....

Type: Observational

Start Date: Nov 2017

open study