View clinical trials related to Infection.
Filter by:Innate immunity plays an important role for fungal recognition and initiation of fungicidal activity. We hypothesize that subtle differences in different molecules of innate immunity may contribute to either the predisposition or clinical course of infection with Cryptococcus neoformans. To test this hypothesis, we propose to analyze the allelic frequencies of 15 different genes (mannose binding lectin, Fc-gamma receptor IIa and IIb, Fc-gamma receptors IIIa and IIIb, myeloperoxidase, tumor necrosis factor-alpha and -beta, interleukin 1A and 1B, interleukin-1 receptor antagonist, interleukin-10, NRAMP-1, chitotriosidase, and chemokine receptor 5) and their intragenic polymorphic forms and to compare this data to the incidence and severity of C neoformans infection. With this study we hope to identify a group of molecules of innate immunity which influence the risk and severity of invasive C neoformans infection.
Bacteria carry substances on their surface called antigens. When antigens come into contact with the right kinds of cells in the body an immune reaction is caused. This reaction is often the symptoms of sickness that a patient feels. In order for the body to fight off the attack of antigens, it creates substances called antibodies. Antibodies counter the action of antigens and make the bacteria harmless. However, the immune system must learn how to make the right antibodies for the right antigens. Sometimes the body creates antibodies that confuse normal tissues as foreign and attack them. This is called an autoimmune reaction and sometimes occurs when the body is exposed to certain bacteria. One bacteria known for causing autoimmune reactions is Group A beta-hemolytic Streptococcus (GABHS). This bacteria often causes throat infections commonly known as "strep throat". Some researchers believe that the autoimmune reaction associated with strep throat infections may cause neuropsychiatric disorders, like obsessive-compulsive disorder and/or tic disorder in children. As a result, each time a child with one of these disorders experiences an infection with GABHS his/her symptoms can reoccur or worsen. Researchers believe that by giving patients a certain antibiotic, they can prevent GABHS infection and thus prevent the return of symptoms. This study is designed to test the effectiveness of the antibiotic Amoxicillin for the treatment of Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal infections (PANDAS). Patients will receive Amoxicillin for six weeks and placebos "inactive sugar pills" for six weeks in order to see if the medication is truly working. Effectiveness of the treatment will be based on the presence or absence of symptoms. If at the end of the study Amoxicillin is proven to be effective treatment for PANDAS patients may be offered the opportunity to continue taking the medication for an additional six months.
This study will try to define how and where HIV infection persists in the body by determining: 1) if there are cells where HIV can live for long periods of time without being seen and destroyed by the immune system; 2) if there are sites where anti-HIV drugs cannot penetrate enough to stop new HIV replication; and 3) if HIV in certain lymph nodes can remain infectious for prolonged periods of time. It will also explore whether immune system damage caused by HIV can be repaired after new virus replication is stopped with treatment. HIV-infected patients 18 years of age and older may be eligible for this study, which will include three groups as follows. Candidates will be screened with a medical history, physical examination, blood and urine tests and possibly chest X-ray and electrocardiogram. Participants will be divided into three groups according to CD4 count levels: > 500 cells/microliter of blood; between 300 and 500 cells/microliter, and < 300 cells/microliter of blood. All participants will be treated with a combination of four antiretroviral drugs: indinavir, zidovudine, lamivudine and nevirapine. (Exceptions to this regimen may be made in certain circumstances for patients who cannot tolerate one of the four drugs.) In addition, they will undergo the following procedures: Blood tests - Blood tests will be done at screening and at study entry to evaluate the patient's health status and measure CD4 T cell count and plasma HIV levels; at the beginning of treatment to look for drug-related side effects; and during the course of the study to evaluate drug effectiveness in inhibiting HIV replication; CD4 T cell levels and function. Lymph node biopsy - Lymph node biopsies are done under local anesthesia. A small incision is made, the node is removed, and the incision is closed with stitches. Up to two nodes may be removed during each procedure. Patients with CD4 counts greater than 500 cells/microliter of blood and those with counts less than 300 cells/microliter will have three lymph node biopsies in order to 1) assess the effectiveness of therapy in inhibiting HIV replication in the nodes (the major site of replication); 2) determine how long HIV-infected cells may persist in the nodes after new replication is stopped by therapy; and 3) determine if immune damage caused by HIV can be repaired when virus replication is stopped. Lymph node biopsy in patients with counts between 300 and 500 cells/microliter of blood is required only at baseline, although follow-up biopsies are encouraged. Leukapheresis - In this procedure, whole blood is collected through a needle placed in an arm vein. The blood circulates through a cell separator machine where the white cells are removed and collected. The rest of the blood is returned to the body, either through the same needle used to draw the blood or through a second needle placed in the other arm. The collected white cells are used for special studies of the level and function of T cells before and after drug treatment. Patients with CD4 counts > 500 cells/microliter and < 300 cells/microliter will undergo leukapheresis up to four times - at study entry and about 2, 6 and 12 months after starting antiretroviral therapy. Patients with CD4 counts between 300 and 500 cells/microliter will have this procedure either at study entry and 6 and 12 weeks after initiation therapy, or on the same schedule as the other patients.
This protocol presents the rationale, 25-year historical review, and methods for multidisciplinary, low-risk studies of individuals referred to the NCI Viral Epidemiology Branch (VEB). Referrals are generally for unusual types of cancer or related conditions, known, or suspected to be related to viruses. Kaposi's sarcoma in two homosexual men evaluated in 1981 is a classic example. These referral cases provide the basis for pilot studies that generate hypotheses, the development of protocols for formal investigations of promising leads, and help to set priorities for VEB. A VEB investigator who is a Staff Member at the NIH Clinical Center, interviews each subject, performs a physical examination, draws a blood sample, and, when appropriate for the disease or virus under study, obtains other clinically indicated biological specimens, such as urine, sputum, saliva, tears, semen, Pap smear, or cervical, anal, oral, or nasal swabs. On occasion, other relatively non-invasive studies may be indicated. Skin testing with conventional, licensed antigens for assessment of cellular immunity may be performed, and skin lesions may be biopsied or excised. Tumor or other tissue biopsies may be obtained when biopsy or surgery is clinically indicated for other reasons. Otherwise no surgery is performed, and no therapy is administered. Clinical referral to other components of NCI, NIH, or the private sector are made as needed. The biological specimens are frozen or otherwise preserved to be batch tested in current assays or future assays that will be developed. Such laboratory testing is performed either at VEB's own support laboratory, or collaboratively in other NCI, NIH, or extramural laboratories that have the needed expertise for the disease or virus under study. Occasionally, repeated or more long-term evaluation is required. More often, a single evaluation in the NIH outpatient clinic, or either at a collaborating physician's office or other suitable site in the field, is sufficient. The VEB investigator provides counseling relevant to the virus or disease under study, and about the interim study results. He or she makes appropriate referral if needed (e.g., to the Genetic Epidemiology Branch for genetic counseling). Clinically relevant results and the VEB investigator's interpretation of these results, are provided in writing to the subject's primary caregiver. Confidentially of the information that is obtained is carefully protected. The results of the study are summarized for publication in the peer review literature.
Children with symptomatic HIV-1 (Human Immunodeficiency Virus) infection are at increased risk for developing severely disabling neurological and neuropsychological deficits. HIV-1 related CNS (Central Nervous System) disease is a clinical syndrome, manifested by varying and sometimes discordant degrees of cognitive, motor and behavioral impairment. A continuum of clinical presentations attributed to the effects of HIV-1 infection on the CNS, ranging from apparently normal development, decreases in the rate of new learning to the loss of acquired skills have been observed. Two domains of psychological functioning appear most susceptible to the effects of HIV infection on the central nervous system in children: expressive behavior and attentional processes (Brouwers, et al, 1994). Attention deficits have been documented as a relative weakness on the "freedom from distractibility" subclass of IQ tests (Brouwers et al, 1989) and on behavior assessment (Moss et al, 1994). Attention, however, has many subcomponents such as focused attention, divided attention, vigilance, etc. Direct assessment of attentional functioning using reaction time has not yet been conducted and questions whether attentional components are differentially affected by the virus have not been addressed. The proposed study would assess different components of attentional functioning in children with HIV-1 disease. A quantitative and systematic method is developed that could complement the existing standardized instruments used for measuring attention and neurocognitive function in this population. Simple alerted visual reaction time will be measured with varying preparatory intervals, a two-choice reaction time in a go/no-go paradigm will be administered, and a continuous performance, divided reaction time test and an object decision task will be given. Performance on these measures will also be related to measures of brain structure and stage of HIV-1 disease.
Patients are exposed to infectious agents regularly, regardless of their immunologic status. Traditionally clinicians have decided to institute prophylaxis based on epidemiologic factors, skin test (i.e. PPD), or immunologic parameters. A quantitative and specific method that is non-invasive, such as quantitative PCR, would be desirable to more precisely define those who would benefit from prophylaxis. Similarly, when patients develop disease and are being treated, quantitative, non-invasive techniques are needed to assess response to therapy. This project is designed to develop and test quantitative tests using blood, urine, or sputum samples.
This protocol will follow patients who participated in NIAID's study Gene Therapy Approach for Chronic Granulomatous Diseases (95-I-0134). No further gene therapy treatments will be given under this protocol. However, because gene therapy is a new technology and involves a permanent change in the genetic code of some cells, patients who have had this treatment require long-term health monitoring. Participants will be asked to provide updated address and telephone information and the names of two contact persons, such as siblings or friends. Patients will be seen about once a year at the NIH Clinical Center to provide an update on their health status and donate a small blood sample (about 2 teaspoons), which will be frozen and stored. If a patient acquires a serious illness, such as cancer, his or her stored blood will be tested; another of blood or tissue sample may also be requested for further study. If a patient develops a medical problem that is thought possibly to be related to gene therapy, the illness will be investigated. The annual follow-up visits will continue indefinitely or until the patient declines to continue participation. Participants may also agree to store some of their blood future research on chronic granulomatous diseases and other medical conditions. Stored samples may be labeled with a code, such as a number, that only the study team can link with the patient. Any identifying information about the patient will be kept confidential as is permitted by law.
The main objectives of this study are: 1) to determine whether various levels of severity of oral candidiasis (thrush) in the child are associated with different levels of speech production, feeding skills, and self-concept, and 2) to assess the effect of the reduction of oral thrush over time on the speech function, feeding skills, and self-concept in HIV-infected patients who already are receiving various antifungal medications for treatment of their thrush (Note: Decisions regarding antifungal therapy are made completely independent from this study). Children with HIV disease, ages 6-21 years, who have oral thrush are eligible to paricipate in the study. The child and his/her parent will be asked to complete a variety of measures at specific time intervals over approximately one month during visits to the National Institutes of Health for treatment on other protocols. First, a nurse will rate the location and severity of thrush in the child's mouth. Then the parent will complete questionnaires assessing the effect of oral thrush on the child's feeding and speech skills and everyday functioning. Finally, the child will be administered a brief speech and oral-motor evaluation and will complete some questionnaires about how the thrush affects his/her day-to-day activities and self-concept. The results of this study may help to better understand the cause of expressive language deficits observed in some children with HIV infection. More specifically, it will determine if any speech and feeding problems of HIV-infected children are associated with oral thrush. Learning more about the impact of oral thrush on the speech, feeding, and the self-concept of children with HIV disease may be used for parent and patient education and to develop rehabilitative recommendations to benefit HIV-infected patients with oral thrush.
This is a single dose, phase I study to evaluate the safety/tolerance and the immunogenicity of HIV-1 Immunogen, gp120-depleted inactivated HIV-1 preparation in Incomplete Freund's Adjuvant (IFA), in children with HIV-1 infection. A total of 32 children with HIV-1 infection will be enrolled in the study. Arm A of the study will enroll children who have no or moderate immune suppression at the time of study entry as defined by CDC classification and who have no history of and do not require antiretroviral therapy. Antiretroviral treatment given for less than 7 weeks (up to 6 weeks and 6 days) prior to entry will be considered as "no history" of treatment (treatment naive). Arm B will enroll children who have no or moderate immune suppression at the time of study entry as defined by CDC classification and who are on or have received antiretroviral treatment for more than 7 weeks. In order to assess the age-associated impact on the immune response rate, we plan to continue to attempt to enroll infants younger than 24 months of age. Children in each arm will receive 10 units of HIV-1 Immunogen intramuscularly at 0, 3, 6, 9, and 12 months. Antiretroviral treatment will commence once patients meet the criteria for an initiation of the treatment as defined in the protocol. All antiretroviral agents that are currently approved by FDA for clinical indications in HIV-1-infected children (pediatric labeling) are permitted in the protocol. If the child has been receiving a single agent other than ddI, or has been on investigational antiretroviral agents, his/her antiretroviral therapy will have to be changed to an optimal combination regimen of the approved agents at least 6 weeks prior to the enrollment.
This is a phase I/II study to determine the safety and tolerance of the protease inhibitor indinavir (MK-0639), alone and then in combination with HIV reverse transcriptase inhibitor therapy in children with HIV infection. Indinavir sulfate (the capsule formulation) has been shown to have potent antiviral activity and an acceptable safety profile in adults. HIV-infected children who have not received prior antiretroviral therapy, and children who have become refractory to prior therapy, or who have experienced toxicity to prior therapy, will be included. In addition, we will explore viral and CD4 cell kinetics before starting therapy and following exposure to antiretroviral agents. The study will be conducted in three parts. 1. In order to help interpret the antiviral activity of indinavir, the virologic and immunologic profile of children will be studied within 2 weeks prior to starting the therapeutic part. For children who have never been treated, this will be before the initiation of any antiretroviral therapy and for children who have already received antiretroviral therapy, this will be done during the initial "wash-out" phase that is routinely interposed between two different treatment regimens. 2. The initial 16 weeks of therapy will then evaluate the toxicities, pharmacokinetics, and preliminary efficacy of single drug therapy with indinavir. 3. Subsequently, all children who are able to tolerate the combination of zidovudine and lamivudine (i.e., have no prior history of intolerance to one of these two agents) will be treated with these two reverse transcriptase inhibitors in addition to the protease inhibitor indinavir. Zidovudine and lamivudine will be added after 16 weeks at a fixed dosage. Toxicity, pharmacokinetics, and preliminary efficacy of indinavir will also be investigated after combination therapy. All patients who wish to remain in this study after 96 weeks of therapy and who do not meet off study criteria will be permitted to receive extended treatment with their current indinavir combination therapy for an additional 48 weeks. The study will determine the pharmacokinetic profile of indinavir, given as single drug or in combination with zidovudine and lamivudine. It will assess the preliminary antiviral and clinical activity by monitoring clinical status, viral burden in plasma, and markers of immunologic status. Based on safety and preliminary efficacy results from studies performed in adults, we will study three dose levels which are expected to result in drug levels above the IC95 of HIV-1 for all or most of the dosing interval.