GLOSSARY OF MEDICAL, STATISTICAL, AND CLINICAL RESEARCH TERMINOLOGY National AIDS Treatment Activist Forum Oct. 15, 1995 Send all Corrections, updates, etc to Carlton Hogan. Additions/corrections are welcomed. E-mail: carlton@gopher.ccbr.umn.edu or use the e-mail button below. E-Mail Carlton here! This document copywrite 1995 by Carlton Hogan and University of MN. Permission to copy and distribute granted to individuals and non-profit groups This is the 22991st time this Glossary has been accessed since being added on March 20, 1996 |A| |B| |C| |D| |E| |F| |G| |H| |I| |J| |K| |L| |M| |N| |O| |P| |Q| |R| |S| |T| |U| |V| |W| |X| |Y| |Z| A ABDOMEN The area of the body between the thorax and pelvis. The abdomen contains the liver, the spleen and most of the digestive organs. ABT-538 See "Ritonavir" ACETAMINOPHEN (TYLENOL) An analgesic and antipyretic ACQUIRED IMMUNE DEFICIENCY SYNDROME (AIDS) Severe manifestation of infection with the human immunodeficiency virus (HIV). The Centers for Disease Control and Prevention lists numerous opportunistic infections and neoplasms which, in the presence of HIV infection, constitute an AlDS diagnosis. In addition, a CD4 count below 200/mm3 in the presence of HIV infection constitutes an AIDS diagnosis. ACID FAST BACILLUS Bacteria capable of living in acidic environments, such as inside macrophages. Tuberculosis and MAI/MAC are acid fast bacilli ACTG See "AIDS Clinical Trials Group." ACTU See "AIDS Clinical Trials Unit". ACTIVE CONTROL TREATMENT A control treatment that involves use of a pharmacologically or medically active substance. Active controls are used when there is already an available treatment, so the use of a placebo or no treatment would be unethical. ACUTE Short term, intense symptomatology or pathology, as distinct from chronic. Many diseases have an acute phase (like HIV seroconversion disease) and a chronic phase. This distinction is sometimes used in treatments, as in highdose ganciclovir for acute (or induction) treatment of CMV retinitis, followed by a lower dose for chronic (or maintenance) treatment ACYCLOVIR (ZOVIRAX) An antiviral drug used in the treatment of herpes simplex virus 1 (HSV-1, fever blisters, cold sores), herpes simplex virus 2 (HSV-2, genital herpes) and herpes zoster (shingles), and sometimes for acute varicella-zoster virus (Chickenpox). ADC See "AIDS Dementia complex" AD HOC REVIEW GROUP A review group that is created for the sole purpose of reviewing a specific application or set of applications. Also referred to as ad hoc study section, especially if the applications are for grant support. ADENOPATHY Enlargement of glands, especially the lymph nodes. ADHERENCE Degree to which patient care exactly follows study protocol. ADMINISTRATION (ROUTE OF ADMINISTRATION) How a drug or therapy is introduced into the body (e.g., intravenously, or orally). ADVERSE EXPERIENCE (AE) A toxic reaction to a treatment under study. In the CPCRA all Grade 4, life-threatening toxicities and deaths are adverse experiences, irrespective of whether or not they are believed to be due to study drug, as are any toxicities that require permanent discontinuation of study drug. ADVERSE REACTIONS Any undesirable effect of a medication. All drugs may cause such reactions, so that periodic monitoring is necessary to detect any that do occur, even though their occurrence may be uncommon. AE See "Adverse experience" AER Adverse experience report: A document in a prespecified format used to collect information on all reportable adverse experiences AEROSOLIZED A form of administration in which a drug, such as pentamidine, is turned into a fine spray or mist by a nebulizer, and inhaled. AFB see acid-fast bacillus. AFB SMEAR A laboratory technique for visualizing mycobacteria under the microscope. Smear results are usually available within a few days, and they correlate strongly with infectiousness, especially in untreated patients. However, a "positive" result cannot distinguish between TB , MAI or other mycobacterial infections. AFEBRILE Without a fever. AIDS CLINICAL TRIALS GROUP (ACTG) A clinical trials network of 59 medical centers, sponsored by the National Institute of Allergy and Infectious Disease, which conducts multicenter trials of treatments for AIDS/HIV and opportunistic infections. AIDS CLINICAL TRIALS UNIT (ACTG) A site within the ACTG. AIDS DEMENTIA COMPLEX A degenerative neurological condition, with a wide variety of clinical presentations, including loss of coordination, mood swings and loss of inhibitions, and finally wide spread cognitive deficit, AIDS dementia complex is generally thought to be caused by HIV itself AIDS VACCINE EVALUATION UNIT (AVEU) One of NIAID's clinical research sites for vaccine trials. AlANINE AMINOTRANSFERASE (ALT) A liver enzyme, measured through a blood test, that indicates the health of the liver. Lower counts are better. Levels may go up because of hepatitis and other infections, or because of drug toxicities ALKALINE PHOSPHATASE A liver enzyme, measured through a blood test, that indicates the health of the liver. Lower counts are better. Levels may go up because of hepatitis and other infections, or because of drug toxicities ALLOCATION RATIO Treatment allocation ratio. For example, 1:1 is equal allocation, 3:1 is 75% in one group, and 25% in the other ALLOCATION STRATA Treatment allocation strata. Allocations are generally balanced within strata such as CPCRA unit ¯ (alpha) LEVEL The probability of a false positive result, or of rejecting the hypothesis of no treatment difference when there is no real difference or of a false positive. Also referred to as the probability of a type I error. ¯ (alpha) SPENDING FUNCTION A function or rule that governs how the total ¯ level or probability of a type I error can be spread out over the interim analysis. Limits the chance of a false positive result when trial data is looked at multiple times. Can be used to set up guidelines for trial monitoring. ALT See "Alanine aminotransferase" ALTERNATIVE HYPOTHESIS 1. In a trial, the alternative hypothesis might be that a treatment of unknown efficacy has more benefit than the standard treatment. The alternative hypothesis is an alternative to the null hypothesis of no difference that specifies some true underlying difference of set of differences between two or more populations or groups with regard to some function, trait, characteristic, or effect. It may be stated in such a way so as to be concerned with a difference(s) in only one direction (one-sided alternative hypothesis) or in either direction (two-sided alternative hypothesis) relative to the null value. 2. Alternative treatment hypothesis. AmFAR American Foundation for AIDS Research AMIKACIN An antibiotic used as a component in combination therapy to treat tuberculosis or mycobacterium avium complex. AMINO ACID Any one of 20 or more organic acids, some of which are the building blocks for proteins and are necessary for metabolism and growth. AMPHOTERICIN B (FUNGIZONE) An antifungal drug that is used to treat fungal infections in persons with HIV, including candida, cryptococcus, histoplasmosis, and others. AMYLASE A pancreatic enzyme. High levels in the blood may indicate pancreatic damage. ANALGESIC A compound used to reduce or treat pain. Examples of analgesics include aspirin, morphine, and acetaminophen. ANALOG (ANALOGUE) A chemical compound with a structure similar to that of another but differing from it in respect to a certain component; it may have a similar or opposite action metabolically. ANALYSIS BY INTENTION TO TREAT A method of data analysis in which the primary tabulations and companion summaries of outcome data are by assigned treatment, regardless of treatment adherence. See also "Analysis By Treatment Administered." ANALYSIS BY TREATMENT ADMINISTERED A method of data analysis in which the primary tabulations and companion summaries of outcome data are by treatment administered, not be treatment assigned (see Taylor et al, 1982, for usage example). See also "Analysis By Intention to Treat." ANAPHYLACTIC SHOCK A life-threatening allergic reaction characterized by a swelling of body tissues (including the throat) and a sudden decline in blood pressure; can be (rarely) triggered by medication. ANCILLARY TRIAL An investigation, stimulated by the trial and intended to generate information of interest to the trial, that is designed and carried out by investigators from one or more of the centers in the trial and that utilizes resources of the trials (e.g., money, study patients, staff time, etc.), but that is not a required part of the design or data collection procedures of the main trial. ANDROGEN A masculinizing hormone, e.g. testosterone ANGIOGENESIS The process of forming new blood vessels. Angiogenesis is essential for the growth of tumors, especially KS ANEMIA A condition in which there is a decreased volume of red cells in the blood. There are many causes for anemia, including drug toxicities and chronic infections. The most common way in which anemia is measured is by the titer of hemoglobin (Hgb) in peripheral venous blood. ANERGIC Refers to the state of being so immunologically suppressed that one is unable to produce cutaneous delayed type hypersensitivity reaction (DTH). Such patients will usually not test positive for TB on a PPD (mantoux) test. ANOREXIA Lack of or complete loss of appetite for food. ANTAGONISM The opposite of synergy. One factor (treatment) reduces or cancels the effect of another ANTENATAL Before the time of birth. ANTERIOR The front, or forward part of something ANTIBIOTIC A chemical substance that kills or inhibits the growth of bacteria; some antibiotics are used to treat infectious diseases. ANTIBODY A protein molecule in the blood serum or other body fluids that destroys or neutralizes bacteria, viruses, or other harmful toxins. Antibody production occurs in response to the presence of an antagonistic, usually foreign substance (antigen) in the body. They are members of a class of proteins known as immunoglobulins that are produced and secreted by B-lymphocytes in response to stimulation by an antigen. The antigen/antibody reaction forms the basis of humoral (non-cellular) immunity. ANTIBODY-DEPENDENT CELL-MEDIATED CYTOTOXICITY (ADCC) An immune response in which antibodies bind to target cells, identifying them for attack by the immune system. ANTIEMETIC An agent that prevents nausea and vomiting. ANTIGEN Any substance that antagonizes or stimulates the immune system to produce antibodies, proteins that fight antigens. Antigens are often foreign substances such as bacteria or viruses that invade the body. ANTIGEN PRESENTING CELL (APC) A white blood cell that devours foreign bodies, breaks them down, and carries characteristic antigen peptides to it's surface. The foreign antigen, complexed with MHC I or II is presented to CD4 or CD8 to initiate an immune response specific to that peptide. ANTIGENEMIA The presence of detectable amounts of an antigen in the blood. ANTISENSE Complementary: an antisense compound is the mirror image of the genetic sequence that it is suppose to inactivate. ANTIOXIDANT A substance that inhibits oxidation or reactions promoted by oxygen or peroxides. Antioxidant nutrients protect human cells from damage caused by "free radicals": highly reactive oxygen compounds. ANTIPYRETIC A compound that reduces fever ANTIRETROVIRAL A substance, drug, or process that destroys a retrovirus, or suppresses it's replication. Often used to describe a drug active against HIV ANTISEPTIC Sterilized, or clean of any microorganisms. ANTIVIRAL A substance, drug, or process which destroys a virus or suppresses its replication. Can apply to anti-HIV activity, or other viruses, such as herpes or CMV APC See "Antigen presenting cell" APHASIA Complete or partial loss of the ability to speak, or understand speech. APTHOUS ULCER A sore of indeterminate origin in the mouth or esophagus. Some apthous ulcers have been linked to CMV or ddC use. APOPTOSIS "Cell suicide". Thought to be primarily a way that the body clears out immune cells that respond to the body's own proteins, apoptosis involves a complete physical destruction of a cell, driven by enzymes. Apoptosis also occurs when one receptor on a CD4 cell is triggered without the normal "co-activation" signal. Abnormal apoptosis may be elevated in persons with HIV. ARC A term never officially defined by the CDC which has been used to describe a variety of symptoms and signs found in some persons infected with HIV. These may include a decrease in CD4 cells, recurrent fevers, unexplained weight loss, swollen lymph nodes, and/or fungus infection of the mouth and throat. Most of the clinical findings which were formerly denoted as ARC are now in groups 3 or 4 of the CDC AIDS classification system, although the term ARC is still popularly used to describe these symptoms and diagnoses. ARC is also commonly described as symptomatic HIV infection. ARCA The AIDS Research Consortium of Atlanta , a CPCRA unit. ARTC The Addiction Research and Treatment Corporation, a CPCRA unit. ASEPTIC Without the presence of disease causing microorganisms. ASPARTATE AMINOTRANSFERASE A liver enzyme, measured through a blood test, that indicates the health of the liver. Lower counts are better. Levels may go up because of hepatitis and other infections, or because of drug toxicities ASPERGILLOSIS A fungal infection resulting from Aspergillus, it is also known as aspergillomycosis. ASPERGILLUS An ubiquitous fungus, most commonly found in compost heaps. Aspergillus is a frequent cause of disease in transplant patients, and is increasingly seen in persons with HIV. ASSOCIATION Synonyms for association include correlation and relationship. An association between two conditions or states means that if one is present, the other is likely to be so as well. Association does not necessarily imply a causal relationship. In addition, association does not necessarily imply a statistically significant relationship. AST See aspartate aminotransferase ASTHENIA Weakness, debilitation ASYMPTOMATIC Without signs or symptoms of disease. ASYMPTOMATIC INFECTION An infection or phase of infection, without symptoms. ATAXIA Problems with coordination or proper use of muscles ATOVAQUONE (MEPRON) Antibiotic sometimes used in treatment of PCP. In trials for prophylaxis of PCP, and for treatment of toxoplasmosis ATTENUATED VIRUS A weakened virus with reduced ability to infect or produce disease. Some vaccines are based on attenuated viruses. AUTOLOGOUS Pertaining to the same organism or one of its parts; originating within an organism itself. AVEU See "AIDS Vaccine Evaluation Unit" AZIDOTHYMIDINE See AZT. AZITHROMYCIN (ZITHROMAX) A macrolide antibiotic sometime used as a component in combination therapy for mycobacterium avium complex. AZOLES A family of antifungal drugs (Fluconazole, itraconazole, etc.) that are used to treat fungal infections in persons with HIV, including candida, cryptococcus, histoplasmosis, and others. AZT Also called zidovudine, Retrovir, or azidothymidine. A thymidine (genetic building block) analog that suppresses replication of HIV. It is the only drug FDA-approved for the initial treatment of HIV infection. Adverse side effects may include anemia, leukopenia, muscle fatigue, muscle wasting, nausea and headaches. B BACTERICIDAL Capable of killing bacteria. BACTEREMIA The presence of bacteria in the blood BACTERIOLOGICAL SPECIMEN Refers to any body fluid, secretion, or tissue sent to the laboratory where smears and cultures for bacteria will be performed. The specimen may consist of blood, sputum, urine, spinal fluid, material obtained at biopsy, etc. BACTERIOSTATIC Capable of inhibiting bacterial growth (but not necessarily capable of killing bacteria). BACTRIM Brand name of trimethoprim-sulphamethoxazole BAL See "Bronchoscopy." BASELINE CHARACTERISTIC A variable that is measured, observed, or assessed on a patient at or shortly before treatment assignment and the initiation of treatment. BASELINE DATA 1. The set of data collected on a specific patient or set of patients prior to randomization. BASELINE EXAMINATION An examination that is carried out as part of the baseline visit and that is designed to assess a patient's eligibility for enrollment into the trial and to produce required baseline data. B-CELL See "B-Lymphocyte." bDNA (BRANCHED DNA ASSAY) A DNA test for detecting and measuring HIV in the blood plasma of people with HIV. The bDNA test is faster and probably more accurate than plasma culture, the test currently used‹it is less sensitive than PCR, another new test. bDNA testing may eventually be useful to monitor the effectiveness of anti-HIV drugs and to gauge HIV disease progression. It is not yet FDA-approved, nor is it widely available. BETA CAROTENE A form of carotene, precursor to vitamin A; a red-orange pigment found in plants and plant-eating animals, and also found in dark green and dark yellow fruits and vegetables. Beta carotene may have beneficial effects on the immune system. BIAS Deviation of results from the truth or mechanisms leading to such deviation, e.g., analysis bias, confounding factors, measurement bias, selection bias, withdrawal bias, and others. BIAS, ANALYSIS Deviation of results or inferences from the truth resulting from flaws in the analysis or interpretation of results. BIAS, CONFOUNDING FACTOR A confounding factor is an variable which is related to one or more of the variables defined in a study. A confounding factor may (1) mask an actual association or (2) falsely demonstrate an apparent association between the study variables where no real association between them exists. For example, alcohol intake may appear to be positively associated with laryngeal cancer but the actual association may be with the confounding factor of cigarette smoking, i.e., people who drink alcohol may be at increased risk for laryngeal cancer because they also smoke cigarettes. If confounding factors are not measured and considered, bias may result. BIAS, MEASUREMENT BIAS Systematic measurement error. For example, a sphygmomanometer which is not correctly calibrated will produce biased blood pressure readings. BIAS, SELECTION BIAS Error due to differences in characteristics of those participants who are selected for a study as compared to those not selected. BIAS, WITHDRAWAL Error due to specific characteristics of those participants who choose to withdraw from a study or become lost to follow up, as opposed to those who remain. BIAXIN Brand name of clarithromycin. BID Common abbreviation for "twice a day" BILATERAL Having, or being distributed on, two sides. BILIRUBIN A bile pigment, bilirubin measurement indicates the health of the liver. BINARY OUTCOME MEASURE An outcome measure that can assume only one of two values, such as in a trial with death as the outcome measure. BIOAVAILABILITY The rate and extent to which a substance is absorbed and circulated in the body. BIOLOGICAL RESPONSE MODIFIERS (BRMs) Substances, either natural or synthesized, that boost, direct, or restore normal immune defenses. BRMs include interferons, interleukins, thymic hormones, and monoclonal antibodies. BIOPSY A diagnostic technique that involves the surgical removal of a small piece of tissue for microscopic examination and sometimes culture(s). BIOTECHNOLOGY The use of living organisms or their products to make or modify a substance. These include recombinant DNA techniques (genetic engineering) and hybridoma technology. BLHC The Bronx-Lebanon Hospital Center, a CPCRA unit BLIND A condition imposed on an individual (or group of individuals) for the purpose of keeping that individual or group of individuals from knowing or learning of some fact or observation, such as treatment assignment. Also called a "mask" BLINDED The condition of having a blind in place, e.g., as in a single-, double-, or triple-blinded trial. BLOCK 1. A group, quantity, section, or segment that is considered as a unit for some purpose, procedure, process, or action. 2. (clinical trials) Treatment block. Analyses are conducted for each block, and then combined over blocks. BLOCK SIZE 1. The number of individual elements making up a block. 2. Treatment block size. BLOCKING The process of establishing defined groups, as in a treatment allocation schedule designed to ensure a specific allocation ratio. BLOOD BRAIN BARRIER A selective barrier between brain blood vessels and brain tissues whose effect is to restrict what may pass from the blood into the brain. Certain compounds readily cross the blood brain barrier. Others are completely blocked. B-LYMPHOCYTES B-lymphocytes are blood cells of the immune system derived from the bone marrow and spleen involved in the production of antibodies. B-lymphocytes float through all body fluids, are able to detect the presence of foreign invaders, and produce antibodies on their own and when primed by T-lymphocytes. B-lymphocytes can later differentiate into plasma and memory cells. B-cells mediate the "humoral" immune response. BODY FLUIDS Term used for a number of fluids manufactured within the body. Usually used when referring to semen, blood, urine, and saliva. BONE MARROW Soft tissue located in the cavities of the bones where blood cells are formed, including erythrocytes, leukocytes, and platelets. BREAKTHROUGH See "Treatment Failure." BRONCHI The hollow branches of the pulmonary tree which connect the trachea to the alveoli. BRONCHITIS An inflammation of the bronchial tubes, generally accompanied by coughing, pain, or shortness of breath. BRONCHOSCOPY Procedure for examining the respiratory tract by means of a fiber-optic instrument (bronchoscope) which is inserted through the mouth or nose into the trachea. Diagnostic specimens such as bronchial washings and transbronchial biopsies of lung tissue can be obtained during bronchoscopy. (This is also known as bronchoscopy and lavage, or "BAL.") C CAB See "Community Advisory Board" CANDIDA ALBICANS A yeast-like fungi, commonly found in the normal flora of the mouth, skin, intestinal tract, and vagina. Generally, candida is harmless, but can become clinically infectious in immune compromised people. CANDIDA KRUSEII Another candida species, similar to Candida albicans, but often less susceptible to the common drugs used to treat C Albicans CANDIDEMIA Candida albicans in the blood CANDIDIASIS An infection with a fungus of the Candida family, generally C. albicans. The most common sites for candidiasis are the mouth, the throat, and the vagina. CARCINOGEN Any cancer-producing substance or agent. CARDIOMYOPATHY A degenerative condition of the heart muscle, cardiomyopathy may be caused by HIV, or by some drugs. CASE-CONTROL STUDY A study that involves the identification of persons with the disease or condition of interest (cases) and a suitable group of persons without the disease or condition of interest (controls). Cases and controls are compared with respect to some existing or past attribute or exposure believed to be causally related to the disease or condition. Also referred to as a retrospective study because the research approach proceeds from effect to cause. The term applies even if cases and controls are accumulated in a prospective manner. CASE REPORT FORM A standardized data entry form used in a clinical trial. Generally, all information collected in trials appears on case report forms, or is referred to and explained by case report forms (as in the case of attached lab slips). Even in circumstances where there is other documentation in addition to CRFs (like the lab slips), generally all key values that will be analyzed appear on the CRF. CATHETER A semi-permanently installed venous line used to inject fluids into the body, or to drain fluids out. CAUSATION There is causation only when one factor necessarily alters the possibility of a second. Statistical methods alone cannot establish a causal relationship between factors. Examples of criteria to test causation include: (1) strength of the association, (2) biologic credibility of the association, (3) consistency of the findings with other investigations, (4) temporal relationship of the association, (5) presence of a dose-response relationship. Randomization allows assessment of causation. CAVITATING Eroding, or creating holes. Often used to describe the characteristic destruction of lung tissue accompanying active tuberculosis. CBC See "Complete blood count" CC The San Francisco Community Consortium, a CPCRA unit CCBR See "Coordinating Center for Biometric Research" CCG See "Community constituency group" CD4 (T4) A protein embedded in the cell surface of helper T-lymphocytes; also found to a lesser degree on the surface of monocyte/macrophage, langerhans cells, astrocytes, keratinocytes, and glial cells. One of the ways HIV invades cells is by first attaching to the CD4 molecule (CD4 receptor). CD4 CELL "Helper" T-cell, responsible for coordinating much of the immune response. CD4 cells are one of the main targets damaged by HIV. CD4 COUNT The number of T-helper lymphocytes per cubic millimeter of blood. The CD4 count is a good predictor of immune health. A CD4 count less than 200 qualifies as a diagnosis of AIDS. CD8 (T8) A protein embedded in the cell surface of killer and suppresser T-lymphocytes. CD8 COUNT The number of killer/suppresser T-lymphocytes in a cubic millimeter of blood. CDC Centers for Disease Control (a part of the United States Public Health Service), Atlanta, Georgia. C. DIFICILE See "Clostridium dificile" CDN The Clinical Directors Network of Region II, Inc., a CPCRA unit CELL LINES Specific cell types artificially maintained in the laboratory (in-vitro) for scientific purposes. CELL-MEDIATED IMMUNITY (CMI) A branch of the immune system responsible for the reaction to foreign material by specific defense cells (T-lymphocytes, killer cells, macrophage and other white blood cells) rather than antibodies. CELLULAR IMMUNITY See "Cell-mediated Immunity." CENSORING A term used in survival or time-to-event analyses to denote an individual who has not experienced the event of interest as of a specific point in follow-up, e.g. time of interim analysis, end of study, or time at lost to follow-up. The process by which patient outcome data cannot be obtained beyond a specific point in time. CENTI- A prefix meaning one one-hundredth, as in a centimeter, which is a hundredth of a meter. CENTO- A prefix meaning a hundred times, as in centogram, a hundred grams. CENTRAL NERVOUS SYSTEM (CNS) Composed of the brain, spinal cord, and its coverings (meninges). CEREBRAL Relating to the brain. CEREBROSPINAL FLUID (CSF) Fluid that bathes the brain and spinal cord. CERVICAL DYSPLASIA The development of abnormal tissue on the cervix, the lower part of the uterus; may progress to cancer of the uterus. CERVIX The cylindrical, lower part of the uterus leading to the vagina. CFR See "Code of Federal Regulations" CHANCE Random variation, i.e., the happening of events without an apparent cause. CHARACTERISTICS Traits or attributes: those qualities that define a describe a thing or person CHEMOPROPHYLAXIS Prevention of disease by chemical means. CHEMOTHERAPY The treatment of disease by chemical agents; usually, but not always refers to cancer treatment. CHI The AIDS Research Alliance - Chicago, a CPCRA unit. CHROMATOGRAPHY The separation of chemical substances and particles (originally plant pigments and other highly colored compounds). CHRONIC Referring to a process, such as a disease process, that occurs slowly and persists over a long period of time; opposite of acute. CHUMC Cooper Hospital/University Medical Center, a CPCRA unit. CIPROFLOXACIN (CIPRO) A flouroquinolone antibiotic sometimes used in combination therapy for treatment of mycobacterium avium complex. CIDOFOVIR (HPMPC) An experimental treatment for CMV CK See "Creatinine kinase" CLARITHROMYCIN (BIAXIN) A macrolide antibiotic sometime used as a component in combination therapy for mycobacterium avium complex. CLINDAMYCIN An antibiotic sometimes used in the treatment of PCP and toxoplasmosis. Clindamycin usage has been associated with severe diarrhea caused by the bacteria c. dificile. CLINIC COORDINATOR The study nurse or other staff person who is primary administrator and contact person for a research effort. CLINICAL Pertaining to or founded on actual observation and treatment of patients, as distinguished from theoretical or basic science. CLINICAL EVENT COMMITTEE A group of physicians used by the CPCRA to review endpoints in trials, and to evaluate their certainty. CLINICAL SCIENCE REVIEW COMMITTEE An internal committee at the division of AIDS in charge of prioritizing research, approving trial designs, coordinating intra- and extramural efforts, and clearing specific protocols for implementation. CLINICAL SITE MONITORING GROUP A contractor within the CPCRA who retrospectively assures data accuracy and completeness of data, through site monitoring visits and special audits , ensuring compliance with Federal regulations and DAIDS procedures. The CSMG also provides on-site training. CLOFAZIMINE An anti-leprosy drug that is used as a component in combination therapy of Mycobacterium avium complex. CLONE A group of genetically identical cells or organisms descended from a common ancestor. To produce such genetically identical copies. CLOSTRIDIUM DIFICILE (C. DIFICILE) A normal gastrointestinal tract bacteria, antibiotics can cause overgrowth of c dificile, and accompanying perforating enterocolitis CLOTRIMAZOLE An topical antifungal drug that is used to treat fungal infections in persons with HIV, particularly candida. CMV See "Cytomegalovirus." CNS See "Central nervous system" COCCIDIOIDOMYCOSIS A fungal disease which results from infection with Coccidioides immitis. Coccidioidomycosis or "valley fever" is common only in a limited geographic area. CODE OF FEDERAL REGULATIONS Listing of United States federal regulations. FDA rulings, for example, are regulations, rather than statute. Generally, new federal regulations are published in the federal register for comment some time before they are actually enacted. CODON A sequence of 3 bases that specifies a particular amino acid; a building block of the cell's genetic material, DNA and RNA. COFACTOR A substance, microorganism or environmental factor that activates or enhances the action of another entity such as a disease-causing agent. Cofactors may influence the progression of a disease or the likelihood of becoming ill. Possible cofactors that have been suggested in AIDS are the herpes viruses, parasites, mycoplasma (a form of life intermediate between bacteria and viruses) and non-HIV retrovirii. COGNITIVE Pertaining to thought, awareness, or the ability to rationally apprehend the world and abstract meaning. COHORT A group of individuals with some characteristic in common. COLITIS Inflammation of the colon COLON A division of the lower intestine, extending from the cecum to the rectum; also called the large intestine. COLONIZATION Residence of bacteria in, or on, part of the body and causing neither disease nor a response by the individual's immune system. COLORECTAL Relating to the colon and rectum, or to the entire large bowel (large intestine). COLPOSCOPY A type of examination of a living tissue surface, under magnification, to identify location and extent of lesions. COMMUNITY ADVISORY BOARD A lay panel. consisting of patients and affected others, who provide guidance and feedback to clinical trials sites with respect to accrual, retention, compliance, access, and ethical issues surrounding clinical trials COMMUNITY CONSTITUENCY GROUP (CCG) A group of delegated representatives from the various community advisory boards in the CPCRA, the CCG is charged with ensuring that the patient perspective is adequately represented at the steering committee, the various standing groups, and in all aspects of CPCRA operations. COMMUNITY PROGRAMS FOR CLINICAL RESEARCH ON AIDS Also known as "Terry Beirn Community Programs for clinical research on AIDS" The community research branch of the NIAID, CPCRA does trial in sites all across the United States. COMPASSIONATE USE A method of providing unapproved drugs to very sick patients who have no other treatment options. Often, case-by-case approval must be obtained from the FDA for "compassionate use" of a drug. See also "Expanded Access." COMPLEMENT A group of proteins in normal blood serum and plasma that, in combination with antibodies, causes the destruction of antigens (particularly bacteria and foreign blood corpuscles). COMPLEMENT CASCADE A precise sequence of events, usually triggered by an antigen-antibody complex, in which each component of the complement system is activated in turn, inactivating and occasionally destroying pathogens. COMPLETE BLOOD COUNT (CBC) A breakdown of the various cells in a sample of blood into white cells, red blood cells, platelets, etc. COMPLIANCE How closely a particular protocol is followed. May be influenced by the willingness and/or ability of patients to conform to treatment by taking medications as prescribed and keeping necessary clinic appointments. Often the resources available to the patient, and the resources and flexibility of the provider will have as great an implication for compliance as any specific patient behavior. COMPUTED TOMOGRAPHY (CAT/CT SCAN). A kind of computer aided imaging that assembles multiple X-rays of "slices' of the body to produce a three dimensional picture. CONCOMITANT DRUGS At the same time. CONFIDENCE INTERVAL The range of values that includes, with a stated probability (e.g. 95%), the actual population descriptor of interest. CONFOUNDING FACTOR See "Bias, confounding factor" CONJUNCTIVITIS Inflammation of the protective membrane surrounding the eye. CONTAGIOUS Any infectious disease capable of being transmitted by casual contact from one person to another. CONTRAINDICATION ("TO INDICATE AGAINST") A specific circumstance when the use of certain treatments could be harmful. CONTROLLED 1. Constrained, monitored, or watched. 2. A system of observation and data collection that provides a basis for comparison, as with a comparison group. CONTROLLED CLINICAL TRIAL A clinical trial involving one or more test treatments, at least one control treatment, and concurrent enrollment, treatment, and follow-up of all patients in the trial. COOPERATIVE CLINICAL TRIAL Term frequently used to denote a multicenter trial. COORDINATING CENTER A center in the structure of a study that is responsible for receiving, editing, processing, analyzing, and storing data generated in a study and that, in addition, has responsibility for coordination of activities required for execution of the study. See "Statistical Center", "Coordinating center for biometric research" COORDINATING CENTER FOR BIOMETRIC RESEARCH The facility at the University of Minnesota that houses the CPCRA Statistical center, it is a part of the division of Biostatistics in the School of Public Health. CORRELATION, PEARSON r A statistical technique used to assess the magnitude and the direction of the relationship between two variables. Values of the Pearson r can range between -1 and +1. The continuum of -1 to 0 indicates the degree of strength of an inverse relationship. The continuum of 0 to +1 indicates the degree of strength of a positive relationship. A Pearson r of 0 indicates no linear relationship. For example, bicycle helmet use and bicycle accident head injury are negatively correlated; asbestos exposure and cumulative incidence of mesothelioma are positively correlated. CORTEX The exterior, or surrounding portion of an organ. CORTICOSTEROIDS Any of a number of steroid substances obtained from the cortex of the adrenal gland or manufactured synthetically. Corticosteroids are immunosuppressive and people with HIV should be cautious about taking them for longer than a few weeks. Steroids appear to be an effective adjunct to standard PCP treatments in people with moderate to severe PCP. CPCRA See "Community Programs for Clinical Research on AIDS" CPK See "Creatinine (phospho) kinase" CREATININE A protein found in muscles and blood and excreted by the kidneys in the urine. The level of creatinine in the blood and urine provides a measure of kidney function. CREATININE KINASE (CREATININE PHOSPHO-KINASE) An enzyme found in the muscles. High levels in the blood indicate breakdown of muscle tissue. In AIDS, may be diagnostic of myopathy. CRIXIVAN Brand name of Indinavir CRF See "Case report form" CROSSED TREATMENTS Two or more study treatments that are used in sequence (e.g., as in a crossover design) or in combination (e.g., as in a factorial treatment structure). CROSSOVER Treatment crossover. A patient who does not comply to assigned treatment and begins to adhere to one of the other treatments. Patient may be a drop-in or drop-out, depending on the direction of the crossover. CROSSOVER DESIGN Crossover treatment design. Patients are given treatments in sequence, and crossover is determined by time, not clinical outcomes. CRYOTHERAPY The use of intense cold as a treatment, as in freezing off warts. CRYPTOCOCCAL MENINGITIS Inflammation of the membranes surrounding the brain and spinal cord by the fungus c. neoformans. Cryptococcal meningitis can have symptoms of headache, stiff neck, visual and other sensory distortions, and if untreated, coma and death. CRYPTOCOCCOSIS An infectious disease seen in HIV-infected patients due to the fungus Cryptococcus neoformans. CRYPTOCOCCUS NEOFORMANS A fungus, pathogenic in the immune suppressed, which is acquired via the respiratory tract. Cryptococcosis most frequently causes meningitis, with symptoms of headache and stiff neck. CRYPTOSPORlDIOSIS An opportunistic infection caused by a protozoan parasite (Cryptosporidium parvum). Cryptosporidiosis causes diarrhea and abdomen pain. CRYPTOSPORIDIUM PARVUM A waterborne enterocyte protozoan, c. parvum is often deposited in water supply by wild or domestic animals. c parvum has caused at least one large epidemic of diarrheal disease through contamination of a municipal water supply. CSF See "Cerebrospinal fluid" CSMG See "Clinical site monitoring group" CSRC See "Clinical Science Review Committee" CT Computed Tomography (CAT Scan). A kind of three-dimensional x-ray. CULTURE The process of growing bacteria or other microorganisms in the laboratory so that organisms can be identified. CUTANEOUS Of, pertaining to, or affecting the skin. CUT-POINT 1. The point or value in an ordered sequence of values that is used to separate those values into two subparts. 2. Subgrouping cut-point. CYTOKINE A chemical messenger protein released by certain white blood cells, including macrophages, monocytes or lymphocytes, the cytokines include the interferons, the interleukins, Tumor necrosis factor, and many others. Cytokines produced by lymphatic cells are also called "Lymphokines" CYTOLYTIC Having a destructive effect on cells, causing them to erupt or burst open. (see lyse) CYTOMEGALOVIRUS (CMV) A herpes virus which is a common cause of opportunistic diseases in people with AIDS and other people with immune suppression. While CMV can infect most organs of the body, people with AIDS are most susceptible to CMV retinitis and colitis. CYTOMETRY The counting of cells, especially blood cells, using a cytometer (a standardized, ruled glass slide or small glass chamber of known volume). CYTOPENIA A lack of specific cellular components in the blood. CYTOTOXIC An agent or process which is toxic to cells that results in suppression of function or cell death. CYTOTOXIC T LYMPHOCYTE (CTL) A lymphocyte that is able to kill foreign cells that have been marked for destruction by the cellular immune system. CYTOVENE See "Ganciclovir" D d4t See "Stavudine" DAIDS The Division of AIDS at the National Institute of Allergy and Infectious Diseases, DAIDS coordinates all of NIAID's AIDS research, and supervises extramural networks, including CPCRA, ACTG, DATRI, AVEU, and SPIRAT. DAPSONE An antibiotic active against Pneumocystis carinii, leprosy, and other pathogens, and to a lesser degree against toxoplasma gondii and MAC. Often used as a second line PCP prophylaxis in those unable to tolerate trimethoprim-sulphamethoxazole. DARAPRIM Brand name of Pyrimethamine DATA (pl. of datum) Factual information, such as measurements, observations, or statistics, which is used as a basis for reasoning, discussion, or calculation. DATA COLLECTION VISIT Any visit by a patient to a study clinic that is used for data collection in the trial. DATA DREDGING A term used to characterize analyses that are done on an ad hoc basis, without benefit of prestated hypotheses. DATA EDITING 1. The process of reviewing data for the purpose of detecting deficiencies or errors in the way they are collected or recorded. 2. The process of detecting deficient or erroneous values on completed data forms. DATA ENTRY 1. The process of keying data, as contained on completed data forms, in order to render information into an arrangement more suitable for storage and subsequent use, usually for tabulations and analyses, especially on a computer. 2. The process of filling out a data form. DATA FIELD 1. A space on a data form or in an electronic record designated to contain, or that actually contains, alphabetic or numeric characters of information recorded in response to a specific data item on the form. 2. The actual collection of alphabetic or numeric characters used to denote information recorded in response to a specified question or statement on a data form. DATA FILE A collection of data records. The collection may be of paper records or of electronic records that are arrayed in some way. DATA, INTERVAL Data classified into equal intervals without an absolute zero point, e.g., IQ of 120 is 60 points higher than an IQ of 60, but this does not necessarily indicate twice as much intelligence. Temperature is another example. DATA ITEM 1. A question or statement appearing on a data form. 2. Data field. DATA, NOMINAL Data classified into unordered categories, e.g., male/female, diabetes/no diabetes, mammogram-yes/mammogram-no. DATA, ORDINAL Data classified into ordered categories, e.g., intensity of pain (+/++/+++/++++), severity of disease (mild/moderate/severe/fatal). DATA AND SAFETY MONITORING BOARD (DSMB) 1. A standing committee responsible for periodically reviewing accumulated data for evidence of adverse or beneficial treatment effects during the trial and for initiating recommendations for modification of a study treatment, including termination of the treatment when appropriate. 2. One of the key committees in the organizational structure of a multicenter trial. Usually composed primarily, if not exclusively, of individuals not directly involved in patient care or data collection in the trial. DATABASE A collection of data files that are organized in a specified manner, and used in analysis of trials. DATRI See "Division of AIDS Treatment Research Initiative" DATUM Singular of data. DC Discontinuation (of treatment) ddC See "Zalcitabine" ddI See "Didanosine" DECA- Preferences meaning ten times, as in decagram, or ten grams. DECI - Prefix meaning one tenth, as in decigram, or a tenth of a gram. DEL The Delaware Community Program for Clinical Research on AIDS, a CPCRA unit DEFICIT Lack, or shortfall. DEGENERATION Deterioration; change from a higher to lower form, especially as in change to less functional or healthy tissue. DELAYED-TYPE HYPERSENSITIVITY (DTH) A cell-mediated immune response that produces a cellular infiltrate and edema (swelling), redness and induration (hardness) between 48 and 72 hours after exposure to an antigen. DTH response is the basis for PPD testing of tuberculosis exposure. DEMARCATE To separate, or to indicate the interface between two areas. DEMENTIA Chronic intellectual impairment (loss of mental capacity) with organic origins, that affects a person's ability to function in a social or occupational setting. See "AIDS Dementia complex" DEN The Denver Community Program for Clinical Research on AIDS, a CPCRA unit. DENDRITIC CELL A type of antigen-presenting immune cell. Dendritic cells have elongated, tentacle like branches in which they trap foreign objects. DERMAL Relating to the skin. DESENSITIZATION The reduction or abolition of allergic sensitivity or reactions to the specific antigen (allergen). DESQUAMATING Shedding or losing skin, particularly as in grade 3 and 4 rashes DHPG See "Ganciclovir" DHR See "di-hydrofolate reductase" DIAGNOSIS The evaluation of a patient's medical history, clinical symptoms and laboratory tests which confirms or establishes the nature/origin of an illness. DIARRHEA Abnormally frequent and liquid stools. DIDANOSINE (ddI) A nucleoside analogue reverse transcriptase inhibitor, didanosine is in the same family of antiviral drugs as AZT. It's primary toxicities are pancreatitis and neuropathy. DIFFUSION To spread out evenly, as in a liquid. DIFLUCAN See "Fluconazole" DIRECT PATIENT CONTACT Patient contacts that are initiated by the study clinic for the purpose of patient recruitment or data collection and that are directed at specified patients without any reliance on interviewing persons, agencies, institutions, or generalized advertising campaigns to make contacts. DISCRETE VARIABLE A variable is capable of assuming only certain values over a defined range. See also "Continuous Variable." DI-HYDROFOLATE REDUCTASE (DHR) The bacterial (or protozoal ) enzyme targeted by trimethoprim-sulphamethoxazole: DHR is necessary for pneumocystis or Toxoplasmosis to survive. DISEASE PROGRESSION See "Progression of Disease." DISSEMINATED Spread throughout the body. DISTRIBUTION, NORMAL (GAUSSIAN) DISTRIBUTION A symmetrical distribution which has a shape defined by its mean and standard deviation. Mean=median=mode. Often called the bell-shaped curve. DIVISION OF AIDS TREATMENT RESEARCH INITIATIVE An extramural program funded by NIAID to due technically challenging cutting edge AIDS clinical research. DNA (DEOXYRIBONUCLEIC ACID) A complex protein that is the carrier of genetic information. HIV can insert itself into a cell's DNA and use cellular mechanisms for replication. DORMANCY See "Latency." DORMANT At rest; clinically silent. DOSAGE A specific quantity of a biologically active compound. DOSE RANGING The establishment of the optimal dosage of a new drug by repeated trials of varying dosages DOUBLE BLIND 1. A procedure in a clinical trial for issuing and administering treatment assignments by code number in order to keep study patients and all members of the clinic staff, especially those responsible for patient treatment and data collection, from knowing the assigned treatments. 2. Any condition in which two different groups of people are purposely denied access to a piece of information in order to keep that information from influencing some measurement, observation, or process. DOUBLE BLINDED CLINICAL TRIAL A clinical trial with double-blinded administration of the study treatments. DRONABINOL (MARINOL) A synthetic form of the active ingredient in marijuana, used to increase hunger and ameliorate nausea in persons with severe involuntary weight loss. DROP-OUT A patient enrolled in a clinical trial who is either unwilling or unable to return to the study clinic for regular follow-up visits. DRUG TRIAL A clinical trial in which the test treatments are drugs. DSMB See "Data and Safety Monitoring Board." DTH Delayed Type Hypersensitivity. DYSMENORRHEA Difficult and painful menstruation. DYSPEPSIA Digestive upset. DYSPHAGIA Difficulty swallowing. DYSPLASIA The abnormal development of tissue. In disease, the alteration of size, shape, and organization of adult cells. DYSPNEA Difficult or labored breathing. DYSREGULATION Refers to interruption or interference of normal process(es). E ED50 Short for "Effective dose 50"; the dosage of a drug or poison that kills, or stops replication in 50% of the organisms it is tested against. Often applies to does of drug against microorganisms. E-MAIL A way of sending messages electronically from computer to computer over the Internet, or via a private carrier like MCI. All CPCRA sites and support contractors have E-mail capability EARLY STOPPING 1. A condition or provision incorporated into the design of a clinical trial that enables investigators to terminate patient recruitment or treatment if data accumulated during the trial strongly indicate an adverse or beneficial treatment effect. 2. A term used to characterize an action involving termination of a study treatment in a trial because of adverse or beneficial treatment effects. EDEMA Swelling. ELISA (ENZYME LINKED IMMUNOSORBENT ASSAY) A laboratory test to determine the presence of antibodies to HIV in the blood. See also "Western Blot." ENCEPHALITIS A general term denoting inflammation of the brain. ENCEPHALOPATHY Lesions in the brain, or general degeneration of brain matter ENDEMIC Pertaining to diseases associated with particular locales or population groups. ENDOCRINE Relating to the internal secretion of hormones into systemic circulation. ENDOCRINE GLANDS The organs in the body that produce hormones. They are ductless glands that empty hormonal secretions directly into the bloodstream. ENDOGENOUS Relating to or produced by the body. ENDOSCOPY Viewing the inside of a body cavity with a device using flexible fiber optics. ENDPOINT A primary or secondary outcome variable used to judge the effectiveness of a treatment This term is confusing because it often incorrectly implies that patients in a study are no longer followed after they experience an endpoint. This is obviously true where the event is death, but need not be so for nonfatal events and never is in the CPCRA. In fact, the design of the trial may require continued treatment and follow-up of patients over the entire course of the trial, regardless of the number of nonfatal "endpoints" observed. See "Event," "Clinical Event," "Primary Outcome," and "Primary Event" for preferred terms. ENTERAL Within or by way of the intestines or gastrointestinal tract. ENTERIC Relating to, or of the intestines or gastrointestinal tract. ENZYME A protein that triggers or accelerates chemical reactions, without itself being consumed in the reaction. EOSINOPHIL One of white blood cell called granulocytes that can digest microorganisms. EPIDEMIOLOGY The science concerned with the determination of the specific causes of a disease or the interrelation between various factors determining a disease, as well as disease trends in a specific population. EPITHELIAL The cell linings covering most of the internal and external surface of the body and its organs. EPITOPE A unique shape or marker carried on an antigen's surface which triggers a corresponding antibody response. EPOGEN Brand name of Erythropoietin EPSTEIN-BARR VIRUS (EBV) A herpes virus that causes infectious mononucleosis and hairy leukoplakia. EBV also has been associated with Burkitt's lymphoma, a cancer of the lymph nodes and the nasopharynx, the part of the pharynx (throat) which lies above the soft palate. EQUAL ALLOCATION Equal treatment allocation. EQUAL TREATMENT ALLOCATION A scheme in which the assignment probability in the randomization process for any one treatment is the same as for every other treatment in the trial. A process that ensures that approximately equal numbers of patients receive each treatment ERYTHEMA Redness, usually of the skin. ERYTHEMATOUS Red or reddened. ERYTHROCYTES Red blood cells. The primary function of erythrocytes is to carry oxygen to cells. ERYTHROPOIETIN (EPO, PROCRIT) A recombinant version of a natural hormone that induces growth of red blood cells, Erythropoietin is used in the treatment of anemia ESTIMATED SAMPLE SIZE The number of patients required for a study, as derived from a sample size calculation or in some other way. ETHAMBUTOL (MYAMBUTOL) An antibiotic used as a component in combination therapy to treat tuberculosis or mycobacterium avium complex. ETIOLOGY The study or theory of factors which cause disease. EVENT 1. An occurrence, incident, or experience, especially one of some significance. 2. Binary outcome measure. 3. Clinical event. 4. The actual occurrence of a condition, trait, or characteristic that is defined by a binary outcome measure. EVENT DRIVEN DATA Data whose collection is triggered by clinically manifest occurrence, as opposed to on a particular schedule. EVENT RATE The number of events experienced by a specified number of patients in a specified unit of time. EXOGENOUS Developed or originating outside the body. EXPANDED ACCESS A general term for methods of distributing experimental drugs to patients who are unable to participate in ongoing clinical efficacy trials and have no other treatment options. Specific types of expanded-access mechanisms include parallel track, Treatment IND, and compassionate use. EXPLANATORY TRIAL Trials that are designed to explain how a treatment works, in which patients are typically analyzed by treatment received and not as assigned. EXTRACELLULAR outside the cells. EXTRACEREBRAL Outside the brain or skull EXTRACORPOREAL Outside the body. EXTRAMURAL Research that is conducted outside of NIH, supported by either contract or grant support. The CPCRA and the ACTG are two extramural programs. EXTRAPULMONARY Outside the lungs. F FACTORIAL TREATMENT STRUCTURE A treatment structure in which one study treatment is used in combination with at least one other study treatment in a trial, or where multiples of a defined dose of a specified treatment are used in the same trial. See "Partial" and "Full Factorial Treatment Structure." FALSE-POSITIVE ERROR The probability of rejecting the null hypothesis of no treatment difference when there is no treatment difference, that is, falsely claiming a treatment difference. Also called type I error. FAMCICLOVIR (FAMVIR) A drug chemically related to acyclovir, used in the treatment of herpetic diseases FANSIDAR A combination of two antibiotics, Pyrimethamine and sulfadoxine, Fansidar was once used in the treatment of PCP. It proved highly toxic, however, with a high rate of allergic reactions and rash, including Stevens-Johnson syndrome. Rarely used anymore. FDA Food and Drug Administration (a regulatory agency of the United States government, located in Rockville, Maryland). FDA decides which drugs may be approved for sale in the United States. FEASIBILITY STUDY A preliminary study designed to determine the practicality of a larger study. See "Pilot Study." FEBRILE With a fever. FIGHT The Philadelphia Field Initiating Group for HIV Trials , a CPCRA unit. FILGRASTIM (GRANULOCYTE COLONY STIMULATING FACTOR, G-CSF) A recombinant version of an endogenous cytokine that stimulates the production of white blood cells. Often used for treatment of neutropenia attendant upon chemotherapy, or treatment with AZT. FINAL DATA ANALYSIS The term given to data analyses carried out at the end of the trial, normally in the termination stage, for describing results of the trial. FIRST-LINE TREATMENT The preferred therapy for a particular condition (e.g., trimethoprim-sulfamethoxazole (TMP-SMX) is the first-line treatment for PCP). 5-FC See "Flucytosine" FLOUROQUINOLONES A family of antibiotics, including Ciprofloxacin, ofloxacin, and Sparfloxacin. Sometimes used as components of combination therapy for mycobacterium avium complex. FLUCONAZOLE An antifungal drug that is used to treat fungal infections in persons with HIV, including candida, cryptococcus, histoplasmosis, and others. FLUCYTOSINE (5-FC) Antifungal drug used as an adjunct to amphotericin for the treatment of cryptococcal meningitis. FOLATE A salt or ester of folic acid, a crystalline vitamin of the B complex. Drugs such as trimethoprim sulfa and trimetrexate work by "starving" bacteria of folate, without starving the human body. FOLLICULITIS An infection or inflammation of the follicle, at the root of a hair. Folliculitis may be aseptic, as in eosinophilic folliculitis. FOLLOW-UP Patient follow-up. FOLLOW-UP DATA Data collected on a patient, or a set of patients, after enrollment into a trial. FOLLOW-UP VISIT Any patient clinic visit that takes place after the randomization visit for study-related purposes. FOSCARNET (FOSCAVIR) An antiviral drug FDA-approved for the treatment of cytomegalovirus (CMV) retinitis and other diseases caused by CMV. It is also used to treat acyclovir-resistant herpes virus infections. Adverse side effects may include kidney toxicity, muscle twitching, nausea and skin ulcers. FULMINATING Serious acute, active infection FUNDOSCOPIC EXAM Visual inspection of the interior of the eye. Often used to diagnose CMV retinitis. FUNGEMIA The presence of fungus in the blood. FUNGIZONE Brand name for Amphotericin B G G-CSF See "Filgrastim" GALLIUM SCAN A diagnostic procedure where mildly radioactive gallium particles are ingested, and then disease (often pneumocystis carinii pneumonia) is diagnosed by scanning the body for radioactive signature. GANCICLOVIR (CYTOVENE) An antiviral drug FDA-approved to treat cytomegalovirus (CMV) retinitis and to prevent CMV disease in transplant patients at risk for CMV. It has also been used to treat CMV colitis, CMV esophagitis, AIDS-related meningoencephalitis and AIDS-related polyradiculopathy; generally administered intravenously. An oral form of the drug is under study for the treatment and prevention of CMV disease in people with HIV infection. GASTRIC Relating to the stomach. GASTROENTERITIS Inflammation of the stomach and/or intestines. GASTROINTESTINAL Relating to the stomach and intestines. GENE A unit of DNA that carries information for the bio-synthesis of a specific product. GENOME The DNA code that comprises the complete genetic composition of an organism. GI See "Gastrointestinal" GIARDIASIS A common protozoal infection of the small intestine spread via contaminated food and water and direct person-to-person contact. GIGA- Prefix meaning a billion times. GLYCOPROTEIN A protein molecule coated with sugars. GM-CSF See "Sargramostim" GONORRHEA A sexually transmitted disease; inflammation of genital mucous membranes caused by the bacteria gonococcus. gp41 A protein on the outer shell, or envelope, of HIV. gp41 is the portion of HIV pierces a helper T-cell's surface protein, CD4, allowing viral entry. The "120" refers to its molecular weight. gp120 Another protein on the outer shell, or envelope, of HIV. gp120 is the portion of HIV that binds to a helper T-cell's surface protein, CD4. The "120" refers to its molecular weight. gp160 The "precursor" protein to both gp41 and gp120, gp160 is cleaved by viral enzymes into the two surface proteins at a late stage of viral assembly. GRAM A metric unit of weight measure. There are approximately 454 grams to an US Pound. GRANULOCYTES A white blood cell type of the immune system filled with granules of toxic chemicals that enable them to digest microorganisms. Basophils, neutrophils, eosinophils, and PMNs are examples of granulocytes. GRANULOCYTE COLONY STIMULATING FACTOR See "Filgrastim" GRANULOCYTE-MACROPHAGE COLONY STIMULATING FACTOR See "Sargramostim" GRANULOCYTOPENIA A lack or low level of granulocytes in the blood. Often used interchangeably with "neutropenia" GROSCHUNG CATHETER An indwelling line used for administering medication and total parenteral nutrition over long durations. Also see "Hickman catheter" H HAIRY LEUKOPLAKIA A whitish, slightly raised lesion that appears on the side of the tongue. Thought to be related to Epstein-Barr virus infection, it was not observed before the HIV epidemic. HALF LIFE The amount of time required for half of a given substance to be eliminated from the body. HAPHAZARD A process occurring without any apparent order or pattern. Distinct from random, in that there is no mathematical basis for characterizing a haphazard process. HARD ENDPOINT Any outcome measure that is not subject to serious errors of interpretation or measurement. Usually death, infection or some other explicit clinical event. HATG The Harlem AIDS Treatment Group, a CPCRA unit. HEALTH AND HUMAN SERVICES ADMINISTRATION (HHS) A large branch of government that encompasses many other branches. The NIH and the Public Health service (among many others) are parts of HHS. HEALTH REIMBURSEMENT SERVICES AGENCY (HRSA) The branch of the federal government with primary responsibility for paying for health care, HRSA runs Medicaid and Medicare. HELPER-SUPPRESSER RATIO The ratio of helper (CD4+) T-cells to suppresser (CD8+) T-cells. HEMATOCRIT A laboratory measurement which determines the percentage of packed red blood cells in a given volume of blood. HEMATOLOGIC Pertaining to, or involving the blood, or it's constituent cells. HEMATOMA Bruise HEMATOPOIETIC Pertaining to the formation of blood cells. HEMIPARESIS Paralysis of only one side of the body. HEMOLYSIS Destruction of blood cells. HEPARIN A chemical that prevents blood from clotting. HEPATIC Pertaining to the liver. HEPATlTlS An inflammation of the liver caused by any of several causes. Often accompanied by jaundice, enlarged liver, fever, fatigue and nausea, and abnormal liver function blood tests. HEPATITIS B A viral liver disease that can be acute or chronic and even life-threatening, particularly in people with poor immune resistance. Like HIV, the hepatitis B virus can be transmitted by sexual contact, contaminated needles or contaminated blood or blood products. Unlike HIV, it is also transmissible through close casual contact. HEPATITIS C A recently recognized viral disease that causes inflammation of the liver, and may cause severe, life-threatening liver damage. Hepatitis C was formerly called "non-A/non-B" hepatitis. HEPATOMEGALY An enlargement of the liver. HEPATOSPLENOMEGALY Enlargement of the liver and spleen. HERPES SIMPLEX VIRUS 1 (HSV-1) A virus that can cause painful "cold sores" or blisters on the lips ("fever blisters") or in the mouth or around the eyes. The symptomatic disease stage occurs at unpredictable intervals of weeks, months or years. The latent (inactive) virus can reactivate due to emotional stress, physical trauma, other infections, or suppression of the immune system. HSV-1 responds well to treatment with acyclovir. HERPES SIMPLEX VIRUS 2 (HSV-2) A virus closely related to HSV-1 that causes similar lesions. However, HSV-2 is usually transmitted sexually, and its lesions generally are in the anogenital area. HERPES VARICELLA ZOSTER VIRUS (HVZ/VZV) The varicella virus causes chicken pox in children and may reappear in adulthood as herpes zoster. Herpes zoster, also called shingles, consists of very painful blisters on the skin that follow nerve pathways. HERPES VIRUS A family of viruses including Herpes simplex I and II, Herpes zoster, Epstein-Barr virus, Cytomegalovirus, and the newly discovered Kaposi's Sarcoma-associated herpes virus. HFH The Henry Ford Hospital, a CPCRA Unit. HHC Hill Health Center, a CPCRA unit HHS See "Health and Human Services Administration" HICKMAN CATHETER An indwelling line used for administering medication and total parenteral nutrition over long durations. Also see "Groschung catheter" HISTOPLASMOSlS A fungal disease resulting from infection with Histoplasma capsulatum. Histoplasmosis is geographically limited, generally appearing only in the Mississippi River Valley. HISTORICAL CONTROL GROUP A group of patients (may be loosely or explicitly defined) considered to have the same disease or condition as the study group, but who were diagnosed and treated in a period of time prior to that of the study group and who received the conventional form of therapy for that time. Historical control groups are generally only useful for evaluations of treatments involving rare diseases with highly predictable outcomes and where it is considered impractical or unethical to carry out a controlled clinical trial. HIV See "Human Immunodeficiency Virus." HIV-1 See "Human Immunodeficiency Virus Type 1." HIV DEMENTIA SYNDROME See "AIDS Dementia complex" HIV ENCEPHALOPATHY See "AIDS Dementia complex" HIVID See "Zalcitabine" HORMONE An active regulatory chemical substance formed in one part of the body and carried by the blood to another part of the body, where it signals the coordination of cellular functions. HOST A cell or organism that supports the growth of a parasite or virus. HRSA See "Health Reimbursement Services Agency" HUMAN IMMUNODEFICIENCY VIRUS or HIV INFECTION Infection with the retrovirus that causes the acquired immunodeficiency syndrome (AIDS). HUMAN IMMUNODEFICIENCY VIRUS TYPE 1 (HIV-1) The probable cause of AIDS. A human retrovirus of the lentivirus family, notable for long duration of asymptomatic infection, often followed by progressive deterioration of cell mediated immune function, and eventual opportunistic infection and neoplasm. The median time for an HIV infected individual to develop full clinical AIDS is probably over ten years.(formerly called HTLV III or LAV). HUMAN PAPILLOMAVIRUS (HPV) A member of the papova family of viruses. HPV causes warts or nipplelike protrusions. HPV has also been associated with cervical cancer in women and anal cancer. HUMATIN Brand name of Paromomycin. HUMORAL IMMUNE RESPONSE The immune response that is mediated by B-cells and involves production of antibodies. Humoral immunity (also known as TH-1 immune response) is associated with the production of the cytokines interleukin-4 and interleukin-10. HUMORAL IMMUNITY The branch of the immune system that relies primarily upon antibodies. See also "Cellular Immunity." HYPERGAMMAGLOBULINEMIA Abnormally high levels of antibodies in the blood. Common in persons with HIV. HYPERPLASIA Excessive cell growth. HYPERSENSITIVITY Abnormal sensitivity; medically, when the body responds in an exaggerated manner to a foreign agent; allergy. HYPERTENSION High blood pressure. HYPOTHESIS, ALTERNATIVE: Ha The investigator's initial supposition that the study will demonstrate that "something is going on," i.e., results observed are more than the outcome of chance. Common examples include that there is a difference in outcome measures between groups, correlation between factors of interest, or association between exposure and disease, i.e., observations are the result of real differences or correlations. HYPOTHESIS, NULL: Ho The investigator's initial supposition that the study will demonstrate that "nothing is going on," i.e., results observed are the outcome of chance. Common examples include that there is no difference in outcome measures between groups, no correlation between factors of interest, or no association between exposure and disease, i.e., observations are the result of random variation. Generally, the goal is to "falsify" the null hypothesis. I I D Identification. IDU See "Injection drug user" IDIOTYPES The unique and characteristic parts of an antibody's variable region, which can themselves serve as antigens. IL 1-12 See "Interleukins 1-12" IM See "Intramuscular" IMMUNE COMPLEX Clusters formed when antigens and antibodies bind together. IMMUNE DEFICIENCY A breakdown or inability of certain parts of the immune system to function, thus making a person more susceptible to certain diseases to which the person would not ordinarily be subject. In disease associated with HIV, cell mediated immunity related to the function of T-helper lymphocytes deteriorates, increasing the likelihood of disease from a number of pathogens, many of which are ubiquitous (opportunistic infection). IMMUNE RESPONSE The activity of the immune system against foreign substances. IMMUNE SYSTEM The complex functions of the body that recognize foreign agents or substances, neutralize them, and recall the response later when confronted with the same challenge. IMMUNE THROMBOCYTOPENIC PURPURA (ITP) An HIV-related loss of platelets in the blood. Its exact cause is unclear. IMMUNITY A natural or acquired resistance to a specific disease. Immunity may be partial or complete, long lasting or temporary. IMMUNOCOMPETENT Having a normally functioning immune system. IMMUNOCOMPROMISED Having a deficient or damaged immune response. IMMUNOGLOBULIN A protein that acts as an antibody to help the body fight off disease. There are 5 classes: IgG, IgA, IgD, IgM and IgE. Recombinant and pooled immunoglobulins from blood donations have been used successfully to help HIV-infected children and some adults resist bacterial infections. IMMUNOMODULATOR Any substance that influences the immune system. Generally the term "immunomodulator" is used. IMMUNOSUPPRESSION A state of the body in which the immune system is damaged and does not perform its normal functions. Immunosuppression may be induced by drugs or result from certain disease processes (such as HIV infection). IMMUNOTHERAPEUTIC Aiming at reconstituting an impaired immune system. INDINAVIR An experimental protease inhibitor drug made by Merck pharmaceuticals IN UTERO Latin for "in the uterus," or womb. INVIRASE A Brand name for Saquinavir IN VIVO Latin for "in life" : Studies conducted within a living organism, e.g., animal or human studies. IN VITRO Latin for "in glass": An artificial environment created outside a living organism, e.g., a test tube or culture plate, used in experimental research to study a disease or process. INACTIVE CONTROL TREATMENT A control treatment that is not considered to have any pharmacological or physiological effect. A placebo treatment or sham procedure. See also "Active Control Treatment." INCUBATION PERIOD The time interval between the initial infection and appearance of the first clinical symptom or sign of disease. IND See "Investigational drug status". INDICATION Sign or symptom. Also, in terms of drug approval, the exact cause or purpose for which a drug is approved by the FDA to be prescribed. Also called "label indication" INDOLENT At rest, or in a quiescent state. INDUCED SPUTUM A test where saline mist is breathed to induce a cough. Resultant sputum is then cultured or stained to look for microorganisms, often pneumocystis carinii. INDUCTION The initiation of a particular therapy. INFECTION Condition in which virulent organisms are able to multiply within the body and cause a response from the host's immune defenses. Infection may or may not lead to clinical disease. INFECTIOUS Capable of being transmitted by infection, with or without actual contact. INFILTRATES Something seeping or filling in a space or cavity. INFLAMMATION Redness, swelling, soreness of tissues. INFORMED CONSENT The voluntary consent given by a patient to participate in a study after being informed of its purpose, method of treatment, procedure for assignment to treatment, benefits and risks associated with participation, and required data collection procedures and schedule. INFUSION Administration of treatment in a dilute form by slow injection into a vein. INH See "Isoniazid" INJECTION DRUG USER (IDU, IVDU, AVDA) Also known as intravenous drug user (IVDU), or intravenous drug abuser (IVDA). None of these terms are very precise: often IVDU will be used to describe someone who injects IM or Sub-Q, and the distinction between "user" and "abuser" is a controversial and emotionally charged one. Nevertheless, a working definition for an IDU is anyone who regularly injects any substances, whether pharmaceutically or illicitly made, not under medical prescription and supervision. INSTITUTIONAL REVIEW BOARD (IRB) A committee of physicians, statisticians, community advocates, and others which ensures that a clinical trial is ethical and that the rights of the study participants are protected. All clinical trials in the United States must be approved by an IRB before they begin. INTENTION-TO-TREAT ANALYSIS A method of data analysis in which the primary tabulations, summaries and comparisons of patient outcome data are by assigned treatment, regardless of compliance to therapy or the protocol. INTEGRASE The HIV enzyme that governs the insertion of HIV's proviral genetic material into the host genome. Integrase is a target for a new generation of HIV drugs. INTERACTION A situation in which the magnitude of the test-control treatment difference for the outcome of interest depends upon the value assumed by a third factor, such as age or prior disease state of the study patients. INTERACTION EFFECT Treatment interaction effect. INTERCURRENT Occurring at the same time, or accompanying. INTERFERONS A family of secreted proteins (lymphokines) in the body with the ability to induce an antiviral state in most cell types. They are secreted by infected host cells to protect uninfected cells from viral infections. There are 3 main classes of interferon: alpha, beta and gamma. The interferons have been synthesized by genetic engineering, and are being tested as treatments for HIV infections and other diseases. Alpha interferon is FDA-approved for treatment of HIV-related Kaposi's sarcoma, chronic hepatitis B and genital warts. INTERIM ANALYSIS Any data analysis done before the trial is finished, for whatever reason, but usually concerned with assessments of treatment effects. INTERIM RESULT 1. Any test-control treatment difference observed during the trial. 2. A test-control treatment difference observed during the trial that results in a treatment protocol change. INTERLEUKIN A chemical hormone messenger (cytokine) secreted by and affecting many different cells in the immune system. INTERLEUKIN-1 (IL-1) A natural cytokine released by monocytes, macrophages, T-cells and other immune cells that fights infection. INTERLEUKIN-2 (IL-2) A cytokine that is produced by both T-helper and suppresser lymphocytes, IL-2 increases the expression of natural killer and other cytotoxic cells. IL-2 is associated with a cell-mediated or TH-2 immune response. A recombinant IL-2 is under study as a treatment for HIV disease (immunomodulator). INTERLEUKIN-4 (IL-4) A cytokine released by lymphocytes (the TH-2 subset of T-helper lymphocytes) that enhances the humoral response, increasing antibody production. INTERLEUKIN 6 (IL-6) A cytokine whose production affects many different cells in the immune system. INTERLEUKIN-10 (IL-10) A cytokine released by lymphocytes (the TH-2 subset of T-helper lymphocytes) that enhances the humoral response, increasing antibody production. INTERLEUKIN-12 (IL-12) A cytokine that induces the production of natural killer and other cytotoxic immune cells. IL-12 is associated with a cell-mediated or TH-1 immune response. A recombinant IL-12 is under study as a treatment for HIV disease (immunomodulator). INSTERSTITIAL A space or gap in a tissue: in the context of "interstitial infiltrates", means between the air passage in a lung INTOLERANT Unable to take a drug because of toxicity. INTRADERMAL Within the layers of the skin. INTRALESIONAL Injected directly into a lesion INTRAMURAL Research that is done at the National Institutes of Health, by one or more institute, often within the NIH clinical research facility. INTRAMUSCULAR Into the muscle: frequently in reference to injections. INTRAPARTUM During childbirth. INTRATHECAL Injection of a substance through the theca of the spinal cord into the subarachnoid space. INTRAVENOUS (IV) Within or into the veins. Intravenous drugs are injected directly into the veins. INTRAVlTREAL Injected in to the vitreous humor of the eye. INVESTIGATIONAL Under study INVESTIGATIONAL NEW DRUG APPLICATION (INDA, also IND) An application directed to the Food and Drug Administration (made by submitting a Notice of Claimed Investigational Exemption for a New Drug) for permission to evaluate a drug (new or old) for a new indication in humans. IRB See "Institutional review board". ISONIAZID An antibiotic that is one of the most common components in treatment for tuberculosis, either alone or in combination. ISOSPORIASIS A Protozoal infection, isosporiasis is usually restricted to the lower gastrointestinal tract. Symptomatically similar to cryptosporidiosis, isosporiasis usually responds well to treatment. ISOTONIC Refers to a solution whose salinity is the same as human blood. ITRACONAZOLE (SPORANOX) An antifungal drug that is used to treat fungal infections in persons with HIV, including candida, cryptococcus, histoplasmosis, and others. IV See "Intravenous" IVDA See IDU IVDU See IDU J JAUNDICE Yellowish discoloration of the skin and eyes due to bile. Usually associated with some form of liver damage or malfunction. JC PAPOVAVIRUS Suggested as a possible cause of progressive multifocal leukoencephalopathy. K KAPLAN-MEIER CURVE A way of graphing patient progress (how many are still alive or free of infection) against time: A lifetable curve showing the percent of people free of a specific event at times following randomization. The Kaplan-Meier method is especially well suited to situations with censored data , such as those encountered in clinical trials, where patients are enrolled over a period of time and followed to a common calendar time point. KAPOSI'S SARCOMA (KS) A tumor of the wall of blood vessels, or the lymphatic system. Usually appears as pink to purple, painless spots on the skin but may also occur internally in addition to or independent of lesions. KARNOFSKY SCORE A subjective score between 0-100, assigned by a physician to describe a patient's ability to function and perform common tasks. KILO- Prefix meaning a thousand time, as in kilogram, a thousand grams. KINASE An enzyme that mediates the addition of phosphorus to chemical groups. The AZT nucleoside must be phosphorylated to become a genetically active nucleotide. KETACONAZOLE (NIZORAL) An antifungal drug that is used to treat fungal infections in persons with HIV, including candida, cryptococcus, histoplasmosis, and others. KILLER T CELL Cytotoxic lymphocyte. A T-cell that directly kills of infected cells of the body. L LaCARP The Louisiana Community AIDS Research Program, a CPCRA unit. LAMIVUDINE (3TC) A nucleoside analogue drug, in the same family as AZT, that is used as an antiretroviral to treat HIV disease. LANGERHANS CELL A type of dendritic cell found in the skin. LAMPRENE Brand name of Clofazimine LATENCY The period when an organism is in the body, shows no symptoms, but is in an inactive state (also known as incubation period). LATERAL To, or on, the side. LD50 Short for "Lethal dose 50"; the dosage of a drug or poison that is toxic to 50% of the organisms it is tested against. Often applies to does of drug against microorganisms. LEGIONELLA PNEUMOPHILAE An ubiquitous bacteria causing pneumonia, or "legionnaire's disease". Recognized fairly recently, L. pneumophilae may be the cause of many pneumonias of indeterminate etiology. Most exposure is from tap water, often aerosolized by a shower head or air-conditioner LENTIVIRUS A sub-family of retrovirii that is cytopathic and causes chronic diseases. HIV is a lentivirus. LESION A change in tissue caused by disease; a point or localized patch of a skin disease. Other words that mean approximately the same thing as lesion are "sore" or "spot." LEUCOVORIN A form of the B vitamin, folate that is preferentially taken up by human cells. Leucovorin thereby protects from the effect of folate-antagonist antibiotics. LEUKINE Brand name of Sargramostim LEUKOCYTES White blood cells which generally fulfill immune functions, as opposed to red blood cells, which are primarily involved in oxygen transport. Leukocytes may be classified as granular or agranular. LEOKOCYTOSIS An abnormal high number of white blood cells in the circulating blood. LEUKOPENIA An abnormally low number of white blood cells in the circulating blood. LIFETABLE ANALYSIS A method of analysis that relies on a count of the number of events observed and the time points at which those events occurred, relative to some zero point. The event may be death or some other event. In clinical trials, the time to an event for a patient is usually measured from the time of randomization. Treatment effects are assessed by comparing event rates in the different treatment groups. LIPOSOME Microscopic globules of fat used to encapsulate drugs, and ensure their delivery to the proper targets, reducing toxicity, and hopefully increasing activity. LIVER FUNCTION TEST (LFT) Any of a number of tests that measure the health of the liver by checking the levels of various liver-secreted chemicals in the blood. See "Alkaline phosphatase", "Aspartate aminotransferase", and "Alanine aminotransferase". LFT See "Liver function test" LLN See "Lower limit of normal" LOCI Plural of locus; a place; usually, a specific site. LOGARITHM A number expressed as the exponent a certain base must be raised to so as to equal the original value. Usually logs are base 10, or calibrated to a special number "e" (approximately 2.7: logarithms based on e are called natural logarithms.). For logs of base 10, 1 log is ten times, 2 logs is a hundred times, etc. LONG TERMINAL REPEAT (LTR) Genetic material at the beginning of the HIV genome that helps control replication. LOST TO FOLLOW-UP A patient who can no longer be followed for the outcome of interest, e.g., a patient who is unwilling or unable to return to the clinic for follow-up examinations in the case of a clinical trial using an outcome measured at the clinic, or a patient who cannot be located for subsequent follow-up in the case of a trial involving mortality or some other outcome that can be measured outside the clinic setting. LOTRIMIN Brand name of Clotrimazole LOWER LIMIT OF NORMAL The bottom of the normal range for a particular laboratory: helps assure between-lab comparability. LTR See "Long terminal repeat" LUMBAR PUNCTURE A procedure in which fluid from the sub-arachnoid space in the lumbar region is tapped for examination; also known as a spinal tap. LYMPH NODES Small bean-sized organs of the immune system, distributed widely throughout the body. Lymph fluid is filtered through the lymph nodes in which all types of lymphocytes take up temporary residence. Antigens which enter the body find their way into lymph or blood and are filtered out by lymph nodes or the spleen respectively, for attack by the immune system. LYMPHADENOPATHY Swollen, firm and possibly tender lymph nodes. The cause may range from an infection such as HIV, the flu, mononucleosis, or lymphoma (cancer of the lymph nodes). LYMPHATIC VESSELS A bodywide network of channels, similar to the blood vessels, which transport lymph to the immune organs and into the bloodstream. LYMPHOCYTE White blood cells that mature and reside in the lymphoid organs, and are responsible for the acquired immune response. LYMPHOKINES Cytokines (Chemical messengers) produced by lymphatic cells. LYMPHOMA Cancers of the lymphatic system, often of T- or B-lymphocytes. There are many categories of lymphoma, including lymphoblastic, cleaved, non cleaved, Burkitt's, and Hodgkin's disease. Many lymphomas count as an AIDS diagnosis LYSE To rupture or destroy a cell. LYSIS The process of lysing or destroying cells. M MAC See "Mycobacterium avium complex" MACROLIDES A family of antibiotics with wide spectrum activity, including Clarithromycin, Azithromycin, and erythromycin. Some macrolides are sometimes used as parts of combination therapy for mycobacterium avium. MACROPHAGE A large scavenger cell that ingests degenerated cells, blood tissue and foreign particles, and secretes messenger proteins (monokines) involved in inflammatory reactions, lymphocyte activation and acute systemic immune responses. Macrophages exist in large numbers throughout the body and are key to the development of immunity to a variety of organisms. Along with their precursor blood cell, the monocyte, macrophages are a major reservoir of HIV infection. MAGNETIC RESONANCE IMAGING (MRI) A diagnostic imaging procedure that uses magnetic fields and radio waves, instead of X-radiation. MRI produces very accurate three dimensional computer generated images. MAI See "Mycobacterium avium complex" MAJOR HISTOCOMPATIBILITY COMPLEX (MHC) Two classes of molecules of the surfaces of antigen presenting cells. Antigen is complexed with MCH I or MHC II, and presented to an effector cell. Antigen without MHC is ignored. Discordant MHC type is the source of graft versus host disease and other rejection phenomena. MHC Class I is used for presentation to CD8 cells. Class II is used to present antigen to CD4 cells. MALAISE A generalized nonspecific feeling of discomfort and/or fatigue. MALIGNANT Cells or tumors growing in an uncontrolled fashion. MALNUTRITION Faulty nutrition resulting from poor diet, under eating or abnormal absorption of nutrients from the gastrointestinal tract. MANAGEMENT TRIAL A trial that is designed primarily to provide information on the value of a treatment in normal usage, typically analyzed by intention to treat. MANIFESTATION The signs or symptoms by which a disease state is known. MANUAL OF OPERATIONS A document or collection of documents that describes the procedures used in a center or set of centers in a clinical trial (e.g., manual of operations for study clinics, coordinating center manual of operations.) MARINOL Brand name for Dronabinol. MAST CELL A type of immune cell that features prominently in allergies. MATCHING PLACEBO A pill (capsule or tablet) that is designed to resemble in shape, texture, size, taste, etc., a therapeutically active drug and that is used as the control treatment. MEAN Commonly referred to as the "average", the mean of a set of quantities is the sum of the quantities, divided by the number of quantities summed. MEAN CORPUSCULAR VOLUME (MCV) The average volume of erythrocytes, conventionally expressed in cubic micrometers per red blood cell. MEDIAN The value such that for a series of ranked quantities, one half are above the median, and one half are below. For example, the median for a set of CD4 counts is that value which half the counts are less than, and half more. MEDICAL DEVICE A diagnostic or therapeutic contrivance that does not interact chemically with a person's body. Includes diagnostic tests, kits, pacemakers, arterial grafts, intraocular lens and orthopedic pins. MEDICAL OFFICER Staff member at the Division of AIDS, NIAID, in charge of a particular protocol. MEDLARS Medical Literature Analysis Retrieval System: The computer on which "Medline" and "AIDS Line" reside at the National Library of Medicine. MEDLINE Medical Literature Analysis Retrieval System on Line. A computer searchable database of published medical literature. MEGA- Prefix meaning a million times, as in megagram, a million grams. MEGACE Brand name of Megestrol Acetate MEGESTROL ACETATE A synthetic hormone used in patients with wasting to increase appetite and weight gain MEMBRANE A thin sheet or layer of pliable tissue (or lipids in the case of cells) that serves as a semi-permeable covering. MEMORY T CELL Persistent T cells that bear a receptor for a specific antigen that was previously encountered in the course of illness or vaccination. Memory T cells allow a rapid response to pathogens that the body has been previously exposed to. MEPRON Brand name of Atovaquone MENINGES Membranes surrounding the brain or spinal cord. Part of the so-called "blood-brain barrier" MENINGITIS An inflammation of the meninges. MeSH Medical subject heading. Term used by National Library of Medicine, and employed in their MEDLINE system META-ANALYSIS A quantitative method for combining the results of many studies into one set of conclusions. Generally done from a literature review, a meta-analysis is more a review than an analysis, properly speaking. METABOLIC Refers to the process of building the body's molecular structures from nutrients (anabolism) and of breaking them down for energy production and excretion (catabolism). MHC See "Major Histocompatibility Complex" MIC See "Minimum inhibitory concentration" MICRO- Prefix mean small, or one one-millionth, as in microgram, a millionth of a gram. MICROBES Microscopic living organisms, including bacteria, protozoa, and fungi. MICRONUTRIENT A trace element; an organic compound like a vitamin that is essential but only in small amounts for physical health, growth and metabolism. MICRO-ORGANISM See "Microbes." MICROSPORIDIOSIS Disease resulting from infection with a protozoal pathogen from the Microsporidia order; similar in symptoms (diarrhea, cramps) and often misdiagnosed as cryptosporidiosis. MITOCHONDRIA Organelles within the cytoplasm of the cells, mitochrondia have their own independent DNA, and serve as a source of energy for the cell. MITOGEN A substance that induces cell division MILLI- Prefix meaning one one-thousandth, as in milligram, a thousandth of a gram. MINIMUM INHIBITORY CONCENTATION The smallest amount of a substance, when diluted, which kill pathogens or stop them from reproducing. Usually means concentration required to achieve ED90. MOLLUSCUM CONTAGIOSUM An infectious skin condition characterized by small whitish papules, generally on the face or the trunk. MONITORING BOUNDARIES The set of values formed by a line or set of lines (or curves), usually specified before or shortly after the start of patient recruitment, which, if exceeded, indicates the existence of a test-control treatment difference that satisfies certain statistical properties (e.g., has a p-value of less than a certain size). The boundaries will be used as a basis for stopping the trial when developed in conjunction with a sequential design, but not necessarily when used in conjunction with a fixed sample size design. Z values larger in absolute values are declared statistically significant. Boundaries are designed to control the overall type I error. MONOCLONAL ANTIBODY An artificially produced antibody, made in the lab by use of an immortalized cell line. Monoclonal antibodies bind to one unique epitope. MONOCYTE An antigen presenting white blood cell, monocytes mature into macrophages. MONOTHERAPY A single drug, prescribed by itself. MOOP See "Manual of Operations" MORBIDITY The condition of being diseased or sick. MORTALITY The condition of being dead. MRI See "Magnetic Resonance Imaging". MUCOCUTANEOUS Pertaining to the mucous membranes and the skin, e.g., mouth, vagina, lips, anal area. MUCOSAL Pertaining specifically to the mucous membranes MULTICENTER CLINICAL TRIAL 1. A clinical trial involving two or more clinical centers and a common study protocol. MULTIPLE COMPARISONS A term used to refer to the fact that two or more treatment comparisons, each involving the same outcome measure, are made or are to be made at a designated time point in the course of the trial. The comparison may involve all members of the treatment groups or subsets (e.g., as in analyses involving subgroups of patients defined by the presence or absence of some baseline characteristic.). Also applies to comparisons among several subgroups and/or use of several endpoints. MULTIPLE COMPARISONS PROBLEM A term referring to the fact that significant findings will appear by chance alone if enough different comparisons are tested. For example, in an infinitely large data set, results with a significance level of 0.05 will occur on the average every twentieth time. MULTIPLE OUTCOMES A term used to refer to the fact that a trial involves several different outcome measures, each of which is used or is to be used to make treatment comparisons. MYCOBACTERIUM AVIUM COMPLEX (MAC) A common opportunistic infection caused by two very similar mycobacterial organisms, Mycobacterium avium and M. intracellulare. In PWAs, it can spread through the bloodstream to infect lymph nodes, bone marrow, liver, spleen, spinal fluid, lungs and intestinal tract. Symptoms of MAC include prolonged wasting, fever, fatigue and enlarged spleen. MAC infection is one of the disease making up the AIDS definition. MYAMBUTOL A brand name of Ethambutol. MYCOBACTERIUM AVIUM-INTRACELLULARAE See "Mycobacterium avium complex". MYCOBACTERIUM KANSASII Another member of the mycobacteria family, sometime mistaken for MAC. MYCOPLASMA A class of microorganism, simpler than a bacteria, but more complex than a virus. Some mycoplasma may play a role in HIV pathogenesis, although the evidence is unclear. MYCOBUTIN Brand name of Rifabutin. MYCOSIS Any disease caused by a fungus. MYCELEX Brand name of Clotrimazole. MYELITIS Inflammation of the spinal cord, or of the bone marrow. MYELOPATHY A degenerative process involving the spinal cord. MYELOTOXIC Toxic to the bone marrow. MYOPATHY A degenerative condition of the muscles. Can be caused by both HIV and AZT. N NAIVE T CELL A newly formed T cell that has not yet been exposed to antigen. NANO- Prefix meaning one one-billionth, as in nanogram, a billionth of a gram. NATAL Relating to birth. NATIONAL INSTITUTES OF HEALTH (NIH) A group of institutes and related support structures located in Bethesda, Maryland, that is part of the United States Public Health Service. Responsible for funding basic and applied research in the health field. Also initiates and carries out medical research on an intramural and extramural basis. NATURAL HISTORY OF DISEASE 1. The course of a disease when left untreated. 2. The course of a disease when treated with standard modes of therapy. NATURAL HISTORY STUDY A prospective follow-up study designed to yield information on the natural course of a disease or condition. Such studies generally focus on the control-treated group in a clinical trial (especially one in which the control treatment is a placebo or standard medical care). NATURAL KILLER (NK) CELL A type of lymphocyte (white blood cell) that lyses infected or cancerous cells. NK response does not require antigen presentation to lymphocytes. NCI National Cancer Institute (part of the NIH). NDA New drug application. A package of information submitted by the sponsor of a treatment to the FDA, containing all of the information in support of the treatment's approval NEBULIZED See "Aerosolized." NEBULIZER A device used to reduce liquid medication to extremely fine cloudlike particles; useful in delivering medication to deeper parts of the respiratory tract (e.g., into the lungs). NEBUPENT Brand name of pentamidine. NECROSIS Cell death and decay. NECROTIZING Causing necrosis. NEGATIVE CONTROL Inactive control treatment. NEUPOGEN Brand Name of Filgrastim NEUROLOGIC Pertaining to the brain or nervous system. NEUROPATHY An abnormal and degenerative state of the nervous system. HIV, some treatments, and other diseases can cause a peripheral neuropathy marked by burning tingling sensations in the extremities, loss of deep tendon responses, and decrease in sensitivity to touch stimulation. NEUTRALIZING ANTIBODY An antibody that neutralizes (renders harmless) the infectivity of microorganisms, particularly viruses. NEUTREXIN Brand name of Trimetrexate. NEUTROPENIA An abnormally low number of neutrophils (white blood cells) in the circulating blood. NEUTROPHILS One of the white blood cells called granulocytes, filled with granules of toxic chemicals that can digest microorganisms. Neutrophils are comprised of two kinds of cells, polymorpho- nuclear cells ("polys" or PMNs), and bands, which are immature polys. Neutrophils are one of the key components of the immune response, especially to bacterial infection, and the neutrophil count is often elevated in acute infection. NEVARIPINE An antiretroviral drug of the non-nucleoside reverse transcription inhibitor family. These drugs target the same enzyme as AZT and the other nucleoside drugs, but are chemically different. NEW DRUG APPLICATION (NDA) An application submitted by the manufacturer of a drug to the Food and Drug Administration for a license to market the drug for a specified indication. (See "Pre Market Approval Application" for corresponding term for medical devices). NIAID The National Institute of Allergy and Infectious Diseases. One of the institutes of the National Institutes of Health (NIH), which is part of the U.S. Public Health Service of the federal government. The NIAID is responsible for most of the federally funded AIDS research. NIH A collection of institutes covering all of the medical specialties and subspecialties, NIH conducts or coordinates the bulk of the biomedical research funded by the united states. A Branch of the Public Health Service of the department of Health and Human Services. NJCRI The North Jersey Community Research Program, a CPCRA unit. NK CELLS See "Natural killer cells" NLM National Library of Medicine (part of the NIH). NNRTI See "Non nucleoside reverse transcriptase inhibitor" NOMAD A database management package used at the CPCRA Statistical center to store and retrieve trial data. NONCOMPLIANCE Not in compliance with a designated procedure. Usually in reference to some treatment or data collection procedure NONCOMPLIANT 1. The absence of a compliant state in relation to a designated procedure. 2. Term used to describe a patient who is unable or unwilling to follow the assigned treatment regimen. NON NUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITOR (NNRTI) A class of drugs including nevaripine and delaviridine that targets the same reverse transcriptase enzyme of HIV as the nucleoside drugs like AZT, ddI, etc. NNRTIs have been characterized by strong antiviral activity, followed by extremely rapid acquisition of resistance by exposed virus. NONREQUIRED FOLLOW-UP VISIT Any visit by the patient to the clinic after the randomization visit that is not required for data collection purposes. The visit may be initiated by the patient or by study personnel, and includes interim follow-up visits, monitoring for toxicities, and post-trial follow-up visits. Event driven data such as adverse experiences and overtly clinical events may be collected, otherwise data generated at such visits are not generally used to satisfy data collection needs for required follow-up visits, unless they take place within the time windows for those visits and all necessary procedures are carried out during the visits. NOSOCOMIAL A term for an infection or illness that was acquired in a hospital, or other health care facility. NNRTI See "Non nucleoside reverse transcriptase inhibitor" NUCLEOSIDE A precursor to the cellular building blocks, nucleotides, from which new DNA is constructed. Nucleosides are phosphorylated to produce nucleotides. NUCLEOSIDE ANALOGUE REVERSE TRANSCRIPTASE INHIBITORS A family of antiviral compounds including AZT, ddI, ddC, d4t, 3tc, FLT, PMEA, and others. These compounds are phosphorylated into nucleotide analogues, and interfere with the activity of the viral enzyme reverse transcriptase. NUCLEOTIDE The basic building blocks genetic material is made of. Nucleotides are produced by the phosphorylation (adding of phosphorus groups) of nucleosides. NULL HYPOTHESIS 1. (statistics) A hypothesis that postulates no underlying difference in the populations or groups being compared with regard to the factor, trait, characteristic, or condition of interest. 2. Null treatment hypothesis. NULL TREATMENT HYPOTHESIS A hypothesis that states that the true underlying effect of the test treatment, as expressed by a specified outcome measure, is no more or less than for the control treatment. NUTRIENT Any item of food that nourishes or promotes growth and metabolism; may be essential or non-essential. NUTRITION The processes involved in the taking in and metabolism of food material by living plants and animals. NYSTATIN A brand name of Clotrimazole. O OAR See "Office of AIDS Research" OBSERVED TREATMENT DIFFERENCE The actual treatment difference observed either at the end of the trial or at some designated time point during the trial. O'BRIEN-FLEMING MONITORING BOUNDARY A set of criteria used to determine how data can be looked at during interim reviews, and how much potential error may be caused through looking. Used in constructing the stopping rules for a trial OBSERVATIONAL STUDY A follow-up study where clinical interventions are not specified by protocol. Ideally, data collection activities are similar to an intervention study. OCULAR Pertaining to the eye. OFFICE OF AIDS RESEARCH A new office within NIH, OAR coordinates AIDS research in all of the institutes. Starting within the FY 1997 budget, OAR will allocate all AIDS related funding at NIH. OFFICE OF PROTECTION FROM RESEARCH RISKS (OPRR) An administrative unit within the Department of Health and Human Services (HHS) that implements HHS regulations for protection of human subjects (45 CFR 46), offers guidance on ethical issues in biomedical and behavioral research, and negotiates assurances on behalf of the department of HHS. OFF LABEL Usage of a medication for other purposes than the specific ones appearing in the labeling (i.e. those approved by FDA) OHL See "Hairy Leukoplakia." ONE-SIDED ALTERNATIVE HYPOTHESIS One-tailed alternative hypothesis. ONE-SIDED TEST (statistics) One-tailed test. ONE-TAILED ALTERNATIVE HYPOTHESIS An alternative to the null hypothesis that specifies a range of permissible values of all which lie to one side of the null value (e.g., all favoring one treatment). See also "Two-tailed Alternative Hypothesis." ONE-TAILED TEST (statistics) A statistical test of significance based on the null value of no difference versus the set of all alternative values that are either to the right or to the left of the null value (e.g., the set indicating a positive treatment effect in a clinical trial). See also "Two-tailed Test." OPEN LABEL TRIAL 1. A clinical trial in which a study physician or study patient decides on the treatment to be administered. Nonrandom clinical trial. 2. A non blinded clinical trial. 3. A clinical trial with an open sequential design. OPERATIONS CENTER A contractor organization within the CPCRA who provides support for meetings, conference calls, and in writing protocol documents. OPPORTUNISTIC INFECTIONS An infection in an immune compromised person caused by an organism that does not usually cause disease in healthy people. Many of these organisms are carried in a latent state by virtually everyone, and only cause disease when given the opportunity of a damaged immune system. OPRR See "Office of Protection from Research Risks" ORAL HAIRY LEUKOPLAKIA (OHL) See "Hairy Leukoplakia." ORGANIC CHEMICAL Any Chemical based on carbon. Frequently including oxygen, hydrogen, and nitrogen. ORPHAN DRUG A category created by FDA for medications used to treat diseases that occur rarely, so there is little financial incentive for industry to develop them. Orphan drug status gives the manufacturer specific financial incentives to provide the drug. OUTCOME VARIABLE An observation recorded for patients in the trial at one or more time points after enrollment for the purpose of assessing the effects of the study treatments. OUTLIER Any value, reading, or measurement that is far outside established limits or the central range of the data and, for this reason, is questioned or considered to be in error. OXIDATIVE STRESS Physiological effects of increased levels of free radicals and oxidating molecules, associated with disease and aging; effects include cell membrane damage and cell death. P p24 ANTIGEN A core protein making up the nucleocapsid of the HIV Virus, p24 was thought at one time to be a surrogate marker for disease progression. Now it is recognized that some long term asymptomatics have relatively high elevations of p24, while others die never having been positive (anything less than 10 picograms/mole is effectively negative) P & P COMMITTEE See "Publications and presentations committee" P VALUE The probability of obtaining a given outcome due to chance alone. For example, a study result with a significance level of p<0.05 implies that 5 times out of 100 the result could have occurred by chance. p24 ANTIGEN The core protein fragment of HIV. The p24 antigen test measures this fragment in the bloodstream. A positive result for the p24 antigen suggests HIV replication, and may mean the individual has a higher chance of developing AIDS in the future. PACKAGE INSERT A document approved by the Food and Drug Administration and furnished by the manufacturer of a drug for use when dispensing the drug, which indicates approved uses, contraindications, and potential side effects. See "Label Insert." PAHO Pan American Health Organization. PALLIATIVE A treatment which provides symptomatic relief, but not a cure. PANCREATITIS Inflammation of the pancreas. Pancreatitis is often characterized by abdominal pain, nausea/vomiting and elevated triglyceride and amylase levels. Pancreatitis, which can be fatal, is a known side effect of ddI PANDEMIC Referring to an-epidemic disease of widespread prevalence. PAP SMEAR (PAPANICOLOU SMEAR) A specimen of vaginal or cervical cells placed on a slide and examined under the microscope for abnormal development. PAPILLOMAVIRUS A family of papova viruses associated with sexually transmitted diseases, including condylomata. Certain papillomavirus variants have also been associated with cervical cancer, particularly in HIV infected women. PAPULE A small raised bump or protrusion on the skin PARALLEL TRACK A system of distributing experimental drugs to patients who are unable to participate in ongoing clinical efficacy trials and have no other treatment options. PARASITE A plant or organism that lives on or in the host, deriving nourishment from it. Some cause inflammation, but others cause infection and destroy tissue. Human parasites include fungi, yeast, bacteria, protozoa, worms and viruses. PARENTERAL Not through the mouth. Intravenous, intramuscular, and intradermal administration are all parenteral PARESTHESIA Abnormal sensations: numbness, tingling, burning. PAROMOMYCIN (HUMATIN) An antibiotic used for treating intestinal infections. PARTIALLY BLINDED CLINICAL TRIAL 1. A clinical trial in which some, but not all, of the study treatments are administered in a single- or double-blinded fashion. 2. A clinical trial in which some, but not all, of the staff in a clinic are blinded to treatment assignment. PARTICIPANT Study participant. PASSIVE IMMUNOTHERAPY/PASSIVE IMMUNIZATION Infusion of antibodies from another individual. AS distinguished from actively stimulating an immune response in the recipient PATHOGEN Any disease-producing microorganism or material. PATHOGENESIS The natural evolution of a disease process in the body without intervention (i.e., without treatment); Description of the development of a particular disease, especially the events, reactions and mechanisms involved at the cellular level. PATIENT CLOSE-OUT The process of separating patients from a clinical trial at the end of treatment and follow-up. PATIENT CLOSE-OUT STAGE The stage of a trial in which patients leave a trial. The end of treatment and follow-up. PATIENT FOLLOW-UP A process involving periodic contact with patients enrolled in a clinical trial for the purpose of administering the assigned treatment(s), observing the effects of treatment(s), modifying the course of treatment(s), or for collecting required data. PATIENT IDENTIFICATION NUMBER A unique sequence of numbers, or numbers and letters, that are used to identify a patient. PATIENT POPULATION Study population. PATIENT RECRUITMENT The process of identifying suitable patients for enrollment into a clinical trial. PATIENT RECRUITMENT GOAL The number of patients scheduled to be enrolled into the trial. Usually set before the trial starts, or shortly thereafter, via a sample size calculation or via practical considerations. PCP See "Pneumocystis Carinii Pneumonia." PCR (POLYMERASE CHAIN REACTION) A highly sensitive test that can detect and/or DNA fragments of viruses or other organisms in blood or tissue. PCR works by repeatedly copying genetic material using heat cycling, and enzymes similar to those used by cells. PEDIATRIC Relating to the medical specialty concerned with the development, care and treatment of children from birth through adolescence. PELVIC INFLAMMATORY DISEASE (PID) A painful gynecological condition usually caused by infection, where disease spreads upward from the vagina into the pelvic cavity. PENTAM Brand name of Pentamidine. PENTAMIDINE An antibiotic effective in an IV formulation against PCP. An aerosolized form is used to prevent PCP. PEPTIDE A short string of amino acids. Peptides are small proteins. PERINATAL Relating to the period around the time of birth. PERIPHERAL Toward the outside, or at the extremities. PERIPHERAL NEUROPATHY A disorder of the nerves that usually involves the feet or hands and sometimes the legs, arms and face. Symptoms may include numbness, a tingling or burning sensation, sharp pain, weakness and abnormal reflexes. PEYER'S PATCH Lymphatic tissue lining the intestines. One of the largest areas of lymphatic tissue in the body. May take over some of the role of the thymus in adults pH A term used to describe the acidity or alkalinity of a solution. It directly measures the hydrogen concentration of a solution. If the pH is low the solution is acidic; if high, alkaline. PHAGOCYSTOSIS The consumption and destruction of foreign materials by white blood cells like macrophages PHARMACOKINETIC Concerning the study of how a drug is processed by the body, with emphasis on the time required for absorption, duration of action, distribution in the body and method of excretion. PHARMACEUTICAL AND REGULATORY AFFAIRS BRANCH That office at NIAID responsible for coordinating communication with FDA and industry. In particular, PRAB is concerned with drugs under IND status, and with prompt reporting, summary, and analysis of adverse events in NIAID sponsored trials. PHASE I TRIAL The first stage in testing a new drug in humans. Performed as part of an approved Investigational New Drug Application under Food and Drug Administration guidelines. The studies are usually done to generate preliminary information on the chemical action and safety of the drug using normal healthy volunteers. Usually done without a comparison group. PHASE II TRIAL The second stage in testing a new drug in humans. Performed as part of an approved Investigational New Drug Application under Food and Drug Administration guidelines. Generally carried out on patients with the disease or condition of interest. The main purpose is to evaluate activity, and possibly provide preliminary information on treatment efficacy and to supplement information on safety obtained from phase I trials. Usually, but not always, designed to include a control treatment and random allocation of patients to treatment. PHASE II/III A special classification arising from the AIDS context where greater testing of efficacy occurs earlier. PHASE III TRIAL The third and usually final stage in testing a new drug in humans. Performed as part of an approved Investigational New Drug Application under Food and Drug Administration guidelines. Concerned primarily with assessment of dosage effects and efficacy and safety. Usually designed to include a control treatment and random allocation to treatment. Once this phase is completed the drug manufacturers may request permission to market the drug by submission of a New Drug Application to the Food and Drug Administration, assuming the results of the phase I, II and III trials are consistent with such a request. PHASE IV TRIAL Generally, a randomized controlled trial that is designed to evaluate the long-term safety and efficacy of a drug for a given indication and that is done with Food and Drug Administration approval. Usually carried out after licensure of the drug for that indication. PICO- Prefix meaning a one one-trillionth, as in picogram, a trillionth of a gram. PID See "Pelvic Inflammatory Disease" PILOT STUDY A preliminary study designed to indicate whether a larger study is practical. See "Feasibility Study." PHOSPHORYLATION The process of adding phosphorus to a compound. Often done within the body by enzymes named "kinases". The nucleoside drugs, like AZT, ddI, ddC, etc. all need to be phosphorylated in the body before they become active. PID Patient identification number. A unique identifier that refers to a particular patient, yet preserves confidentiality for record keeping PIETC See "Protocol Implementation, Education and Training Committee" PLACEBO A pharmacologically inactive agent given to a patient as a substitute for an active agent and where the patient is not informed whether he is receiving the active or inactive agent. PLACEBO-CONTROLLED CLINICAL TRIAL A clinical trial in which patients assigned to the control treatment receive a placebo. PLACEBO EFFECT The effect produced by a placebo due to the expectations of the patient. The effect in placebo-controlled clinical trials is generally measured by comparison of the effect observed in patients receiving the placebo treatment with the effect observed in patients receiving the active treatment. PLACENTA A combination of fetal and maternal cells that serves as the organ of exchange for nutrients and other chemicals between mother and fetus during pregnancy. PLATELET Blood cells that are essential to clotting. PML See "Progressive Multifocal Leukoencephalopathy" PNEUMOCYSTIS CARINII PNEUMONIA An opportunistic pneumonitis often seen in HIV-infected patients. PCP generally produces a dry, hacking cough. Although previously thought to be a protozoa, and responsive to anti-protozoal treatment, recent genetic analysis suggest that p carinii is closer to the funguses. PO Abbreviation for "by mouth" (as opposed to Intravenous, intramuscular, etc.). POLYNEUROPATHY Neuropathy involving a number of different nerves POSTERIOR Rear side, or behind. POST-HERPETIC NEURALGIA (PHN) Literally "pain following herpes." The term is usually applied to the severe pain that sometimes follows the healing of herpes zoster lesions. POST HOC ANALYSES Analyses conducted after the results are available that were not defined before the start of the trial. Such analyses are particularly prone to false-positive claims or type I error. POSTHUMOUS After Death POST-MARKETING SURVEILLANCE Term used by the Food and Drug Administration to characterize any procedure, implemented after licensure of a drug for a given indication, that is designed to provide information on the actual use of the drug for that indication and on the occurrence of related side effects. The surveillance usually involves survey techniques rather than controlled trials. POST-MORTEM After death, or after the event. POST-PARTUM After giving birth. POST-STRATIFICATION The process of classifying patients into strata after they have been enrolled in the study‹usually for data analysis purposes. POWER The probability of finding a treatment effect that actually exists, or of rejecting the null hypothesis when the alternative hypothesis is in fact true. In clinical trials, the power of the study design is the ability of the study to detect a postulated difference between treatment groups if it in fact exists. For example, if there is "something going on" in the study, does the study design have the power to demonstrate it? PPD See "Purified Protein Derivative", also an acronym for the clinical site monitoring group for the CPCRA PRAB See "Pharmaceutical and regulatory affairs branch" PRECLINICAL Generally refers to research that has been done before a compound is tried on humans, i.e. in vitro and animal studies PREMATURE TERMINATION Early termination of a trial before data are sufficiently strong to be convincing. PRENATAL Relating to the period before birth. PRERANDOMIZATION EXAMINATION Any examination that is part of the evaluation process of a patient for enrollment into a trial and that is carried out before the randomization examination. PRERANDOMIZATION VISIT Any visit made to the clinic by a potential study patient for the purpose of evaluation for enrollment into the trial and that takes place prior to the randomization visit. PRESUMPTIVE Presumed. In the context of diagnosis, one that is not definitely made, but where signs and symptoms make it exceedingly likely to be the proper one, even without confirmatory evidence. Diagnosis of CMV retinitis by characteristic appearance, without using a biopsy is an example if a presumptive diagnosis. PRIMARY DRUG RESISTANCE (PDR) Resistance of bacteria or other pathogens to drugs which exists prior to the beginning of treatment. PRIMARY OUTCOME 1. The event or condition the trial is designed to ameliorate, delay, or prevent. 2. The actual occurrence of a primary event in a study patient. PRIMARY OUTCOME VARIABLE The outcome variable that is designated or regarded as key in the design or analysis of the results of a trial. Generally, the variable used for sample size calculations in the design of the trial or, when no sample size calculation is made, for the main avenue of data analyses. The primary outcome monitored in interim analyses. PRINCIPAL INVESTIGATOR 1. The designation used by the National Institutes of Health to denote the individual named on a grant who is responsible for directing the proposed research. 2. The lead scientist in a research project. (Usage note: It is best to avoid use of the term to designate the head of a center in a multicenter trial. It should be used in such settings only when there is a single individual, such as the chair of the study, who is regarded by everyone in the trial as the principal investigator. Otherwise some other term, such as center director, should be used.) PRN Abbreviation meaning "Take as needed:, usually applied to prescription drugs. PROCRIT Brand name of Erythropoietin PRODRUG A chemical precursor of a drug that is converted into the desired substance in the body. PRODROMAL Pertaining to symptoms indicating the onset of a disease. May include symptoms prior to those adequate for accurate diagnosis. PROGNOSIS The probable future course of a disease. PROGRESSION OF DISEASE A common endpoint used in AIDS clinical trials. The entity "progression of disease" usually consists of new occurrences of non-recurrent AIDS-defining illnesses or death. PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY A rapidly degenerative neurological condition associated with HIV, characterized by diffuse gray-matter pallor on CT, and no focal lesions. Thought to be associated with JC Papovavirus. PROJECT OFFICER 1. The individual in the sponsoring agency who is responsible for dealing with technical, scientific, and programmatic aspects of a grant or contract-funded project. 2. Health scientist administrator in National Institutes of Health grant-funded projects. PROKINE Brand name of Sargramostim PROPHYLACTIC TRIAL A trial that is designed to assess the efficacy of a treatment procedure aimed at preventing the development or progression of a specific disease or condition. PROPHYLAXIS Treatment intended to preserve health and prevent the occurrence or recurrence of a disease. PROSPECTIVE FOLLOW-UP STUDY A study in which people with a specific attribute or characteristic are identified and then observed for some period of time thereafter for the occurrence of the outcome or condition of interest, usually disease or death. The study may or may not involve a comparison group. Clinical trials represent a special subset of prospective follow-up studies. PROTEASE An enzyme that cleaves proteins. HIV protease is required to separate the long gag-pol polyprotein into it's constituent parts during the process of viral replication. PROTEASE INHIBITOR A new class of experimental antiretroviral drugs that work by inhibiting the HIV protease. Some examples include Saquinavir, Indinavir, and Ritonavir. PROTEIN A large group of substances made up of amino acids that are formed naturally by plants and all living organisms. An essential human nutrient, proteins provide the structures essential for the growth and repair of living cells and tissue. PROTOCOL A detailed plan for studying a treatment for a specific condition. PROTOCOL IMPLEMENTATION, EDUCATION AND TRAINING COMMITTEE A group of CPCRA staff representing all of the sites, as well as the various contractors, who provides guidance to the steering committee in regard to all of the listed issues. PROTOCOL MANAGER The staff person at the CPCRA Statistical Center who is over all coordinator for a particular protocol. They serve as liaison between the protocol team and the senior statistician, resolve any ambiguities or questions, and in general take care of most of the day-to-day maintenance. PROTOCOL MONITOR The staff person at the CPCRA Statistical Center who is primary clinic contact, and who coordinates the flow of data between the sites and the statistical center. PROTOZOA A family of unicellular organisms including amoebas, that are the simplest form of animal life. Protozoa can be a cause of parasitic disease. In AIDS, Toxoplasmosis, Pneumocystis carinii, Giardia, and Cryptosporidium belii are among the most harmful protozoa. PROVIRUS Viral genetic material, in the form of DNA, that has been integrated into the host genome. HIV, when it is dormant in human cells, is in a proviral form PRURITIC Causing itching PRURITUS An itching rash PUBLICATIONS AND PRESENTATIONS COMMITTEE The group of CPCRA investigators who coordinate all publications using CPCRA data. PULMONARY Pertaining to the lungs. PURIFIED PROTEIN DERIVATIVE (PPD) The most common test for exposure to m. tuberculosis, the bacteria that causes TB. In the PPD test, a small amount of protein from TB is injected under the skin. If the patient has been previously infected, they will mount a delayed type hypersensitivity reaction, characterized by a hard red bump called an induration. PURULENT Infected and producing pus. PYRIMETHAMINE (DARAPRIM) An antibiotic used in treating toxoplasmosis, and rarely for the treatment or prophylaxis of PCP Q Q4H Common abbreviation for "every four hours". Also, q5h, would be every five hours, q6h would be every six, etc. QAPACC See "quality assurance, performance assessment, and capacity committee" QID Common abbreviation for "four times a day" QUADRANT One section of something that has been divided into four equal parts QUALITY ASSURANCE Any procedure, method, or philosophy for collecting, processing, or analyzing data that is aimed at maintaining or improving the reliability or validity of the data and the associated procedures used to generate them. QUALITY ASSURANCE, PERFORMANCE ASSESSMENT, AND CAPACITY COMMITTEE A group of CPCRA staff representing all of the sites, as well as the various contractors, who provides guidance to the steering committee in regard to all of the listed issues, which impact data quality within the CPCRA QUALITATIVE Of, relating to, or expressed in relative or subjective terms‹impossible to precisely quantify. QUANTITATIVE Of, relating to, or expressed in terms of quantity. R RAC The Richmond AIDS Consortium, a CPCRA unit. RADICULOPATHY Infection or other damage of the peripheral nerves and spinal roots, accompanied by weakness, numbness, and eventual paralysis. Radiculopathy is distinguished from peripheral neuropathy frequently by its asymmetric presentation RADIOLOGY The science of diagnosis and/or treatment using radiant energy. Includes X-rays, MRI, destruction of tumors by radiation, etc. RADIOGRAPHY The use of X-rays in diagnosis RALES Sounds in the lungs, often indicative of disease. RANDOM (general) 1. Having no specific pattern or objective. Of or designating a chance process in which the occurrence of previous events is of no value in predicting future events. From Old French, random, meaning force, violence, impetuosity. 2. Sometimes used as a synonym for haphazard. Usage also refers to a formal process meeting, or believed to meet, the conditions specified under the statistical definition of random. RANDOM ALLOCATION A method for assigning patients to treatment using a random process. RANDOM NUMBER A number generated or drawn via some defined random process. RANDOM PROCESS Any method or procedure whose output is random (i.e., cannot be predicted by any means). RANDOM VARIABLE A variable that may assume any one of a number of different values, where the set of possible values is determined by a probability distribution, such as binomial or normal. RANDOMIZATION 1. The process of assigning patients to treatment using a random process, such as via use of a table of random numbers. 2. The process of deriving an order or sequence of items, determinations, specimens, readings, or the like using a random process. RANDOMIZATION VISIT The visit where the participant is randomly assigned to treatment. RANDOMIZED Having been assigned to a treatment via a random process. Normally considered to have occurred when the randomization schedule is sent to the unit pharmacist, so they can then dispense the appropriate drug. RANDOMIZED CONTROLLED CLINICAL TRIAL A clinical trial that involves at least one test treatment and one control treatment, concurrent enrollment and follow-up of the test- and control-treated groups, and in which the treatments to be administered are selected by a random process, such that neither the patients nor the persons responsible for their selection or treatment can influence the assignments, and where the assignments remain unknown to the patients and clinic staff until the patients have been determined to be eligible for enrollment into the trial (and then in blinded trials may be revealed to patients and clinic personnel only by letter or number codes). RAW DATA 1. Measurements and observations recorded on study data forms. 2. Unedited computer-generated listings of data from study data forms, prior to use of reduction and summary procedures needed for data analysis. RECOMBINANT Produced by genetic engineering in the laboratory. RECORD A paper or electronic document that contains or is designed to contain a set of facts related to some occurrence, transaction, or the like RECRUITMENT GOAL See "Patient recruitment goal" RECRUITMENT, OUTREACH, AND RETENTION COMMITTEE A group of CPCRA staff representing all of the sites, as well as the various contractors, who provides guidance to the steering committee in regard to all of the listed issues. specifically recruitment, accrual, retention, followup, and outreach strategies are all within the mission of ROAR RECTUM The very bottom-most portion of the lower intestine, including the anus. RECURRENCE The return or flare up of a condition thought cured or in remission REFRACTORY Resistant to treatment, as o