Sirolimus: A macrolide compound obtained from Streptomyces hygroscopicus that acts by selectively blocking the transcriptional activation of cytokines thereby inhibiting cytokine production. It is bioactive only when bound to IMMUNOPHILINS. Sirolimus is a potent immunosuppressant and possesses both antifungal and antineoplastic properties.Immunosuppressive Agents: Agents that suppress immune function by one of several mechanisms of action. Classical cytotoxic immunosuppressants act by inhibiting DNA synthesis. Others may act through activation of T-CELLS or by inhibiting the activation of HELPER CELLS. While immunosuppression has been brought about in the past primarily to prevent rejection of transplanted organs, new applications involving mediation of the effects of INTERLEUKINS and other CYTOKINES are emerging.Tacrolimus: A macrolide isolated from the culture broth of a strain of Streptomyces tsukubaensis that has strong immunosuppressive activity in vivo and prevents the activation of T-lymphocytes in response to antigenic or mitogenic stimulation in vitro.Kidney Transplantation: The transference of a kidney from one human or animal to another.Cyclosporine: A cyclic undecapeptide from an extract of soil fungi. It is a powerful immunosupressant with a specific action on T-lymphocytes. It is used for the prophylaxis of graft rejection in organ and tissue transplantation. (From Martindale, The Extra Pharmacopoeia, 30th ed).Mycophenolic Acid: An antibiotic substance derived from Penicillium stoloniferum, and related species. It blocks de novo biosynthesis of purine nucleotides by inhibition of the enzyme inosine monophosphate dehydrogenase. Mycophenolic acid is important because of its selective effects on the immune system. It prevents the proliferation of T-cells, lymphocytes, and the formation of antibodies from B-cells. It also may inhibit recruitment of leukocytes to inflammatory sites. (From Gilman et al., Goodman and Gilman's The Pharmacological Basis of Therapeutics, 9th ed, p1301)Calcineurin: A CALCIUM and CALMODULIN-dependent serine/threonine protein phosphatase that is composed of the calcineurin A catalytic subunit and the calcineurin B regulatory subunit. Calcineurin has been shown to dephosphorylate a number of phosphoproteins including HISTONES; MYOSIN LIGHT CHAIN; and the regulatory subunits of CAMP-DEPENDENT PROTEIN KINASES. It is involved in the regulation of signal transduction and is the target of an important class of immunophilin-immunosuppressive drug complexes.Graft Rejection: An immune response with both cellular and humoral components, directed against an allogeneic transplant, whose tissue antigens are not compatible with those of the recipient.Drug Substitution: The practice of replacing one prescribed drug with another that is expected to have the same clinical or psychological effect.Lymphangioleiomyomatosis: A disease characterized by the progressive invasion of SMOOTH MUSCLE CELLS into the LYMPHATIC VESSELS, and the BLOOD VESSELS. The majority of the cases occur in the LUNGS of women of child-bearing age, eventually blocking the flow of air, blood, and lymph. The common symptom is shortness of breath (DYSPNEA).Angiomyolipoma: A benign tumor containing vascular, adipose, and muscle elements. It occurs most often in the kidney with smooth muscle elements (angiolipoleiomyoma) in association with tuberous sclerosis. (Dorland, 27th ed)TOR Serine-Threonine Kinases: A serine threonine kinase that controls a wide range of growth-related cellular processes. The protein is referred to as the target of RAPAMYCIN due to the discovery that SIROLIMUS (commonly known as rapamycin) forms an inhibitory complex with TACROLIMUS BINDING PROTEIN 1A that blocks the action of its enzymatic activity.Graft Survival: The survival of a graft in a host, the factors responsible for the survival and the changes occurring within the graft during growth in the host.Lymphangiomyoma: A tumorlike condition characterized by SMOOTH MUSCLE and ENDOTHELIUM proliferation of LYMPHATIC VESSELS and LYMPH NODES in the MEDIASTINUM and retroperitoneum, also in the lung. It may be manifested by chylous PLEURAL EFFUSION and ASCITES.Injections, Intraocular: The administration of substances into the eye with a hypodermic syringe.Coronary Restenosis: Recurrent narrowing or constriction of a coronary artery following surgical procedures performed to alleviate a prior obstruction.Drug Therapy, Combination: Therapy with two or more separate preparations given for a combined effect.Treatment Outcome: Evaluation undertaken to assess the results or consequences of management and procedures used in combating disease in order to determine the efficacy, effectiveness, safety, and practicability of these interventions in individual cases or series.Chyle: An opaque, milky-white fluid consisting mainly of emulsified fats that passes through the lacteals of the small intestines into the lymphatic system.Liver Transplantation: The transference of a part of or an entire liver from one human or animal to another.Polyenes: Hydrocarbons with more than one double bond. They are a reduced form of POLYYNES.Transplantation, Homologous: Transplantation between individuals of the same species. Usually refers to genetically disparate individuals in contradistinction to isogeneic transplantation for genetically identical individuals.Drug-Eluting Stents: Stents that are covered with materials that are embedded with chemicals that are gradually released into the surrounding milieu.CreatinineKidney: Body organ that filters blood for the secretion of URINE and that regulates ion concentrations.Cardiovascular Agents: Agents that affect the rate or intensity of cardiac contraction, blood vessel diameter, or blood volume.Time Factors: Elements of limited time intervals, contributing to particular results or situations.Drug Monitoring: The process of observing, recording, or detecting the effects of a chemical substance administered to an individual therapeutically or diagnostically.Islets of Langerhans Transplantation: The transference of pancreatic islets within an individual, between individuals of the same species, or between individuals of different species.Drug Implants: Small containers or pellets of a solid drug implanted in the body to achieve sustained release of the drug.Glomerular Filtration Rate: The volume of water filtered out of plasma through glomerular capillary walls into Bowman's capsules per unit of time. It is considered to be equivalent to INULIN clearance.Transplantation: Transference of a tissue or organ from either an alive or deceased donor, within an individual, between individuals of the same species, or between individuals of different species.Fluorescence Polarization Immunoassay: Fluoroimmunoassay where detection of the hapten-antibody reaction is based on measurement of the increased polarization of fluorescence-labeled hapten when it is combined with antibody. The assay is very useful for the measurement of small haptenic antigens such as drugs at low concentrations.Antibiotics, Antineoplastic: Chemical substances, produced by microorganisms, inhibiting or preventing the proliferation of neoplasms.Stents: Devices that provide support for tubular structures that are being anastomosed or for body cavities during skin grafting.Immunosuppression: Deliberate prevention or diminution of the host's immune response. It may be nonspecific as in the administration of immunosuppressive agents (drugs or radiation) or by lymphocyte depletion or may be specific as in desensitization or the simultaneous administration of antigen and immunosuppressive drugs.Thrombotic Microangiopathies: Diseases that result in THROMBOSIS in MICROVASCULATURE. The two most prominent diseases are PURPURA, THROMBOTIC THROMBOCYTOPENIC; and HEMOLYTIC-UREMIC SYNDROME. Multiple etiological factors include VASCULAR ENDOTHELIAL CELL damage due to SHIGA TOXIN; FACTOR H deficiency; and aberrant VON WILLEBRAND FACTOR formation.Tubulin Modulators: Agents that interact with TUBULIN to inhibit or promote polymerization of MICROTUBULES.Oxaloacetic Acid: A dicarboxylic acid ketone that is an important metabolic intermediate of the CITRIC ACID CYCLE. It can be converted to ASPARTIC ACID by ASPARTATE TRANSAMINASE.Coated Materials, Biocompatible: Biocompatible materials usually used in dental and bone implants that enhance biologic fixation, thereby increasing the bond strength between the coated material and bone, and minimize possible biological effects that may result from the implant itself.Citrus paradisi: A plant species of the genus CITRUS, family RUTACEAE that produces the familiar grapefruit. There is evidence that grapefruit inhibits CYTOCHROME P-450 CYP3A4, resulting in delayed metabolism and higher blood levels of a variety of drugs.Polycystic Kidney, Autosomal Dominant: Kidney disorders with autosomal dominant inheritance and characterized by multiple CYSTS in both KIDNEYS with progressive deterioration of renal function.Azathioprine: An immunosuppressive agent used in combination with cyclophosphamide and hydroxychloroquine in the treatment of rheumatoid arthritis. According to the Fourth Annual Report on Carcinogens (NTP 85-002, 1985), this substance has been listed as a known carcinogen. (Merck Index, 11th ed)Acetic Anhydrides: Compounds used extensively as acetylation, oxidation and dehydrating agents and in the modification of proteins and enzymes.Heart Transplantation: The transference of a heart from one human or animal to another.Follow-Up Studies: Studies in which individuals or populations are followed to assess the outcome of exposures, procedures, or effects of a characteristic, e.g., occurrence of disease.Drug Interactions: The action of a drug that may affect the activity, metabolism, or toxicity of another drug.Unrelated Donors: Providers of tissues for transplant to non-related individuals.Retrospective Studies: Studies used to test etiologic hypotheses in which inferences about an exposure to putative causal factors are derived from data relating to characteristics of persons under study or to events or experiences in their past. The essential feature is that some of the persons under study have the disease or outcome of interest and their characteristics are compared with those of unaffected persons.Antilymphocyte Serum: Serum containing GAMMA-GLOBULINS which are antibodies for lymphocyte ANTIGENS. It is used both as a test for HISTOCOMPATIBILITY and therapeutically in TRANSPLANTATION.Tuberous Sclerosis: Autosomal dominant neurocutaneous syndrome classically characterized by MENTAL RETARDATION; EPILEPSY; and skin lesions (e.g., adenoma sebaceum and hypomelanotic macules). There is, however, considerable heterogeneity in the neurologic manifestations. It is also associated with cortical tuber and HAMARTOMAS formation throughout the body, especially the heart, kidneys, and eyes. Mutations in two loci TSC1 and TSC2 that encode hamartin and tuberin, respectively, are associated with the disease.Oral Ulcer: A loss of mucous substance of the mouth showing local excavation of the surface, resulting from the sloughing of inflammatory necrotic tissue. It is the result of a variety of causes, e.g., denture irritation, aphthous stomatitis (STOMATITIS, APHTHOUS); NOMA; necrotizing gingivitis (GINGIVITIS, NECROTIZING ULCERATIVE); TOOTHBRUSHING; and various irritants. (From Jablonski, Dictionary of Dentistry, 1992, p842)Renal Insufficiency: Conditions in which the KIDNEYS perform below the normal level in the ability to remove wastes, concentrate URINE, and maintain ELECTROLYTE BALANCE; BLOOD PRESSURE; and CALCIUM metabolism. Renal insufficiency can be classified by the degree of kidney damage (as measured by the level of PROTEINURIA) and reduction in GLOMERULAR FILTRATION RATE.Kidney Function Tests: Laboratory tests used to evaluate how well the kidneys are working through examination of blood and urine.Perivascular Epithelioid Cell Neoplasms: A family of mesenchymal tumors composed of histologically and immunohistochemically distinctive perivascular epithelioid cells. These cells do not have a normal anatomic homolog. (From Fletcher CDM, et. al., World Health Organization Classification of Tumors: Pathology and Genetics of Tumors of Soft Tissue and Bone, 2002).Ribosomal Protein S6 Kinases, 70-kDa: A family of ribosomal protein S6 kinases that are considered the major physiological kinases for RIBOSOMAL PROTEIN S6. Unlike RIBOSOMAL PROTEIN S6 KINASES, 90KDa the proteins in this family are sensitive to the inhibitory effects of RAPAMYCIN and contain a single kinase domain. They are referred to as 70kDa proteins, however ALTERNATIVE SPLICING of mRNAs for proteins in this class also results in 85kDa variants being formed.Paclitaxel: A cyclodecane isolated from the bark of the Pacific yew tree, TAXUS BREVIFOLIA. It stabilizes MICROTUBULES in their polymerized form leading to cell death.Biliary Fistula: Abnormal passage in any organ of the biliary tract or between biliary organs and other organs.Biopsy: Removal and pathologic examination of specimens in the form of small pieces of tissue from the living body.Clinical Audit: A detailed review and evaluation of selected clinical records by qualified professional personnel to improve the quality of patient care and outcomes. The clinical audit was formally introduced in 1993 into the United Kingdom's National Health Service.Adrenal Cortex HormonesKetoconazole: Broad spectrum antifungal agent used for long periods at high doses, especially in immunosuppressed patients.Oligomenorrhea: Abnormally infrequent menstruation.Transplantation Conditioning: Preparative treatment of transplant recipient with various conditioning regimens including radiation, immune sera, chemotherapy, and/or immunosuppressive agents, prior to transplantation. Transplantation conditioning is very common before bone marrow transplantation.Respiratory System Agents: Drugs used for their effects on the respiratory system.Mucorales: An order of zygomycetous fungi, usually saprophytic, causing damage to food in storage, but which may cause respiratory infection or MUCORMYCOSIS in persons suffering from other debilitating diseases.Prospective Studies: Observation of a population for a sufficient number of persons over a sufficient number of years to generate incidence or mortality rates subsequent to the selection of the study group.Steroids: A group of polycyclic compounds closely related biochemically to TERPENES. They include cholesterol, numerous hormones, precursors of certain vitamins, bile acids, alcohols (STEROLS), and certain natural drugs and poisons. Steroids have a common nucleus, a fused, reduced 17-carbon atom ring system, cyclopentanoperhydrophenanthrene. Most steroids also have two methyl groups and an aliphatic side-chain attached to the nucleus. (From Hawley's Condensed Chemical Dictionary, 11th ed)Postoperative Complications: Pathologic processes that affect patients after a surgical procedure. They may or may not be related to the disease for which the surgery was done, and they may or may not be direct results of the surgery.Absorbable Implants: Implants constructed of materials designed to be absorbed by the body without producing an immune response. They are usually composed of plastics and are frequently used in orthopedics and orthodontics.Cytochrome P-450 CYP3A: A cytochrome P-450 suptype that has specificity for a broad variety of lipophilic compounds, including STEROIDS; FATTY ACIDS; and XENOBIOTICS. This enzyme has clinical significance due to its ability to metabolize a diverse array of clinically important drugs such as CYCLOSPORINE; VERAPAMIL; and MIDAZOLAM. This enzyme also catalyzes the N-demethylation of ERYTHROMYCIN.Living Donors: Non-cadaveric providers of organs for transplant to related or non-related recipients.Benzenesulfonates: Organic salts and esters of benzenesulfonic acid.Dose-Response Relationship, Drug: The relationship between the dose of an administered drug and the response of the organism to the drug.Intention to Treat Analysis: Strategy for the analysis of RANDOMIZED CONTROLLED TRIALS AS TOPIC that compares patients in the groups to which they were originally randomly assigned.Graft Occlusion, Vascular: Obstruction of flow in biological or prosthetic vascular grafts.Coronary Angiography: Radiography of the vascular system of the heart muscle after injection of a contrast medium.Proteinuria: The presence of proteins in the urine, an indicator of KIDNEY DISEASES.