Harrison's Internal Medicine Chapter 67. Applications of Stem Cell Biology in Clinical Medicine
Applications of Stem Cell Biology in Clinical Medicine: Introduction Organ damage and the resultant inflammatory responses initiate a series of repair processes, including stem cell proliferation, migration, and differentiation, often in combination with angiogenesis and remodeling of the extracellular matrix.
Harrison's Internal Medicine Chapter 64. The Practice of Genetics in Clinical Medicine
Implications of Molecular Genetics for Internal Medicine
The field of medical genetics has traditionally focused on chromosomal abnormalities (Chap. 63) and Mendelian disorders (Chap. 62).
Other Organ Systems and the Future The use of stem cells in regenerative medicine has been studied for many other organ systems and cell types, including skin, eye, cartilage, bone, kidney, lung, endometrium, vascular endothelium, smooth muscle, striated muscle, and others. In fact, the potential for stem cell regeneration of damaged organs and tissues is virtually limitless. However, numerous obstacles must be overcome before stem cell therapies can become a widespread clinical reality.
Harrison's Internal Medicine Chapter 66. Stem Cell Biology
Stem Cell Biology: Introduction
Stem cell biology is a relatively new field that explores the characteristics and possible clinical applications of the different types of pluripotential cells that serve as the progenitors of more differentiated cell types. In addition to potential therapeutic applications (Chap. 67), patient-derived stem cells can also provide disease models and a means to test drug effectiveness.
Population Screening Mass genetic screening programs require tests of high enough sensitivity and specificity to be cost-effective. An effective screening program should fulfill the following criteria: that the tested disorder is prevalent and serious; that it can be influenced presymptomatically through lifestyle changes, screening, or medications; and that identification of risk does not result in undue discrimination or harm.
Harrison's Internal Medicine Chapter 68. Hematopoietic Stem Cells
Hematopoietic Stem Cells: Introduction All of the cell types in the peripheral blood and some cells in every tissue of the body are derived from hematopoietic (hemo: blood; poiesis: creation) stem cells. If the hematopoietic stem cell is damaged and can no longer function (e.g., due to the nuclear accident at Chernobyl), a person would survive 2–4 weeks in the absence of extraordinary support measures.
Diabetes Mellitus The success of islet cell and pancreas transplantation provides proof of concept for a cell-based approach for type I diabetes. However, the demand for donor pancreata far exceeds the number available, and maintenance of long-term graft survival remains a problem. The search for a renewable source of stem cells capable of regenerating pancreatic islets has therefore been intensive.
Follow-Up Care after Testing Depending on the nature of the genetic disorder, posttest interventions may include (1) cautious surveillance and appropriate health care screening, (2) specific medical interventions, (3) chemoprevention, (4) risk avoidance, and (5) referral to support services. For example, patients with known pathologic mutations in BRCA1 or BRCA2 are offered intensive screening as well as the option of prophylactic mastectomy and oophorectomy.
Strategies for Stem Cell Replacement Stem cell transplantation is not a new concept and it is already part of established medical practice. Hematopoietic stem cells (HSCs) (Chap. 68) are responsible for the long-term repopulation of all blood elements in bone marrow transplant recipients. HSC transplantation is now the gold standard against which other stem cell transplantation therapies will be measured.
Harrison's Internal Medicine Chapter 75. Evaluation and Management of Obesity
Evaluation and Management of Obesity: Introduction Over 66% of U.S. adults are currently categorized as overweight or obese, and the prevalence of obesity is increasing rapidly throughout most of the industrialized world.
Molecular analysis is generally more informative if testing is initiated in a symptomatic family member, since the identification of a mutation can direct the testing of other at-risk family members (whether they are symptomatic or not). In the absence of additional familial or environmental risk factors, individuals who test negative for the mutation found in the affected family member can be informed that they are at general population risk for that particular disease.
Harrison's Internal Medicine Chapter 70. Nutritional Requirements and Dietary Assessment
Nutritional Requirements and Dietary Assessment: Introduction Nutrients are substances that must be supplied by the diet because they are not synthesized in the body in sufficient amounts. Nutrient requirements for groups of healthy persons have been determined experimentally. For good health we require energy-providing nutrients (protein, fat, and carbohydrate), vitamins, minerals, and water.
Recall of family history is often inaccurate. This is especially so when the history is remote and families become more dispersed geographically. It can be helpful to ask patients to fill out family history forms before or after their visits, as this provides them with an opportunity to contact relatives. Attempts should be made to confirm the illnesses reported in the family history before making important and, in certain circumstances, irreversible management decisions.
Many disorders exhibit the feature of locus heterogeneity, which refers to the fact that mutations in different genes can cause phenotypically similar disorders. For example, osteogenesis imperfecta (Chap. 357), long QT syndrome (Chap. 226), muscular dystrophy (Chap. 382), homocystinuria (Chap. 358), retinitis pigmentosa (Chap. 29), and hereditary predisposition to colon cancer (Chap. 87) or breast cancer (Chap. 86) can each be caused by mutations in distinct genes.
Therapeutic Interventions Based on Genetic Risk for Disease Specific treatments are now available for an increasing number of genetic disorders, whether identified through population-based screening or directed testing (Table 64-2). Although the strategies for therapeutic interventions are best developed for childhood hereditary metabolic diseases, these principles are making their way into the diagnosis and management of adult-onset disorders.
Harrison's Internal Medicine Chapter 69. Tissue Engineering
Tissue Engineering: Introduction The origins of tissue engineering date to the sixteenth century when complex skin flaps were used to replace the nose. Modern tissue engineering combines the disciplines of materials sciences and life sciences to replace a diseased or damaged organ with a living, functional substitute.
The most common tissue engineering approach combines cells and matrices to produce a living structure (Fig.
Harrison's Internal Medicine Chapter 77. Approach to the Patient with Cancer
Approach to the Patient with Cancer: Introduction The application of current treatment techniques (surgery, radiation therapy, chemotherapy, and biological therapy) results in the cure of nearly two of three patients diagnosed with cancer. Nevertheless, patients experience the diagnosis of cancer as one of the most traumatic and revolutionary events that has ever happened to them.
Harrison's Internal Medicine Chapter 59. Bleeding and Thrombosis
Bleeding and Thrombosis: Introduction The human hemostatic system provides a natural balance between procoagulant and anticoagulant forces. The procoagulant forces include platelet adhesion and aggregation and fibrin clot formation; anticoagulant forces include the natural inhibitors of coagulation and fibrinolysis.
Preventive measures and therapeutic interventions are not restricted to metabolic disorders. Identification of familial forms of long QT syndrome, associated with ventricular arrhythmias, allows early electrocardiographic testing and the use of prophylactic antiarrhythmic therapy, overdrive pacemakers, or defibrillators (Chap. 226).
Harrison's Internal Medicine Chapter 71. Vitamin and Trace Mineral Deficiency and Excess
Vitamin and Trace Mineral Deficiency and Excess: Introduction
Vitamins and trace minerals are required constituents of the human diet since they are either inadequately synthesized or not synthesized in the human body. Only small amounts of these substances are needed for carrying out essential biochemical reactions (e.g., acting as coenzymes or prosthetic groups).