DIAGNOSIS

the process of determining the nature of a disease or disorder and distinguishing it from other possible conditions. The term comes from the Greek gnosis, meaning knowledge. The diagnostic process is the method by which health professionals select one disease over another, identifying one as the most likely cause of a person's symptoms. Symptoms that appear early in the course of a disease are often more vague and undifferentiated than those that arise as the disease progresses, making this the most difficult time to make an accurate diagnosis. Reaching an accurate conclusion depends on the timing and the sequence of the symptoms, past medical history and risk factors for certain diseases, and a recent exposure to disease. The physician, in making a diagnosis, also relies on various other clues such as physical signs, nonverbal signals of distress, and the results of selected laboratory and radiological tests. From the large number of facts obtained, a list of possible diagnoses can be determined, which are referred to as the differential diagnosis. The physician organizes the list with the most likely diagnosis given first. Additional information is identified, and appropriate tests are selected that will narrow the list or confirm one of the possible diseases. the process of determining the nature of a disease or disorder and distinguishing it from other possible conditions. This is accomplished by considering the patient's history and symptoms and by examining the patient in various other ways. The term diagnosis also refers to the identification reached by the physician or other examiner. The tools of the diagnostician include (1) a medical history, (2) a physical examination, and (3) tests and diagnostic procedures such as a complete blood count, an electroencephalogram (EEG), or a surgical biopsy. A medical history is constructed from a medical interview conducted between physician and patient. It includes information about the present illness, past medical conditions of the patient and of the patient's family, occupational background, and psychosocial history, as well as a review of the major body systems. The family history is especially important for alerting the physician to any diseases family members may have or have had that would indicate the patient's increased risk for those conditions. The occupational history may provide information about exposure to substances in the workplace that might heighten the risk of contracting certain diseases. Emotional factors, such as stress, that could cause or exacerbate the condition may be revealed in the psychosocial background. The review of body systems, in which the physician discusses each major system of the body with the patient, can uncover symptoms or problems overlooked or unnoticed by the patient. Following the medical interview, a physical examination of the patient is performed. This includes a visual inspection of the patient, palpation of organs, percussion of an area of the body (that is, tapping the surface of the body and evaluating the resulting sound) to determine the density of an organ or the presence of fluids, and auscultation (listening) with a stethoscope to evaluate sounds produced by the heart, lungs, bowels, or blood vessels. The next step, called clinical decision making, is to assess the information collected from the medical history and physical examination and develop a list of possible causes. This list, known as the differential diagnosis, is culled by ordering tests and procedures that will provide further salient data about the disorder. The most likely candidate disease of the differential diagnosis is addressed first; if one of the less likely diseases is life-threatening, however, it will take precedence. Caution must be exercised to order only the most necessary diagnostic tests and procedures so that the patient is not subjected to unnecessary risk, discomfort, or cost. While clinical testing may provide information that cannot be obtained from the medical history or physical examination, it may also yield false-positive or false-negative results that can complicate rather than aid the diagnostic process. Some diseases are easily diagnosed; others are marked by vague symptoms that do not progress, and their diagnoses remain elusive. The ability of the physician to diagnose complex conditions requires not only keen observational skills but also a proficiency in reasoning. The experienced diagnostician also will rely on intuition developed from years of treating patients. Computers, which are used with increasing frequency as diagnostic tools, can be valuable, but they are not able to replace the experience and intuition of a skilled diagnostician. Additional reading Ralph H. Major, A History of Medicine, 2 vol. (1954), covers medical history from its beginnings to modern times; unlike many history books, it is easy reading. Mark H. Swartz, Textbook of Physical Diagnosis: History and Examination, 2nd ed. (1994), an excellent illustrated text, covers the techniques of physical diagnosis. Paul Ekman and Wallace V. Friesen, Unmasking the Face: A Guide to Recognizing Emotions from Facial Clues (1975, reprinted 1984), is a classic text in facial expression and emotion that uses composite photographs to show the importance of such areas as the brow, eyes, or mouth. American Psychiatric Association, Diagnostic and Statistical Manual of Mental Disorders: DSM-IV, 4th ed. (1994), the standard reference, contains the diagnostic criteria for mental diseases as determined by the American Psychiatric Association. Paul Cutler, Problem Solving in Clinical Medicine: From Data to Diagnosis, 2nd ed. (1985), covers the fundamentals of problem solving and includes many examples. An unusual reference containing technical information not found in standard medical dictionaries is James L. Bennington, Dictionary & Encyclopedia of Laboratory Medicine and Technology (1984). Robert E. Rakel, Textbook of Family Practice, 4th ed. (1990), is the standard textbook for family physicians covering the breadth of the discipline and emphasizing clinical diagnosis and treatment. A handy pocket reference presented in outline format containing diagnostic essentials for most medical conditions is David C. Dugdale and Mickey S. Eisenberg, Medical Diagnostics (1992). Robert R. Edelman and Steven Warach, Magnetic Resonance Imaging, The New England Journal of Medicine, 328(10):708716 (March 11, 1993) and 328(11):785791 (March 18, 1993), provide a complete discussion of MRI including physical principles, uses, and cost-benefit considerations. Annually an issue of JAMA, the journal of the American Medical Association, is devoted to recent discoveries in every medical discipline and is an excellent source of up-to-date information on new developments in medicine; one such development is treated in Richard C. Reba, Nuclear Medicine, JAMA, 270(2):230232 (July 14, 1993). Current Medical Diagnosis & Treatment (annual), contains concise diagnostic information and treatment for a large number of medical diseases. James B. Wyngaarden, Lloyd J. Smith, Jr., and J. Claude Bennett, Cecil Textbook of Medicine, 19th ed. (1992), is one of the best standard textbooks of medicine, compiled by leading authorities and containing thorough information on common and rare diseases. Richard D. DeShazo and David L. Smith (eds.), Primer of Allergic and Immunologic Diseases, JAMA, 268(20):27852996 (Nov. 25, 1992), is an entire issue devoted to allergy and immunology, containing articles ranging from the basics of the immune response to autoimmune diseases and immunization; prepared by the American Academy of Allergy and Immunology, it provides complete coverage of the subject. Robert Edwin Rakel Medical history Tests and diagnostic procedures Clinical laboratory tests Laboratory tests can be valuable aids in making a diagnosis, but, as screening tools for detecting hidden disease in asymptomatic individuals, their usefulness is limited. The value of a test as a diagnostic aid depends on its sensitivity and specificity. Sensitivity is the measure of the percentage of individuals with the disease who have a positive test result (i.e., people with the disease who are correctly identified by the procedure), and specificity is the measure of the percentage of people without the disease who have a negative test result (i.e., healthy individuals correctly identified as free of the disease). If a test is 100 percent sensitive and the test result is negative, it can be said with certainty that the person does not have the disease, because there will be no false-negative results. If the test is not specific enough, however, it will yield a large number of false-positive results (positive test results for those who do not have the disease). The ideal test would be 100 percent sensitive and 100 percent specific; an example would be an early pregnancy test that was so accurate that it was positive in every woman who was pregnant and was never positive in a woman who was not pregnant. Unfortunately no such test exists. The normal value for a test is based on 95 percent of the population tested being free of disease, meaning that 1 out of every 20 test results in healthy individuals will be outside the normal range and therefore positive for the disease. In the past, physicians would order selected tests based on the likelihood that the person had a certain disease. With the advent of automated analyzers, an increasing number and variety of tests have been made available at greatly reduced cost so that as many as 18 or more tests can be performed for what it previously cost to carry out three or four individual tests. A panel of chemical tests for blood and urine have become routine components of the basic medical workup. A disadvantage of this strategy is that each test produces some false-positive results and requires additional tests to rule out these diseases. The trend is reversing to perform only those tests most likely to be cost-effective. A normal laboratory value is one that falls within a range that represents most healthy individuals. It is clear, however, that some healthy persons will have values outside that range and some individuals with disease will have values within the normal range. Thus, no sharp line divides normal and abnormal values. Tables of normal reference values must be updated regularly to react to changes in laboratory technique. Many normal values vary dramatically with age and gender. Worldwide, the standard for reporting laboratory measurements is the International System of Units (SI units). The United States is the only major industrialized country that has not adopted the International System and continues to use customary units of measurement. Most tables provide both units to facilitate communication and understanding. Body fluid tests Blood Blood is composed of plasma and blood cells. The blood cellserythrocytes (red blood cells), leukocytes (white blood cells), and thrombocytes (platelets)are suspended in the plasma with other particulate matter. Plasma is a clear, yellowish fluid that makes up more than half the volume of blood. It is distinguished from serum, which is the clear, cell-free fluid from which fibrinogen has been removed. Tests to measure the concentration of substances in the blood may use plasma, serum, or whole blood that has been anticoagulated to keep all the contents in suspension. A complete blood count (CBC) is a measure of the hematologic parameters of the blood (see Table 2 for reference values). Included in the CBC is the calculation of the number of red blood cells (red blood cell count) or white blood cells (white blood cell count) in a cubic millimetre (mm3) of blood, a differential white blood cell count, a hemoglobin assay, a hematocrit, calculations of red cell volume, and a platelet count. The differential white blood cell count includes measurements of the different types of white blood cells that constitute the total white blood cell count: the band neutrophils, segmented neutrophils, lymphocytes, monocytes, eosinophils, and basophils. A specific infection can be suspected based on the type of leukocyte that has an abnormal value. Viral infections usually affect the lymphocyte count, whereas bacterial infections increase the percentage of band neutrophils. Eosinophils are increased in those with allergic conditions and parasitic infection. Infection with the human immunodeficiency virus (HIV), which causes acquired immunodeficiency syndrome (AIDS), damages the body's ability to fight infection. The immune system of a healthy individual responds to infection by increasing the number of white blood cells, while the immune system of a person infected with HIV is unable to mount a defense of white blood cells (namely, lymphocytes) and cannot defend the body against viral or bacterial assault. Of the calculations of red cell volume, the mean corpuscular volume (MCV) is the most useful for indicating anemia. The reticulocyte count, which measures the number of young red blood cells being produced, is used to distinguish between anemias resulting from a decrease in production of erythrocytes and those caused by an increase in destruction or loss of erythrocytes. An increase in the number of red blood cells (polycythemia) is normal for persons living at high altitudes, but in most of the population it indicates disease. Platelets, small structures that are two to four micrometres in diameter, play a role in blood clotting. A decrease in the platelet count can result in bleeding if the number falls to a value below 50 103 per cubic millimetre. Hematopoiesis (the production of blood cells) occurs in the bone marrow, and many types of blood disorders can be diagnosed best by analyzing a sample of bone marrow removed by a needle from the centre of the pelvic bone or the sternum (bone marrow biopsy). Bleeding disorders are suspected when blood is seen in the skin (purpura) or a wound is delayed in clotting. In addition to a low platelet count in the peripheral blood, there may be a decrease in megakaryocytes, cells in the bone marrow that form platelets. A bleeding time greater than 20 minutes indicates an abnormality of platelet function. Other screening tests for coagulation disorders include the prothrombin time (PT) test, the partial thromboplastin time (PTT) test, and the plasma fibrinogen assay (see Table 2). Blood factors, which are protein elements essential to the clotting of blood, should be assayed if a disorder associated with one of them is suspected. For example, factor VIII or IX can be assayed if the patient is thought to have hemophilia. The erythrocyte sedimentation rate (ESR) is the rate at which red blood cells settle in a column of blood in one hour. It is a nonspecific indicator of inflammatory disease that is also increased in anemia (see Table 2). The Coombs, or antiglobulin, test (AGT) is used to test blood cells for compatibility when doing a cross match to detect antibodies that would interfere with a blood transfusion. It also is used to detect antibodies to red blood cells in hemolytic disease of the newborn and drug-induced hemolytic anemias. Formulating a diagnosis