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Physiologic Solutions, Buffers, Acid-Base Indicators, Standard Reference Materials, and Temperature Conversions

Physiologic Solutions A physiologic solution is one that contains various salts in concentrations that closely approximate the composition of fluids in the human body. The simplest of these is physiologic saline, which has the same osmotic pressure as the blood. There are more elaborate solutions, for example, to maintain tissues in a metabolically active state for longer periods of time. Table A1.1 lists formulas of some…

High-Throughput Genomic and Proteomic Technologies in the Postgenomic Era

Key Points Completion of the Human Genome Project has provided scientists with a detailed map of the human genome and predicted coding regions that have facilitated the emergence of high-throughput genomic and proteomic technologies. A number of mature platforms exist for high-throughput profiling of gene expression in human tissue, including serial analysis of gene expression (SAGE), deoxyribonucleic acid (DNA) microarrays, and real competitive polymerase chain reaction.…

Molecular Genetic Pathology Of Solid Tumors

Key Points Solid-tissue (predominantly epithelial cell) tumors are mainly caused by genetic lesions of three types: deletion or inactivation of tumor suppressor genes, mutation in or overexpression of oncogenes (i.e., genes encoding proteins that are vital in control of the cell cycle), and hypermethylation of the promoter regions. These genetic lesions can be detected using the techniques described in Part 8 of this textbook involving real-time…

Molecular Diagnosis of Hematopoietic Neoplasms

Key Points General considerations in the diagnosis, classification, prognosis, and monitoring of hematolymphoid disorders Summary of the major genetic abnormalities and molecular detection methods in chronic and acute myeloid neoplasms. Basis of lymphoid antigen receptor gene rearrangements and molecular techniques to assess lymphoid clonality Concept of risk-adapted therapy for optimized management of childhood acute lymphoblastic leukemias and significance of minimal residual disease assessment Summary of the…

Oncoproteins And Early Tumor Detection

Key Points As a result of the vast progress that has been made very recently in sequencing the entire human genome and in illuminating pathways that are involved in tumorigenesis, it has become clear that the malfunctioning of mutant proteins is the central cause of human cancers. These proteins—growth factors, growth factor receptors, G-proteins such as ras-p21, the mitogen-activated protein kinases, and nuclear proteins such as…

Diagnosis and Management of Cancer Using Serologic and Other Body Fluid Markers

Key Points This chapter discusses the use of proteins, whose serum levels are often elevated in patients with malignancies, in the diagnosis and management of cancer. Many of these are so-called oncofetal antigens —that is, proteins that are expressed in fetal tissue during development but are not normally found in the tissues of adults. These include α-fetoprotein and carcinoembryonic antigen, whose serum levels are frequently elevated…

Pharmacogenomics and Personalized Medicine

KEY POINTS High-throughput array technologies such as genomics and proteomics have provided unprecedented ability to personalize output of biomarkers implicated in select disease states. Pharmacogenomics, through utilization of novel technologies, can detect unique genomic alterations to serve as diagnostic, prognostic, or predictive biomarkers, which relate to an individual or group response to particular therapies. Elucidation of unique genomic markers related to personal responses can tailor therapy…

Identity Testing: Use of Dna Analysis In Parentage, Forensic, And Missing Persons Testing

Key Points Standardized marker systems are used in testing panels to generate allelic phenotypes; short tandem repeats (STRs) form the basis of commercially available kits. Forensic testing requires documentation of all steps taken during collection, extraction, and testing so results can withstand legal challenges. Deoxyribonucleic acid (DNA) can be obtained from any sample that contains cellular material. The stability of DNA allows it to withstand harsh…

Molecular Genetics of Neuropsychiatric Disorders: Current Research and Perspectives

Key Points Genome-wide association studies (GWAS) on neuropsychiatric disorders have been expanding to increasingly large populations and are now including multiethnic groups. These studies are aimed at identifying specific single nucleotide polymorphisms (SNPs) that may be associated with specific diseases at high frequencies. Characteristic high-frequency SNPs seem to occur in schizophrenia, bipolar disorder (BD), substance use, major depression disorder (MDD), posttraumatic stress disorder (PTSD), Alzheimer disease…

Molecular Diagnosis of Genetic Diseases

Key Points Molecular testing for inherited disorders is one of the most rapidly growing areas of molecular pathology owing to the plethora of disease genes discovered through the Human Genome Project and the introduction of exome and genome sequencing. The mutations for single-gene disorders, whether dominant or recessive, can be detected by a variety of molecular diagnostic techniques, either specific to the mutation in question, if…

Applications of Cytogenetics in Modern Pathology

Key Points Identification of chromosomal abnormalities often correlates to disease and phenotypic abnormalities and thus will aid in clinical diagnosis and treatment. Identification of a cytogenetically abnormal clone in a cancer can provide information on diagnosis, prognosis, treatment, and disease progression. Standard morphology and a specific banding pattern have been established for all human chromosomes. A variety of different technologies, including karyotype analysis, fluorescence in situ…

Hybridization Array Technologies

Key Points Array technology provides a unique and powerful approach to screen a sample for dozens to thousands of genes. Current array fabrications allow for diverse platforms with better detection and reduced cost for high-density applications. Positive signals are generated when a tagged nucleic acid moiety hybridizes with its complementary probe localized on a solid support (i.e., “chip”). Care must be taken when performing and interpreting…

Polymerase Chain Reaction And Other Nucleic Acid Amplification Technology

Key Points Although the polymerase chain reaction is the most mature and widely used nucleic acid amplification method, other methods have diagnostic applications with unique properties and advantages. These techniques have analytic sensitivity unparalleled in laboratory medicine, creating new opportunities for the clinical laboratory to impact patient care. Clinical applications of the technology cut across the traditional disciplines in laboratory medicine. An understanding of the basic…

Molecular Diagnostics: Basic Principles And Techniques

Key Points Familiarity with the basics of nucleic acid biochemistry and biology is required to understand molecular diagnostic testing. The chemical stability of double-stranded DNA stands in contrast to the lability of single-stranded RNA. Base pairing of nucleic acids is dictated by energetically favorable rules and forms the basis for DNA replication, RNA transcription, and hybridization assays. The chemical similarity of nucleic acid molecules, regardless of…

Introduction To Molecular Pathology

Key Points The revolution in molecular biology continues to have a profound impact on the field of anatomic and clinical pathology (diagnostic medicine). Techniques, including polymerase chain reaction and other amplification and hybridization methods, are capable of detecting DNA in very small quantities in tissue and body fluids, enabling detection of various disease states, including cancer. The human genome project has created robust high-throughput and highly…

Specimen Collection and Handling for Diagnosis of Infectious Diseases

Key Points Collect specimens from site of infection before initiating therapy. Collect an adequate volume of sample for testing required. Tissue, fluid, or aspirates are always superior to a swab specimen. The only exception is collecting culture material from a hard-to-reach spot such as a throat or cervix. Use required collection and transport materials to preserve specimen integrity. Communicate clear orders and source information. Expedite the…

Medical Parasitology

Key Points Accurate diagnosis of parasitic infection usually depends on macroscopic or microscopic examination of specimens that have been appropriately collected and preserved. Thick and thin blood smears are useful for detecting and characterizing organisms found in the blood. Fecal specimens may be fresh (if they can be examined rapidly) or may be placed into fixatives such as formalin and polyvinyl alcohol or single-vial commercial fixatives.…

Viral Infections

Key Points Viruses cause more human infections than any other group of microorganisms and produce diseases that range from benign to highly lethal. Viral pathogens, including SARS-CoV-2, influenza A subtypes, arboviruses, and hemorrhagic fever viruses, are continuously being discovered or identified in different geographic areas and have the potential to cause widespread disease. Accurate and timely viral diagnosis is essential to optimize patient management, enable appropriate…

Rickettsiae and Other Related Intracellular Bacteria

Key Points Treatable rickettsial infections, including life-threatening Rocky Mountain spotted fever, boutonneuse fever, epidemic typhus, murine typhus, scrub typhus, human monocytotropic ehrlichiosis, and human granulocytotropic anaplasmosis, are seldom diagnosed serologically during the acute stage of illness owing to absence of an early antibody response. Immunohistochemistry and molecular diagnostics are effective in diagnosing rickettsioses and ehrlichioses, respectively. Q fever endocarditis is a chronic infection that usually is…

Chlamydial And Mycoplasmal Infections

Key Points Chlamydia trachomatis , the most common notifiable condition in the United States, is the most common bacterial cause of sexually transmitted disease in the United States and its prevalence is rising. The most sensitive method for detecting C. trachomatis , nucleic acid amplification, now is also commercially available for testing extragenital sites. Chlamydophila pneumoniae (formerly Chlamydia pneumoniae ) is responsible for at least 10%…