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Thalassemia is best thought of as a group of disorders rather than a single disease. They demonstrate a hemoglobin synthesis disorder in which there exists a defect in the rate of production of one or more of the globin chains. This defect results from either a heterozygous or homozygous deletion or inactivation of a globin chain gene.

Alpha thalassemia intermedia (Hemoglobin H Disease) is a result from a deletion of three out of four alpha chain loci. Infants born with alpha thalassemia intermedia appear normal at birth but often develop anemia and splenomegaly by the end of their first year. Hepatomegaly is not a common finding and there may be some association with mental retardation. Due to the hemolytic nature of this anemia, there may be an increase in respiratory infections, leg ulcers and gallstones. Skeletal changes are not commonly seen in hemoglobin H disease. Every ethnic group can have occurrences of hemoglobin H disease; but it is most often seen in Southeast Asian, the Middle East and the Mediterranean islands. Development and life expectancy are usually normal, but some may require splenectomy and transfusion therapy.

The Silent Carrier form of alpha thalassemia results from one alpha chain loci deletion. Individuals who are silent carriers show no clinical disease and demonstrate normal results during routine laboratory testing. This form of alpha thalassemia is usually discovered upon family studies.

The normal RBC count (4.84 x 1012/L) in this case, together with the decreased hemoglobin (8.4 g/dL) and MCV (59 fl) is an indicator of ineffective erythropoeisis that often points to thalassemia.The RBC morphology shows slight hypochromic microcytosis with codocytes, schizocytes, and basophilic stippling. Schizocytes form by several mechanisms, one being the removal of rbc inclusions.This patient's elevated bilirubin correlates with her presentation of sclera icterus; and her splenomegaly is consistent with increased rbc destruction.The Hb electrophoresis demonstrated a normal pattern, initially, but the unstable Hemoglobin H was revealed upon repeat electrophoresis with reduced incubation time. Hemoglobin H is the result of beta globin chain tetramer formation due to the insufficient supply of alpha globin chains in alpha thalassemia intermedia.People with Hemoglogin H disease (alpha thalassemia intermedia) usually have a normal life expectancy without treatment. However, hemolysis may lead to moderate anemia that may be treated with splenectomy.

Clot formation is always abnormal and is often due to increased levels of protein, especially fibrinogen. When the protein level is 1000 mg/dL, clot formation will most likely occur but clots may also form at lower levels of protein. Some clots may be very fine and appear as a thin membrane or "scum" on the surface of the CSF specimen. This type of clot is referred to as a pellicle. Pellicles are composed of fibrinogen and white blood cells. The type of clot formed may give some specific information about the disease state. Some examples are provided in the following table: Example of ConditionType of Clotbacterial meningitispellicle forms in a short time; large clot formation followsTB meningitisweb-like clot (pellicle) after 12-24 hours (enhanced by refrigeration)paresis (type of neurosyphilis)incomplete clotblockage of CSF circulationcompletely clotted due to protein

Normal urine contains very little protein, usually less than 10mg/dL, and the major serum protein that is found in normal urine is albumin. The presence of an increased amount of protein in the urine (proteinuria) can be an indicator of renal disease. The two mechanisms which can lead to proteinuria are glomerular damage or a defect in the reabsorption process of the tubules in the nephron. The concentration of protein in the urine is not necessarily indicative of the severity of renal disease.

The presence of low levels of albumin (microalbumin) in the urine is an important finding in an individual with either type 1 or type 2 diabetes. The development of clinical nephropathy leads to reduced glomerular filtration and eventually may lead to renal failure. For this reason, early detection of microalbumin is important in order to avert renal complications in a diabetic patient. The presence of microalbuminuria has also been associated with an increased risk for cardiovascular disease. Reagent strips that are used for routine urinalysis cannot detect low levels of albumin excretion (1 to 2 mg/dL). Special reagent strips that are sensitive for these low levels of albumin are useful for periodic monitoring of patients with diabetes, hypertension, or peripheral vascular disease.

The presence of significant amounts of glucose in the urine is called glycosuria (or glucosuria). The amount of glucose present in urine is dependent upon the blood glucose level, the rate of glomerular filtration, and the degree of tubular reabsorption of the sugar. Usually glucose will not be present in the urine until the blood level exceeds 160-189 mg/dl, which is the normal renal threshold for glucose. The main reason for glycosuria is an elevated blood glucose level, called hyperglycemia. Diabetes mellitus is the most common disease that causes hyperglycemia. However, stress, obesity, brain injury, myocardial infarction, hyperthyroidism, pregnancy, and a lowered renal threshold due to kidney damage can all cause glycosuria.

Smith KR, Fisher HC III, Hook, EW III: Prevalence of fluorescent monoclonal antibody-nonreactive Neisseria gonorrhoeae in five North American sexually transmitted disease clinics.J Clin Microbiol 34:1551-1552, 1996We compared a direct fluorescent monoclonal antibody (DFA) test with alternative enzymatic and fermention tests for identifying presumptive gonococcal isolates in a systematic sample from patients attending five sexually transmitted disease clinics in five cities.Fourteen (2.5%) of 556 isolates from three clinics were nonreactive with the DFA confirmatory reagent and reactive by both the Quad-Ferm and Rapid NH tests. The prevalence of DFA-nonreactive Neisseria gonorrhoeae isolates varies geographically and is independent of local methods for the identification of possible gonococci.On the basis of our findings, we recommend that for use in medicolegal and other instances in which a diagnosis of gonorrhea has the potential to have far-reaching effects, it is appropriate to test DFA reagent-nonreactive, oxidase-positive, gram-negative diplococci by alternative methods of gonococcal confirmation.Although the prevalence of such isolates could change, the fluorescent monoclonal antibody confirmation reagents remain useful for many clinical situations. Their ease of use and ready applicability for screening large numbers of isolates make them useful for many laboratories.

A 67 year-old man entered the hospital with cough, right lower chest pain accentuated by deep breathing, and fever. He had a history of chronic obstructive pulmonary disease secondary to a long history of smoking. The temperature on admission was 39.2C, and auscultation of the chest revealed rales in the right lower lung field. The admission white blood count was 13,500/ml with 80% segmented neutrophils and a shift to the left. A blood culture was obtained.

Suppola JP. Kuikka A. Vaara M. Valtonen VV. Comparison of risk factors and outcome in patients with Enterococcus faecalis vs Enterococcus faecium bacteremia. Scandinavian Journal of Infectious Diseases. 30(2):153-7, 1998.The purpose of our study was to determine retrospectively the risk factors for the acquisition of Enterococcus faecalis vs E. faecium bacteremia, as well as the clinical outcomes of these patients.62 patients with Enterococcus faecalis bacteremia were compared to 31 patients with E. faecium bacteremia. Haematologic malignancies, neutropenia, high-risk source and previous use of aminoglycosides, carbapenems, cephalosporins and clindamycin were significantly associated with E. faecium bacteremia. Instead, urinary catheterization was found to be related to Enterococcus faecalis bacteremia. The mortality rates within 7 d and 30 d were 13% and 27%, respectively, in patients with E. faecalis bacteremia and 6% and 29%, respectively, in patients with E. faecium bacteremia.There was no difference in mortality between E. faecalis and E. faecium bacteremia, nor was there a difference in seriousness of disease at the time of bacteremia. In the subgroups of patients with monomicrobial or clinically significant E. faecalis vs E. faecium bacteremia, the mortality rates were similar to the results of all subjects.Our results do not support the theory that E. faecium would be a more virulent organism than E. faecalis

Spencer RC.: Invasive streptococcEuropean Journal of Clinical Microbiology & Infectious Diseases. 14 Suppl. 1:S26-32, 1995.Before the introduction of antibiotics, serious infections caused by Streptococcus pyogenes (Lancefield Group A streptococci) were common. Before World War II, this bacterium was responsible for as many as 50% of postpartum deaths and was the major cause of death in patients with burns. Also common were the sequelae of streptococcal infections-rheumatic fever and post-streptococcal glomerulonephritis.With the use of penicillin, however, Streptococcus pyogenes was believed to be virtually eliminated as a pathogen. The organism was consigned to the history books, but not for long.In the mid-1980s, focal resurgences of rheumatic fever began to be reported from different areas in the USA, such as Salt Lake City, Utah. In such communities, where increases in cases of rheumatic fever had been reported, the serotypes M-1, 3, 5, 6 and 18 were isolated which, on culture, produced characteristic mucoid colonies. At the same time, reports of increases in invasive streptococcal disease began to surface in both the USA and Europe.Two syndromes were described; invasive streptococcal infection, occurring in previously healthy children and adults, commonly associated with septicaemia resulting from a deep focus of infection such as bone or lung; and streptococcal toxic shock syndrome, involving a cutaneous focus, accompanied by necrotizing or bullous soft tissue changes. Septicaemia is rare in streptococcal toxic shock syndrome, but the most characteristic feature is one of rapidly progressing multi-organ failure. A high proportion of the strains of Streptococcus pyogenes associated with this condition are serotype M-1, and fatality rates approaching 50% have been reported.

Low JC. Donachie W.: A review of Listeria monocytogenes and listeriosis. Veterinary Journal. 153:9-29, 1997Following the initial isolation and description in 1926, Listeria monocytogenes has been shown to be of world-wide prevalence and is associated with serious disease in a wide variety of animals, including man.Our knowledge of this bacterial pathogen and the various forms of listeriosis that it causes has until recently been extremely limited, but recent advances in taxonomy, isolation methods, bacterial typing, molecular biology and cell biology have extended our knowledge. It is an exquisitely adaptable environmental bacterium capable of existing both as an animal pathogen and plant saprophyte with a powerful array of regulated virulence factors.Most cases of listeriosis arise from the ingestion of contaminated food and in the UK the disease is particularly common in ruminants fed on silage.Although a number of forms of listeriosis are easily recognized, such as encephalitis, abortion and septicaemia, the epidemiological aspects and pathogenesis of infection in ruminants remain poorly understood. The invasion of peripheral nerve cells and rapid entry into the brain is postulated as a unique characteristic of its virulence, but relevant and practical disease models are still required to investigate this phenomenon.

A platelet function assay (PFA) is a screening test for the evaluation of platelets/primary hemostasis. Common clinical applications include the following: Preoperative evaluation of platelet function Determining the presence of drug-induced platelet dysfunction Determining platelet functionality in high-risk pregnancy Evaluation of patients with suspected inherited or acquired platelet disorders such as von Willebrand disease Evaluation of a bleeding patientA PFA instrument is able to differentiate between drug-induced platelet defects and other platelet defects. PFA tests are superior to the bleeding time test. The bleeding time is often not reproducible and, in spite of attempts at standardization, remains prone to variations in test results between persons performing the test. It is also relatively insensitive to platelet function. The bleeding time cannot be used to identify patients who may have recently ingested aspirin or non-steroidal anti-inflammatory drugs or patients who may have a platelet defect attributable to these drugs. The bleeding time is used to assess platelet function, but may be affected by platelet quantity. NOTE: Aspirin, and some other drugs, may falsely prolong bleeding times. Patients must be asked about aspirin use, and be aspirin free for 7-10 days prior to testing, for valid results.

Von Willebrands Disease is a platelet disorder. This disorder is characterized by a functional defect in Von Willebrands factor (vWF) itself. This disease often clinically manifests with a concurrent deficiency of factor VIII, but will present with a normal platelet count. As far as genetics and inheritance, both men and women are affected equally. Von Willebrands factor is essential for platelet binding, therefore, a defect in vWF causes impaired platelet adhesion and aggregation. The treatment of Von Willebrands Disease involves the administration cryoprecipitate, as it is rich in vWF.

The liver is the site of production for the vast majority of our clotting factors. Therefore, impaired liver function could adversely affect these hemostatic proteins. Some early indicators of a potential liver problem include: An increase in factor VIII. It is not produced in the liver and will be present in elevated numbers as the body attempts to compensate. The PT is sensitive to liver function, so an unexpected, prolonged PT should be evaluated. A lack of fibrinogen is often indicative of severe liver disease. It is difficult to treat liver disease, so therapy typically centers around replacing the missing factors by way of administration of fresh frozen plasma.

Molecular based clinical diagnostic test methodologies differ according to the target of interest. For example, patients suspected of having different diseases will require the identification of different targets. These targets might be found in different cells of the body and may therefore require different specimens to provide the answers. Patient A suspected of having Disease 1-requires the identification of a target of missequenced DNA- might require specimen of whole blood Patient B suspected of having Disease 2-requires identification of a target of antibody production-methodology might require specimen of serum Using this specific approach of disease diagnosis based on unique target identification, tests can provide answers that are more rapid sensitive specific

Much research has been conducted to identify the alphabet of the human cellular language otherwise known as the human genome. This identification or roadmap of the human genetic material has opened the door to the mainstreaming of molecular diagnostics within the clinical laboratory setting.While the mapping of the human genome project is complete, many times it is not necessary to be able to identify the entire sequence; rather, we can use the specific portion of the code that is unique to the disease or condition in question. These short portions of the genetic molecular sequence or oligonucleotides, can then be used as probes to seek out and detect or amplify the target sequence.

A person who receives the results of an HIV test shall maintain the confidentiality of the information received and of the person tested.A person who violates the confidentiality provisions commits a misdemeanor of the first degree.A person who obtains information that identifies an individual who has a sexually transmissible disease and maliciously, or for monetary gain, disseminates this information commits a felony of the third degree.

Agents in Category B are considered the second highest priority agents and are included in this group because they: Are moderately easy to disseminate Cause moderate morbidity and low mortality Require specific enhancements of Centers for Disease Control and Prevention’s (CDC) diagnostic capacity and enhanced disease surveillance

Most likely means of dissemination: Solid or aerosolPrimary route of entry: Inhalation, absorption, or ingestionGeneral signs and symptoms: Sudden fever, chills, headaches, muscle aches, joint pain, dry cough, progressive weakness, and pneumonia.The disease is not transmissible through human contact.  When used as a WMD, infection would be acquired by handling infected material, eating or drinking contaminated food or water or by breathing in the bacterium.

Biological attacks involve bacteria, viruses or natural toxins. The effects of toxins can be immediate but for bacteria and viruses the effects may not be apparent for weeks. A bio-terrorist may attack by infecting animals, contaminating food and water, spraying bacteria or viruses into the air. In infections such as smallpox and plague, once a few individuals are infected they can further spread the disease from person to person. An attack could also come from through a building’s ventilation system, the mail, or even through exposure to an infected terrorist seeking to spread disease during an infectious stage.

Below is additional information that you can obtain off the internet to help you “Be Prepared”.www.ready.gov: This site has emergency preparedness guidance from the United States Dept. of Homeland Security. It also has an excellent training program for kids.www.redcross.org: Preparedness information from the International Red Cross.www.neighborhoodpreparedness.info: From the Los Angeles Fire Department. www.americaswaterwaywatch.org: Prepared by the United States Coast Guard. Discusses what to look for as far as suspicious activities.www.bt.cdc.gov: Discusses agents, disease, and other threats.www.ojp.usdoj.gov: The Citizens’ Preparedness Guide provides suggestions for preparedness in homes, neighborhoods, and schools.www.fema.gov/areyouready: FEMA’s most comprehensive source on individual, family, and  community preparedness.

A bone marrow biopsy involves removing a small portion of the bone marrow without destroying the architecture of the marrow. This type of biopsy is necessary when the marrow cannot be aspirated (dry tap) due to a disease process, and also provides additional information complementary to that derived from the aspirate: biopsy specimens are more accurate for assessing cellularity, and infiltrative processes, such as metastatic carcinoma, fibrosis, amyloid, and lymphoma. A biopsy specimen is processed as follows: touch preparation tissue section

After the marrow is evaluated, the diagnosis is established and extent of the disease is determined. Follow up bone marrow examinations may be needed to monitor changes in the marrow following treatment or when signs and symptoms of relapse occur. To summarize, a bone marrow examination can provide valuable information to aid in the diagnosis of a variety of disorders. Due to the expense involved and the discomfort to the patient, clear indications of need should be present before this examination is undertaken.

The predominant immunoglobulin class for the B antibodies produced by individuals with group A phenotype and the A antibodies produced by individuals with group B phenotype is IgM. Small quantities of IgG may also be present. IgG is the predominant immunoglobulin for the anti-A and anti-B antibodies found in individuals with group O phenotype. Infants of group O mothers are at higher risk for hemolytic disease of the newborn (HDN) than those born to mothers with group A or B because IgG immunoglobulins readily cross the placenta. IgM molecules do not readily cross the placenta because of their larger size. It is important to note that immune antibodies are usually IgG. Both naturally occurring and immune ABO antibodies are critically important in transfusion since both sensitize and usually hemolyze red cells with the corresponding antigen.

Specialists in radioassay use radionuclides to determine the chemical makeup of body fluids such as blood and urine. Specialists in blood gas analysis evaluate lung and breathing function by levels of oxygen, carbon dioxide, pH, and hemoglobin with automated tests. Specialists in histology examine cellular and tissue samples using fixation, dehydration, embedding, microtomy, frozen sectioning, staining, and other similar techniques. Histology specialists licensed as technicians can perform specimen processing, embedding, cutting, staining, and frozen sectioning only under the general supervision of a director, supervisor, or technologist. Specialists in cytology process and interpret samples relating cytopathological disease. Non-gynecological cytology preparations can be screen by a specialist in cytology but final review and interpretation must be done by a physician.

Billing: Highest risk activity a laboratory has. All laboratory activities contribute to the billing process. Many of the risk areas included in this program are components of the billing function. Medical necessity: Medicare is only allowed, by law, to pay for tests that are reasonable and necessary for the diagnosis and treatment of disease. Medical necessity is an underlying principle of the Medicare program. Tests performed for screening or routine exams are not considered medically necessary by the Medicare program.

LMRPs (Local Medical Review Policies) are published by Medicare for some laboratory tests. Developed for tests that can be used for screening or diagnosis of disease. CPT codes describe laboratory tests and ICD-9CM codes determine when coverage is allowed. If an LMRP test is ordered by a physician, an ICD-9CM code that is included in the LMRP must be given to the laboratory or the Medicare program will not pay for the test. It is against the law for laboratory to change or add an ICD-9 code submitted by a physician. The Balanced Budget Act of 1997 made it illegal for physicians to order LMRP tests and not supply an ICD-9CM code with the order.

ICD-9CM (International Classification of Disease, 9th Edition, Clinical Modification) codes are used for the classification of disease and conditions and for describing signs, symptoms and medical circumstances.These codes are used to indicate the medical necessity of a particular test.ICD-9 codes can only be supplied by the ordering physician or a representative of that physician. "Code steering" means to steer or direct a physician to supply an ICD-9 code that is payable. ICD-9 codes cannot be used from a previous laboratory order. If a physician supplies a narrative description instead of an ICD-9 code the laboratory must accurately translate that code using only certified coders.It is against the law to use the wrong ICD-9 code for the purpose of causing or increasing payment for a test.

Since these recommendations have been adopted by many groups, including the College of American Pathologists and the Centers for Disease Control, we will be using them as our criteria for differentiating between bands and segs.This definition was first reported by the Committee for Clarification of the Nomenclature of Cells and Diseases of the Blood and Blood Forming Organs, in the American Journal of Clinical Pathology (18:443-450, 1948).

TDM provides a quantitative measure of the circulating concentration of a drug. The physician determines if the dosage of the drug needs to be adjusted based on this information.If a drug concentration is determined to be outside the therapeutic range, it may be for one of the reasons listed in the table below. Reason Discussion Noncompliance Patients may (intentionally or unintentionally) not take the drug. TDM can thus help monitor compliance. Dosing errors The dose may have been erroneous or inappropriate given the patient's condition. Malabsorption The TDM result will reveal if the drug cannot be absorbed well through the gut and an alternative route of administration will be needed. Drug interactions Many drugs interfere with the absorption or metabolism of other drugs. These interactions will be revealed by TDM. Kidney or liver disease Any pathology that affects elimination will cause an elevation in a drug level that will be unmasked by TDM. Altered protein binding Changes in serum proteins can lead to big changes in the amount of free drug in serum. Variations in the genetics of drug-metabolizing enzymes can also affect drug concentrations in the body. This is the field of pharmacogenomics that will be discussed later in the course.

Drug-binding proteins in serum can fluctuate in disease states. For example, if albumin levels fall, as can occur in liver failure or nephrotic syndrome, less albumin will be available for drug binding; a subsequent dose may produce a toxic concentration of free drug.The image on the right illustrates the loss of equilibrium between a protein-bound drug and a free drug when drug-binding proteins are diminished.Doses of drugs that are highly protein-bound may need to be adjusted in patients with lower drug-binding protein levels. Examples of some common drugs that are highly protein-bound include thyroxine, warfarin, diazepam, heparin, imipramine and phenytoin. �

Lipids are fats dispersed in plasma. They include: Triglycerides Cholesterol Lipoproteins The amount and ratios of various lipids in the blood will determine a person’s risk of getting coronary artery disease.

Sensitivity is the ability of a test to correctly identify individuals who do have a particular disease or disorder. To determine sensitivity, we use the following equation: True Positives (TP) Divided by True Positives (TP) plus False Negatives (FN) Times 100 or (TP ÷ (TP + FN)) x 100 The result will be a percentage.

In 2003, the Center for Disease Control and Prevention and the Center for Medicare and Medicaid Services published the Clinical Laboratory Improvement Amendment (CLIA).Under CLIA, the term "Non-waived" replaces the terms “Moderate” and “High Complexity” testing. Before a laboratory can report patient results for a non-waived, FDA-approved test for the first time, the laboratory must verify that the test’s performance is similar to the manufacturer’s claims for accuracy, precision, and reportable range.

The gram stain reaction and appearance can be used to identify most cellular material seen in a direct smear. Identification of cellular elements present in a direct clinical smear is important because most of these elements play an important role in the disease process. For example, the quality of a sputum sample can be assessed by determining the relative numbers of squamous epithelial cells and polymorphonuclear leukocytes (segmented neutrophils) present.

Schistocyte is a general term for a fragmented red blood cell that may assume various shapes, some with horn-like projections (keratocytes), triangle-forms (triangulocytes), and helmet shapes, as illustrated in the upper photograph. Schistocytes are formed when erythrocytes are forced through a vessel blocked with interlacing fibrin strands and the red cells are sliced into fragments. True schistocytes are devoid of central pallor. These damaged cells continue to circulate while healing their torn edges. Finally, they are removed by the spleen. Bite cells (lower photograph) appear when an abnormal hemoglobin aggregate (Heinz body) is nibbled out of a red cell's cytoplasm by the spleen leaving a bitten apple appearance. Glucose 6-PD deficiency secondary to chemical poisoning or injury by oxidant drugs are settings for Heinz body formation, and the telltale bite cells remain as evidence. Hemolytic anemia associated with severe liver disease is another setting where bite cells are formed.

Jaundice was recognized in a day-old infant. Notice particularly the size variation (anisocytosis) of the erythrocytes on the infant's peripheral smear. What does this observation mean? Does it provide immediate information that might serve as guidance in expediting diagnosis and treatment? Note that normal-sized red blood cells, microcytes, microspherocytes, macrocytes, and nucleated red blood cells are all present. Red cell variations are expected findings in healthy neonates, but the variations here are exaggerated. Hyposplenic functional features may appear, including acanthocytes, spherocytes, and possibly Howell-Jolly bodies, especially if hemolysis is particularly vigorous. A high (3-7%) reticulocyte count is not unusual during the first three or four days after birth, however, the marrow in this jaundiced infant is proliferating vigorously in response to hemolysis. A call for more red cells is urgent. Immature red cells (in the form of nucleated red cells) and red cells with stippling of RNA (basophilic stippling) are readily identified. Red cell maturation sequence has not been totally processed in the marrow nor is all residual red cell debris removed by the spleen. In the lower photograph are reticulocytes stained by supravital stain (new methylene blue). Basophilic stippling (specks of RNA) stains with both supravital stains and with routine Wright-Giemsa stain.

This photograph of a peripheral blood smear from an 18-year-old North African woman with anemia reveals sickle cells. Target cells are not conspicuous. This shifts the diagnostic evidence away from HbSC disease. Cells tagged by arrows are variants of sickle cells. These may appear when multiple abnormal hemoglobin combinations are responsible for the clinical problem. The cell marked by the single arrow is an envelope formed not only in HbS disease but in HbC disease as well. Two arrows tag a blister cell, which, when seen in several fields, should prompt a hemoglobin electrophoresis to determine the presence of an undiagnosed hemoglobinopathy. Blister cells with fuzzy edged pseudo-vacuoles (see photo) are to be distinguished from the pseudo-vacuoles (blister)with razor sharp edges suggesting a microangiopathic state.

Examples of stomatocytes can be seen in the center of this slide and to the left of the center. Conditions in which a significant number of in vivo stomatocytes can be seen include hereditary stomatocytosis, neoplastic disorders, liver disease and Rh null disease. The largest numbers of in vivo stomatocytes are seen in hereditary stomatocytosis and their identification is necessary to make the diagnosis.

Waxy casts appear as cylinders of smooth, highly refractive material. They are yellow, homogeneous and their ends may be square or broken off. Cracks may occur within the cast, giving it a segmented appearance. Waxy casts are believed by some to be the final stage of degeneration of the fine granules of granular casts. Since the granules need time to degrade, this finding implies localized nephron obstruction. Waxy casts are seen in chronic renal failure, and acute and chronic renal allograft rejection. Unusually broad waxy casts are known as renal failure casts. These very broad casts are created in the dilated tubules seen in end-stage renal disease.

Tyrosine crystals appear as fine silky needles arranged in sheaves or bundles in acid urine. They are rarely present and may appear together with leucine crystals in liver disease. Do not confuse tyrosine with crystals caused by x-ray dye. X-ray dyes will cause the urine specific gravity to be greatly increased (1.040), Tyrosine crystals are soluble in alkali or dilute mineral acid.

Cholesterol crystals may be seen in renal tubular disease. These crystals look like plates of glass, sometimes with a notch out of one corner. Under polarized light, they exhibit a stained glass effect. These crystals are rarely seen unless the specimen has been refrigerated, because the lipids remain in droplet form. Large amounts of protein, lipid droplets, fatty casts or oval fat bodies should be found along with cholesterol crystals. Cholesterol crystals are found in acid or neutral urine.

The tuberculosis (TB) incidence rate in 2007 was the lowest recorded since national reporting began in 1953. However, the average annual percentage decline in the TB rate has slowed. Multi-drug resistant tuberculosis cases have increased. There is persistent disparity in the incidence of tuberculosis between different ethnic groups and also between foreign-born persons and US-born persons. Reference: Pratt R, Robison V, Navin T. Trends in tuberculosis. MMWR/57(11);281 - 285; Centers for Disease Control and Prevention: March 21, 2008. Available at: http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5711a2.htm Accessed on May 23, 2008.

The Centers for Disease Control (CDC) issued Guidelines for Prevention of Tuberculosis in Healthcare Settings in 2005.These guidelines have broader applications than the Guidelines for Prevention of Tuberculosis in Healthcare Facilities issued by CDC in 1994.

Administrative controls reduce the risk of exposure to persons who might have TB disease.Environmental controls prevent the spread and reduce the concentration of infectious droplet nuclei in ambient air.Respiratory protection controls are for situations that pose a high risk of exposure to further reduce risk of exposure of HCWs to infectious droplet nuclei that have been expelled into the air from a patient with infectious TB disease.

Laboratory workers who handle infectious materials in the microbiology laboratory should be aware of the work practices, safety equipment, and barriers that will protect them and others in the area from infectious agents. The Centers for Disease Control and Prevention (CDC) and the National Institutes of Health (NIH) created guidelines to assist laboratories in developing safe practices based on the infectious agents that are handled. These guidelines are referred to as Biosafety Levels 1 through 4. Each increasing number represents increased risk, requiring more stringent work practice and increasingly protective safety equipment and barriers. A copy of the Guidelines can be obtained from the CDC or accessed online at:http://www.cdc.gov/OD/ohs/biosfty/bmbl5/bmbl5toc.htm

It is important to be able to recognize the presence of these changes and then identify them for several reasons:If the changes are pathological, their identification may aid the physician in diagnosing a specific condition.If the changes are not pathological, their identification alerts the physician to the fact that the changes are present, thus avoiding a possible misdiagnosis.If reactive, it indicates that although the cells are functioning normally, they are reacting to a stimulus. Indicating the presence of such cells may aid in determining the diagnosis or monitoring the course of disease once a diagnosis has been made.