| Review 3 Ladhani S. Joannou CL. Lochrie DP. Evans RW. Poston SM.:
Clinical, microbial, and biochemical aspects of the exfoliative toxins causing staphylococcal scalded-skin syndrome.
Clinical Microbiology Reviews. 12:224-242, 1999The exfoliative (epidermolytic) toxins of Staphylococcus aureus are the causative agents of the staphylococcal scalded-skin syndrome (SSSS), a blistering skin disorder that predominantly affects children. Clinical features of SSSS vary along a spectrum, ranging from a few localized blisters to generalized exfoliation covering almost the entire body.The toxins act specifically at the zona granulosa of the epidermis to produce the characteristic exfoliation, although the mechanism by which this is achieved is still poorly understood.Despite the availability of antibiotics, SSSS carries a significant mortality rate, particularly among neonates with secondary complications of epidermal loss and among adults with underlying diseases. | View Page |
| The staphylococcal toxins causing the scalded skin syndrome (SSSS) have as their site of action in which of the following layers of skin: | View Page |
| Review 1 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. | View Page |
| A major complication of toxic shock syndrome related to group A streptococci, leading to 50% mortality is: | View Page |
| Review 2 Cunningham MW.:
Pathogenesis of group A streptococcal infections.
Clinical Microbiology Reviews. 13):470-511, 2000Group A streptococci are model extracellular gram-positive pathogens responsible for pharyngitis, impetigo, rheumatic fever, and acute glomerulonephritis. A resurgence of invasive streptococcal diseases and rheumatic fever has appeared in outbreaks over the past 10 years, with a predominant M1 serotype as well as others identified with the outbreaks.Emm (M protein) gene sequencing has changed serotyping, and new virulence genes and new virulence regulatory networks have been defined. The emm gene superfamily has expanded to include antiphagocytic molecules and immunoglobulin-binding proteins with common structural features.At least nine superantigens have been characterized, all of which may contribute to toxic streptococcal syndrome. An emerging theme is the dichotomy between skin and throat strains in their epidemiology and genetic makeup. Eleven adhesions have been reported, and surface plasmin-binding proteins have been defined.The strong resistance of the group A streptococcus to phagocytosis is related to factor H and fibrinogen binding by M protein and to disarming complement component C5a by the C5a peptidase. Molecular mimicry appears to play a role in autoimmune mechanisms involved in rheumatic fever, while nephritis strain-associated proteins may lead to immune-mediated acute glomerulonephritis. Vaccine strategies have focused on recombinant M protein and C5a peptidase vaccines, and mucosal vaccine delivery systems are under investigation. | View Page |
| Most Eikenella cellulitis infections result from: | View Page |
| To avoid infection with E. corrodens, patients with insulin-dependent diabetes mellitis (IDDM) are advised not to: | View Page |
| Introduction We are all aware of the clinical laboratory's role in assessing overall health and we are also aware that measuring a patient's serum lipids will provide some insight into their cardiovascular health. The traditional measurements of low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides are the 'classic' cardiovascular risk markers.Laboratorians, and even the general public are now well-aware that LDL-C ('bad' cholesterol) concentrations should be low while HDL-C ('good' cholesterol) concentrations should be high. Triglycerides should be kept in check as well. Optimal levels are shown in the table below. So what is the risk if these values are not within optimal ranges?Cardiovascular risk can be simply defined as increasing the odds of having a pathology which affects blood flow and/or the heart. The most common cardiovascular pathology is atherosclerosis. Other cardiovascular pathologies whose odds increase as serum lipids and other cardiovascular markers become suboptimal are myocardial infarction (heart attack), stroke, congestive heart disease and coronary artery disease. Other diseases such as diabetes and the metabolic syndrome are also strongly associated with the classic cardiovascular risk markers LDL-C, HDL-C and triglycerides. | View Page |
| ApoB/ApoA1: The Test Measuring ApoB and ApoA1 can be performed using standard immunoassay techniques. Nephelometry is popular, as are ELISA-based methods that are performed on automated chemistry analyzer platforms. The power of the ApoB/ApoA1 ratio as a cardiovascular risk marker is getting widespread attention. An individual with seemingly normal LDL-C may in fact have high ApoB concentrations. When this individual has his or her ApoB/ApoA1 ratio calculated, the risk is evident. Studies have also shown that patients with metabolic syndrome and type-2 diabetes can also easily be identified with the ApoB/ApoA1 ratio, whereas these patients cannot always be identified by measuring LDL-C and HDL-C.In 2004, the global INTERHEART study of risk factors for acute myocardial infarction concluded that the ApoB/ApoA1 ratio was the most important risk factor in all geographic regions. The ApoB/ApoA1 ratio is easy to use because the risk is integrated into a single number that indicates the balance between atherogenic and antiatherogenic particles.There have been many studies concerning the predictive power of the ApoB/ApoA1 ratio. One study, which involved thousands of patients who were followed for an average of 10 years, showed that the ApoB/ApoA1 ratio was a strong predictor of stroke in addition to other cardiovascular events. Due to the evidence presented in studies like these, the National Academy of Clinical Biochemistry (NACB) has recommended that the ApoB/ApoA1 ratio be used as an alternative to the usual total cholesterol (TC)/HDL cholesterol ratio when determining lipoprotein-related risk for cardiovascular disease. Some believe that ApoB/ApoA1 testing will eventually replace traditional LDL-C and HDL-C measurements. | View Page |
| LDL Phenotype by Electrophoresis When LDL is resolved with electrophoresis, it reveals several subfractions. These subfractions are simply different size populations of LDL particles. Age, gender and lipid status can all affect the LDL subfractionation profile. Individuals who have less dense (so called 'buoyant') LDL have most of their LDL in subfractions 1 and 2. These results are referred to as pattern or phenotype "A" and are normal. Those with significant amounts of subfractions 3- 7 (more dense particles) are at higher cardiovascular risk. These patients have pattern or phenotype "B". The B pattern rarely occurs as an isolated disorder. It is usually accompanied by characteristics of the metabolic syndrome: hypertriglyceridemia, reduced HDL-C , abdominal obesity, insulin resistance, etc. | View Page |
| Examine the image on the right. What problems can you see that may result in MSDs for this laboratory worker if her job involves frequent use of the computer for prolonged periods of time? | View Page |
| Repetitive Motion Injuries Repetitive motions can cause a variety of disorders that affect nerves, tendons, and muscles. Symptoms can include tingling or numbness in the fingers or hands, decreased range of motion, decreased grip strength, sleep interupted by numbness or discomfort in the hands, pain in fingers, hands, or wrist, or pain shooting up into the forearms or arms.Some common afflictions that could affect laboratory workers due to the nature of their jobs are listed in the table below. Condition Symptoms Cause Carpal tunnel syndrome Pain that radiates up the arm, numbness or tingling in the thumb, index, or middle finger and weakness in the wrist and hand Compression of the median nerve that runs from the forearm into the hand Thoracic outlet syndrome Numbness and tingling in the hand, intensified with overhead activities Compression of the nerves and blood vessels between the neck and shoulder Radial tunnel syndrome Elbow pain, pain near the base of thumb, or pain anywhere in between. A common symptom is wrist weakness. Compression or entrapment of the radial nerve; may be caused by repetitive wrist and finger extension or repetitive forearm turning. Tendinitis Stiffness, tightness, and burning sensation; may experience a deep nonspecific pain. Grip impairment. Occurs most often in the tendons of the fingers, thumb, forearm, elbow, and shoulder. Repetitive motions or maintaining an awkward position that stresses tendons beyond their strength. Friction from overuse can cause inflammation. Tenosynovitis Pain, swelling, difficulty moving the joint in the affected area Inflammation of the tendon sheath | View Page |
| Light sensitivity and headaches are symptoms of what disorder? | View Page |
| Note the view of a peripheral blood smear in the photograph. Pictured are scattered acanthocytes, echinocytes, target cells, spherocytes, and schistocytes. The condition in which each of these atypical RBC's may be found in varying numbers in the same peripheral blood smear is: | View Page |
| Match the form of red cell inclusions in each of the frames of photographs with a corresponding clinical condition. | View Page |
| The presence of erythrocytes with altered morphology (as photographed here) has a close association with each of the following conditions except: | View Page |
| A 5-year-old girl was brought to a physician's office because of fever and viral-type illness symptoms. Her blood pressure was elevated.Hemogram: hemoglobin 9.1g/dL (normal 12.0 - 16.0 g/dL), hematocrit 28% (normal 37 - 48%), MCV 80 fl (normal 86 - 98 fl), RDW 13.1% (normal 11 - 15%), platelets 90.1 X 109/L (normal 150 - 450 X 109/L) WBC 9.6x109/L (normal 4.3 - 10.8 x 109/L).The peripheral blood smear is represented in the photograph.Which of the following are the most likely associated conditions? | View Page |
| Hb E disease (continued) The family (cited in the previous case history) was from a region of Thailand where the physician knew HbE carriers are prevalent. Homozygous hemoglobin E is common in Southeast Asia and presents with very mild anemia and seldom requires transfusion. Over 30 million people in the world are HbE carriers, making this abnormal hemoglobin almost as common as HbS. Hemoglobin E is uncommon in North America and in Europe, but with changing immigration patterns, hemoglobinopathy E cannot be ignored. Peripheral blood smear findings of target cells, microspherocytes, red cell hypochromia, a few red blood cell fragments, and nucleated red blood cells require evidence from hemoglobin electrophoresis to establish a diagnosis. Clinically, a very important and severe syndrome is hemoglobin E/beta thalassemia in which there is hemolysis requiring repeated transfusions. The patient has a severe anemia, low MCV (50's), and high RBC. This is characteristic of Hgb E/beta thalassemia. | View Page |
| Neutrophil with Chediak-Higashi In the center of this slide is a neutrophil from a patient with Chediak-Higashi syndrome. Notice that some of the granules are very large and purple. | View Page |
| Auer rods are significant when they are seen in the cytoplasm of blast cells because they are diagnostic for: | View Page |
| Albinism Albinism, one of the striking physical characteristics of Chediak-Higashi syndrome, is also thought to be related to the general dysfunction of cells. Albinism has been specifically related to the aggregation of melanosomes, the pigment producing cells in the body. | View Page |
| Granules in Chediak-Higashi Syndrome versus Toxic Granulation The neutrophils found in Chediak-Higashi can be differentiated from toxic granulation.
In conditions causing toxic granulation, the granules are smaller and more numerous and only the neutrophils are affected.
In Chediak-Higashi, eosinophils, basophils, lymphocytes and monocytes are affected. In eosinophils larger than normal eosinophilic granules may be seen, basophils may exhibit larger than normal basophilic granules, lymphocytes, large azurophilic granules. Larger pale granules/bodies may appear in monocytes. | View Page |
| Chediak-Higashi Chediak-Higashi syndrome is a rare autosomal recessive disorder. It results from a mutation of the gene LYST which encodes a protein with multiple phosphorylation sites. This defect causes a cellular abnormality involving the fusion of cytoplasmic granules. Early in neutrophil maturation normal azurophilic granules form, but they fuse together to form megagranules. Later during the myelocyte stage, normal specific granules form. The mature neutrophils contain both normal specific granules and abnormal azurophilic granules.
These large abnormal granules can be seen in the cytoplasm of neutrophils, eosinophils, basophils, monocytes and lymphocytes.
These abnormal granules are able to kill bacteria in neutrophils and monocytes; however, the process is much less effective than in normal cells in part, because these neutrophils have impaired locomotion. For these reasons, individuals with Chediak-Higashi have recurrent infections.
An accelerated lymphoma-like phase occurs, with lymphadenopathy, hepatosplenomegaly, and pancytopenia. Death often occurs at an early age.
| View Page |
| Match the letters representing the peripheral white blood cells with the most likely associated clinical conditions. | View Page |
| The combination of neutrophil cytoplasmic inclusions(see upper photograph) and giant platelets (lower photograph) are found in each of the following conditions except: | View Page |
| The nuclear appendage at the tip of the arrow is a normal finding in females but not in males. | View Page |
| Additional comments on this exercise The following pages in this presentation includes a series of white blood cell abnormalities that may be identified in a peripheral blood smear. Many of the cases will simulate the practice of a peripheral smear review by a hematology morphologist. He/she must asses what responses in patient care may be triggered by the clinician attempting to interpret the reported findings on a peripheral smearObservations of white blood cell abnormalities in the peripheral blood smear should be reported so as to direct the physician to an immediate specific diagnosis, such as: (1) atypical lymphocytes suggesting infectious mononucleosis rather than leukemia, (2) toxic granules in neutrophils as in acute infections, or atypical granules suggesting a genetic disorder, (3) an unusual mix of cells, such as too many or too few neutrophils, monocytes, or other myeloid cells, and (4) the presence of giant platelets, myelocytes, or other cells suggesting a myelodysplastic syndrome.In summary, laboratory data should be presented to clinicians in a user friendly way to promote effective decision making. The design of the data base of information must be directed toward providing clinically helpful information clearly and quickly in order to facilitate appropriate action in terms of optimizing patient care outcomes.d | View Page |
| Leukemoid reaction revisited The term leukemoid reaction is used to describe peripheral white blood cells that on the stained blood smear may have some resemblances to leukemia cells. Quantatively in a leukemoid reaction, the neutrophil count is >50,000 cumm with more immature cells, particularly myelocytes, than are usually present in toxic left shift syndromes. The presence of immature cells in a leukemoid reaction awakens thoughts of leukemia. Great care must be taken to make a distinct differentiation between aberrant white blood cell proliferations and a benign but exaggerated granulocytic proliferative response. Our material is from a 1-month-old girl with Down's syndrome. Her total white blood count was 37,000/mm3 interpreted as leukocytosis with left shift. Leukocytosis with a left shift, and leukemoid reactions with high alkaline phosphatase are conditions to be mindful of in patients with Down's syndrome. The alkaline phosphatase score is high in leukemoid reactions, low in granulocytic leukemia. | View Page |
| Familial disorders: summary Several additional familial and congenital disorders associated with atypical inclusions in WBCs are now recorded. These individual syndromes carry the following names: Fechtner, Alport, Epstein, Sebastian, and Paris-Trousseau.Fechtner syndrome( Peterson etal,Blood 65:397-406,1985)was described with 8 family members spanning 4 generations presenting with varying degrees of nephritis, deafness,and congenital cataracts. The syndrome is likely a variant of Alport syndrome with the addition of leukocyte inclusions and macrocytothemia. Several more cases involving other families have been reported. The inclusions resemble toxic Doehle bodies or those of the May-Hegglin anomaly by light microscopy, but are ultrastructurally unique.Alport syndrome in itself is autosomal dominant, X-linked , hereditary and characterized by sensorineural deafness and hereditary nephritis. It is believed to result from abnormal glycopeptide synthesis in renal basement membranes. Recurrent hematuria and slowly progressive renal insufficiency are clinical findings. Cataracts and platelet abnormalities may be added features.Epstein syndrome is essentially Alport syndrome with the addition of macrothrombocytopenia (Seri, et al. Hum Genet 110:182-186, 2002). Neutrophil inclusions are absent in this disorder; neutrophilic inclusions are considered part of the Fechtner syndrome. The Sebastian platelet syndrome is a variant of hereditary macrothrombocytopenia combined with neutrophil inclusions that differ from Doehle bodies, but are similar to those inclusions in Fechtner syndrome. (Greinacher, et al, Blut 61:282-288, 1990).Paris-Trousseau syndrome includes large platelets containing giant alpha granules identifiable in the peripheral blood.(Breton-Gorius, Blood 85:1805,1995) | View Page |
| Chediac-Higashi anomaly In 1952 Chediak (a Cuban physician) reported a childhood disorder in which abnormal cytoplasmic inclusions appeared in the neutrophils of four family members. In 1954 Higashi reported a similar abnormality in an 11-month old Japanese infant. These inclusions were identified as lysosomal in origin and found in this rare autosomal recessive disorder Death was usually related to recurrent infections or hemmorhage though now some of the affected patients live to reproduce. Ocular and cutaneous albinism, increased susceptibility to pyogenic infections, abnormal granules in neutrophils, and a bleeding tendency are prominent findings. The striking neutrophilic inclusions appear as coarse intra-cytoplasmic azurophilic granules (see photograph).These granules arise from dilated portions of the Golgi-endoplasmic reticulum lysosomal apparatus. Aleutian mink and other animals are known to have Chediak-Higashi syndrome. Azurine pelts from infected mink were once prized by coat makers. | View Page |
| Alder- Reilly Anomaly Large inclusions in leukocyte cytoplasm appear with Alder-Reilly syndrome. Inheritance patterns are not completely clear. The condition is characterized by larger than usual azurophilic and deeply violet staining granules clustered throughout the cytoplasm (even covering the nucleus)in all granulocytes. There are variations in which some lymphocytes and monocytes may be affected. These inclusions represent partially degraded mucopolysaccharides within lysosomes.Alder-Reilly bodies may be found independently of genetic mucopolysaccharidoses as an inherited anomaly (Jordan's anomaly). Cytoplasmic vacuoles of toxic origin are not present in Alder-Reilly cells. The background condition in Alder-Reilly syndrome is mucopolysaccharidosis with various types of bone and cartilage disorders, reported first in gargoylism, then in Hunter and Hurler syndromes. Accompanying conditions are hepatosplenomegaly, corneal opacities, and mental retardation. Reference: Brunning, Richard D. Morphologic Alterations in Nucleated Blood and Marrow Cells in Genetic Disorders. Human Pathol: 99-124, March, 1970 | View Page |
| WBC inclusions: summary The presence of atypical inclusions within the cytoplasm of neutrophils and other leukocytes should lead to a clinical investigation of the setting for these findings.Atypical neutrophil inclusions may be seen in the following disorders: Chediak-Higashi syndrome, May-Hegglin anomaly, Alder-Reilly anomaly, Fechtner , Sebastian, Epstein and Alport-like syndromes and in infectious and toxic conditions (in the form of Doehle bodies).Although a specific entity may not be evident from examination of the peripheral blood alone, it is important that hematology technologists include a comment reporting on the presence of these inclusions or granules. A clinical investigation with further hematologic and genetic studies may then appropriately be considered.Many of the disorders with atypical neutrophil cytoplasmic granules are also associated with platelet abnormalities, particularly giant platelets (lower photograph).Therefore, when atypical granules are recognized, scanning of the peripheral blood smear for atypical platelets may be revealing. These observations serve as readily identifiable markers for acquired and genetic human maladies, and as a guide for unraveling the reasons for a patient's suffering and impaired health. | View Page |
| The pale-staining cytoplasmic bodies marked by the arrow in the photograph may be seen in each of the following conditions except: | View Page |
| Eosinophilia Follow-Up As mentioned on the previous page, high percentages of eosinophils may be present in the peripheral blood smears of patients with a variety of conditions--asthma, urticaria, Loeffler's syndrome, larval parasitic infections and in chronic eosinophilic leukemia. One exception to the association of eosinophilia with parasitic infections is a fatal case of disseminated strongyloidiasis reported many years ago by Miale (Hematology--5th Edition, Mosby, pg. 776, 1977) in which the peripheral blood eosinophilia was masked by the administration of corticosteroids. | View Page |
| The small club-shaped(drumstick)nuclear appendage attached to one lobe of a neutrophil (marked by the blue arrow in the photograph) may be found in: | View Page |