Joel C. Marrs, PharmD, FCCP, FASHP, FNLA, BCPS (AQ Cardiology), BCACP, CLS

• Associate Professor, University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences, Aurora, Colorado

http://www.ucdenver.edu/academics/colleges/pharmacy/Departments/ClinicalPharmacy/DOCPFaculty/H-P/Pages/MarrsJoelCPharmD.aspx

An extracellular matrix of fibronectin treatment math definition buy betoptic mastercard, collagen and laminin combine with these cells to provide a setting in which stem cells can grow and divide treatment jaundice buy betoptic 5ml amex. In the bone marrow medicine x 2016 buy betoptic from india, hemopoiesis occurs in the extravascular part of the red marrow which consists of a fine supporting reticulin framework interspersed with vascular channels and developing marrow cells medicine 2015 purchase betoptic overnight. A single layer of endothelial cells separates the extravascular marrow compartment from the intravascular compartment medications known to cause seizures safe 5 ml betoptic. When the hemopoietic marrow cells are mature and ready to circulate in the peripheral blood symptoms jaw pain betoptic 5 ml with visa, the cells leave the marrow parenchyma by passing through fine "windows" in the endothelial cells and emerge into the venous sinuses joining the peripheral circulation. Increased demands for cells as a consequence of disease or physiologic 14 Hematology change are met by increased cell production. In addition, there are several different cytokines that regulate hematopoiesis of different blood cell types. Cytokines are small glycoproteins produce by red bone marrow cells, leucocytes, macrophages, and fibroblasts. They act locally as autocrines or paracrines that maintain normal cell functions and stimulate proliferation. Formation of Red blood cells (Erythropoiesis) 17 Hematology Erythropoiesis is the formation of erythrocytes from committed progenitor cells through a process of mitotic growth and maturation. At the same time the nuclear chromatin pattern becomes more compact tan clumped until, at the level of the orthochromatophilic normoblast, there remains only a small dense nucleus, which is finally ejected from the cell. Pronormoblast (Rubriblast) Pronormoblast is the earliest morphologically recognizable red cell precursor. Nucleus: small and central or eccentric with condensed homogeneous structure less chromatin. Reticulocyte After the expulsion of the nucleus a large somewhat basophilic anuclear cell remains which when stained with new methylene blue, is seen to contain a network of bluish granules. As the bone marrow reticulocyte matures the network becomes smaller, finer, thinner, and finally within 3 days disappears. Regulation of Erythropoiesis Erythropoietic activity is regulated by the hormone erythropoietin which in turn is regulated by the level of tissue oxygen. Ineffective erythropoiesis/Intramedullary hemolysis Erythropoiesis is not entirely efficient since 10-15% of eryhtropoiesis in a normal bone marrow is ineffective, i. In megaloblastic erythropoiesis, the nucleus and cytoplasm do not mature at the same rate so that nuclear maturation lags behind cytoplasmic hemoglobinization. The mature neutrophil remains in the circulation for only about 10 to 14 hours before entering the tissue, where it soon dies after performing its phagocytic function. It has a thin nuclear membrane and finely dispersed, granular, purplish, pale chromatin with well-demarcated, pink, evenly distributed parachromatin: 2-5 light blue-gray nucleoli surrounded by dense chromatin are seen. Cytoplasm: the cytop la sm ic m a ss is sm a llin comparison to the nucleus, producing a nuclear/ cytoplasmic ratio of 7:1. It stains basophilic (bluish) and shows a small indistinct, paranuclear, lighter staining halo (golgi apparatus). It is round or oval, eccentric, possibly slightly indented, and surrounded by a thin membrane. The nuclear membrane is thick and heavy, and the chromatin is concentrated into irregular thick and thin areas. Band Granulocyte (Stab Cell) the juvenile cell or the band cell are the youngest granulocytes normally found in the peripheral blood. Cytoplasm: contains specific and a few non-specific granules and is pink or colorless. The neutrophilic granules are very fine in texture and do not overlay the nucleus. Nucleus: usually bilobed, rarely single or tri-lobed and 29 Hematology contains dense chromatin masses. It is difficult to see the nucleus because it contains less chromatin and is masked by the cytoplasmic granules. The chromatin is delicate blue to purple stippling with small, regular, pink, pale or blue parachromatin areas. Cytoplasm: Ab unda nt,op a que,gra y-b lue,a nd unevenly stained and may be vacuolated. The nuclear membrane is distinct and 33 Hematology one or two pink nucleoli are present and are usually well outlined. Cytoplasm: there is a thin rim of basophlic, homogeneous cytoplasm that may show a few azurophilic granules and vacuoles. Formation of platelets (Thrombopoiesis) Platelets are produced in the bone marrow by fragmentation of the cytoplasm of megakaryocytes. The precursor of the megakaryocyte-the megakaryoblast arises by a process of differentiation for the hemopoietic s t e m c e l l. The final stage of platelet production occurs when the mature megakaryocyte sends cytoplasmic projections into the marrow sinusoids and sheds platelets into the circulation. It takes approximately 5 days from a megakaryoblast to become a mature megakaryocyte. Cytoplasm: the cytoplasm form s a scanty, bluish, patchy, irregular ring around the nucleus. What are the hemopoietic tissues during fetal life, in infancy, in childhood and in adulthood Blood must be collected with care and adequate safety precautions to ensure test results are reliable, contamination of the sample is avoided and infection from blood transmissible pathogens is prevented. Unless an appropriately designed procedure is observed and strictly followed, reliability can not be placed on subsequent laboratory results even if the test itself is performed carefully. Care must be taken when handling especially, syringes and needles as needle-stick injuries are the most commonly encountered accidents. The composition of venous blood varies and is dependent on metabolic activity of the perfused organ or tissue. Increased pressure in the arterioles yields a specimen enriched in arterial blood. Venous Blood Collection A venous blood sample is used for most tests that require anticoagulation or larger quantities of blood, 47 Hematology plasma or serum. The veins in the antecubital fossa of the arm are the preferred sites for venipuncture. They are larger than those in the wrist or ankle regions and hence are easily located and palpated in most people. The gauge and the length of the needle used depend on the size and depth of the vein to be punctured. The point of the needle will thus be embedded in the stopper without puncturing it and loosing the vacuum in the tube. Identify the patient and allow him/her to sit 50 Hematology comfortably preferably in an armchair stretching his/ her arm. If the needle is properly in the vein, blood will begin to enter the syringe spontaneously. With the vacutainer system, remove the tube from the vacutainer holder and if the tube is with added anticoagulant, gently invert several times. It also frequently allows the performance of additional tests that may be suggested by the results of those already ordered or that may occur to the clinician as afterthoughts. The total leucocyte and neutrophil counts are higher by about 8% and the 54 Hematology monocyte count by 12%. Conversely, the platelet count appears to be higher by about 9% in venous than peripheral blood. The multiple sample needle used in the vacutainer method has a special adaptation that prevents blood from leaking out during exchange of tubes. Increased pressure in the arteries makes it more difficulty to stop bleeding with the undesired development of a hematoma. Arterial selection includes radial, brachial, and femoral arteries in order of choice. Do not eject the blood from the syringe through the needle as this may cause mechanical destruction of the cells. Blood should not be stored in a freezer because the red cells will hemolyse on thawing. What are the anatomical sites of collection in these sources in the different age groups How do you minimize or avoid the occurrence of hemolysis in blood samples for hematological investigations What is the difference between samples collected from these two sources in terms of hematological parameters The substances responsible for this removal or inactivation are called anticoagulants. While clotted blood is desirable for certain laboratory investigations, most hematology procedures require an anticoagulated whole blood. It is especially 60 Hematology the anticoagulant of choice for platelet counts and platelet function tests since it prevents platelet aggregation. It exerts its effect by tightly binding (chelating) ionic calcium thus effectively blocking coagulation. Balanced or double oxalate Salts of oxalic acid by virtue of their ability to bind and precipitate calcium as calcium oxalate serve as suitable anticoagulants for many hematologic investigations. Heparin Heparin is an excellent natural anticoagulant extracted from mammalian liver or pancreas. It is more expensive than the artificial ones and has a temporary effect of 62 Hematology only 24 hours. It is unsatisfactory for leucocyte and platelet and leucocyte counts as it causes cell clumping and also for blood film preparation since it causes a troublesome diffuse blue background in Wright-stained smears. Write the proportion of the volume of blood to the volume of each if these anticoagulants. Of course, in a laboratory without access to such automated information, the microscopic examination of the peripheral blood film is invaluable. Examination of the blood film is an important part of the hematologic evaluation and the validity or reliability of the information obtained from blood film evaluation, the differential leucocyte count in particular depends heavily on well-made and well stained films. While blood film preparation is a disarmingly simple straight forward procedure, there is abundant and continuing evidence that the quality of blood films in routine hematology practice leaves much room for improvement. Another slide, the spreading slide placed in front of the drop of blood at an angle of 300 to the slide and then is moved back to make contact with the drop. The drop will spread out quickly along the line of contact of the spreader with the slide. It is essential that the slide used as a spreader have a smooth edge and should be narrower in breadth than the slide on which the film is prepared so that the edges of the film can be readily examined. If the edges of the spreader are rough, films with ragged tails will result and gross qualitative irregularity in the distribution of cells will be the rule. If these are not available, writing can be done by scratching with the edge of a slide. Spinner method 70 Hematology Blood films that combine the advantages of easy handling of the wedge slide and uniform distribution of cells of the coverglass preparation may be made with special types of centrifuges known as spinners. This is of little practical significance, but it does result in slightly lower monocyte counts in wedge films. Preparation of thick blood smears Thick blood smears are widely used in the diagnosis of blood parasites particularly malaria. Five minutes spent in examining a thick blood film is equivalent to one hour spent in traversing the whole length of a thin blood film. Method Place a small drop of blood on a clean slide and spread it with an applicator stick or the corner of another slide until small prints are just visible through the blood smear. Principle of staining Acidic dyes such as eosin unites with the basic components of the cell (cytoplasm) and hence the cytoplasm is said to be eosinophilic (acidic). Conversely, basic stains like methylene blue are attracted to and combine with the acidic parts of the cell (nucleic acid and nucleoproteins of the nucleus) and hence these structures are called basophilic. Wright stain In its preparation, the methylene blue is polychromed by heating with sodium carbonate. Place the air-dried smear film side up on a staining rack (two parallel glass rods kept 5cm apart).

Lipofbromatous hamartoma of the median nerve: A comprehensive review and systematic approach to evaluation medicine world purchase betoptic pills in toronto, diagnosis medications during pregnancy chart discount betoptic 5ml with amex, and treatment symptoms gestational diabetes cheap betoptic online amex. Stringent delineation of Pallister-Hall syndrome in two long surviving patients: Importance of radiological anomalies of the hands medications parkinsons disease order betoptic without prescription. They appear within the frst few days or weeks of birth as a solitary cutaneous lesion that progressively enlarges over months and then slowly regresses medications errors discount betoptic 5 ml without prescription. Dorsal surfaces were involved more commonly than ventral on both the upper and lower extremities treatment coordinator buy betoptic 5ml low price. This proliferation produced an uplifting and an overcurva ture of the nail in both the longitudinal and transverse axes, giving it a pseudoclubbing appearance. The nail matrix was only uplifted and not damaged by the vascular tumor and the nail plate was completely normal. For this reason, a regular monitoring of the spontaneous regression is probably a better approach than any other treatment. They are most frequently found on the abdomen, lower limbs, trunk, head, and neck and less frequently on the upper limb. Clinically, it has a violaceous color, with a nodular growth pattern mimicking a malignant tumor. Because of the effect on function of the fnger and the potential for progressive growth of the lesion, a second surgical excision was performed and the defcit was covered with a mini free vascularized groin fap. Cutaneous lesions are violaceous to brown-red papules or plaques ranging from a few millimeters to 5 cm. Curettage and grafting of the tumor using autogenous bone from the iliac crest were performed. Microscopically the tumor consisted of atypical epithelioid cells forming a nest in a hyalinized back ground and vascular channels. The resection of the entire middle phalanx with surrounding soft tissues including the fexor tendon sheath was performed. It starts around the nail with a tiny red papule, which rapidly grows to reach the size of a few to 10 mm in diameter. Tenderness and a ready tendency to bleed are characteristic features of this tumor. Immobilization, hypoxia, and drugs might have acted as potential causative factors. Vascular Malformations Vascular malformations are divided into four groups: simple malformations, combined malformations, malformations of major named vessels, and malformations associated with other anomalies. The combined vascular malformations are named specifcally for the vessels involved in the malformation. They may be associated with soft tissue or bone overgrowth and with other vascular and nonvascular anomalies and syndromes. When they involve a whole limb, they are usually darker in acral location such as the hands and feet. There was an association between extent of staining (number of regions involved) and soft tissue syndactyly. Evaluation of the neu roaxis for fast-fow lesions is usually recommended, but further studies are needed to examine the optimal approach to screening patients and family members for internal arteriovenous lesions. They frequently appear early in life but may be subtle during childhood necessitating careful examination. They are most evident on the lips, tongue, face, and fngers, and the nasal and buccal mucosa. They appear as pink to red, pinpoint to pinhead-size lesions, or occasionally as larger, even raised purple lesions. Various associated congenital anomalies have been reported, and among these, hypertrophy or atrophy of affected limb is one. The described anomalies include shortened fngers and toes, loss of terminal phalanges, syndactyly, clubfoot, absence of toes or limbs, and hypoplastic nails. They are usually present at birth and grow proportionately with the child, but in many cases, particularly those with predomi nantly intramuscular disease, these are often present later in life with pain provoked by physical activity. No case of blue rubber bleb nevus of the fnger extremities or nail has been specifcally reported in the literature, but blue rubber bleb nevus of the hand and fngers may be accompanied by leukonychia. However, recurrence due to recruitment of reconstituted arterial fow into the nidus, repeated surgery, and even deformity requiring amputation are common problems. The exci sion is diffcult because there is a risk to damage the normal vascularization of the digit, with subsequent development of ischemia or necrosis. Thus, there is a need for long-term observation of these patients, even after apparent remission. They can manifest at birth or later in life by chronic, unilateral or bilateral edema involving the dorsum of the foot, sometimes extending above the knee. However, such a detailed ungual examination has never been reported in children with congenital lymphedema. Combined Vascular Malformations Combined vascular malformations associate two or more vascular malformations in one lesion. Vascular Malformations Associated with Other Anomalies Vascular malformations may be associated with anomalies of bone, soft tissue, or viscera. In addi tion, he had macrodactyly of the frst, second, and third toes with small nails, and cutaneous syndactyly of the second and third toes of the ipsilateral foot. Local temperature is increased, a pulse or thrill can be palpated, and a murmur is heard on auscultation. The enlargement of a limb is present at birth, and the axial overgrowth can enlarge in postnatal period. Toes involvement is frequent, depending on the extent of the lesions, with hypertro phy and secondary trophic changes of toes and nails. Compression therapy is used to reduce symptoms of chronic venous insuffciency and lymphatic edema. Skin lesions are blue, noncompressible, subcutaneous or cutaneous nodules, typically occurring on the fngers or feet. The malformation is of venous type, but it is histologically a spindle cell hemangioendothelioma. Radiographic signs are nearly pathognomonic, with multiple enchondromas associated with soft tissue swelling and phleboliths. It enlarged with the concomitant appearance of several black dots at the periphery. It generally occurs in children and the majority of patients are females and most lesions are located on the upper or lower extremities. Diffuse capillary malformation with overgrowth: A clinical subtype of vascular anomalies with hypertrophy. Value of capillary microscopy in the diagnosis of hereditary hemorrhagic telangiectasia. Radical resection of a venous malformation in middle fnger and immediate recon struction using medial plantar artery perforator fap: A case report. Collection of rare anomalies: Multiple digital glomuvenous malformations, epidermal naevus, temporal alopecia, heterochromia and abdominal lipoblastoma. Cutaneous lymphatic malformations in disappearing bone (Gorham-Stout) disease: A novel clue to the pathogenesis of a rare syndrome. Klippel-Trenaunay syndrome in a boy with concomitant ipsilat eral overgrowth and undergrowth. Verrucous hemangioma: A clinicopathological and immunohistochemical analysis of 74 cases. Two objective measures for diagnosing early clubbing have been proposed: the digital index and the phalangeal depth ratio. It results from the accumulation of connective tissues and increased vascularity between the matrix and the periostium. A review of systems should focus on constitutional, pulmo nary, gastrointestinal, and musculoskeletal symptoms for the evidence of malignancy, infection, or infammation. Leukonychia striata has been described independently of orange-brown chromonychia and may be partial, with discoloration localized to the proximal part of the nail. The follow-up results were different in the two series, as capillary changes were still present in the follow-up in one study,11 whereas they were normalized in the second, with only edema still present after 6 months. The circumscribed ecchymosis of skin and the symmetrical gangrene of the extremities (Figure 11. The three features are not always present together and the diagnosis can be done when two of them are present and even nail changes alone can be enough for diagnosis. Tissue trans glutaminase seems to be the predominant autoantigen both in the intestine and in the skin. Generalized osteoporosis, urticaria, and koilonychia were reported as unusual fndings in a series of fve children with liver cell adenoma. Nail Changes in Renal Transplant Recipients A study on 302 kidney transplant patients, which included children above the age of 11, found nail changes in about 40% of the patients. Among the few cases reported in the literature, two had digital gangrene of the toes that, in one case, led to amputation. Avascular areas are more common in patients with type 1 diabetes complications and indicate microvascular disease (retinopathy or microalbuminuria), while microhemorrhages are common in children with recently elevated HbA1c. Typical clinical features include short stature, rounded face, shortened fourth metacarpals and other bones of the hands and feet, obesity, dental hypoplasia, and soft-tissue calcifcations/ossifcations. Brachydactyly, broad thumb, and nail pitting were reported in a child with pseudohypoparathyroidism and visual disturbances. Thyroid acropachy is a triad consisting of digital clubbing, soft-tissue swelling of the hands and feet, and periosteal new bone formation. Reticular hyperpigmentation of the skin and nail changes usually appear frst, often below the age of 10 and then bone marrow failure develops frequently below the age of 20, with up to 80% of patients showing signs of bone marrow failure by the age of 30. Mucosal leukoplakia is a pathognomonic feature and occurs in approximately 80% of patients. Capillary abnormalities can be seen in several diseases of different etiology, but they are typical of autoimmune rheumatic diseases, where capillary changes are similar to those seen in adults. These patients were diffcult to diagnose as the clinical and laboratory fnd ings were consistent for an adult-onset Still disease or systemic juvenile idiopathic arthritis sine arthritis. Nail changes may be due to oppor tunistic fungal infections, especially due to Candida, with total onychomycosis often associated with periungual infammation. Extensive Trichophyton rubrum infection of the skin with onychomycosis of the fngernails and toenails is also reported. In children and adolescents, acquired zinc defciency can result from decreased dietary intake, due to low breast milk zinc levels, anorexia nervosa, total parenteral nutrition, or diet high in cereal grains and low in meats. Cutaneous manifestations secondary to the sensory and autonomic damage of the median nerve fbers are rare, unilateral, and associated with long-standing severe cases. Severe biting injuries of the fngertips appear at the time of tooth eruption and include nail and pulp injuries with skin scarring and fnger mutilations. They are more common in the toenails and usually arise from the proximal nail fold, appearing as pink fliform or nodular skin-colored masses. Compression of the underlying nail matrix produces a longitudinal groove in the nail plate (Figure 11. Other skin changes may be related to concomitant drug consumption or self-aggressing behaviors, which are seen very often in young patients with eating disorders. Drug-induced nail changes usually involve several or all 20 nails and appear in temporal correlation with drug intake. Some nail changes are asymptomatic and only cause cosmetic problems, while others cause pain and discomfort. Cancer chemotherapeutic agents are reported to induce nail changes in about 10% of the children. Longitudinal or total melanonychia, sometimes associated with skin hyperpigmentation, is a common side effect of hydroxyurea in children, being reported in up to 10% of thalassemic children receiving the drug (Figure 11. Reversal of digital clubbing after lung transplantation in cystic fbrosis patients: A clue to the pathogenesis of clubbing. Development and assessment of a new early scoring system using non-specifc clinical signs and biological results to identify children and adult patients with a high prob ability of infective endocarditis on admission. Unilateral clubbing as a clinical manifesta tion of lower limb venous malformation. Rhabdomyosarcoma associated hypertrophic osteoarthropathy in a child: Detection by bone scintigraphy.

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Syndromes

• Joint pain
• Electromyogram (EMG, a recording of electrical activity in the muscles)
• Childhood disintegrative disorder (rare condition where a child learns skills, then loses them by age 10)
• ·   Avoid dairy products.
• Having a partner or many partners who are active in high-risk sexual activities
• Frequent need to urinate at night
• Fatigue
• Infection (pneumonia, bloodstream infection, peritonitis)
• Fever