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By O. Armon. Southern Methodist University. 2019.

Molecular structure of the cephalosporins registered for use in animal practice including their hydrolysis product buy generic malegra dxt plus 160mg. There is no general answer to this question buy malegra dxt plus 160mg with visa, because this highly depends on the purpose of the method in question generic malegra dxt plus 160 mg otc. In chapter 2 it was elaborated that selectivity is related to the sample clean-up and that usually a tradeoff between selectivity and the number of compounds included in the method occurs. The result can be compared to a threshold value but no sharp boundary between ‘selective’ and ‘non-selective’ exists. Because consequences of a non- compliant result for banned substances are higher than for a non-compliant finding of a registered substance, this is an acceptable concept. A second consideration in the selectivity needed is the kind of interferences that can be expected. In monitoring programs, usually a broad screening is carried out first, followed by a confirmatory analysis of suspect samples. Ideally, a screening analysis focusses on a broad range of compounds, which compromises selectivity as was discussed in chapter 2. A confirmatory method should by definition result in an unequivocal identification and thus a high selectivity is mandatory. Future perspectives on monitoring programs and their effects on selectivity are further discussed in this chapter. An example of a method in which selectivity is intentionally compromised is the analysis of ß-lactams as presented in chapter 5. Because, ceftiofur metabolises rapidly, off-label use is best detected if protein-bound residues are included. By definition, when applying a derivatization, selectivity is compromised: instead of the drug focused at, a derivative is detected and thus the method is not able to differentiate the parent drug from other drugs that result in the same derivative. It is concluded that selectivity should be fit for purpose and therefore remains a matter of experts’ judgment. The obtained result is the basis for determining if selectivity is adequate and thus the described procedure is highly valuable when the selectivity of the confirmatory method is challenged in a court case. When selectivity is considered inadequate, additional methods or techniques can be applied to increase method selectivity. First techniques that in my view are highly valuable to further increase selectivity are presented and discussed. As a result, instead of aiming for the detection of just one compound or compounds from a single antibiotic group, multi-compound methods are being developed that include different antibiotic groups. As a result extraction and sample-clean-up procedures have become more generic and selectivity is compromised. Using specific software tools and applying an additional internal calibration, mass accuracy is enhanced to even sub-ppm errors [12,17-19]. For instance, only a few elemental compositions are possible for a compound at m/z = 100. It was concluded that at a higher mass range, a better mass accuracy is required for unequivocal identification compared to the lower mass range. However, this conclusion was based upon the theoretical mathematical number of elemental compositions possible, instead of upon the number of existing molecules or chemically possible elemental compositions. When applying these rules, the number of optional molecular formulas can be severely limited. Logically the number of peaks fitting in a spectrum is proportional to the mass resolution. The reported approach is highly theoretical and some important issues are overlooked. First, the chance of the occurrence of precursor masses is unequally distributed over the mass range as demonstrated in chapter 3. Second, as was also presented in chapter 3, not all product ions are as likely, as a matter of fact some product ion masses are impossible. Third, it is suggested that selectivity is related to the selected scan range, which is not the case. The probability distribution of the precursor ion m/z at 2 ppm mass accuracy is presented in figure 6. Probability distribution of the precursor ion m/z at 2 ppm mass accuracy over a m/z range of (a) 100 – 1000 and (b) 350 – 353. The separation is based on different drift velocities (mobility) of compounds in low and high electric fields and enables differentiation by mass, charge and collision cross section (derived from structural parameters of size, shape, and the charge location or distribution) [27]. Therefore it is a separation mechanism that is orthogonal to liquid chromatography and mass spectrometry [28,29]. The ions in the drift region move toward a detector down a voltage gradient through a gas −1 −1 atmosphere. Velocities in electric fields of 300 V cm are often 2 m s, so a spectrum can be generated every 5 to 25 ms. The velocity of the ions (drift velocity, vd) is proportional to the strength of the electric field (E) with the vd mobility (K) of the ions being constant: K= [27,30-33]. While waiting for previously injected ions to separate, many ions are being discarded. The different ion mobility during the application of high and low electric fields causes the ions to drift toward one of two electrodes. A compensation voltage is applied to correct the trajectory of targeted ions along the radial axis and thus to avoid ion discharge. As a drawback, the addition of the chiral modifier to the drift gas reduced the mobility of both enantiomers and thus cycle times severely increase [34]. As a result the selection 295 of product ions used for quantitation and confirmation becomes less critical and more abundant product ions can be selected for monitoring. In some cases these are not baseline separated, which negatively influences the automatic peak integration performance. As a result, the integration should be checked carefully and additional manual integration is usually mandatory. As a result, besides the gain in selectivity, the quantitation process is simplified and more robust. In the off-line mode two chromatographic systems with orthogonal separation principles are used of which the first chromatogram is fractionated using a fraction collector and each fraction is subsequently injected in the second chromatographic system. The first challenge mainly relates to solvent incompatibility, which is usually caused by solvent immiscibility or because a strong solvent in one mode is a weak solvent in the other [49]. While the second dimension separation takes place, a new fraction is collected in the first dimension. However, this is not the case due to inefficient transfer of separated compounds from one dimension to the other resulting in remixing of the compounds [50]. Two parallel columns can be used for the second dimension to limit the fractions collected in the first dimension [52]. It may be possible to develop a single system that is able to analyse all major antibiotic groups (including the highly polar aminoglycosides) within a single run. The supercritical state occurs when pressure and temperature are both above the thermodynamic critical point.

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Anemia in biological characteristics/Acute leukemia/1 acute leukemia is usually present from the onset and may be severe; however malegra dxt plus 160mg free shipping, there is no inherent 2 buy generic malegra dxt plus 160mg on-line. Which type of anemia is usually present in a nutritional deficiency leading to either a microcytic purchase malegra dxt plus 160mg line, patient with acute leukemia? Normocytic, normochromic red cells is called leukoerythroblastosis and frequently D. In leukemia, which term describes a peripheral blood finding of leukocytosis with a shift to the 4. D A normal physiological response to anemia would left, accompanied by nucleated red cells? Te basic pathophysiological mechanisms responsible for producing signs and symptoms in leukemia include all of the following except: A. Decreased erythropoietin production Hematology/Correlate clinical and laboratory data/ Leukemia/2 21 22 Chapter 1 | Hematology 5. Which type of acute myeloid leukemia is called Answers to Questions 5–9 the true monocytic leukemia and follows an acute or subacute course characterized by monoblasts, 5. Acute myeloid leukemia, minimally differentiated distinctive clinical manifestation of monocytic B. Acute myeloid leukemia without maturation involvement resulting in skin and gum hyperplasia. B A disproportionate increase in the myeloid most often associated with which of the following component of the bone marrow is usually the types of acute leukemia? Acute myeloid leukemia without maturation approximately 4:1 in adults with normal cellularity. Acute monocytic leukemia cytoplasm of myeloblasts and monoblasts in Hematology/Evaluate laboratory data to recognize patients with acute leukemia. Myelofibrosis Hematology/Evaluate laboratory data to recognize health and disease states/Bone marrow/M:E/2 9. Tey are nonspecific esterase positive Hematology/Apply knowledge of fundamental biological characteristics/Leukocytes/Auer rods/1 1. Acute myelomonocytic leukemia Leukocytes/Cytochemical stains/2 Hematology/Evaluate laboratory data to make identifications/Leukemia/3 Answers to Questions 10–14 11. C In acute erythroid leukemia, more than 50% of with a fever, pallor, lymphadenopathy, and nucleated bone marrow cells are erythroid and more hepatosplenomegaly. Tese stain positive for both Sudan Black B are characteristically negative with these stains. C Phospholipids, neutral fats, and sterols are stained by of the following disorders is most likely? The addition of fluoride renders the monocytic cells (and blasts) negative, thus allowing for differentiation from the granulocytic cells, which remain positive. Any percentage health and disease states/Leukemia/Immunochemical Hematology/Apply knowledge of special procedures/ reactions/2 Leukemias/Classifications/2 16. A patient’s peripheral blood smear and bone prognosis than other immunologic subtypes of marrow both show 70% blasts. Hematology/Apply principles of special procedures/ Leukemia/Cytochemical stains/2 17. Acute myeloid leukemias with recurrent genetic of megakaryoblasts and atypical megakaryocytes. Acute megakaryoblastic categorized leukemia is defined as an acute leukemia in which D. Acute leukemias of ambiguous lineage greater than or equal to 50% of the blasts are of Hematology/Apply knowledge of special procedures/ megakaryocytic lineage. Hematology/Evaluate laboratory data to recognize Iron deficiency anemia is a predictable complication health and disease states/Anemia/2 of therapeutic phlebotomy because approximately 2. In essential thrombocythemia, the platelets are: 250 mg of iron is removed with each unit of blood. Decreased in number and functional function, leading to both bleeding and thrombotic D. Which of the following cells is considered It is a large, binucleated cell with a dense nucleolus pathognomonic for Hodgkin’s disease? Flame Hematology/Evaluate laboratory data to recognize cells are plasma cells with distinctive red cytoplasm. In myelofibrosis, the characteristic abnormal red blood cell morphology is that of: 4. Features of secondary polycythemia include all of Answers to Questions 6–11 the following except: A. Erythropoietin is increased and oxygen saturation is decreased in secondary Hematology/Evaluate laboratory data to recognize polycythemia. Te erythrocytosis seen in relative polycythemia plasma rather than an increase in red blood cell occurs because of: volume or mass. Decreased plasma volume of circulating blood levels are high only in secondary polycythemia. Hematology/Apply knowledge of fundamental biological characteristics/Polycythemia/1 10. All of these options Hematology/Evaluate laboratory data to recognize health and disease states/Myeloproliferative neoplasms/3 28 Chapter 1 | Hematology 12. What influence does the Philadelphia (Ph1) Answers to Questions 12–17 chromosome have on the prognosis of patients with chronic myelocytic leukemia? Te prognosis is better if Ph1 is present arm deletion of chromosome 22, but is actually C. Te prognosis is worse if Ph1 is present a translocation between the long arms of D. This results in production Hematology/Evaluate laboratory data to recognize of a chimeric protein with tyrosine kinase activity health and disease states/Genetic theory and that activates the cell cycle. An increase in basophils An increase in basophils and eosinophils is a Hematology/Evaluate laboratory data to recognize common finding. Multiple myeloma and Waldenström’s macroglobulinemia have all the following in common except: A. Osteolytic lesions Hematology/Evaluate laboratory data to recognize health and disease states/Myeloma/Characteristics/2 1. What is the characteristic finding seen in the Answers to Questions 18–22 peripheral smear of a patient with multiple myeloma? All of the following are associated with the the triad of diagnostic markers for multiple myeloma. Serum and/or urine M component (monoclonal a lower concentration of monoclonal protein is protein) usually seen. Philadelphia chromosome plasma cells comprise less than 10% of nucleated Hematology/Correlate clinical and laboratory data/ cells in the bone marrow.

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More than 98% of affected infants have elevated sweat sodium and chloride and low serum levels purchase malegra dxt plus 160 mg. When performing a sweat chloride collection malegra dxt plus 160 mg amex, Answers to Questions 68–70 which of the following steps will result in analytical error? Using unweighed gauze soaked in pilocarpine of pilocarpine to stimulate sweating purchase malegra dxt plus 160mg with amex, and the use nitrate on the inner surface of the forearm to of iontophoresis (application of 0. Collecting more than 75 mg of sweat in iontophoresis, the skin on the inner surface of the 30 minutes forearm is washed with deionized water and dried, C. Rinsing the collected sweat from the gauze pad gauze must be completely covered to prevent using chloride titrating solution contamination and loss of sweat by evaporation. Chemistry/Apply knowledge of fundamental biological A minimum mass of 75 mg sweat is required for characteristics/Electrolytes/2 collection in gauze and 15 μL sweat for collection in macroduct tubing. Chemistry/Calculate/Osmolality/2 Because sodium associates with a counter ion, two times the sodium estimates the millimoles per liter of electrolytes. Dividing glucose by 18 converts from milligrams per deciliter to millimoles per liter. Which of the following biochemical processes is Answers to Questions 1–3 promoted by insulin? Uptake of glucose by cells enzymes, and inhibits formation of glucose from Chemistry/Apply knowledge of fundamental biological pyruvate and Krebs cycle intermediates. Which of the following hormones promotes gluconeogenesis and epinephrine stimulates hyperglycemia? Chemistry/Apply knowledge of fundamental biological Aldosterone is the primary mineralocorticoid hormone characteristics/Carbohydrates/1 and stimulates sodium reabsorption and potassium 3. Requires an oral glucose tolerance test for promotes activation of angiotensinogen and diagnosis aldosterone secretion. Type 1 accounts for only Chemistry/Correlate clinical and laboratory data/ about 10%–20% of cases of diabetes mellitus, Biological manifestation of disease/2 and is usually diagnosed by a fasting plasma glucose. Approximately 95% of patients produce autoantibodies against the beta cells of the pancreatic islets. Which of the following is characteristic of Answers to Questions 4–7 type 2 diabetes mellitus? Hyperglycemia is often controlled without obese and over 40 years of age, although the insulin replacement incidence is increasing in both children and young D. Which of the following results falls within the prevent ketosis and hyperglycemia can be controlled diagnostic criteria for diabetes mellitus? Two-hour plasma glucose of 180 mg/dL following criteria for diagnosing diabetes mellitus: following a 75 g oral glucose challenge fasting glucose ≥ 126 mg/dL, casual (random) D. Random plasma glucose of 250 mg/dL and glucose ≥ 200 mg/dL in the presence of symptoms presence of symptoms (polyuria, increased thirst, weight loss), glucose Chemistry/Evaluate laboratory data to recognize health ≥ 200 mg/dL at 2 hours after an oral dose of 75 g of and disease states/Carbohydrates/2 glucose, and hemoglobin A1c ≥ 6. Select the most appropriate adult reference range of diabetes mellitus is indicated if any one or for fasting blood glucose. Te patient remains ambulatory for 3 days prior for impaired fasting plasma glucose (prediabetes) to the test recommended by the American Diabetes Association. No food, coffee, tea, or smoking is allowed associated clinical hypoglycemia, and neonates have a 8 hours before and during the test lower limit of approximately 40 mg/dL owing to D. Such and disease states/Glucose tolerance/2 persons are classified as having prediabetes and 9. Is diagnosed using the same oral glucose such as respiratory distress syndrome, high birth tolerance criteria as in nonpregnancy weight, and neonatal jaundice. Converts to diabetes mellitus after pregnancy usually screened between 24 and 28 weeks’ in 60%–75% of cases gestation. Presents no increased health risk to the fetus nonfasting and consists of an oral 50-g glucose D. Is defined as glucose intolerance originating challenge followed by serum or plasma glucose during pregnancy measurement at 1 hour. A result ≥ 140 mg/dL is Chemistry/Evaluate laboratory data to recognize health followed by a 2-hour or 3-hour oral glucose and disease states/Glucose tolerance test/2 tolerance test to confirm gestational diabetes. Which of the following findings is characteristic the 3-hour test, a 100-g dose of glucose is used of all forms of clinical hypoglycemia? A fasting blood glucose value below 55 mg/dL exceeded: fasting, ≥ 95 mg/dL or higher; 1 hour, B. Neuroglycopenic symptoms at the time of low higher; 3 hour, ≥ 140 mg/dL or higher. C Clinical hypoglycemia can be caused by insulinoma, drugs, alcoholism, and reactive hypoglycemia. Reactive hypoglycemia is characterized by delayed or excessive insulin output after eating and is very rare. High fasting insulin levels (usually > 6 μg/L) are seen in insulinoma, and patients with insulinoma almost always display fasting hypoglycemia, especially when the fast is extended to 48–72 hours. In hypoglycemia, low levels indicate an exogenous insulin source, whereas high levels indicate overproduction of insulin. Which statement regarding glycated (glycosylated) Answers to Questions 11–14 Hgb (G-Hgb) is true? C G-Hgb results from the nonenzymatic attachment of the β chain a sugar such as glucose to the N-terminal valine of B. Will be abnormal within 4 days following an are three G-Hgb fractions designated A1a, A1b, and episode of hyperglycemia Alc. Hemoglobin A1c makes up about 80% of glycated hemoglobin, and is used to determine Chemistry/Correlate laboratory data with physiological the adequacy of insulin therapy. The time-averaged processes/Glycated hemoglobin/2 blood glucose is approximated by the formula 12. A glycated hemoglobin test should Chemistry/Evaluate laboratory data to recognize health be performed at the time of diagnosis and every and disease states/Glucose/2 6 months thereafter if the result is < 6. Levels do not need to be done fasting performed every 3 months until control is B. Samples should be measured within 2 hours of 2–3 months prior to blood collection, the dietary collection status of the patient on the day of the test has no D. Refrigerated whole-blood Chemistry/Apply knowledge to recognize sources of samples are stable for up to 1 week. Hgb A is 1C error/Glycated hemoglobin/2 assayed by cation exchange high-performance liquid chromatography or immunoassay 14. Which stationary phase is used for the (immunoturbidimetric inhibition) because both measurement of hemoglobin A1c by high methods are specific for stable Hgb A1C, and do performance liquid chromatography? Normal hemoglobin A has a weak positive charge at an acidic pH and binds weakly to the resin. Glycated hemoglobin has an even weaker positive charge and is eluted before hemoglobin A.

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The myelin sheath covering the axons in the cen- tral nervous system is formed by oligodendrocytes Neuroglia rather than Schwann cells buy malegra dxt plus 160 mg free shipping. Oligodendrocytes do not The term neuroglia literally means nerve glue produce neurilemma order 160mg malegra dxt plus with visa, thus injury or damage to neu- because these cells were originally believed to serve rons located in the central nervous system is irrepara- only one function: to bind neurons to each other ble buy discount malegra dxt plus 160mg on-line. They are now known to segments of myelin sheath are called (8) nodes of supply nutrients and oxygen to neurons and assist Ranvier. They also play an impulses down the axon because an impulse jumps important role when the nervous system suffers across the nodes at a faster rate than it is able to trav- injury or infection. They provide three-dimensional Impulses must travel from the (10) axon terminal mechanical support for neurons and form tight of one neuron to the dendrite of the next neuron or sheaths around the capillaries of the brain. Anatomy and Physiology 429 sheaths provide an obstruction, called the blood- of the brain and spinal cord. The brain is protect- brain barrier, that keeps large molecular substances ed by the bony skull and the spinal cord is protect- from entering the delicate tissue of the brain. Researchers must take the the body, the brain is highly complex in structure blood-brain barrier into consideration when and function. Microglia, the smallest of • cerebellum the neuroglia, possess phagocytic properties and • diencephalon may become very active during times of infection. Ependyma are ciliated cells that line fluid-filled cavities of the central nervous system, especially Cerebrum the ventricles of the brain. Nervous System Divisions The fissure does not completely separate the The nervous system consists of two main divisions: hemispheres. A structure called the (2) corpus cal- the central nervous system and the peripheral nerv- losum joins these hemispheres, permitting com- ous system. Its nervous tissue is classi- The cerebral surface consists of numerous folds, fied as white matter or gray matter. The gyri are separated axons with their white lipoid myelin sheath consti- by furrows or fissures called sulci. A thin layer tutes white matter and unmyelinated fibers, den- called the cerebral cortex covers the entire cere- drites, and nerve cell bodies make up gray matter brum and is composed of gray matter. Table 14-1 Nervous System Structures and Functions This table lists the structures of the nervous system along with their functions. The cerebellum also aids in maintaining equilib- perception and interpretation, language, voluntary rium and balance. Diencephalon The (8) diencephalon (also called interbrain) Cerebellum is composed of many smaller structures, includ- The second largest structure of the brain, the ing the thalamus and the hypothalamus. The (7) cerebellum, occupies the posterior portion of (9) thalamus receives all sensory stimuli except the skull. All functions of the cerebellum involve olfactory and processes and transmits them to Anatomy and Physiology 431 the appropriate centers in the cerebral cortex. In dense, and composed primarily of connective tis- addition, the thalamus receives impulses from sue. Because of its thickness, this membrane is also the cerebrum and relays them to efferent nerves. A sub- arachnoid space contains cerebrospinal fluid, a Brainstem colorless fluid that contains proteins, glucose, urea, The brainstem completes the last major section of salts, and some white blood cells. It is composed of three structures: the lates around the spinal cord and brain and through (11) midbrain (also called mesencephalon), separating ventricles located within the inner portion of the the cerebrum from the brainstem; the (12) medulla, brain. It provides nutritive substances to the cen- which attaches to the spinal cord; and (13) the pons, tral nervous system and adds additional protection or “bridge,” connecting the midbrain to the medulla. Normally, cerebrospinal fluid is absorbed conduction between the brain and spinal cord. The as rapidly as it is formed, maintaining a constant brainstem is the origin of 10 of the 12 pairs of cranial fluid volume. Any interference with its absorption nerves and controls respiration, blood pressure, and results in a collection of fluid in the brain; a condi- heart rate. This ing heart in a fetus) and the end of life (the cessation membrane directly adheres to the brain and spinal of respiration and heart activity) it is sometimes cord. It contains numerous blood vessels and lymphatics that nourish the Spinal cord underlying tissues. Because of the thinness and The spinal cord transmits sensory impulses from delicacy of the arachnoid and pia mater, these two the body to the brain and motor impulses from the meninges are collectively called the leptomeninges. The sen- Peripheral Nervous System sory nerve tracts are called ascending tracts because the direction of the impulse is upward. A cross-section of the consists of 12 pairs of cranial nerves and 31 pairs spinal cord reveals an inner gray matter composed of spinal nerves. The somatic nervous system consists of nerve The entire spinal cord is located within the fibers that transmit sensory information to the spinal cavity of the vertebral column, with spinal brain and spinal cord, and nerve fibers that trans- nerves exiting between the intervertebral spaces mit impulses from the brain and spinal cord to throughout almost the entire length of the spinal muscles under conscious or voluntary control, such column. The specific names, the spinal nerves are identified by autonomic nervous system consists of nerves that the region of the vertebral column from which control involuntary movement, such as digestion, they exit. To a large extent, tion from three coverings called meninges (singu- these subdivisions oppose the action of the other, lar, meninx). These coverings include the dura although in certain instances, they may exhibit mater, arachnoid, and pia mater. In general, The dura mater is the outermost covering of the sympathetic subdivision produces responses the brain and spinal cord. An increases in skeletal muscles to prepare an individ- example of a mixed nerve is the facial nerve. It acts ual to either fight or retreat from a threatening in a motor capacity by transmitting impulses for situation. However, it also acts in a sen- generally responds when immediate action is sory capacity by transmitting taste impulses from not required or a threatening situation subsides. This subdivision is sometimes called the “rest and relax” or “rest and digest” condition. Sensory nerves are attachment to the spinal cord: an anterior (ven- afferent, and receive impulses from the sense tral) root and a posterior (dorsal) root. Some to form the spinal nerve that has both afferent and cranial nerves are composed of both sensory and efferent qualities. Table 14-2 Actions Regulated by Sympathetic and Parasympathetic Systems This table summarizes some of the responses regulated by the sympathetic and parasympathetic divi- sions of the peripheral nervous system. Sympathetic Division Parasympathetic Division Dilates pupils Constricts pupils Inhibits the flow of saliva Increases the flow of saliva Relaxes bronchi Constricts bronchi Accelerates heart rate Slows heart rate Slows digestive activities Accelerates digestive activities Constricts visceral blood vessels Dilates visceral blood vessels Anatomy and Physiology 433 Connecting Body Systems–Nervous System The main function of the nervous system is to identify and respond to internal and external changes in the environment to maintain homeostasis. Specific functional relationships between the nervous system and other body systems are discussed below. Blood, Lymph, and Immune Genitourinary • Nervous system identifies changes in • Nervous tissue in reproductive organs blood and lymph composition and pro- receives pleasure responses. Cardiovascular Integumentary • Nervous tissue, especially the conduction • Sensory nervous system supplies recep- system of the heart, transmits a contrac- tors in the skin that respond to environ- tion impulse. Digestive Musculoskeletal • Nervous stimuli of digestive organs propel • Nervous system provides impulses for food by peristalsis. It is time to review nervous system structures by completing Learning Activity 14–1.

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