We feel that authors should be encouraged to strive for publication in the peer-reviewed literature rather than trade publications and news magazines cheap metoprolol master card. Appendices Another of the challenges in this report to do with retrieval of studies from the bibliographic databases and also for abstraction and combining data order metoprolol 12.5mg with mastercard, were inconsistencies in the use of terminology cheap 25 mg metoprolol with mastercard. In the pharmaceutical world benefit can be thought of as being “can it work” often under ideal situations (i cheap 100mg metoprolol otc. Impact, or pragmatic studies, refer to measuring the effect of an intervention in the real world. Trials of this nature are complex, long- term, have large numbers of people/situations being studied, and are done on mature and well- functioning systems. Their location is likely best at those centers in the United States that have established and mature health care systems that have solid support for technology, strong research teams, experience with qualitative and quantitative methods and expertise in collaborative projects that include clinicians, experienced informaticians, and patients and their families. Cost and economics are complex issues and important to many people, groups, organizations, and governments. Well- designed studies with an economic evaluation component included, is the best way to move forward in this area. Many studies have provided cost data, but useful economic data involves far more input. An 446 example of a cost study with data that is limited in its use is by Chisolm and colleagues, who did a before-after study of children with asthma in a children’s hospital. In addition, we identified gaps in research quality centering on research design and analysis. Many of the major endpoints sought were found to show positive and statistically significant improvements, especially those that dealt with process and issues related to use, usability, knowledge, skills, and attitudes. We also identified gaps in the study of the phases of medication, people involved, locations of studies, and research methods. They have found that studies assessing the benefits of the technologies in process and clinical outcomes are far more frequent than those assessing the return on investment. This trend is supported by the considerable evidence presented in the current report; while we include numerous studies assessing process changes and clinical outcomes, the body of evidence on cost- effectiveness is sparse. A number of barriers to measuring return on investment in health technologies exist. Technologies do not result in a direct income stream and the benefits often accrue to organizations other than the ones making the investment as, for example, clinical benefit to patients and financial benefits to payers rather than the hospitals making the 785 investments. Certainly the body of literature looking at return on investment for the various technologies covered in this report, across the various settings, is very limited. We recognize that this framework does not include patients as an element, but we believe that the framework could be applied to the patient perspective and incorporate value propositions for patients where applicable. The required information to make an assessment of benefits is different depending on the stakeholder. The costs incurred by primary care physicians in practice will be different and balanced against different organizational benefits than those incurred in hospitals, and influenced 786 by factors such as practice size, the sophistication of the technology, and others. Similarly, what constitutes benefits to a patient will be different from that of other users. Ideally, such an assessment would be available for each stakeholder using each technology in each setting. This is not often the case so realistically we will broadly look at factors taken into account in making a value assessment and determine what we know and where the gaps lie. The few studies included in our review suggested that some cost savings may exist, which could be substantial over time. The economic information looks more favorable after the technology has been in place for an extended period of time so that the large upfront investment gets spread over time and then do we start to see a return on investment. However, a full economic evaluation requires the comparative analysis of alternative courses of action in terms of both costs and consequences, which provides the best information for making a decision to adopt an intervention or not, and very few of these have been rigorously completed in this field. Also, the initial expenditure and ongoing costs were rarely reported and the included cost analyses were based on projections of savings given reported changes in care processes rather than improved clinical outcomes for patients. Gains achieved by reductions in outcomes such as lengths of stay or rehospitalizations have been 716 less successful, though Durieux and colleagues do report a significant decline in hospital length of stay in a review of drug dosing decision support technologies. A number of studies 584,586,628 reported positive improvements in efficiency outcomes such as drug turnaround times, 439,600 and time to administering drugs. One study reported that nurses spent about the same time 561 on computer documentation as paper documentation. In our review, efficiencies were rarely the main endpoints of any of the studies; they were frequently reported as secondary outcomes or additional measures analyzed, but without any assessment of the power of the analysis. Because of the quality of the studies, it is difficult to attribute true productivity gains except in the cases 607 of some well-established systems as suggested by Chaudhry and colleagues. The qualitative 439,547,632 evidence indicates that stakeholders believe that gains in productivity have occurred. These studies included a number of settings and stakeholders, and most reported improvements in processes of prescribing changes, adherence to guidelines or quality measures, error reductions, preventive care procedures done, and monitoring initiated. In more than 80 percent of the cases in which an 81 improvement in process was sought, it was found to be positive. The findings of improvement were consistent across settings, levels of care, providers, and medication management phase. To balance this positive nature of the results, a growing body of evidence delineates unintended consequences of some technologies that will also contribute to the value 632,734,752 proposition of stakeholders. We reported on 78 studies that assessed clinical outcomes as their primary endpoints, the majority of which focused on prescribing and monitoring phases. However, when clinical measures were the primary endpoint, often no differences between the intervention and control groups in the higher quality studies were seen (see Table 15). We found that efficacy was greater in interventions targeting specific populations or applications. Thus, a value assessment on patient outcomes would warrant a look at specific technologies, populations, and settings beyond the scope of this report. For implementation, adoption, and ongoing use of any technology to be successful, the people using the system need to find it useful, usable, and nondisruptive. Levels of satisfaction and positive perceptions were shown to be positively correlated with measures such as ease of use, 654-657,661,673 productivity, quality of care, and reliability. When determining the proposition values, the type of technology and how well it meets expectations and workflow are important considerations for users, greatly impacting their perceptions and openness to adoption/use. Some literature has focused on comparing perceptions and attitudes of different health care 656,678 providers, such as nurses compared with physicians and trainees; and residents compared 654,657,677 with physicians using the same technologies. The type of system and how it affects health care providers’ work will impact how satisfied these stakeholders are with the technologies. For any one technology or setting, insufficient data exist to determine levels of satisfaction among all stakeholders. A focus of the greater body of research, especially commentaries and narrative reviews, is on the use of technologies to reduce medication errors. Such benefits could have repercussions on risk mitigation, but also needs to be balanced with the fact that some technologies have been shown to result in new kinds of errors. Certainly, from the literature, we see no clear understanding of what information is needed from the standpoint of each stakeholder. Hospital administrators place emphasis on other aspects such as costs, return on investment, and organizational change. The relative importance of these factors will vary among physicians practicing in different settings, with cost being more important to physicians in private practice than in hospitals, and other related issues. Similarly, the importance of these factors will vary among pharmacists depending on their practice setting and the type of technology. Work needs to be done to identify the needed critical information before we can truly assess what is missing. From the information garnered in this report, a growing body of evidence supports the use of some technologies (e. Each of the 21 articles included in this section established 800 653,789,791,793,798 evidence on likelihood to use, one on purchase, and five on implementation. A sizeable number (n = 20) of articles were on the prescribing and ordering phases, with only one 45 on the administering phase of medication management. However, the literature is sparse and evidence from studies with stronger methods that can address this question is lacking. Fundamental issues related to system characteristics included the availability and accessibility of hardware, technical support and training, system integration into clinical workflow, timeliness of clinical messages, and acceptance of the system by various 803 stakeholders.

Estrogens are also subject to extensive first-pass effects (it has been shown that these first-pass effects occur predominantly in the intestinal wall purchase metoprolol 100mg, rather than in the liver) after oral administration order discount metoprolol on line. Again order generic metoprolol from india, vaginal administration of estradiol results in higher bioavailability than via the oral route (Figure 11 metoprolol 100mg with visa. A number of different types of vaginal rings containing various progesterones and estrogens have been investigated as a steroidal contraceptive since the mid-1970s, the most successful being a Silastic toroidal- shaped ring. This is designed for insertion into the vagina and positioned around the cervix for 21 days, in order to achieve a constant plasma progestin level and cyclic intravaginal contraception. Although the device is successful in achieving the prolonged release of levonorgestrel, irregular bleeding is a major drawback associated with its use. In postmenopausal women with symptoms of urogenital aging, the vaginal ring gives significantly better, or equal, improvements of vaginal mucosal maturation value and restoration of vaginal pH levels than estradiol—containing vaginal pessaries or conjugated estrogen vaginal creams and is significantly more acceptable. Vaginal administration of progesterone is associated with a “first-uterine-pass effect”, i. Using a human ex vivo uterine perfusion model, the vaginal administration of radioactive progesterone was shown to result in the progressive migration of [ H]3 progesterone into the uterus, where it reached high concentrations in both the endometrium and the myometrium. Furthermore, vaginal administration of micronized progesterone has been shown to enhance progesterone delivery to the uterus by about 10-fold in comparison to im injection, despite the markedly higher (about 7- fold) circulating drug concentration achieved with im injection. Uterine selectivity after vaginal 288 administration has further been observed for both danazol and the β-agonist terbutaline and the vaginal-to- uterine delivery of misoprostol is currently being investigated for the reliable termination of early pregnancy (see below). Hence considerable evidence has accumulated demonstrating that the vaginal route permits targeted drug delivery to the uterus. This phenomenon opens new therapeutic options for the administration of compounds whose primary site of action is the uterus, thereby maximizing the desired effects, while minimizing the potential for adverse systemic effects. The retrieval system comprises a Dacron polyester net which proximally surrounds the insert and has a long ribbon end. The insert is placed in the posterior fornix of the vagina; insertion is performed digitally, thereby obviating the need for speculum examination. The system is effective in producing cervical ripening at term by releasing a small amount of the drug over a prolonged period. Furthermore, the system allows the obstetrician to control the dose administered and to terminate drug delivery by removal of the device, if uterine hyperstimulation or abnormal fetal heart rate changes should occur during the ripening process. Thus the system offers particular advantages in cases where there is concern about fetal condition or a risk of uterine over-activity. Misoprostol The most widely used medical method of terminating second-trimester pregnancy for fetal malformations or previous fetal death is the intravaginal use of prostaglandins; in particular, clinical interest is growing in the use of a synthetic prostaglandin E1 analog, misoprostol. The bioavailability of vaginally administered misoprostol is 3 times higher than that of orally administered misoprostol, which may explain why intravaginal misoprostol has been reported to be more effective than oral misoprostol for medical abortion. Recently, there has been renewed interest in the possibility of delivering therapeutic peptides and proteins via the vaginal epithelium. However, in this investigation, the analog was applied selectively at the early and mid-follicular phases, when the vaginal epithelium is thick and cohesive; greater bioavailability is to be expected during the luteal phase of the cycle, when the epithelium is porous and thin. The uptake of leuprorelin via a variety of routes (iv, sc, rectal, nasal, oral, and vaginal) has been compared in diestrous rats. Insulin Rapid dose-related changes in the plasma glucose and insulin levels have been demonstrated in alloxan- induced diabetic rats and rabbits, after vaginal administration of insulin suspended in a poly(acrylate) aqueous gel (0. However, the hypoglycemic effect was less than that achieved using the rectal route in the same base, or using the ip route. Penetration enhancers may be used to promote peptide absorption across the vaginal epithelium. However, less extensive investigations on the use of penetration enhancers for the vaginal route have been carried out in comparison to other routes, such as intranasal and transdermal (see Sections 9. The mechanism of enhancement of vaginal absorption of peptides by organic acids has been attributed to their acidifying and chelating abilities. In the case of the peptide leuprorelin, it seems that the effect of lowering the pH causes self-association or conformational changes of the peptide resulting in changes in the charge of leuprorelin and the epithelial surface. Removal of Ca2+ from the tight junctions of the epithelial cells by the chelators results in opening of the junctions, thereby creating a leaky epithelium and enhancing drug delivery via the paracellular route. The chelating effects are reversible, for example changes in the vaginal epithelium produced by citric acid were rapidly reversed after the epithelium was washed with physiological saline solution. Cyclodextrins can be used to solubilize drugs and thus potentially increase the concentration gradient driving passive diffusion across membranes. New research suggests that their enhancing effect may also be partly due to the removal of fatty acids, such as palmitic and oleic acids, which are minor membrane components. Toxic effects A major disadvantage associated with the use of penetration enhancers is their potential deleterious effect on the epithelial tissue. The damaging effects of various absorption enhancers have been investigated in vaginal absorption studies of gentamicin using ovariectomized rats. It was found that the penetration enhancers laureth-9 and lysophosphatidylcholine caused severe desquamation of the epithelium, whereas citric acid and palmitoylcarnitine were able to enhance absorption while causing only minor epithelial damage. The vaginal absorption of insulin was studied in ovariectomized rats and in the absence of any enhancer, no decrease in blood glucose was observed. Co-administration of various absorption enhancers was able to significantly increase the degree of hypoglycemia. The histological changes in the vaginal epithelium after treatment with the enhancer systems were variable and often severe: • palmitoylcarnitine chloride exhibited the greatest local toxicity including reduction of epithelial thickness and cell death. However, no conclusions can be drawn at this stage about the likely tolerability, safety and efficacy of the gel in the context of sexual intercourse. Antiviral vaginal devices Nonoxynol-9 is an approved spermicide with strong antiviral activity. The device, available as a diaphragm or a disk pessary, is fabricated from silicone elastomer matrix system. The drug release profile demonstrates square root time kinetics (M ∞ t / ) (see1 2 Section 4. While the spermicide-containing reusable diaphragms currently on the market are relatively effective when used in combination with a spermicidal formulation, they require careful fitting, insertion and maintenance. Moreover, adverse reactions, such as urinary tract infections, alterations in vaginal flora and occurrence of toxic shock syndrome, have been associated with their use. In contrast the silicone-based device described above has been reported to be stable, non-irritating and non-toxic. A vaginal sponge has also been recently developed comprising a soft poly(urethane) sponge impregnated with a gel containing 1% benzalkonium chloride, 0. The sponge therefore combines the actions of: • a physical barrier that blocks the cervix; • a material that absorbs the ejaculate; • a spermicide; • an antiviral agent. Antiviral liposomal preparations Intramuscular injection of α interferon was shown to be fairly efficacious in the treatment of genital warts; however, this route was associated with a number of side-effects including fever, myalgia, headache, nausea and fatigue. A liposomal preparation of α interferon for topical vaginal delivery has been developed, which offers the advantage of treating latent human papillomavirus infections as well as visible genital warts. The liposomal preparation can be self-administered intravaginally, without the need for multiple painful local, or im, injections. In the vagina, mucosal immune responses are initiated by the uptake of antigens from the vaginal surfaces (Figure 11. Whereas the gastrointestinal tract has identifiable aggregates of lymphoid tissue within the epithelium known as the Peyer’s patches (see Section 6. Antigen-specific effector lymphocytes (B cells and T cells) migrate through the lymphatics and exit via the thoracic duct into the bloodstream. The primed B and T cells home to various mucosal sites including the genital mucosa, where they undergo maturation and secretion. A vaginal vaccine has been developed for the treatment of recurrent urinary tract infections. The multi- strain vaccine, composed of 10 heat-killed bacterial uropathogenic strains, has been shown to be efficacious against cystitis in non-human primates when administered by the vaginal route. Bladder infections were significantly reduced and both systemic and local immune responses were generated. It was determined that vaginal immunization resulted in two different types of immune responses in mice: high and low. High responders to the immunizations had been immunized in the diestrous phase of the cycle. As explained above, the vaginal epithelium is thin and porous during this phase, which facilitates vaccine uptake. Similarly, rectal immunization induced high levels of specific IgA and IgG in rectal secretions, but not in female genital tract secretions. Thus, generation of optimal immune responses to sexually transmitted organisms in both the rectal and the genital mucosa of women may require local immunization at both of these sites.

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If the patient is stabilized in the emergency room and hematemesis or bloody nasogastric aspirate has been documented buy 100 mg metoprolol fast delivery, upper endoscopy is the standard of care for diagnosis and for segregating patients into low- and high-risk groups discount 100 mg metoprolol otc. Endoscopic treatment of those with major stigmata of ulcer hemorrhage is recommended generic 100 mg metoprolol otc. Surgical consultation should be obtained and the likelihood for surgical intervention will depend on the etiology of the bleed buy cheap metoprolol online. The first step in management of patients who present with rectal bleeding, stable or unstable, is a rigid sigmoidoscopy to exclude rectal lesions as a cause. If the patient is stable but has evidence of ongoing bleeding and the sigmoidoscopy is unrevealing, angiography and radionuclide scanning can be consid- ered, with radionuclide scanning being the preferred first test. The major- ity of patients with bleeding diverticula (70–82%) stop bleeding, but 12% to 30% continue to bleed and require intervention. Urgent colonoscopy for the diagnosis and treatment of severe diverticular hemorrhage. To recognize surgical conditions that require further evaluation and eventual operation. Cases Case 1 A 78-year-old man with a history of myocardial infarction and coro- nary artery bypass surgery is brought to the hospital by ambulance because of severe abdominal pain that suddenly began 6 hours ago. The patient is confused and disoriented, but he indicates that the pain is excruciating. The patient’s wife reports that he had an urgent desire to defecate when the pain began, but no further stool or flatus has been noted. She provides a list of current medications that includes digoxin, pindolol (a beta-blocker), a baby aspirin, and a nitrate patch. Wise On examination, he appears gravely ill with cool ashen skin, an irregular pulse of 120, blood pressure of 85/50, and respirations at 28. Case 2 An 18-year-old male college student is awakened with an aching pain in the periumbilical area, anorexia, and nausea. He skips morning classes and chews a few antacid tablets, but, later in the day, the pain becomes worse, more constant, and moves to the right lower quadrant. Unable to eat, he vomits once and notes that the pain is worse when he tries to walk. At the hospital infirmary, he is found to have lower right quadrant tenderness, involuntary guarding, an oral temperature of 100. Case 3 A 59-year-old man is referred to the hospital emergency department by his physician because of lower abdominal pain, fever, and difficulty walking. The patient has noted intermittent cramps and changing bowel habits over the past 2 months. Recently, he has become constipated, but he also has had occasional episodes of diarrhea. For the past 18 hours, he has had constant, severe pain and soreness in the left lower quad- rant. Physical exam exhibits a blood pressure of 135/85, pulse of 100, and temperature of 39°C (102°F). There is mild, lower abdominal distention, but no scars or protuberances are noted. Palpation demon- strates involuntary guarding and tenderness in the left lower quadrant. A small amount of brown stool in the examining glove is negative for occult blood. Case 4 A 62-year-old African-American woman comes to the hospital emer- gency department complaining of severe, crampy, midabdominal pain that began approximately 36 hours ago. She simultaneously noted nausea that quickly was followed by multiple episodes of vomiting dark, thick, greenish fluid. The pain and vomiting have persisted, and she feels distended and unable to hold down fluids. She thinks her last bowel movement was 2 days ago and that she has not passed flatus over the past 24 hours. Abdominal Pain 377 about a week ago; her condition improved when she reduced her oral intake to clear fluids. On physical examination, she appears uncomfortable and rocks back and forth intermittently. Her blood pressure is 115/70, pulse is 80, res- pirations are 18, and temperature is 38°C (100. There is a well-healed, lower midline abdominal scar that she explains resulted from a complete hysterectomy per- formed 20 years ago. Her bowel sounds are hyperactive, with intermit- tent high-pitched whines and gurgles. Rectal examination demonstrates no masses or tenderness, and the ampulla contains no stool. An indicator of either functional or organic pathology of the abdominal wall and the intraab- dominal contents, it usually is mild, of short duration, and self-limited. Persistent, chronic, or recurrent pain usually can be evaluated safely by systematic observation and diagnostic studies over time and managed electively. On the other hand, severe abdominal pain that persists for 6 hours or longer must be diagnosed and treated promptly, as it may portend serious, life-threatening complications. The so-called acute abdomen has many causes and often requires timely surgical intervention to ensure the best clinical outcome. In most instances, the acute surgical abdomen is caused by one of three patho- logic processes: (1) inflammation that has extended beyond or perfo- rated the wall of the organ of origin; (2) acute vascular insufficiency (ischemia) or hemorrhage; (3) acute high-grade obstruction of the ali- mentary tract and ducts draining secretory or excretory organs. The general surgeon has become the specialist of choice for as- sessing patients with potentially serious abdominal problems. Is this a catastrophic event that requires immediate recognition, resuscitation, and emergency surgery to avert almost certain death? Severe, persistent abdominal pain associated with hemorrhagic, hypo- volemic, or septic shock, severe systemic sepsis unresponsive to anti- biotic therapy and fluid replacement, or the “board-like” abdomen of severe generalized peritonitis are typical presentations for these dis- astrous situations. Most of these cases present with signs of localized peritonitis and a mild to moderate systemic inflammatory reaction. Because the patient is at risk for or already has serious complications, here, too, a prompt and accurate diagnosis must be made. This is followed by a decision for relatively urgent surgery or initial, intensive medical care. Catastrophic Ruptured abdominal aortic aneurysm Intestinal infarction Free perforation Gastroduodenal ulcer Colonic diverticulitis or carcinoma Advanced suppurative ascending cholangitis Necrotizing infected pancreatitis Urgent Acute appendicitis Cholecystitis Diverticulitis Bowel obstruction Incarcerated hernia Complete small- or large-bowel obstruction Elective Biliary colic Partially obstructing colon carcinoma Crohn’s disease Nonsurgical Irritable bowel Gastroenteritis Simple pancreatitis Hepatitis Pelvic inflammatory disease Urinary tract infection/pyelonephritis Herpes zoster Diabetic ketoacidosis Myocardial infarction 3. Is this a transient or recurrent pain caused by a lesion that ulti- mately requires surgical removal, but that allows an orderly diag- nostic workup to be completed safely and an elective date to be set for the procedure? Is this a nonsurgical disorder such as irritable bowel syndrome or a self-limiting and medically treatable organic condition such as viral gastroenteritis or bacterial gastroenteritis? These are the causes of abdominal pain in the majority of patients; these patients are not considered for surgical therapy. The diagnosis of abdominal pain begins with the acquisition of sub- jective and objective data. As the clinical history is obtained and the physical examination is performed, it is important to determine if the patient’s pain is visceral or somatic in nature. Abdominal Pain 379 the abdomen is detected and transmitted to the central nervous system via two separate pathways. Visceral receptors are confined to the abdominal organs and their supporting mesenteric structures. These receptors are stimulated by stretching, tension, or ischemia, and their signals are transmitted via the slow C afferent fibers of the regional autonomic nerves. These include vagal and pelvic parasympathetic nerves and the Somatic Pain Visceral Pain Intercostal Splanchnic autonomic and and phrenic afferent vagal afferent somatic nerves somatic nerves Vascular disruption Ulceration Perforation Hemorrhage Aneurysm Necrosis Trauma Trauma Hollow viscus Intravisceral Necrosis Neoplasm Fluid collection Intraperitoneal Ulceration Compression by: Vascular occlusion Adhesive band Ischemia Obstruction Embolus Congenital bands Thrombosis Necrosis Hollow viscus Hernia mass Trauma Congestion or duct Narrowing by: Torsion Edema Circulatory failure Infiltration Portal hypertension Hematoma Inflammation Fibrotic stricture Neoplasm Visceral or peritoneal Volvulus Intussusception Intraluminal obstruction by: Infection Stone Immune reaction Foreign body Trauma Neoplasm Noxious fluids Congenital web or Biologic Ogenesis Extrinsic A variety of etiologic factors cause the five pathogenetic processes that produce the disorders that result in abdominal pain. Over time, the primary pathology may progress to induce other pathogenic processes. Physiologic responses and pathologic mediators stimulate visceral pain receptors evocative of visceral pain. When mediators extend beyond the organ of origin to pain receptors adjacent to the parietal peritoneum, somatic pain signals are sent to the brain, producing the reflexes and sensations characteristic of peritoneal irritation. Within the abdomen, the sympa- thetic nerves follow the embryonic arterial circulation: the celiac access to the foregut, the superior mesenteric artery to the mid-gut, and the inferior mesenteric artery to the hindgut. Accordingly, pain arising from the foregut structures—stomach, duodenum, liver, biliary tract, pancreas, and spleen—is perceived in the midepigastrium; pain arising from the mid-gut structures—the small intestine distal to the ligament of Treitz to the distal transverse colon, which includes the appendix—is perceived in the periumbilical region; and pain arising from the hindgut—the left colon and rectum—is perceived in the suprapubic area.

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Cation exchange Chemistry/Apply principles of special procedures/ High-performance liquid chromatography/1 184 Chapter 5 | Clinical Chemistry 58 purchase metoprolol visa. Termal conductance from a flame is used to excite the analytes as they elute from the column order metoprolol 50mg. The flame is made by igniting Chemistry/Apply principles of special procedures/ a mixture of hydrogen discount metoprolol 50mg with visa, carrier gas metoprolol 50 mg, and air. Current is Gas chromatography/1 produced when an outer shell electron is ejected 59. A The order of elution is dependent upon the velocity volatiles is usually based upon the: of the analyte. The Kd is the partition Chemistry/Apply principles of special procedures/ coefficient, and is a measure of the relative affinity Biochemical/2 of solutes for the stationary phase. The pK is the the solute migrates divided by the distance the negative logarithm of K, the ionization constant, and solvent migrates is the: is a measure of ionization. More than a High-performance liquid chromatography/1 90% of the drug will be nonionized and will extract in ethyl acetate or another organic solvent. Neutral solution of ethyl acetate Chemistry/Apply principles of special procedures/ Biochemical/2 5. A Internal standards should have the same affinity as injection the analyte for the extraction reagents. To correct for background absorbance peak height (or area) of all samples (standards and C. To compensate for changes in flow rate unknowns) by the peak height (or area) of the D. To correct for coelution of solutes internal standard reduces error caused by variation in extraction recovery and injection volume. What is the confirmatory method for measuring substance has a unique and characteristic spectrum drugs of abuse? Cations can be formed by various Chemistry/Select instruments to perform test/Drugs of methods, the most common of which is electron abuse/2 bombardment (electron ionization). Cations caused by electron loss or proton a nitrogen laser causes transfer of a proton from the attachment matrix (an acid) to the protein. Chemistry/Define fundamental characteristics/ Instrumentation/1 186 Chapter 5 | Clinical Chemistry 68. Electrospray ionization uses a small-bore tube that forms a 1–4 μ nozzle at the mass Chemistry/Identify basic principle(s)/Mass spectroscopy/1 filter inlet and which is charged by several kilovolts. In mass spectroscopy, the term base peak typically The sample enters the tube along with inert drying refers to: gas. A natural isotope of the molecular ion reaches the nozzle, it becomes highly charged. Te first peak to reach the mass detector size of the droplet is decreased owing to evaporation. Chemistry/Define fundamental characteristics/ This causes the charge density to become excessive, Instrumentation/1 and the droplets break apart. These particles are drawn into the for errors of amino and organic acid metabolism? Electrospray ionization tandem-mass parent or “molecular” ion, a process called soft spectroscopy ionization. B The base peak is typically the “molecular ion” or Chemistry/Select instruments to perform test/Newborn parent ion, meaning that it is the initial fragment screening/2 made by releasing an electron. The cation thus formed has a charge of +1, and therefore, its m/z ratio is equal to its mass. It is the most abundant and most stable ion, and gives the best sensitivity for quantitative analysis. C While two-dimensional thin-layer chromatography can separate both amino and organic acids, it is not sufficiently sensitive for newborn screening. Electrospray ionization allows a small alcohol-extracted whole-blood sample to be analyzed by two mass spectrometers without prior separation by liquid or gas chromatography. Disorders of both organic and fatty acid metabolism are identified by the specific pattern of acylcarnitine ions produced. Amino acids are detected as amino species that have lost a carboxyl group during ionization, a process called neutral loss. In tandem-mass spectroscopy, the first mass filter Answers to Questions 71–73 performs the same function as: A. Te vacuum system molecular or parent ions of interest by excluding ions outside a specified size range. Therefore, it effectively Chemistry/Apply principles of special procedures/ separates the analyte(s) of interest from unwanted Instrumentation/1 compounds. Results of an Autotune test are drawn into a second mass filter where they are showed the appearance of a base peak at 16 with bombarded by argon atoms. Te carrier gas is contaminated The process can be repeated in a third mass filter C. Why is vacuum necessary in the mass filter of a acid, amino acid, and organic acid metabolism. It removes electrons from the ion source atmosphere also contains small quantities of two D. It prevents contamination isotopes with molecular weights of 17 and 18 owing to one and two extra neutrons, respectively. What method is used to introduce the sample into Answers to Questions 74–76 a mass spectrometer for analysis of a trace element? This is done by introducing the sample into a very hot plasma (6,000–10,000°K) called a torch. The Chemistry/Apply principles of special procedures/ torch is made by circulating argon through inner and Instrumentation/2 outer quartz tubes. Which component is needed for a thermal cycler coil of wire that receives a radio frequency. Sealed airtight constant-temperature chamber argon is ignited by a spark, it forms the plasma. Temperature-controlled ionization chamber sample is mixed with argon at the other end to create Chemistry/Define fundamental characteristics/ an aerosol. When it reaches the torch, the solvent is Instrumentation/1 evaporated and the energy from the torch and collisions with argon ions cause ejection of outer- 76. Annealing requires a Instrumentation/1 temperature between 40°C–65°C and allows the primers to bind to the target base sequence. Extension requires a temperature of 72°C and allows the heat-stable polymerase to add complementary bases to the primer in the 5’ to 3’ direction. Rapid heating and cooling is usually achieved using a thermoelectric block that is cooled by forced air flow. They are used to correct the measurements from each well so that the same concentration of fluorescent dye gives the same signal intensity regardless of the well. A line is drawn from the threshold value on the y-axis through the curve, and a perpendicular dropped to the x-axis. A The relative centrifugal force (number times the force of gravity) is proportional to the square of the rotor speed in revolutions per minute and the radius in centimeters of the head (distance from the shaft to A. B Electronic balances do not use substitution weights needed to calculate the relative centrifugal force or knife edges to balance the weight on the pan. Diameter of the centrifuge tube type of balance used, all need to be located on a D. Doors must be Chemistry/Define fundamental characteristics/ closed to prevent air currents from influencing the Instrumentation/1 weighing, and the pan and platform must be clean and free of dust and chemical residue. Which of the following situations is likely to cause an error when weighing with an electronic 80. Failure to close the doors of the balance before involves dilution, gravimetric analysis is associated reading the weight with greater certainty. Using the balance without allowing it to warm up for at least 10 minutes Chemistry/Identify sources of error/Balances/3 80. Which of the following represents the Answers to Questions 1–5 Henderson–Hasselbalch equation as applied to blood pH? Most Chemistry/Apply knowledge of fundamental biological laboratories consider less than 7.

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