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Total iron binding 250–425 μg/dL ↑iron deficiency anemia Iron added to saturate transferrin geodon 40 mg line. Rough estimate of F: 10–120 μg/L chronic infections 80 mg geodon mastercard, malignancies body iron content buy generic geodon 80 mg on-line. Temperature Increase of 10ºC doubles rate of rxn until around 37°C is most commonly used in U generic geodon 40 mg on-line. In acute pancreas abdominal diseases, mumps pancreatitis, levels↑2–12 hr after attack, peak at 24 hr, return to normal in 3–5 days. Bilirubin Metabolism Clinical Chemistry Review 104 Normal metabolism of bilirubin. Usually not helpful in Dx of hypothyroidism because last test to become abnor- mal. Graves’ disease (type of autoimmune disease) is most common cause of hyperthyroidism. Water & electrolyte ↑and loss of diurnal variation in Cushing’s syndrome,↓in balance. Epinephrine & (adrenaline, noradrenaline) Stimulation of sympathetic norepinephrine = catecholamines. Maintenance of pregnancy Progesterone Preparation of uterus for ovum implantation, Also produced by placenta. Placenta Estrogen (estriol) No hormonal activity Used to monitor fetal growth & development. Human placental Estrogen & progesterone production by corpus Used to assess placental function. Development of mammary glands Testes Testosterone Development of male reproductive organs & Also produced in adrenal cortex. Glucagon Glycogenolysis, gluconeogenesis, lipolysis Produced in alpha cells of islets of Langerhans. Usually reached after 5–7 half-lives Half-life Time required for concentration of drug to be↓by half. Pharmacokinetics Rates of absorption, distribution, biotransformation, & excretion Most common methods: immunoassay, chromatography. Cancer antigen 15-3 Breast Stage disease, monitor therapy, Two different assays for same marker. Carcinoembryonic Colorectal Monitor therapy, detect Fetal antigen re-expressed in tumors. Calculated value on blood gas analyzer –2 to +2 mEq/L Difference between titratable bicarbonate of sample & that of normal blood sample Oxygen saturation Amount of oxygenated hemoglobin Measured by oximeter 94%–100% *Negative values indicate base deficit. Some Calibration curve pre- reflectance at isobestic point (wavelength where also measure carboxyhe- pared from specimens reduced & oxyhemoglobin have same absorbance moglobin, methemoglobin, with 0% & 100% or reflectance, e. Amylase: creatinine Urine amylase (U/L) × serum creatinine (mg/L) 2%–5% ↑acute pancreatitis. If all deter- minations are↑or↓, possible instrument error in 1 of the determinations. Creatinine urine creatinine (mg/dL) × urine mL per 24hr/1,440 M: 97–137 mL/min ↓renal disease (early indicator). Urine-to-serum Urine osmolality 1–3 ↓renal tubular deficiency, osmolality Serum osmolality diabetes insipidus. No vaccine ventilation & waste management to or therapy prevent release into environment. Sterilization and Disinfection Clinical Microbiology Review 139 Temperature Most reliable Steam under pressure Autoclave. Chemicals Alcohols Ethyl & isopropyl (70%–80%) frequently used as antiseptics & disinfectants. Sterilization and Disinfection continued Clinical Microbiology Review 140 Glutaraldehyde Effective against most vegetative cells other than mycobacteria. Gases Ethylene oxide Widely used in hospitals to sterilize materials that can’t withstand steam. Yes No Specimen Collection Guidelines Clinical Microbiology Review 142 • Obtain during acute phase of infection (within 2–3 days • Obtain sufficient quantity. Wood, cotton, & calcium alginate may be • Syringes with needles attached should never be toxic. Don’t refrigerate Neisseria gonorrhoeae Amies transport medium with charcoal, Transgrow, 25°C. Refrigera- specimen can’t be cultured within 2 hr of collection tion may killShigella Stool for ova & parasites Depending on procedures to be performed: polyvinyl Can hold formed specimens at 4°C. For delay >24 hr, freeze at −70°C Fragile Organisms Clinical Microbiology Review 144 • Anaerobes • Salmonella • Chlamydia • Shigella • Haemophilus influenzae • Streptococcus pneumoniae • Neisseria gonorrhoeae • Viruses • Neisseria meningitidis • Parasites Criteria for Rejection of Specimens Clinical Microbiology Review 145 in Microbiology • Unlabeled or improperly labeled specimen • Syringes with needles attached • Improper collection site • Culture for anaerobes requested on inappropriate • Prolonged transit (over 2 hr without preservation) sources • Improper temperature during transport or storage • Specimen received in formalin (other than stool for ova • Leaking specimens & parasites) • Specimens in nonsterile containers • Saliva instead of sputum • Improper transport medium • Foley catheter tip • Culturette ampule not broken, swab dried out • Insufficient quantity • Improper swab, e. Gram negative Thin peptidoglycan layer covered with proteins, phospholipids, Safranin Pink & lipopolysaccharides. Group A–selective strep agar S Group A strep from respiratory Contains antibiotics to suppress normal throat flora. Sub- stools & rectal swabs culture onto selective differential agar after 6–8 hr & 18–24 hr incubation. Campylobacterbroth E Campylobacterfrom stool Subculture to Campy-selective agar after overnight incubation at 4°C. Corynebacteriumspp produce gray to black colonies due to diphtheriae reduction of tellurite. Bismuth sulfite agar Selective forSalmonella Bismuth sulfite & brilliant green inhibit most others. Bordet-Gengou agar Selective enrichment medium for Potato-glycerol-based medium enriched with blood. Buffered charcoal-yeast Enrichment medium for isolation of Yeast extract & L-cysteine enhance growth ofLegionella. Strepto- Bubbles after 20–30 sec aren’t hydrogen peroxide (H2O2) to cocci & enterococci neg considered pos rxn. Hemolysis Strep sore throat, Usually beta due to O2-stable rheumatic fever, hemolytic (wide streptolysin S & O2- glomerulonephritis, zone). Contains ethylhydrocupreine 6-mm disk or≥ 16 mm with Viridans strep resistant hydrochloride. Staphylococcus aureus Significant resistance to multiple antibiotics, including Yes vancomycin. Group A streptococci Universally susceptible to penicillin, cephalosporins, No vancomycin. No (may be done when isolated from baby) Streptococcus pneumoniae Increasingly resistant to penicillin & other antibiotics. Yes Enterococci Usually resistant to penicillin & several other commonly Yes used antibiotics.

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Eventually geodon 40mg low cost, the patient dies of complications related to the debilitation of immune response buy discount geodon 40 mg, often by a variety of secondary infections or even various cancers buy geodon 20mg visa. During the asymptom- atic stage best geodon 20mg, it is known that the level of the steady state viremia correlates with the future progression of the disease and the life span of the patient. None of them is curative and there is considerable variation in the response to antiretroviral drugs among individuals. This concerns both the interin- dividual differences in pharmacokinetics, and in toxicity. A growing number of entry inhibitors are under clinical development, with some already approved. With the emergence of virus strains that are largely resistant to existing reverse transcriptase and protease inhibitors, the development of entry inhibitors comes at an opportune time. Env density, receptor expression levels, and differences in affinity and receptor presenta- tion are all factors that could influence the clinical response to this promising class of new antiviral agents. Quest Diagnostics has licensed the heteroduplex tracking technology used in SensiTrop test and is developing a validated test based on this. There are a number of pharmacogenetic determinants of antiretroviral drug exposure, toxicity, and activity. Several prospective clinical trials and cohort studies have identified a number of associations between human genetic variants, drug metabolism and toxicity. ViroSeq’s high throughput processing provides an integrated system from sample preparation to the final interpretive resistance report to aid in treatment decisions. While such testing is rou- tine in Western countries and used repeatedly over the course of treatment to see if interventions are effective it is unavailable to many people in the developing world, especially in rural areas. Accordingly, combination therapies have been used to address the rapidly evolving virus. Both approaches share the requirement for a considerable increase in the number of protease mutations to lead to clinical resistance, thereby increasing the genetic barrier. Most reports on drug resistance deal with subtype B infections in developed countries. The addition of new drugs to the existing therapeutic arsenal will improve treatment options and clinical pros- pects particularly for those patients failing current drug regimens based primarily on combinations of reverse transcriptase and protease inhibitors. The large number of therapy options makes it difficult to select an optimal ther- apy, particularly in patients that develop resistance to some drugs. Universal Free E-Book Store Personalized Management of Viral Infections 399 1 2 3 Patient Viral load measurement Genome sequencing 4a 4b 4c Via rule-based system Via mutation table Via statistical model 5 Resistance profile 6 7 Additional information on patient Therapy prediction engine 9 8 Manual therapy selection Therapy ranking Fig. In the case of anticipated therapy change the viral genome is sequenced from the patient’s blood serum (3). Interpretations of the viral genome sequence is effected either manually using a mutation table (4a), or via a rules-based system (4b), or with a statistical model derived from clinical resistance data (4c). The interpretation results in a resistance profile (5) that is quali- tative in the first two cases and quantitative when using statistical models. In doing so, additional information on the patient is also taken into account (patient history, habits, drug side effects, etc. Therapy prediction engines (7) can assist this process by a quantitative analysis that yields a list of therapies ranked by their likelihood of success (8) (Source: Lengauer et al. Additionally, by examining patient samples taken at different time points, it is also possible to determine how previously rare mutations became more common. However, short-read approaches lose the linkage relationship between the mutations although they can detect multiple mutations, but not whether they were all in one strain or housed among a few strains circulating in the patient. Reads longer than 10 kilobases are common, and efforts are being made to further increase the average read length. Knowing which mutations are present and their phasing information can help clinicians decide upon a drug treatment regimen for the patient. Different drugs might be needed to target a virus strain with two mutations as compared to two strains with one mutation each. The combination test is performed from the same blood sample and the results are in one report. The patient virus is also sequenced, with the genotypic data provided alongside the susceptibility results. Finally, it measures the ability of the viral protease and reverse transcriptase to drive replication – known as replication capacity, one component of viral fitness. Further studies on the development of newer molecular methods for a better management of chronic hepa- titis B will minimize morbidity (Chakravarty 2012 ). With the increasing progress in nucleic acid technologies, investigation of viral genetic biomarkers may be integrated in clinical diagnostic routine. It is offered as a web-based deci- sion support tool to assist physicians to optimize and individualize the treatment schedule of patients with chronic hepatitis B. The complications of chronic hepatitis C, including cirrhosis and hepatocellular carci- noma, are expected to increase dramatically world-wide over the next 10–20 years. Liver biopsy provides valuable information about the baseline severity and subsequent progression of hepatitis C. Severe fibrosis or cirrhosis on the pre-treatment liver biopsy is associ- ated with decreased response rates. Response rates to currently approved therapies also vary by genotype, with genotype 2 and 3 patients enjoying a 76 % response rate to the current standard of care while patients with genotype 1a and 1b have only a 46 % response to the current standard of care. In addition to limited efficacy, treatment is often poorly tolerated because of side effects that prevent some patients from completing therapy. For these reasons, identification of a biomarker of response to treatment is a high priority. Poor response rate across Hispanics of all nationalities indicates that strategies to improve the sustained virologic response in Latinos are needed. Almost 80 % of those with the favorable response genotype eradicated the virus, while only about 30 % with the less favorable response genotype did so. Because the genotype leading to better response is in substantially greater frequency in European than African popu- lations, this genetic polymorphism also explains approximately half of the differ- ence in response rates between African-Americans and patients of European ancestry. Unexpectedly though, the authors reported that the C alleles actually appeared to be linked to higher rather than lower baseline viral loads. Genotype non-1 and a low viral load are the most sig- nificant pre-treatment indicators of sustained virologic response. Covarying positions were common and linked together into networks that differed by response to therapy. Using this analysis to detect patterns within the networks, the authors could predict the outcome of therapy with >95 % coverage and 100 % accuracy, raising the possibility of a prognostic test to reduce therapeutic failures. Furthermore, the hub positions in the networks are attractive antiviral tar- gets to suppress evolution of resistant variants. Lab21 is developing proprietary new assays to monitor the emergence of these genotypic variants. A high-throughput “massively parallel sequencing” approach followed by individual genotyping has been used to identify new, highly sensitive genetic predictors of drug response (Smith et al.

The period between the telophase and the S phase is termed G1 generic geodon 20 mg without prescription, and the period between the S phase and the prophase is termed G2 (Fig discount 80 mg geodon visa. During the G1 and G2 periods discount geodon 20 mg with amex, no functional activity related to cell division occurs generic 20 mg geodon fast delivery. The period of the entire cell cycle including the M and S phases varies with the types of cells. The S phase normally is the longest and G1 is the most variable phase in the cell cycle. M is the period of mitosis during which the prophase, metaphase, anaphase, and telophase take place. G1 is the period between the telophase and S, and G2 is the period between S and the prophase. It has a double-helical structure consisting of two strands, which are like the two rails of a ladder (Fig. The two strands are connected to each other by rungs made of four bases: thymine (T), adenine (A), guanine (G), and cytosine (C) (Fig. The rungs of the ladderlike structure are formed by bases connected to each other by the hydrogen band (dashed line) and to the sugar molecule on the strands on both sides. Effects of Radiation 231 cule on the strands on both sides, and are paired to each other by hydro- gen bonds. These four bases are arranged in a very specific manner to form a specific gene in every living species and provide the unique characteris- tics to these species. These changes result in so-called mutations, which have adverse effects on the genetic codes. At low-dose exposures, the breaks are single stranded and can be repaired by joining the broken components in the original order. At higher exposures, however, double strand breaks occur and the odds for repair decrease. If the cell is not repaired, it may suffer a minor functional impairment or a major consequence (cell death). However, chromosomes themselves can be cleaved by radiation producing single or double breaks in the arms. These aberrations are categorized as chromatid aberrations and chromosome aberrations. Whether chromosome aberrations are induced by single-strand breaks or double-strand breaks in the structure determines the fate of the cell. In single-strand breaks, the chromosome tends to repair by joining the two fragments in a process called restitution, provided sufficient time is allowed. Random combination of these fragments will then produce acentric and dicentric chromatids as illustrated in Figure 15. Such chromosomes suffer severe consequences due to the mismatch of genetic information. Radiation Biology A G T G T A T C A C A A G T G T B T C A C A A G G T C T C A A G T G T D T C A C A G A G T G T G E C T C A C A C F Fig. Radiation Biology If radiation produces single-strand breaks in two separate chromosomes, then there are four ways of recombining the broken ends as shown in Figure 15. However, these cells suffer severe consequences because of the mismatch of genetic information from two separate damaged chromosomes. The translocation is a process in which two fragments—one with a centromere from one chromosome and one without a centromere from another chromosome—combine to form a new chromosome (Fig. In another scenario, radiation can cause two breaks in one arm of a chromosome, resulting in three fragments, only two of which combine with the loss of the third. Trans- location and deletion, although not as harmful to the cell, cause late effects such as carcinogenesis and hereditary effects due to mismatch or loss of genetic material. An alternative to deletion is the combination of all three fragments into a chromosome with changes along the broken line as shown in Figure 15. This process is called inversion, which has all the original genetic material except a change in the sequence of genes and hence is not as detrimental to the cell. Chromosome aberrations by double-strand breaks occur more frequently at high-dose rates than at low- dose rates because of less time to repair and fewer chances of combining Dicentric Acentric Translocation A B Fig. Combination of these four fragments leads to dicentric and acentric chromosomes (A) or translocation (B). For example, a-particles, protons, and neu- trons will cause more chromosome aberrations than g-rays. Damaged cells that survive may later induce carcinogenesis or other abnormalities. A variety of reactions that can occur after radiation interacts with water molecules is shown below. The number of free radicals produced by ionizing radiation depends on the total dose but not on the dose rate. It has been found that the majority of radiation-induced damage results from the indirect action mechanism be- cause water constitutes nearly 70% of the composition of the cell. Radiosensitivity of Cells In living matter, there are two types of cells: differentiated and undifferen- tiated. Undifferentiated cells do not have any specific physiologic function except to develop into mature cells. In contrast, all mature cells are differentiated and perform specific functions in the living body. According to the law of Bergonié and Tribondeau, undifferentiated cells that are undergoing active mitosis are most sensitive to radiation, and dif- ferentiated or mature cells are least affected by radiation. For differentiated cells, it means loss of cellular function, whereas for undifferentiated cells it means loss of reproductivity. As can be seen, lymphocytes, though mature cells, are most sensitive to radi- ation, owing to a large nucleus; nuclear material is more radiosensitive. Nerve cells and muscle cells are totally differentiated cells and therefore 238 15. The tissue or organ that contains more radiosensitive cells will be highly radiosensitive and vice versa. For example, bone marrow containing radiosensitive erythroblasts is very radiosensitive, whereas nerves and muscles containing radioresistant cells are less radiosensitive. Cell Survival Curves When mammalian cells are irradiated, not all cells are affected to the same extent. The cellular response to radiation is illustrated by what is called the cell survival curve. It is obtained by plotting the dose along the linear X-axis and the surviving fraction along the logarithmic Y-axis. Surviving cells are those cells that retain all reproductive as well as func- tional activities after irradiation, whereas the death of cells is indicated by the loss of their function in differentiated cells and by the loss of repro- Cell Survival Curves 239 ductive activity in undifferentiated cells. It should be noted that thousands of grays are needed to kill differentiated cells, whereas only hundreds of grays are needed for undifferentiated cells. This straight line portion on the semilog plot is an exponential curve on a linear plot. This curve based on a multitarget model is characterized by three parameters: D0 (dose at which 37% of cells survive), the extrapolation number n, and the quasithreshold dose Dq, and they are related by the expression logen = Dq/D0 (15.

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The level the lungs travels by the tongue purchase geodon 80mg without a prescription, soft palate purchase geodon 20 mg amex, uvula order geodon 40 mg amex, of immunity among persons who were vaccinated and tonsils order 80mg geodon. In people exposed to the back of the throat tighten to hold these struc- smallpox who are not immune to the disease, the tures in place and prevent them from collapsing and vaccine can lessen the severity of or even prevent vibrating in the airway. Otherwise, patients who snore may want to try different sleep positions, nose clips, or similar smell The sense that provides information about steps to prevent unwanted snoring. See also sleep an object’s scent, often giving clues to the palatabil- apnea, obstructive; somnoplasty. The organs of smell are made up of patches of tissue social phobia A paralyzing fear of interacting called the olfactory membranes that are each about with others. These membranes are sweating, trembling, rapid heartbeat, muscle ten- located in a pair of clefts just under the bridge of the sion, nausea, and extreme anxiety. Most air breathed in normally flows through can occur in very young children or emerge at a the nose, but only a small part reaches the olfactory later age. It can be disabling to a person’s work and clefts—just enough to get a response to an odor. Many people with When a person sniffs to detect a smell, air moves social phobia have trouble reaching their educa- faster through the nose, increasing the flow to the tional and professional goals or even maintaining olfactory clefts and carrying more odor to these sen- employment. In extreme cases, a person with social pho- smoldering leukemia See leukemia, smoldering. Treatment options include smooth muscle Along with skeletal and cardiac using medications and cognitive-behavioral therapy, muscle, one of the types of muscle tissue in the which employs exposure and response prevention. Smooth muscle generally forms the support- Medications for social phobias include antidepres- ing tissue of blood vessels and hollow internal sants called selective serotonin reuptake inhibitors organs, such as the stomach, intestine, and bladder. Within the medical system, a social worker bites can nonetheless cause painful puncture might help uninsured families who need medical wounds that require treatment. If a snakebite victim care find help; work with grieving parents, spouses, knows a snake was poisonous, or if the person did or other family members; provide individual therapy; not see or recognize the snake, he or she should or help patients find resources to meet their needs immediately seek emergency treatment. Somatotropin acts by stimu- socialization The learning process a child goes lating the release of another hormone called through as he or she learns how to interact appro- somatomedin by the liver, thereby causing growth to priately with other people. Somatotropin is given to children with pitu- itary dwarfism (short stature due to underfunction socialized medicine A medical system like that of the anterior pituitary) to help them grow. Also of a socialist country, in which medical facilities and known as somatropin, growth hormone. The chemical somnoplasty A surgical treatment for snoring in notation for sodium is Na+. When sodium is com- which heat energy is used to remove tissues of the bined with chloride, the resulting substance is a uvula and soft palate. Too much or too little sodium in the blood (called hyperna- S1–S5 Symbols that represent the five sacral tremia or hyponatremia respectively) can cause cells vertebrae. Normal blood sodium level is 135–145 milliEquivalents/liter space, pleural See pleural space. A soft palate The muscular part of the roof of the muscle spasm can be quite painful, with the muscle mouth. Spasms in various types of soft tissue All tissues within the body that serve tissue may be caused by stress, medication, and to support, insulate, or connect the internal struc- overexercise. For example, a person with specific developmental disorder See develop- clinical depression may complain of stomach pains mental disorder, specific. These struc- which a gamma camera rotates around the patient tures include the vas deferens, arteries, veins, lym- to produce images from many angles, which a com- phatic vessels, and nerves. The sphenoid bone has been called the “keystone” of the cranial speech, apraxia of See apraxia of speech. Speech disorders may affect spherocytosis, hereditary A genetic disorder articulation (phonetic or phonological disorders), of the red blood cell membrane that is character- fluency (stuttering or cluttering), and/or voice ized by anemia, jaundice, and enlargement of the (tone, pitch, volume, or speed). A speech pathologist can diagnose speech dis- than the biconcave-disk shape of normal red cells. See also aphasia; These fragile red cells (spherocytes) tend to get apraxia of speech; articulation disorder; clutter- trapped in narrow blood passages, particularly in ing; stuttering. If this occurs, they break up (hemolyze) where they have lodged, leading to hemolytic ane- speech dyspraxia See dyspraxia of speech. The breakup of the speech therapist See speech-language red cells releases hemoglobin, and the heme part pathologist. The approach used often appears in infancy or early childhood, causing depends on the disorder. Treatment involves evaluates and treats people with communication removing the spleen (splenectomy). In some states a state congenital hemolytic jaundice, severe atypical sphe- license is also required. The sperm has an oval head that contains its genetic matter, and sphincter A muscle that surrounds and, by its it is propelled by a flagellating tail. A sperm is car- contraction, closes a normal opening such as that ried into the female reproductive tract within the from the intestinal tract or the urinary tract. If the sperm is able to travel up to the anal and urethral sphincters can cause fecal into a fallopian tube, it must then break through the and urinary incontinence, respectively. Sphincters cell wall of the egg (the female gamete, or ovum) to tend to be ring-like and, when contracted, to con- fertilize the egg and form a zygote. People with spina bifida often have neurological deficits below the level of the sphygmomanometer Blood pressure cuff, an lesion and can suffer from bladder and bowel instrument for measuring blood pressure, particu- incontinence, limited mobility (due to paralysis of larly in arteries. The two basic types of manual sphygmo- bifida varies according to country, ethnic group, manometers are the mercury column and the gauge and socioeconomic status. The manual sphygmomanometer in spina bifida occurs in 1 in every 1,000 to 2,000 most frequent use today consists of a gauge attached births. The risk of spina bifida and other neural to a rubber cuff that is wrapped around the upper tube defects, such as anencephaly, can be signifi- arm and is inflated to constrict the arteries. A blood cantly decreased if women take ample folic acid pressure reading consists of two numbers: systolic before conception and during pregnancy. Systolic refers to systole, the phase when the heart pumps blood out into the aorta. Diastolic refers to diastole, the resting period when the heart refills with blood. At each heartbeat, the spina bifida occulta A bony defect in the verte- blood pressure is raised to the systolic level, and, bral column that causes a cleft in that column. Treatment is usually cuff inflated with air, a stethoscope is placed over an not required. As the air in the cuff is released, the pressure reading spinal column See vertebral column. As the release of air from spinal cord The major column of nerve tissue the cuff continues, a point is reached when the sound that is connected to the brain and lies within the ver- diminishes and then is no longer heard. The pressure tebral canal and from which the spinal nerves at which the last sound is heard marks the diastolic emerge. The blood pressure reading might show the in the spinal cord: 8 cervical, 12 thoracic, 5 lumbar, systolic and diastolic pressures to be, for example, 5 sacral, and 1 coccygeal. Children and adults with smaller- spinal cord is covered by three connective-tissue or larger-than-average-sized arms may need special- envelopes called the meninges.

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