By D. Mirzo. Iona College. 2018.
Use outside expert consultation for problem Pap smears generic 250 mg azithromycin free shipping, when appro- priate order azithromycin 100 mg without a prescription. Restrict discussions about potential claims to individuals within your practice group generic azithromycin 500 mg online. Limit the number of people within your group who review a potential problem Pap smear order 250mg azithromycin fast delivery, because anyone who reviews it may be subsequently deposed. Notify your insurance company early if you suspect that a claim may be filed. Chapter 13 / Pap Smear Litigation 177 Long-Term Solutions and Questions to Explore Long-term solutions and questions that should be explored include the following: 1. We need a reasonable practitioner standard or a process standard, not an outcome standard; following the proce- dures proven to minimize the false-negative rate (complying with CLIA 88 regulations is a minimum standard) should become the stan- dard of care rather than the current unattainable standard of having a zero false-negative rate. Develop criteria that define an expert witness and create a national registry of certified expert witnesses. Identify how to effectively respond to misleading testimony given by a plaintiff’s “expert” witness. The Guidelines for Review of PAP Smears in the Context of Litigation or Potential Litigation (a state and national professional society-endorsed process for objective slide review) are recommended (11). Determine if pathologists who are board certified in cytopathology are less apt to make interpretative errors than general pathologists, less apt to experience liability claims when errors are made, and are easier to defend when a claim is filed. Determine if laboratories with low volumes (<5000–10,000 Pap smears per year) and laboratories without cytotechnologists (where the screening is done by a pathologist) are at a higher risk of mal- practice. The results of a CAP Interlaboratory Comparison Program in Cervical Cytology published in 1993 concluded that pathologist false-negative and false-positive rates and technologist false-nega- tive rates were lower in laboratories processing more than 20,000 Pap smears each year, compared with labs processing less than 10,000 Pap smears each year (14). Beginning in 1999, there appears to have been a decrease in frequency of Pap smear claims— unfortunately offset by an increase in claims severity. Because risk management can only affect frequency, whereas severity is a reflection of societal values and our legal system, it is tempting to speculate that these recommendations, coupled with the efforts of professional soci- eties also attempting to identify sources of error in the Pap smear (15), were in some measure effective. These strategies have greater sensitivity than the conventional Pap smear with correspondingly lower false- negative rates. Most are based on our understanding that human papillomavirus (HPV) infection is the underlying cause of cervical cancer and its precursors. Carcinogenic high-risk HPV types can be identified in liquid-based cytology specimens or in specimens obtained subsequent to collecting a conventional Pap smear. The National Cancer Institute’s ASC-US/LSIL Triage Study (ALTS; 16 ) involved 3488 women with ASC-US and 1572 with LSIL and evaluated three alternative methods of management: immediate colposcopy, cytologic follow-up, and triage by HPV DNA testing (for 13 oncogenic HPV types utilizing liquid-based cytology). In women with a diagnosis of ASC-US, HPV DNA testing is as sen- sitive as colposcopy in detecting HSIL/carcinoma, particularly in women older than age 29 years. When ASC-US is diagnosed, auto- matically testing for HPV permits triaging those who are HPV-posi- tive to colposcopy (55%), whereas those who are HPV-negative can be followed with a repeat Pap test in 12 months (45%). Reflex HPV testing is not an effective triage method for LSILs because of the high prevalence of high-risk HPV types. Most women with LSILs should be referred for colposcopic examination, although management options may differ for adolescent, pregnant, and postmenopausal women. Both HPV-positive patients with ASC-US and LSIL can be followed after colposcopy with 12-month HPV testing. HPV testing also shows promise as a primary screening test, because its sensitivity exceeds that of cytology. However, its specificity is somewhat lower, especially in women younger than age 30 years. HPV DNA testing combined with a cytology test (“DNA with Pap” Test) is now approved by the Food and Drug Administration for women age 30 years and older. Its sensitivity for detecting HSIL/ carcinoma approaches 100% and has the potential to eliminate screen- ing false-negatives, thereby decreasing risk for both patients and laboratories (17). These ALTS conclusions were the basis for the Consensus Guide- lines for the Management of Women With Cervical Cytological Abnor- Chapter 13 / Pap Smear Litigation 179 malities developed by the ASCCP (14). Pathologists and clinicians should become familiar with these guidelines, and pathologists should consider making follow-up recommendations in their Pap reports. For liquid-based cytology ASC-US cases, a recommendation such as “con- sider immediate HPV DNA testing, diagnostic colposcopy, or a repeat Pap test in 4 to 6 months” may be appropriate. Over the past 7 years, there has been an increase in the proportion of cervical cancers that are adenocarcinomas (approx one in three).
Physiological significance of mechanism of glucose absorption in the New perspectives on mechanisms in- volume-regulatory transporters generic azithromycin 500 mg on line. Annu Rev Physiol volved in generating epithelial cell po- Physiol 1999;276:C995–C1011 buy 250mg azithromycin mastercard. CHAPTER The Action Potential order 100mg azithromycin, Synaptic Transmission trusted 100mg azithromycin, and Maintenance of 33 Nerve Function Cynthia J. CHAPTER OUTLINEPASSIVE MEMBRANE PROPERTIES, THE ACTIONNEUROCHEMICAL TRANSMISSION POTENTIAL, AND ELECTRICAL SIGNALING BYTHE MAINTENANCE OF NERVE CELL FUNCTION NEURONSSYNAPTIC TRANSMISSION KEY CONCEPTS 1. Propagation of an action potential depends on local cur- potential of neurons; voltage-gated ion channels are re- rent flow derived from the inward sodium current depolar- sponsible for the action potential and the release of neuro- izing adjacent regions of an axon to threshold. Ligand-gated ion channels cause membrane depolariza- the thickness of its myelin sheath, if present. Nongated ion channels are distributed throughout the neu- other action potential because of the inactivation of the ronal membrane; voltage-gated channels are largely re- voltage-gated sodium channels. When an action potential invades the nerve terminal, volt- channels predominate on the cell body (soma) and den- age-gated calcium channels open, allowing calcium to en- dritic membrane. Membrane conductance and capacitance affect ion flow in release of neurotransmitter. An action potential is a transient change in membrane po- of neurotransmitters that activate specific receptors on tential characterized by a rapid depolarization followed by their postsynaptic target cells. Most neurotransmitters are stored in synaptic vesicles and activation of voltage-gated sodium channels and the repo- released upon nerve stimulation by a process of calcium- larization phase to an inactivation of the sodium channels mediated exocytosis; once released, the neurotransmitter and the delayed activation of voltage-gated potassium binds to and stimulates its receptors briefly before being channels. Metabolic maintenance of neurons requires specialized hillock is depolarized to a threshold for rapid activation of a functions to match their specialized morphology and com- large number of voltage-gated sodium channels. It activates muscles for move- transmission of information from one cell to another by ment, controls the secretion of hormones from glands, reg- conducting electrical impulses and secreting chemical neu- ulates the rate and depth of breathing, and is involved in rotransmitters. The electrical impulses propagate along the modulating and regulating a multitude of other physiolog- length of nerve fiber processes to their terminals, where ical processes. To perform these functions, the nervous sys- they initiate a series of events that cause the release of 37 38 PART I CELLULAR PHYSIOLOGY chemical neurotransmitters. The release of neurotransmit- structure formed by glial cells (oligodendrocytes in the ters occurs at sites of synaptic contact between two nerve CNS or Schwann cells in the peripheral nervous system, cells. Regular intermittent gaps in the myelin sheath on the postsynaptic cell membrane. The speed with which an axon receptors either excites or inhibits the postsynaptic neuron. The end rotransmitters, and the activation of receptors constitute the of the axon, the axon terminal, contains small vesicles means whereby nerve cells communicate and transmit in- packed with neurotransmitter molecules. When a neuron is activated, an action potential is gen- transmission, and discuss aspects of neuronal structure nec- erated in the axon hillock (or initial segment) and con- essary for the maintenance of nerve cell function. The action potential causes the re- lease of a neurotransmitter from the terminal. These neurotransmitter molecules bind to receptors located on PASSIVE MEMBRANE PROPERTIES, THE target cells. ACTION POTENTIAL, AND ELECTRICAL The binding of a neurotransmitter to its receptor typi- cally causes a flow of ions across the membrane of the post- SIGNALING BY NEURONS synaptic cell. This temporary redistribution of ionic charge Neurons communicate by a combination of electrical and can lead to the generation of an action potential, which it- chemical signaling. Generally, information is integrated and self is mediated by the flow of specific ions across the mem- transmitted along the processes of a single neuron electri- brane. These electrical charges, critical for the transmission cally and then transmitted to a target cell chemically. The of information, are the result of ions moving through ion chemical signal then initiates an electrical change in the tar- channels in the plasma membrane (see Chapter 2). Electrical signals that depend on the passive prop- erties of the neuronal cell membrane spread electrotonically over short distances. These potentials are initiated by local Channels Allow Ions to Flow Through current flow and decay with distance from their site of initi- the Nerve Cell Membrane ation. Alternatively, an action potential is an electrical sig- Ions can flow across the nerve cell membrane through three nal that propagates over a long distance without a change in types of ion channels: nongated (leakage), ligand-gated, amplitude. Nongated ion channels are al- of channel openings and closings in the membrane.
Inward extensions of the cortex may be present tion within the islet may play a role in regulating hormone along the axes of blood vessels toward the center of the secretion comes from the finding that islet cells have both islet 500 mg azithromycin otc, giving the appearance that the islet is subdivided into gap junctions and tight junctions discount azithromycin 100 mg with mastercard. These cells are typically located outer membrane leaflets of contiguous cells could result in in the periphery of the islet order azithromycin 250 mg mastercard, often between beta cells and the formation of microdomains in the interstitial space cheap 500mg azithromycin free shipping, the surrounding mantle of alpha cells. Somatostatin pro- which may also be important for paracrine communication. The arrangement of the vascular supply to islets is also consistent with paracrine involvement in regulating islet se- F Cells. Afferent blood vessels penetrate nearly to the cen- creting cells of islets, representing only about 1% of the to- ter of the islet before branching out and returning to the tal cell population. The innermost cells of the islet, there- similar to that of delta cells. F cells secrete pancreatic fore, receive arterial blood, while those cells nearer the sur- polypeptide. Since there is a definite anatomical arrangement of cells in Increased Blood Glucose Stimulates the the islet (see Fig. In general, the effluent from smaller islets passes through neighboring pancreatic acinar tissue before A variety of factors, including other pancreatic hormones, entering into the hepatic portal venous system. The primary the effluent from larger islets passes directly into the ve- physiological regulator of insulin secretion, however, is the nous system without first perfusing adjacent acinar tissue. The gene for insulin is located on ously, an elevated blood glucose level is the most important the short arm of chromosome 11 in humans. In humans, the threshold hormones and secretory proteins, insulin is first synthe- value for glucose-stimulated insulin secretion is a plasma sized by ribosomes of the rough ER as a larger precursor glucose concentration of approximately 100 mg/dL (5. Based on studies using isolated animal pancreas prepara- The insulin gene product is a 110-amino acid peptide, tions maintained in vitro, it has been determined that insulin preproinsulin. Proinsulin consists of 86 amino acids is secreted in a biphasic manner in response to a marked in- (Fig. An initial burst of insulin secretion chain of insulin, residues 31 to 65 form the connecting pep- may last 5 to 15 minutes, resulting from the secretion of tide, and residues 66 to 86 constitute the A chain. This response is fol- that “connecting peptide” should not be confused with “C- lowed by more gradual and sustained insulin secretion that peptide. Among the It is of clinical significance that insulin and C-peptide amino acids, arginine is the most potent secretagogue for are co-secreted in equal amounts. Among the fatty acids, long-chain fatty acids (16 to lating C-peptide levels may sometimes provide important 18 carbons) generally are considered the most potent stim- information regarding beta cell secretory capacity that ulators of insulin secretion. Several hormones secreted by could not be obtained by measuring circulating insulin lev- the gastrointestinal tract, including gastric inhibitory pep- els alone. An oral dose of glucose produces a greater increment in in- Insulin Secretion. As indicated previ- oral glucose promotes the secretion of GI hormones that Connecting peptide NH2 COOH Proinsulin C-peptide NH COOH 2 A chain NH2 COOH B chain Insulin FIGURE 35. Direct infusion pecially arginine, are potent stimulators of glucagon secre- of acetylcholine into the pancreatic circulation stimulates tion. Somatostatin inhibits glucagon secretion, as it does insulin secretion, reflecting the role of parasympathetic in- insulin secretion. Sulfonylureas, a class of drugs used orally in the treatment of type 2 dia- betes, promote insulin’s action in peripheral tissues but also Increased Blood Glucose and Glucagon Stimulate directly stimulate insulin secretion. The hypothalamus also produces pancreatic somatostatin plays a role in regulating insulin se- this protein, but the regulation of somatostatin secretion cretion, but the importance of this effect has not been fully from the hypothalamus is independent of that from the established. Upon insertion of preprosomato- catecholamines, are also potent inhibitors of insulin secre- statin into the rough ER, it is initially cleaved and converted tion. The prohormone is converted into ac- ing periods of stress and high catecholamine secretion, the tive hormone during packaging and processing in the Golgi desired response is mobilization of glucose and other nutri- apparatus. Insulin generally promotes the opposite re- Factors that stimulate pancreatic somatostatin secretion sponse, and by inhibiting insulin secretion, the cate- include hyperglycemia, glucagon, and amino acids.
New York: Lippincott- (E) Lactoferrin (A) The liver can no longer efficiently Raven cheap 250mg azithromycin, 1994 generic 100 mg azithromycin overnight delivery. The level of drug metabolizing convert 25-hydroxycholecalciferol to Black ER purchase 250mg azithromycin visa. Diagnostic strategies and test al- enzymes in the liver determines how 1 discount azithromycin 100 mg mastercard,25-dihydroxycholecalciferol gorithms in liver disease. Clin Chem fast a drug is removed from the (B) The liver can no longer efficiently 1997;43:1555–1560. Therefore, it would be convert vitamin D to cholecalciferol Chang EB, Sitrin MD, Black DD. Gas- expected to find drug metabolizing (C) The liver can no longer efficiently trointestinal, Hepatobiliary, and Nutri- enzymes convert vitamin D to 25- tional Physiology. Philadelphia: Lip- (A) Higher in smokers than in hydroxycholecalciferol pincott-Raven, 1996. The detoxification enzyme sys- (B) Similar in smokers and nonsmokers convert cholecalciferol to 1,25- tems. Mechanisms and conse- nonsmokers (E) The intestine has impaired quences of portal hypertension. Drugs (D) Stimulated by malnutrition absorption of 1,25- 1992;44(Suppl 2):1–13, 70–72. The liver removes LDLs in the blood vances in liver-directed gene therapy: refer to the by the LDLs binding to Implications for the treatment of dys- (A) Conjugation of drugs with (A) LDL receptors and then lipidemia. CASE STUDIES FOR PART VII • • • macological approaches include calcium channel blockers CASE STUDY FOR CHAPTER 26 (e. She experiences chest pain while at- Reference tempting to eat and often regurgitates swallowed food. In: Yamada T, Fluoroscopic examination of a barium swallow reveals a Alpers DH, Owyang C, Powell DW, Silverstein FE, eds. Text- dilated lower esophagus with considerable residual bar- book of Gastroenterology. Lactose Intolerance Questions A 9-year-old Chinese American boy regularly complains 1. What is the most likely explanation for the failure of the rhea after drinking milk. A gastroenterologist adminis- lower esophageal sphincter relaxation during the swallow? What are the possible treatments for the woman’s condi- an increase in the boy’s expired hydrogen gas. The monosaccharides are ment is pneumatic dilation of the lower esophageal sphinc- then absorbed by sodium-dependent secondary active ter, by placing a balloon in the lumen of the sphincter. If the lactase enzyme is deficient, lactose will not be broken crease renal excretion of sodium and water) and inter- down and will remain in the intestinal lumen. The osmotic mittent paracentesis (insertion of a needle into the peri- activity of the lactose draws water into the intestinal lumen toneal space, evacuating fluid, which relieves the ab- and results in a watery diarrhea. She subsequently tabolize the lactose to lactic acid, carbon dioxide, and hy- undergoes placement of a transjugular intrahepatic por- drogen gas. The extra fluid and gas in the intestine result in tosystemic shunt (TIPS), which serves to lower portal distension and increased motility (cramps). What is the probable explanation for her abdominal pain, tivity is high during childhood, but falls after ages 5 to 7 to distension, and weight gain over 6 months? What is the rationale for giving an anticoagulant, and how adults is about 100% in Asian Americans, 95% in Native does warfarin work? Americans, 81% in African Americans, 56% in Mexican Americans, and 24% in white Americans. A common explanation for abdominal discomfort, disten- ance is common (about 50 to 70%) in adult Americans of sion, and weight gain in women is pregnancy. Her age Mediterranean descent, but is low (0 to only a few %) in makes this unlikely but not impossible.