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Physiology_Levy	Fig. 29.7 In the gastric phase the presence of food in the stomach is detected and activates vagovagal reflexes to stimulate secretion. Food in the stomach results in distention and stretch, which are detected by afferent (or sensory) nerve endings in the gastric wall. These are the peripheral terminals of vagal afferent nerves that transmit information to the brainstem and thereby drive activity in vagal efferent fibers, a vagovagal reflex (see Fig. 29.6 ). In addition, digestion of proteins increases the concentration of oligopeptides and free amino acids in the lumen, which are detected by chemosensors in the gastric mucosa. Oligopeptides and amino acids also stimulate vagal afferent activity. The exact nature of the	Physiology_Levy. Fig. 29.7 In the gastric phase the presence of food in the stomach is detected and activates vagovagal reflexes to stimulate secretion. Food in the stomach results in distention and stretch, which are detected by afferent (or sensory) nerve endings in the gastric wall. These are the peripheral terminals of vagal afferent nerves that transmit information to the brainstem and thereby drive activity in vagal efferent fibers, a vagovagal reflex (see Fig. 29.6 ). In addition, digestion of proteins increases the concentration of oligopeptides and free amino acids in the lumen, which are detected by chemosensors in the gastric mucosa. Oligopeptides and amino acids also stimulate vagal afferent activity. The exact nature of the
Neurology_Adams	Nonparalytic poliomyelitis The prodromal symptoms consist of listlessness, generalized, nonthrobbing headache, fever of 38 to 40°C (100.4 to 104°F), stiffness and aching in the muscles, sore throat in the absence of upper respiratory infection, anorexia, nausea, and vomiting. These symptoms may subside to a varying extent, to be followed after 3 to 4 days by recrudescence of headache and fever and by symptoms of nervous system involvement; more often the second phase of the illness blends with the first. Tenderness and pain in the muscles, tightness of the hamstrings (spasm), and pain in the neck and back become increasingly prominent. Other early manifestations of nervous system involvement include irritability, restlessness, and emotional instability; these are frequently a prelude to paralysis. Added to these symptoms are stiffness of the neck on forward flexion and the characteristic CSF findings of aseptic meningitis. This may constitute the entire illness; alternatively,	Neurology_Adams. Nonparalytic poliomyelitis The prodromal symptoms consist of listlessness, generalized, nonthrobbing headache, fever of 38 to 40°C (100.4 to 104°F), stiffness and aching in the muscles, sore throat in the absence of upper respiratory infection, anorexia, nausea, and vomiting. These symptoms may subside to a varying extent, to be followed after 3 to 4 days by recrudescence of headache and fever and by symptoms of nervous system involvement; more often the second phase of the illness blends with the first. Tenderness and pain in the muscles, tightness of the hamstrings (spasm), and pain in the neck and back become increasingly prominent. Other early manifestations of nervous system involvement include irritability, restlessness, and emotional instability; these are frequently a prelude to paralysis. Added to these symptoms are stiffness of the neck on forward flexion and the characteristic CSF findings of aseptic meningitis. This may constitute the entire illness; alternatively,
Neurology_Adams	Exogenous agents may produce myopathic changes in several ways. They may act directly on muscle cells, either diffusely or locally, as occurs with intramuscular injections, or the muscle damage can be a result of diverse secondary factors—electrolyte disturbances (hypokalemia), renal failure, excessive energy requirements of muscle (as occur with drug-induced seizures and malignant hyperthermia), or inadequate delivery of oxygen and nutrients. Of course, there is a derivative category of drug-induced coma with compressive-ischemic injury to muscle. However, the most important group is that of direct toxic effects on the muscle membrane on the internal apparatus of the cell.	Neurology_Adams. Exogenous agents may produce myopathic changes in several ways. They may act directly on muscle cells, either diffusely or locally, as occurs with intramuscular injections, or the muscle damage can be a result of diverse secondary factors—electrolyte disturbances (hypokalemia), renal failure, excessive energy requirements of muscle (as occur with drug-induced seizures and malignant hyperthermia), or inadequate delivery of oxygen and nutrients. Of course, there is a derivative category of drug-induced coma with compressive-ischemic injury to muscle. However, the most important group is that of direct toxic effects on the muscle membrane on the internal apparatus of the cell.
InternalMed_Harrison	The spatial resolution of ultrasound is dependent on the wavelength: the smaller the wavelength and the higher the frequency of the ultrasound beam, the greater are the spatial resolution and ability to discern small structures. Increasing the frequency of ultrasound will increase resolution but at the expense of reduced penetration. Higher frequencies can be used in pediatric imaging or transesophageal echocardiography where the transducer can be much closer to the structures being interrogated, and this is a rationale for using trans-esophageal echocardiography to obtain higher quality images. Three-dimensional ultrasound transducers use a waffle-like matrix array transducer and receive a pyramidal data sector. Three-dimensional echocardiography is being increasingly used for assessment of congenital heart disease and valves, although current image quality lags behind two-dimensional ultrasound (Fig. 270e-2).	InternalMed_Harrison. The spatial resolution of ultrasound is dependent on the wavelength: the smaller the wavelength and the higher the frequency of the ultrasound beam, the greater are the spatial resolution and ability to discern small structures. Increasing the frequency of ultrasound will increase resolution but at the expense of reduced penetration. Higher frequencies can be used in pediatric imaging or transesophageal echocardiography where the transducer can be much closer to the structures being interrogated, and this is a rationale for using trans-esophageal echocardiography to obtain higher quality images. Three-dimensional ultrasound transducers use a waffle-like matrix array transducer and receive a pyramidal data sector. Three-dimensional echocardiography is being increasingly used for assessment of congenital heart disease and valves, although current image quality lags behind two-dimensional ultrasound (Fig. 270e-2).
Obstentrics_Williams	American College of Obstetricians and Gynecologists: Magnesium sulfate before anticipated preterm birth for neuroprotection. Patient Safety Checklist No.n7, August 2012 American College of Obstetricians and Gynecologists: Magnesium sulfate use in obstetrics. Committee Opinion No. 652, January 2016a American College of Obstetricians and Gynecologists: Management of preterm labor. Practice Bulletin No. 171, October 2016b American College of Obstetricians and Gynecologists: Prediction and prevention of preterm birth. Practice Bulletin No. 130, October 2012, Reairmed 2016c American College of Obstetricians and Gynecologists: Premature rupture of membranes. Practice Bulletin No. 172, October 2016d American College of Obstetricians and Gynecologists: Antenatal corticosteroid therapy for fetal maturation. Committee Opinion No. 713, August 2017a	Obstentrics_Williams. American College of Obstetricians and Gynecologists: Magnesium sulfate before anticipated preterm birth for neuroprotection. Patient Safety Checklist No.n7, August 2012 American College of Obstetricians and Gynecologists: Magnesium sulfate use in obstetrics. Committee Opinion No. 652, January 2016a American College of Obstetricians and Gynecologists: Management of preterm labor. Practice Bulletin No. 171, October 2016b American College of Obstetricians and Gynecologists: Prediction and prevention of preterm birth. Practice Bulletin No. 130, October 2012, Reairmed 2016c American College of Obstetricians and Gynecologists: Premature rupture of membranes. Practice Bulletin No. 172, October 2016d American College of Obstetricians and Gynecologists: Antenatal corticosteroid therapy for fetal maturation. Committee Opinion No. 713, August 2017a
InternalMed_Harrison	Strategies to eliminate rheumatic heart disease may depend on active case-finding, with confirmation by echocardiography, among high-risk groups as well as on efforts to expand access to surgical interventions among children with advanced valvular damage. Partnerships between established surgical programs and areas with limited or nonexistent facilities may help expand the capacity to provide life-saving interventions to patients who otherwise would die early and painfully. A long-term goal is the establishment of regional centers of excellence equipped to provide consistent, accessible, high-quality services.	InternalMed_Harrison. Strategies to eliminate rheumatic heart disease may depend on active case-finding, with confirmation by echocardiography, among high-risk groups as well as on efforts to expand access to surgical interventions among children with advanced valvular damage. Partnerships between established surgical programs and areas with limited or nonexistent facilities may help expand the capacity to provide life-saving interventions to patients who otherwise would die early and painfully. A long-term goal is the establishment of regional centers of excellence equipped to provide consistent, accessible, high-quality services.
Cell_Biology_Alberts	Developmental events unfold over minutes, hours, days, weeks, months, or even years, with each organism following its own strict timetable. The cascades of inductive interactions and transcriptional regulatory events described earlier take time, as signals are transmitted and transcription regulators are synthesized and then bind to DNA to activate or repress their target genes. At the beginning of this chapter, we compared development with an orchestral performance. There are many players, and each must do the right thing at the right time; yet there is no leader or conductor to set the tempo and coordinate the timing of all the different events. Each developmental process must thus occur at an appropriate rate, tuned by evolution to fit with the timing of other processes in the embryo or in the environment. The control of timing is one of the most important problems in developmental biology, but also one of the least understood.	Cell_Biology_Alberts. Developmental events unfold over minutes, hours, days, weeks, months, or even years, with each organism following its own strict timetable. The cascades of inductive interactions and transcriptional regulatory events described earlier take time, as signals are transmitted and transcription regulators are synthesized and then bind to DNA to activate or repress their target genes. At the beginning of this chapter, we compared development with an orchestral performance. There are many players, and each must do the right thing at the right time; yet there is no leader or conductor to set the tempo and coordinate the timing of all the different events. Each developmental process must thus occur at an appropriate rate, tuned by evolution to fit with the timing of other processes in the embryo or in the environment. The control of timing is one of the most important problems in developmental biology, but also one of the least understood.
Neurology_Adams	This is directed along several lines. At the outset, a single dose of antitoxin (3,000 to 6,000 U of tetanus human immune globulin) should be given along with a 10-day course of penicillin (1.2 million U of procaine penicillin daily), metronidazole (500 mg q6h intravenously or 400 mg rectally), or tetracycline (2 g daily). These drugs are effective against the vegetative forms of C. tetani. Immediate surgical treatment of the wound (excision or debridement) is imperative, and the tissue around the wound should be infiltrated with antitoxin.	Neurology_Adams. This is directed along several lines. At the outset, a single dose of antitoxin (3,000 to 6,000 U of tetanus human immune globulin) should be given along with a 10-day course of penicillin (1.2 million U of procaine penicillin daily), metronidazole (500 mg q6h intravenously or 400 mg rectally), or tetracycline (2 g daily). These drugs are effective against the vegetative forms of C. tetani. Immediate surgical treatment of the wound (excision or debridement) is imperative, and the tissue around the wound should be infiltrated with antitoxin.
Histology_Ross	The gallbladder concentrates and stores bile. The gallbladder is a blind pouch that leads, via a neck, to the cystic duct. Through this duct it receives dilute bile from the chapter 18 Digestive System III: Liver, Gallbladder, and Pancreas GALLB LADDE R 643 hepatic duct. The gallbladder can store and remove about Localized concentrations of mitochondria in the apical 90% of the water from the incoming bile, which results in an and basal cytoplasm increase of bile salts, cholesterol, and bilirubin concentrations Complex lateral plications up to 10-fold. Hormones secreted by the enteroendocrine cells of the small intestine, in response to the presence of fat in the proximal duodenum, stimulate contractions of the smooth muscle of the gallbladder. Because of these contractions, concentrated bile is discharged into the common bile duct, which carries it to the duodenum. Mucosa of the gallbladder has several characteristic features.	Histology_Ross. The gallbladder concentrates and stores bile. The gallbladder is a blind pouch that leads, via a neck, to the cystic duct. Through this duct it receives dilute bile from the chapter 18 Digestive System III: Liver, Gallbladder, and Pancreas GALLB LADDE R 643 hepatic duct. The gallbladder can store and remove about Localized concentrations of mitochondria in the apical 90% of the water from the incoming bile, which results in an and basal cytoplasm increase of bile salts, cholesterol, and bilirubin concentrations Complex lateral plications up to 10-fold. Hormones secreted by the enteroendocrine cells of the small intestine, in response to the presence of fat in the proximal duodenum, stimulate contractions of the smooth muscle of the gallbladder. Because of these contractions, concentrated bile is discharged into the common bile duct, which carries it to the duodenum. Mucosa of the gallbladder has several characteristic features.
InternalMed_Harrison	of access to pathologic brain tissue except upon death and the inherent limitations of animal models for disorders defined largely by behavioral abnormalities (e.g., hallucinations, delusions, guilt, suicidality) that are inaccessible in animals.	InternalMed_Harrison. of access to pathologic brain tissue except upon death and the inherent limitations of animal models for disorders defined largely by behavioral abnormalities (e.g., hallucinations, delusions, guilt, suicidality) that are inaccessible in animals.
Obstentrics_Williams	Heartburn is another common complaint of gravidas and is caused by gastric content reflux into the lower esophagus. The greater frequency of regurgitation during pregnancy most likely results from upward displacement and compression of the stomach by the uterus, combined with relaxation of the lower esophageal sphincter. Avoiding bending over or lying flat is preventive. In most pregnant women, symptoms are mild and relieved by a regimen of more frequent but smaller meals. Antacids may provide considerable relief (Phupong, 2015). Specifically, aluminum hydroxide, magnesium trisilicate, or magnesium hydroxide is given alone or in combination. Management of heartburn or nausea that does not respond to simple measures is discussed in Chapter 54 (p. 1045).	Obstentrics_Williams. Heartburn is another common complaint of gravidas and is caused by gastric content reflux into the lower esophagus. The greater frequency of regurgitation during pregnancy most likely results from upward displacement and compression of the stomach by the uterus, combined with relaxation of the lower esophageal sphincter. Avoiding bending over or lying flat is preventive. In most pregnant women, symptoms are mild and relieved by a regimen of more frequent but smaller meals. Antacids may provide considerable relief (Phupong, 2015). Specifically, aluminum hydroxide, magnesium trisilicate, or magnesium hydroxide is given alone or in combination. Management of heartburn or nausea that does not respond to simple measures is discussed in Chapter 54 (p. 1045).
InternalMed_Harrison	(See also Chap. 65) PATHOPHYSIOLOGY OF HYPOCALCEMIA: CLASSIFICATION BASED ON MECHANISM Chronic hypocalcemia is less common than hypercalcemia; causes include chronic renal failure, hereditary and acquired hypoparathyroidism, vitamin D deficiency, pseudohypoparathyroidism, and hypomagnesemia (Table 424-5).	InternalMed_Harrison. (See also Chap. 65) PATHOPHYSIOLOGY OF HYPOCALCEMIA: CLASSIFICATION BASED ON MECHANISM Chronic hypocalcemia is less common than hypercalcemia; causes include chronic renal failure, hereditary and acquired hypoparathyroidism, vitamin D deficiency, pseudohypoparathyroidism, and hypomagnesemia (Table 424-5).
Surgery_Schwartz	systemic inflamma-tory response, characterized by increased body temperature, heart rate, respirations, and white blood cell count, are similar to those observed with infection (Table 2-1). However, it is widely accepted that systemic inflammation following trauma is sterile, resulting from endogenous molecules that are produced as a consequence of tissue damage or cellular stress.5 Termed damage-associated molecular patterns (DAMPs) or alarmins, DAMPs interact with specific cell receptors that are located both on the cell surface and intracellularly.6Trauma DAMPs are structurally diverse endogenous mol-ecules that are immunologically active. Table 2-2 includes a par-tial list of DAMPs that are released either passively from necrotic/damaged cells or actively from physiologically “stressed” cells by upregulation or overexpression. Once they are outside the cell, DAMPs promote the activation of innate immune cells, as well as the recruitment and activation of antigen-presenting cells,	Surgery_Schwartz. systemic inflamma-tory response, characterized by increased body temperature, heart rate, respirations, and white blood cell count, are similar to those observed with infection (Table 2-1). However, it is widely accepted that systemic inflammation following trauma is sterile, resulting from endogenous molecules that are produced as a consequence of tissue damage or cellular stress.5 Termed damage-associated molecular patterns (DAMPs) or alarmins, DAMPs interact with specific cell receptors that are located both on the cell surface and intracellularly.6Trauma DAMPs are structurally diverse endogenous mol-ecules that are immunologically active. Table 2-2 includes a par-tial list of DAMPs that are released either passively from necrotic/damaged cells or actively from physiologically “stressed” cells by upregulation or overexpression. Once they are outside the cell, DAMPs promote the activation of innate immune cells, as well as the recruitment and activation of antigen-presenting cells,
InternalMed_Harrison	Transfusion-transmitted viral infections are increasingly rare due to improved screening and testing. As the risk of viral infection is reduced, the relative risk of other reactions increases, such as hemolytic transfusion reactions and sepsis from bacterially contaminated components. Pretransfusion quality assurance improvements further increase the safety of transfusion therapy. Infections, like any adverse transfusion reaction, must be brought to the attention of the blood bank for appropriate studies (Table 138e-3). IMMUNE-MEDIATED REACTIONS Acute Hemolytic Transfusion Reactions Immune-mediated hemolysis occurs when the recipient has preformed antibodies that lyse donor erythrocytes. The ABO isoagglutinins are responsible for the majority of these reactions. However, alloantibodies directed against other RBC antigens, i.e., Rh, Kell, and Duffy, are responsible for more fatal hemolytic transfusion reactions.	InternalMed_Harrison. Transfusion-transmitted viral infections are increasingly rare due to improved screening and testing. As the risk of viral infection is reduced, the relative risk of other reactions increases, such as hemolytic transfusion reactions and sepsis from bacterially contaminated components. Pretransfusion quality assurance improvements further increase the safety of transfusion therapy. Infections, like any adverse transfusion reaction, must be brought to the attention of the blood bank for appropriate studies (Table 138e-3). IMMUNE-MEDIATED REACTIONS Acute Hemolytic Transfusion Reactions Immune-mediated hemolysis occurs when the recipient has preformed antibodies that lyse donor erythrocytes. The ABO isoagglutinins are responsible for the majority of these reactions. However, alloantibodies directed against other RBC antigens, i.e., Rh, Kell, and Duffy, are responsible for more fatal hemolytic transfusion reactions.
Pharmacology_Katzung	The directions for use (element [11]) must be both drug-specific and patient-specific. The simpler the directions, the better; and the fewer the number of doses (and drugs) per day, the better. Patient noncompliance (also known as nonadherence, failure to adhere to the drug regimen) is a major cause of treatment failure. To help patients remember to take their medications, prescribers often give an instruction that medications be taken at or around mealtimes and at bedtime. However, it is important to inquire about the patient’s eating habits and other lifestyle patterns, because many patients do not eat three regularly spaced meals a day.	Pharmacology_Katzung. The directions for use (element [11]) must be both drug-specific and patient-specific. The simpler the directions, the better; and the fewer the number of doses (and drugs) per day, the better. Patient noncompliance (also known as nonadherence, failure to adhere to the drug regimen) is a major cause of treatment failure. To help patients remember to take their medications, prescribers often give an instruction that medications be taken at or around mealtimes and at bedtime. However, it is important to inquire about the patient’s eating habits and other lifestyle patterns, because many patients do not eat three regularly spaced meals a day.
Histology_Ross	The thymus is fully formed and functional at birth. It persists as a large organ until about the time of puberty, when T-cell differentiation and proliferation are reduced and most of the lymphatic tissue is replaced by adipose tissue (involution). The organ can be restimulated under conditions that demand rapid T-cell proliferation. General Architecture of the Thymus Connective tissue surrounds the thymus and subdivides it into thymic lobules. The thymus possesses a thin connective tissue capsule from which trabeculae extend into the parenchyma of the organ. The capsule and trabeculae contain blood vessels, efferent (but not afferent) lymphatic vessels, and nerves. In addition to collagen fibers and fibroblasts, the connective tissue of the thymus contains variable numbers of plasma cells, granulocytes, lymphocytes, mast cells, adipose cells, and macrophages.	Histology_Ross. The thymus is fully formed and functional at birth. It persists as a large organ until about the time of puberty, when T-cell differentiation and proliferation are reduced and most of the lymphatic tissue is replaced by adipose tissue (involution). The organ can be restimulated under conditions that demand rapid T-cell proliferation. General Architecture of the Thymus Connective tissue surrounds the thymus and subdivides it into thymic lobules. The thymus possesses a thin connective tissue capsule from which trabeculae extend into the parenchyma of the organ. The capsule and trabeculae contain blood vessels, efferent (but not afferent) lymphatic vessels, and nerves. In addition to collagen fibers and fibroblasts, the connective tissue of the thymus contains variable numbers of plasma cells, granulocytes, lymphocytes, mast cells, adipose cells, and macrophages.
Biochemistry_Lippinco	D. Lysosomal degradation A small amount (1%–3%) of glycogen is degraded by the lysosomal enzyme, acid α(1→4)-glucosidase (acid maltase). The purpose of this autophagic pathway is unknown. However, a deficiency of this enzyme causes accumulation of glycogen in vacuoles in the lysosomes, resulting in the serious GSD type II: Pompe disease (see Fig. 11.8). [Note: Pompe disease is the only GSD that is a lysosomal storage disease.] Lysosomal storage diseases are genetic disorders characterized by the accumulation of abnormal amounts of carbohydrates or lipids primarily due to their decreased lysosomal degradation resulting from decreased activity or amount of lysosomal acid hydrolases. V. GLYCOGENESIS AND GLYCOGENOLYSIS REGULATION	Biochemistry_Lippinco. D. Lysosomal degradation A small amount (1%–3%) of glycogen is degraded by the lysosomal enzyme, acid α(1→4)-glucosidase (acid maltase). The purpose of this autophagic pathway is unknown. However, a deficiency of this enzyme causes accumulation of glycogen in vacuoles in the lysosomes, resulting in the serious GSD type II: Pompe disease (see Fig. 11.8). [Note: Pompe disease is the only GSD that is a lysosomal storage disease.] Lysosomal storage diseases are genetic disorders characterized by the accumulation of abnormal amounts of carbohydrates or lipids primarily due to their decreased lysosomal degradation resulting from decreased activity or amount of lysosomal acid hydrolases. V. GLYCOGENESIS AND GLYCOGENOLYSIS REGULATION
Obstentrics_Williams	Because magnesium is cleared almost exclusivey by renal excre . tion, the dosages described wil become excessive if glomerular il tration is substantialy decreased. The initial 4-g loading dose of magnesium sulfate can be safely administered regardless of renal function. It is important to administer the standard load ing dose and not to reduce it under the mistaken conception that diminished renal function requires it. This is because after distribution, a loading dose achieves the desired therapeutic level, and the infusion maintains the steady-state level. Thus, ony the maintenance infusion rate should be altered with dimin ished glomerular iltration rate. Renal function is estimated by measuring plasma creatinine. Whenever plasma creatinine lev els arer> 1.0 mg/mL, serum magnesium levels are determined to guide the infusion rate.	Obstentrics_Williams. Because magnesium is cleared almost exclusivey by renal excre . tion, the dosages described wil become excessive if glomerular il tration is substantialy decreased. The initial 4-g loading dose of magnesium sulfate can be safely administered regardless of renal function. It is important to administer the standard load ing dose and not to reduce it under the mistaken conception that diminished renal function requires it. This is because after distribution, a loading dose achieves the desired therapeutic level, and the infusion maintains the steady-state level. Thus, ony the maintenance infusion rate should be altered with dimin ished glomerular iltration rate. Renal function is estimated by measuring plasma creatinine. Whenever plasma creatinine lev els arer> 1.0 mg/mL, serum magnesium levels are determined to guide the infusion rate.
InternalMed_Harrison	4. Even though primary dapsone resistance is exceedingly rare and multidrug therapy is generally recommended (at least for lepromatous leprosy), there is a paucity of information from experimental animals and clinical trials on the optimal combination of antimicrobial agents, dosing schedule, and duration of therapy.	InternalMed_Harrison. 4. Even though primary dapsone resistance is exceedingly rare and multidrug therapy is generally recommended (at least for lepromatous leprosy), there is a paucity of information from experimental animals and clinical trials on the optimal combination of antimicrobial agents, dosing schedule, and duration of therapy.
InternalMed_Harrison	these doses, the drug was nephro-2035 toxic. Even at 30 mg/d, creatinine elevations of 44 μmol/L (0.5 mg/ dL) occurred in 10% of patients; however, at the HBV-effective dose of 10 mg, such elevations of creatinine are rarely encountered. If any nephrotoxicity does occur, it rarely appears before 6−8 months of therapy. Although renal tubular injury is a rare potential side effect, and although creatinine monitoring is recommended during treatment, the therapeutic index of adefovir dipivoxil is high, and the nephrotoxicity observed in clinical trials at higher doses was reversible. For patients with underlying renal disease, frequency of administration of adefovir dipivoxil should be reduced to every 48 h for creatinine clearances of 30−49 mL/min; to every 72 h for creatinine clearances of 10−29 mL/min; and once a week, following dialysis, for patients undergoing hemodialysis. Adefovir dipivoxil is very well tolerated, and ALT elevations during and after withdrawal of therapy are	InternalMed_Harrison. these doses, the drug was nephro-2035 toxic. Even at 30 mg/d, creatinine elevations of 44 μmol/L (0.5 mg/ dL) occurred in 10% of patients; however, at the HBV-effective dose of 10 mg, such elevations of creatinine are rarely encountered. If any nephrotoxicity does occur, it rarely appears before 6−8 months of therapy. Although renal tubular injury is a rare potential side effect, and although creatinine monitoring is recommended during treatment, the therapeutic index of adefovir dipivoxil is high, and the nephrotoxicity observed in clinical trials at higher doses was reversible. For patients with underlying renal disease, frequency of administration of adefovir dipivoxil should be reduced to every 48 h for creatinine clearances of 30−49 mL/min; to every 72 h for creatinine clearances of 10−29 mL/min; and once a week, following dialysis, for patients undergoing hemodialysis. Adefovir dipivoxil is very well tolerated, and ALT elevations during and after withdrawal of therapy are
InternalMed_Harrison	Plain and upright or lateral decubitus radiographs of the abdomen may be of value in cases of intestinal obstruction, perforated ulcer, and a variety of other conditions. They are usually unnecessary in patients with acute appendicitis or strangulated external hernias. In rare instances, barium or water-soluble contrast study of the upper part of the gastrointestinal tract may demonstrate partial intestinal obstruction that may elude diagnosis by other means. If there is any question of obstruction of the colon, oral administration of barium sulfate should be avoided. On the other hand, in cases of suspected colonic obstruction (without perforation), a contrast enema may be diagnostic.	InternalMed_Harrison. Plain and upright or lateral decubitus radiographs of the abdomen may be of value in cases of intestinal obstruction, perforated ulcer, and a variety of other conditions. They are usually unnecessary in patients with acute appendicitis or strangulated external hernias. In rare instances, barium or water-soluble contrast study of the upper part of the gastrointestinal tract may demonstrate partial intestinal obstruction that may elude diagnosis by other means. If there is any question of obstruction of the colon, oral administration of barium sulfate should be avoided. On the other hand, in cases of suspected colonic obstruction (without perforation), a contrast enema may be diagnostic.
InternalMed_Harrison	EBV infections occur worldwide. These infections are most common in early childhood, with a second peak during late adolescence. By adulthood, more than 90% of individuals have been infected and have antibodies to the virus. IM is usually a disease of young adults. In lower socioeconomic groups and in areas of the world with deficient standards of hygiene (e.g., developing regions), EBV tends to infect children at an early age, and IM is uncommon. In areas with higher standards of hygiene, infection with EBV is often delayed until adulthood, and IM is more prevalent.	InternalMed_Harrison. EBV infections occur worldwide. These infections are most common in early childhood, with a second peak during late adolescence. By adulthood, more than 90% of individuals have been infected and have antibodies to the virus. IM is usually a disease of young adults. In lower socioeconomic groups and in areas of the world with deficient standards of hygiene (e.g., developing regions), EBV tends to infect children at an early age, and IM is uncommon. In areas with higher standards of hygiene, infection with EBV is often delayed until adulthood, and IM is more prevalent.
Cell_Biology_Alberts	Bacteria Are Diverse and Occupy a Remarkable Variety of Ecological Niches	Cell_Biology_Alberts. Bacteria Are Diverse and Occupy a Remarkable Variety of Ecological Niches
Pediatrics_Nelson	Assisted ventilation with high peak inspiratory pressures and positive end-expiratory pressures may cause overdistention of alveoli in localized areas of the lung. Rupture of the alveolar epithelial lining may produce pulmonary interstitial emphysema as gas dissects along the interstitial space and the peribronchial lymphatics. Extravasation of gas into the parenchyma reduces lung compliance and worsens respiratory failure. Gas dissection into the mediastinal space produces a pneumomediastinum, occasionally dissecting into the subcutaneous tissues around the neck, causing subcutaneous emphysema. Alveolar rupture adjacent to the pleural space produces a pneumothorax (Fig. 61-3). If the gas is under tension, the pneumothorax shifts the mediastinum to the opposite side of the chest, producing hypotension, hypoxia, and hypercapnia.	Pediatrics_Nelson. Assisted ventilation with high peak inspiratory pressures and positive end-expiratory pressures may cause overdistention of alveoli in localized areas of the lung. Rupture of the alveolar epithelial lining may produce pulmonary interstitial emphysema as gas dissects along the interstitial space and the peribronchial lymphatics. Extravasation of gas into the parenchyma reduces lung compliance and worsens respiratory failure. Gas dissection into the mediastinal space produces a pneumomediastinum, occasionally dissecting into the subcutaneous tissues around the neck, causing subcutaneous emphysema. Alveolar rupture adjacent to the pleural space produces a pneumothorax (Fig. 61-3). If the gas is under tension, the pneumothorax shifts the mediastinum to the opposite side of the chest, producing hypotension, hypoxia, and hypercapnia.
Gynecology_Novak	134. Steckel J, Badillo F, Waldbaum RS. Uretero-fallopian tube fistula secondary to laparoscopic fulguration of pelvic endometriosis. JUrol 1993;149:1128–1129. 135. Woodland MB. Ureter injury during laparoscopy-assisted vaginal hysterectomy with the endoscopic linear stapler. Am J Obstet Gynecol 1992;167:756–757. 136. Parpala-Sparman T, Paananen I, Santala M, et al. Increasing numbers of ureteric injuries after the introduction of laparoscopic surgery. Scand J Urol Nephrol 2008;42:422–427. 137. Nezhat C, Nezhat FR. Safe laser endoscopic excision or vaporization of peritoneal endometriosis. Fertil Steril 1989;52:149–151. 138. Nezhat C, Nezhat F. Laparoscopic repair of ureter resected during operative laparoscopy. Obstet Gynecol 1992;80:543–544. 139. Irvin W, Andersen W, Taylor P, et al. Minimizing the risk of neurologic injury in gynecologic surgery. Obstet Gynecol 2004;103:374– 382. 140.	Gynecology_Novak. 134. Steckel J, Badillo F, Waldbaum RS. Uretero-fallopian tube fistula secondary to laparoscopic fulguration of pelvic endometriosis. JUrol 1993;149:1128–1129. 135. Woodland MB. Ureter injury during laparoscopy-assisted vaginal hysterectomy with the endoscopic linear stapler. Am J Obstet Gynecol 1992;167:756–757. 136. Parpala-Sparman T, Paananen I, Santala M, et al. Increasing numbers of ureteric injuries after the introduction of laparoscopic surgery. Scand J Urol Nephrol 2008;42:422–427. 137. Nezhat C, Nezhat FR. Safe laser endoscopic excision or vaporization of peritoneal endometriosis. Fertil Steril 1989;52:149–151. 138. Nezhat C, Nezhat F. Laparoscopic repair of ureter resected during operative laparoscopy. Obstet Gynecol 1992;80:543–544. 139. Irvin W, Andersen W, Taylor P, et al. Minimizing the risk of neurologic injury in gynecologic surgery. Obstet Gynecol 2004;103:374– 382. 140.
InternalMed_Harrison	Lesions of the hypothalamic-pituitary region that disrupt hypothalamic dopamine synthesis, portal vessel delivery, or lactotrope responses are associated with hyperprolactinemia. Thus, hypothalamic tumors, cysts, infiltrative disorders, and radiation-induced damage cause elevated PRL levels, usually in the range of 30–100 μg/L. Plurihormonal adenomas (including GH and ACTH tumors) may hypersecrete PRL directly. Pituitary masses, including clinically nonfunctioning pituitary tumors, may compress the pituitary stalk to cause hyperprolactinemia.	InternalMed_Harrison. Lesions of the hypothalamic-pituitary region that disrupt hypothalamic dopamine synthesis, portal vessel delivery, or lactotrope responses are associated with hyperprolactinemia. Thus, hypothalamic tumors, cysts, infiltrative disorders, and radiation-induced damage cause elevated PRL levels, usually in the range of 30–100 μg/L. Plurihormonal adenomas (including GH and ACTH tumors) may hypersecrete PRL directly. Pituitary masses, including clinically nonfunctioning pituitary tumors, may compress the pituitary stalk to cause hyperprolactinemia.
Pharmacology_Katzung	FIGURE 7–3 Structures of some cholinomimetic alkaloids. A. Mechanism of Action Activation of the parasympathetic nervous system modifies organ function by two major mechanisms. First, acetylcholine released from parasympathetic nerves activates muscarinic receptors on effector cells to alter organ function directly. Second, acetylcholine released from parasympathetic nerves interacts with muscarinic receptors on nerve terminals to inhibit the release of their neurotransmitter. By this mechanism, acetylcholine release and circulating muscarinic agonists indirectly alter organ function by modulating the effects of the parasympathetic and sympathetic nervous systems and perhaps nonadrenergic, noncholinergic (NANC) systems.	Pharmacology_Katzung. FIGURE 7–3 Structures of some cholinomimetic alkaloids. A. Mechanism of Action Activation of the parasympathetic nervous system modifies organ function by two major mechanisms. First, acetylcholine released from parasympathetic nerves activates muscarinic receptors on effector cells to alter organ function directly. Second, acetylcholine released from parasympathetic nerves interacts with muscarinic receptors on nerve terminals to inhibit the release of their neurotransmitter. By this mechanism, acetylcholine release and circulating muscarinic agonists indirectly alter organ function by modulating the effects of the parasympathetic and sympathetic nervous systems and perhaps nonadrenergic, noncholinergic (NANC) systems.
InternalMed_Harrison	Acute hypercapnia follows sudden occlusion of the upper airway or generalized bronchospasm as in severe asthma, anaphylaxis, I. Alkalosis A. Central nervous system stimulation 1. 2. Anxiety, psychosis 3. 4. 5. Meningitis, encephalitis 6. 7. B. Hypoxemia or tissue hypoxia 1. 2. Pneumonia, pulmonary edema 3. 4. C. Drugs or hormones 1. Pregnancy, progesterone 2. 3. D. Stimulation of chest receptors 1. 2. 3. 4. E. Miscellaneous 1. 2. 3. 4. 5. II. A. 1. Drugs (anesthetics, morphine, sedatives) 2. 3. B. Airway 1. 2. C. Parenchyma 1. 2. 3. 4. 5. D. Neuromuscular 1. 2. 3. 4. E. Miscellaneous 1. 2. 3.	InternalMed_Harrison. Acute hypercapnia follows sudden occlusion of the upper airway or generalized bronchospasm as in severe asthma, anaphylaxis, I. Alkalosis A. Central nervous system stimulation 1. 2. Anxiety, psychosis 3. 4. 5. Meningitis, encephalitis 6. 7. B. Hypoxemia or tissue hypoxia 1. 2. Pneumonia, pulmonary edema 3. 4. C. Drugs or hormones 1. Pregnancy, progesterone 2. 3. D. Stimulation of chest receptors 1. 2. 3. 4. E. Miscellaneous 1. 2. 3. 4. 5. II. A. 1. Drugs (anesthetics, morphine, sedatives) 2. 3. B. Airway 1. 2. C. Parenchyma 1. 2. 3. 4. 5. D. Neuromuscular 1. 2. 3. 4. E. Miscellaneous 1. 2. 3.
Neurology_Adams	The tumor is oval, round, or lobulated and has a smooth surface. The wall of the cyst and the solid parts of the tumor consist of cords and whorls of epithelial cells (often with intercellular bridges and keratohyalin) separated by a loose network of stellate cells. If there are bridges between tumor cells, which have an epithelial origin, the tumor had in the past been classed as an adamantinoma, a term not used in recent classifications. The cyst contains dark albuminous fluid, cholesterol crystals, and calcium deposits; the calcium can be seen in plain films or CT of the suprasellar region in 70 to 80 percent of cases. The sella beneath the tumor tends to be flattened and enlarged. The majority of the patients are children, but the tumor is not infrequent in adults, and we have encountered patients up to 60 years of age.	Neurology_Adams. The tumor is oval, round, or lobulated and has a smooth surface. The wall of the cyst and the solid parts of the tumor consist of cords and whorls of epithelial cells (often with intercellular bridges and keratohyalin) separated by a loose network of stellate cells. If there are bridges between tumor cells, which have an epithelial origin, the tumor had in the past been classed as an adamantinoma, a term not used in recent classifications. The cyst contains dark albuminous fluid, cholesterol crystals, and calcium deposits; the calcium can be seen in plain films or CT of the suprasellar region in 70 to 80 percent of cases. The sella beneath the tumor tends to be flattened and enlarged. The majority of the patients are children, but the tumor is not infrequent in adults, and we have encountered patients up to 60 years of age.
Psichiatry_DSM-5	Dwayne Kruse, M.S., M.F.T. Ajay S. Kuchibhatla, M.D. Shubha N. Kumar, M.D. Helen H. Kyomen, M.D., M.S. Rebecca M. Lachut, M.Ed., Ed.S. Alexis Lake, M.S.S. Ramaswamy Lakshmanan, M.D. Brigitta Lalone, L.C.S.W.-R John W. Lancaster, Ph.D. Patience R. Land, L.I.C.S.W., M.S.W., M.P.A. Amber Lange, M.A., Ph.D. Jeff K. Larsen, M.A. Nathan E. Lavid, M.D. Michelle Leader, Ph.D. Stephen E. Lee, M.D. Cathryn L. Leff, Ph.D., L.M.F.T. Rachael Kollar Leombruno, L.M.F.T. Arlene I. Lev, M.S.W., L.C.S.W.-R Gregory K. Lewis, M.A.-L.M.F.T. Jane Hart Lewis, M.S. Melissa S. Lewis, M.S.W., L.I.C.S.W. Norman Gerald Lewis, F.R.A.N.2.C.P. Robin Joy Lewis, Ph.D. Ryan Michael Ley, M.D. Tammy R. Lias, M.A. Russell F. Lim, M.D. Jana Lincoln, M.D. Ted Lindberg, L.M.S.W., L.M.F.T., M.S.W. Peggy Solow Liss, M.S.W. Andrea Loeb, Psy.D. William David Lohr, M.D. Mary L. Ludy, M.A., L.M.H.C., L.M.F.T. Nathan Lundin, M.A., L.P.C. Veena Luthra, M.D. Patti Lyerly, L.C.S.W.	Psichiatry_DSM-5. Dwayne Kruse, M.S., M.F.T. Ajay S. Kuchibhatla, M.D. Shubha N. Kumar, M.D. Helen H. Kyomen, M.D., M.S. Rebecca M. Lachut, M.Ed., Ed.S. Alexis Lake, M.S.S. Ramaswamy Lakshmanan, M.D. Brigitta Lalone, L.C.S.W.-R John W. Lancaster, Ph.D. Patience R. Land, L.I.C.S.W., M.S.W., M.P.A. Amber Lange, M.A., Ph.D. Jeff K. Larsen, M.A. Nathan E. Lavid, M.D. Michelle Leader, Ph.D. Stephen E. Lee, M.D. Cathryn L. Leff, Ph.D., L.M.F.T. Rachael Kollar Leombruno, L.M.F.T. Arlene I. Lev, M.S.W., L.C.S.W.-R Gregory K. Lewis, M.A.-L.M.F.T. Jane Hart Lewis, M.S. Melissa S. Lewis, M.S.W., L.I.C.S.W. Norman Gerald Lewis, F.R.A.N.2.C.P. Robin Joy Lewis, Ph.D. Ryan Michael Ley, M.D. Tammy R. Lias, M.A. Russell F. Lim, M.D. Jana Lincoln, M.D. Ted Lindberg, L.M.S.W., L.M.F.T., M.S.W. Peggy Solow Liss, M.S.W. Andrea Loeb, Psy.D. William David Lohr, M.D. Mary L. Ludy, M.A., L.M.H.C., L.M.F.T. Nathan Lundin, M.A., L.P.C. Veena Luthra, M.D. Patti Lyerly, L.C.S.W.
Gynecology_Novak	Radiation therapy alone, without excision of the tumor, is associated with a high local failure rate, as is local excision without radiation (57–60). Throughout the last quarter of the 20th century, a paradigm shift occurred in the surgical management of breast cancer. Data from the NSABP B-04 trial, for which 25-year follow-up exists, established the equivalency of radical versus total mastectomy with regard to overall survival. Shortly after initiation of the B-04 trial, a number of studies were designed to evaluate the efficacy of breast preservation among women with early-stage breast cancers. The Milan trial, a major prospective randomized trial that began accruing patients in 1973, compared treatment with either radical mastectomy or a combination of quadrantectomy, axillary lymph node dissection, and postoperative radiation therapy. In total, 701 clinically node-negative patients with noncentrally located, small tumors (<2 cm) (T1 N0 M0) were enrolled. After 25 years of	Gynecology_Novak. Radiation therapy alone, without excision of the tumor, is associated with a high local failure rate, as is local excision without radiation (57–60). Throughout the last quarter of the 20th century, a paradigm shift occurred in the surgical management of breast cancer. Data from the NSABP B-04 trial, for which 25-year follow-up exists, established the equivalency of radical versus total mastectomy with regard to overall survival. Shortly after initiation of the B-04 trial, a number of studies were designed to evaluate the efficacy of breast preservation among women with early-stage breast cancers. The Milan trial, a major prospective randomized trial that began accruing patients in 1973, compared treatment with either radical mastectomy or a combination of quadrantectomy, axillary lymph node dissection, and postoperative radiation therapy. In total, 701 clinically node-negative patients with noncentrally located, small tumors (<2 cm) (T1 N0 M0) were enrolled. After 25 years of
InternalMed_Harrison	mg/kg per day. If new lesions continue to appear after 1–2 weeks of treatment, the dose may need to be increased and/or prednisone may need to be combined with other immunosuppressive agents such as azathioprine (2–2.5 mg/kg per day), mycophenolate mofetil (20–35 mg/kg per day), or cyclophosphamide (1–2 mg/kg per day). Patients with severe, treatment-resistant disease may derive benefit from plasmapheresis (six high-volume exchanges [i.e., 2–3 L per exchange] over ~2 weeks), IV immunoglobulin (IVIg) (2 g/kg over 3–5 days every 6–8 weeks), or rituximab (375 mg/m2 per week × 4, or 1000 mg on days 1 and 15). It is important to bring severe or progressive disease under control quickly in order to lessen the severity and/or duration of this disorder. Accordingly, some have suggested that rituximab and daily glucocorticoids should be used early in PV patients to avert the development of treatment-resistant disease.	InternalMed_Harrison. mg/kg per day. If new lesions continue to appear after 1–2 weeks of treatment, the dose may need to be increased and/or prednisone may need to be combined with other immunosuppressive agents such as azathioprine (2–2.5 mg/kg per day), mycophenolate mofetil (20–35 mg/kg per day), or cyclophosphamide (1–2 mg/kg per day). Patients with severe, treatment-resistant disease may derive benefit from plasmapheresis (six high-volume exchanges [i.e., 2–3 L per exchange] over ~2 weeks), IV immunoglobulin (IVIg) (2 g/kg over 3–5 days every 6–8 weeks), or rituximab (375 mg/m2 per week × 4, or 1000 mg on days 1 and 15). It is important to bring severe or progressive disease under control quickly in order to lessen the severity and/or duration of this disorder. Accordingly, some have suggested that rituximab and daily glucocorticoids should be used early in PV patients to avert the development of treatment-resistant disease.
Surgery_Schwartz	or the proximal tibia in young people. This condition may also occur at the proximal humerus, proximal femur, or pelvis. It usually presents itself as a high-grade extracompartmental disease. It can metastasize to the bone, which is called a “skip lesion,” but the lung is the primary site of metastases. Long term survival is 75% with adequate treatment. The response to chemotherapy (98% necrosis of the Table 43-1Common locations of bone tumorsFEMURDistal posteriorParosteal osteosarcomaDistal anteriorPeriosteal osteosarcoma, periosteal chondroma or chondrosarcoma, myositis ossificansTIBIAAdamantinoma, chondromyxoid, fibromaHANDS AND FEETEnchondroma, exostosisCalcaneusUnicameral bone cyst, lipoma, chondroblastoma, osteosarcomaSPINEAnteriorMetastatic, myeloma, Paget’s disease, vascular malformation, giant cell tumorPosteriorOsteoid osteoma, osteoblastoma; aneurysmal bone cystPELVISMetastatic, myeloma, chondrosarcoma, giant cell tumor, aneurysmal bone cyst, Paget’s disease, Ewing’s	Surgery_Schwartz. or the proximal tibia in young people. This condition may also occur at the proximal humerus, proximal femur, or pelvis. It usually presents itself as a high-grade extracompartmental disease. It can metastasize to the bone, which is called a “skip lesion,” but the lung is the primary site of metastases. Long term survival is 75% with adequate treatment. The response to chemotherapy (98% necrosis of the Table 43-1Common locations of bone tumorsFEMURDistal posteriorParosteal osteosarcomaDistal anteriorPeriosteal osteosarcoma, periosteal chondroma or chondrosarcoma, myositis ossificansTIBIAAdamantinoma, chondromyxoid, fibromaHANDS AND FEETEnchondroma, exostosisCalcaneusUnicameral bone cyst, lipoma, chondroblastoma, osteosarcomaSPINEAnteriorMetastatic, myeloma, Paget’s disease, vascular malformation, giant cell tumorPosteriorOsteoid osteoma, osteoblastoma; aneurysmal bone cystPELVISMetastatic, myeloma, chondrosarcoma, giant cell tumor, aneurysmal bone cyst, Paget’s disease, Ewing’s
Obstentrics_Williams	Hypotension. Sympathetic blockade from epidurally injected analgesic agents can cause hypotension and decreased cardiac output. Despite precautions, hypotension is the most frequent side efect and is severe enough to require treatment in a third of women (Sharma, 1997). According to Miller and coworkers (2013), hypotension is more common-20 percent-in women with an admission pulse pressure <45 mm Hg, compared with 6 percent in those whose pulse pressure is >45 mm Hg. In normal gravidas, hypotension induced by epidural analgesia usually can be prevented by rapid infusion of 500 to 1000 mL of crystalloid solution as described for spinal analgesia. Maintaining a lateral position also minimizes hypotension.	Obstentrics_Williams. Hypotension. Sympathetic blockade from epidurally injected analgesic agents can cause hypotension and decreased cardiac output. Despite precautions, hypotension is the most frequent side efect and is severe enough to require treatment in a third of women (Sharma, 1997). According to Miller and coworkers (2013), hypotension is more common-20 percent-in women with an admission pulse pressure <45 mm Hg, compared with 6 percent in those whose pulse pressure is >45 mm Hg. In normal gravidas, hypotension induced by epidural analgesia usually can be prevented by rapid infusion of 500 to 1000 mL of crystalloid solution as described for spinal analgesia. Maintaining a lateral position also minimizes hypotension.
Gynecology_Novak	125. Niloff JM, Klug TL, Schaetzl E, et al. Elevation of serum CA125 in carcinoma of the fallopian tube, endometrium, and endocervix. Am J Obstet Gynecol 1984;148:1057–1058. 126. Patsner B, Mann WJ, Cohen H, et al. Predictive value of preoperative serum CA 125 levels in clinically localized and advanced endometrial carcinoma. Am J Obstet Gynecol 1988;158:399–402. 127. Hsieh CH, Chang Chien CC, Lin H, et al. Can a preoperative CA125 level be a criterion for full pelvic lymphadenectomy in surgical staging of endometrial cancer? Gynecol Oncol 2002;86:28–33. 128. Dotters DJ. Preoperative CA125 in endometrial cancer: is it useful? Am J Obstet Gynecol 2000;182:1328–1334. 129. Jhang H, Chuang L, Visintainer P, et al. CA125 levels in the preoperative assessment of advanced-stage uterine cancer. Am J Obstet Gynecol 2003;188:1195–1197. 130.	Gynecology_Novak. 125. Niloff JM, Klug TL, Schaetzl E, et al. Elevation of serum CA125 in carcinoma of the fallopian tube, endometrium, and endocervix. Am J Obstet Gynecol 1984;148:1057–1058. 126. Patsner B, Mann WJ, Cohen H, et al. Predictive value of preoperative serum CA 125 levels in clinically localized and advanced endometrial carcinoma. Am J Obstet Gynecol 1988;158:399–402. 127. Hsieh CH, Chang Chien CC, Lin H, et al. Can a preoperative CA125 level be a criterion for full pelvic lymphadenectomy in surgical staging of endometrial cancer? Gynecol Oncol 2002;86:28–33. 128. Dotters DJ. Preoperative CA125 in endometrial cancer: is it useful? Am J Obstet Gynecol 2000;182:1328–1334. 129. Jhang H, Chuang L, Visintainer P, et al. CA125 levels in the preoperative assessment of advanced-stage uterine cancer. Am J Obstet Gynecol 2003;188:1195–1197. 130.
Obstentrics_Williams	In the past, some had set arbitrary time limits to permit vaginal delivery. Instead, experiences illustrate that maternal outcome depends on the diligence with which adequate luid and blood replacement therapy are pursued rather than on the interval to delivery. Observations from Parkland Hospital described by Pritchard and Brekken (1967) are similar to those from the University of Virginia reported by Brame and associates (1968). Specifically, women with severe abruption who were transfused during 18 hours or more before delivery had similar outcomes to those in whom delivery was accomplished sooner. Expectant Management with a Preterm Fetus	Obstentrics_Williams. In the past, some had set arbitrary time limits to permit vaginal delivery. Instead, experiences illustrate that maternal outcome depends on the diligence with which adequate luid and blood replacement therapy are pursued rather than on the interval to delivery. Observations from Parkland Hospital described by Pritchard and Brekken (1967) are similar to those from the University of Virginia reported by Brame and associates (1968). Specifically, women with severe abruption who were transfused during 18 hours or more before delivery had similar outcomes to those in whom delivery was accomplished sooner. Expectant Management with a Preterm Fetus
InternalMed_Harrison	Approximately 35% of drinkers (and a much higher proportion of alcoholics) experience a blackout, an episode of temporary anterograde amnesia, in which the person forgets all or part of what occurred during a drinking evening. Another common problem, one seen after as few as one or two drinks shortly before bedtime, is disturbed sleep. Although alcohol might initially help a person fall asleep, it disrupts sleep throughout the rest of the night. The stages of sleep are altered, and time spent in rapid eye movement (REM) and deep sleep is reduced. Alcohol relaxes muscles in the pharynx, which can cause snoring and exacerbate sleep apnea; symptoms of the latter occur in 75% of alcoholic men older than age 60 years. Patients may also experience prominent and sometimes disturbing dreams later in the night. All of these sleep problems are more pronounced in alcoholics, and their persistence may contribute to relapse.	InternalMed_Harrison. Approximately 35% of drinkers (and a much higher proportion of alcoholics) experience a blackout, an episode of temporary anterograde amnesia, in which the person forgets all or part of what occurred during a drinking evening. Another common problem, one seen after as few as one or two drinks shortly before bedtime, is disturbed sleep. Although alcohol might initially help a person fall asleep, it disrupts sleep throughout the rest of the night. The stages of sleep are altered, and time spent in rapid eye movement (REM) and deep sleep is reduced. Alcohol relaxes muscles in the pharynx, which can cause snoring and exacerbate sleep apnea; symptoms of the latter occur in 75% of alcoholic men older than age 60 years. Patients may also experience prominent and sometimes disturbing dreams later in the night. All of these sleep problems are more pronounced in alcoholics, and their persistence may contribute to relapse.
Psichiatry_DSM-5	ADHD presentation should still be diagnosed. Population surveys suggest that ADHD occurs in most cultures in about 5% of children and about 2.5% of adults. Many parents first observe excessive motor activity when the child is a toddler, but symp- toms are difficult to distinguish from highly variable normative behaviors before age 4 years. ADHD is most often identified during elementary school years, and inattention be- comes more prominent and impairing. The disorder is relatively stable through early ad- olescence, but some individuals have a worsened course with development of antisocial behaviors. In most individuals with ADHD, symptoms of motoric hyperactivity become less obvious in adolescence and adulthood, but difficulties with restlessness, inattention, poor planning, and impulsivity persist. A substantial proportion of children with ADHD remain relatively impaired into adulthood.	Psichiatry_DSM-5. ADHD presentation should still be diagnosed. Population surveys suggest that ADHD occurs in most cultures in about 5% of children and about 2.5% of adults. Many parents first observe excessive motor activity when the child is a toddler, but symp- toms are difficult to distinguish from highly variable normative behaviors before age 4 years. ADHD is most often identified during elementary school years, and inattention be- comes more prominent and impairing. The disorder is relatively stable through early ad- olescence, but some individuals have a worsened course with development of antisocial behaviors. In most individuals with ADHD, symptoms of motoric hyperactivity become less obvious in adolescence and adulthood, but difficulties with restlessness, inattention, poor planning, and impulsivity persist. A substantial proportion of children with ADHD remain relatively impaired into adulthood.
InternalMed_Harrison	Although the associations of human disease with particular HLA alleles or haplotypes predominantly involve the class II region, there are also several prominent disease associations with class I alleles. These include the association of Behçet’s disease (Chap. 387) with HLA-B51, psoriasis vulgaris (Chap. 71) with HLA-Cw6, and, most notably, the spondyloarthritides (Chap. 384) with HLA-B27. Twenty-five HLA-B locus alleles, designated HLA-B27:01–B27:25, encode the family of 373e-7 B27 class I molecules. All of the subtypes share a common B pocket in the peptide-binding groove—a deep, negatively charged pocket that shows a strong preference for binding the arginine side chain. In addition, B27 is among the most negatively charged of HLA class I heavy chains, and the overall preference is for positively charged peptides. HLA-B*27:05 is the predominant subtype in whites and most other non-Asian populations, and this subtype is very highly associated with ankylosing spondylitis (AS)	InternalMed_Harrison. Although the associations of human disease with particular HLA alleles or haplotypes predominantly involve the class II region, there are also several prominent disease associations with class I alleles. These include the association of Behçet’s disease (Chap. 387) with HLA-B51, psoriasis vulgaris (Chap. 71) with HLA-Cw6, and, most notably, the spondyloarthritides (Chap. 384) with HLA-B27. Twenty-five HLA-B locus alleles, designated HLA-B27:01–B27:25, encode the family of 373e-7 B27 class I molecules. All of the subtypes share a common B pocket in the peptide-binding groove—a deep, negatively charged pocket that shows a strong preference for binding the arginine side chain. In addition, B27 is among the most negatively charged of HLA class I heavy chains, and the overall preference is for positively charged peptides. HLA-B*27:05 is the predominant subtype in whites and most other non-Asian populations, and this subtype is very highly associated with ankylosing spondylitis (AS)
Pediatrics_Nelson	Testing of pancreatic function is difficult. Direct measurement of enzyme concentrations in aspirated pancreatic juice is not routine and is technically difficult. Stools can be tested for the presence of maldigested fat, which usually indicates poor fat digestion. Measuring fecal fat can give either a qualitative assessment of fat absorption (fecal Sudan stain) or a semiquantitative measurement (72-hour fecal fat determination) of fat maldigestion. Another way to assess pancreatic function is to test for the presence of pancreatic enzymes in the stool. Of these, measuring fecal elastase-1 by immunoassay seems to be the most accurate method of assessment. Depressed fecal elastase-1 concentration correlates well with the presence of pancreatic insufficiency.	Pediatrics_Nelson. Testing of pancreatic function is difficult. Direct measurement of enzyme concentrations in aspirated pancreatic juice is not routine and is technically difficult. Stools can be tested for the presence of maldigested fat, which usually indicates poor fat digestion. Measuring fecal fat can give either a qualitative assessment of fat absorption (fecal Sudan stain) or a semiquantitative measurement (72-hour fecal fat determination) of fat maldigestion. Another way to assess pancreatic function is to test for the presence of pancreatic enzymes in the stool. Of these, measuring fecal elastase-1 by immunoassay seems to be the most accurate method of assessment. Depressed fecal elastase-1 concentration correlates well with the presence of pancreatic insufficiency.