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Patients who have ingested massive amounts of digoxin should receive large doses of activated charcoal. Digoxin immune Fab can be used to reverse potentially life-threatening intoxication. Fluid restriction-Fluid restriction is rarely used in pediatric cardiology due to the effectiveness of diuretics. Azeka E et al: Delisting of infants and children from the heart transplantation waiting list after carvedilol treatment. Rosenthal D et al: International Society for Heart and Lung Transplantation: Practice guidelines for management of heart failure in children. The sinus venosus defect is frequently associated with abnormal pulmonary venous return, as the location of the sinus venosus is intimately related to the right upper pulmonary vein. Pulmonary hypertension and growth failure are uncommon complications in infancy and childhood. After the third decade, atrial arrhythmias or pulmonary vascular disease may develop. In the setting of pulmonary vascular disease, leftto-right shunting decreases, and right-to-left shunting becomes the major clinical abnormality (Eisenmenger syndrome). The most common genetic abnormality is a microdeletion in the long arm of chromosome 22 (22q11) associated with DiGeorge syndrome. Intrauterine factors such as maternal diabetes, alcohol consumption, progesterone use, viral infection, and other maternal teratogen exposure are associated with an increased incidence of cardiac malformations. Genetic diagnosis may allow for more accurate prediction of recurrence risk in subsequent pregnancies. A mid-diastolic murmur is often heard in the fourth intercostal space at the left sternal border. This murmur is caused by increased flow across the tricuspid valve during diastole. The presence of this murmur suggests high flow with a pulmonary-to-systemic blood flow ratio greater than 2:1. Spontaneous closure occurs, most frequently in children with a defect less than 4 mm in diameter. Exercise tolerance and oxygen consumption in surgically corrected children are generally normal, and restriction of physical activity is unnecessary. The main pulmonary artery may be dilated and pulmonary vascular markings increased in large defects owing to the increased pulmonary blood flow. Assessment of all pulmonary veins should be made to rule out associated anomalous pulmonary venous return. Presentation and course depend on size of defect and the pulmonary vascular resistance. Cardiac Catheterization Oximetry shows significant increase in oxygen saturation at the atrial level. The pulmonary artery pressure and pulmonary vascular resistance are usually normal. Defects in the ventricular septum occur both in the membranous portion of the septum (most common) and the muscular portion. In the asymptomatic child with a large hemodynamically significant defect, closure is performed electively at age 1­3 years. Many defects are amenable to nonoperative device closure during cardiac catheterization, but the defect must have adequate tissue rims on all sides on which to anchor the device. In general, small defects in the muscular interventricular septum will close sooner than those in the membranous septum. The first sound at the apex is normal, and the second sound at the pulmonary area is split physiologically. A systolic thrill may be palpable at the lower left sternal border between the third and fourth intercostal spaces. A mitral diastolic flow murmur indicates that the pulmonary blood flow is significantly increased by the large shunt. Large ventricular septal defects with pulmonary hypertension-The precordium is prominent, and the sternum bulges. S2 is usually single or narrowly split, with accentuation of the pulmonary component. Occasionally, when the defect is large or ventricular pressures approach equivalency, a murmur is difficult to hear.

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The skin test in the patient or family contacts is frequently valuable in differentiating these conditions from tuberculosis. Specific Measures Most children with tuberculosis in the United States are hospitalized initially. If the infecting organism has not been isolated from the presumed contact for susceptibility testing, reasonable attempts should be made to obtain it from the child using morning gastric aspirates, sputum, bronchoscopy, thoracentesis, or biopsy when appropriate. Unfortunately, cultures are frequently negative in children, and the risk of these procedures must be weighed against the yield. Therapy is given daily for 14 days and then reduced to 2­3 times per week for the duration of the course. Directly observed administration of all doses of antituberculosis therapy by a trained health care professional is essential to ensure compliance with therapy. Children with positive skin tests (see Table 40­2) without evidence of active disease have latent tuberculosis and should receive 9 months of isoniazid (10 mg/kg/d orally; maximum 300 mg) therapy. In children with active pulmonary disease, therapy for 6 months using isoniazid (10 mg/kg/d), rifampin (15 mg/kg/d), and pyrazinamide (25­30 mg/kg/d) in a single daily oral dose for 2 months, followed by isoniazid plus rifampin (either in a daily or twice-weekly regimen) for 4 months appears effective for eliminating isoniazid-susceptible organisms. In communities with resistance rates greater than 4%, initial therapy should usually include four drugs. Isoniazid-The hepatotoxicity from isoniazid seen in adults and some adolescents is rare in children. Transient elevation of aminotransferases (up to three times normal) may be seen at 6­12 weeks, but therapy is continued unless clinical illness occurs. Routine monitoring of liver function tests is unnecessary unless prior hepatic disease is known or the child is severely ill. Peripheral neuropathy associated with pyridoxine deficiency is rare in children, and it is not necessary to add pyridoxine unless significant malnutrition coexists. Rifampin-Although it is an excellent bactericidal agent, rifampin is never used alone owing to rapid development of resistance. The orange discoloration of secretions is benign but may stain contact lenses or clothes. Pyrazinamide-This excellent sterilizing agent is most effective during the first 2 months of therapy. Although pyrazinamide elevates the uric acid level, it rarely causes symptoms of hyperuricemia in children. Use of this drug is now common for tuberculous disease in children, and resistance is almost unknown. Isoniazid Chemoprophylaxis Daily administration of isoniazid (10 mg/kg/d orally; maximum 300 mg) is advised for children who are exposed by prolonged close or household contact with adolescents or adults with active disease. At the end of this time, a Mantoux test should be done, and therapy should be continued for an additional 7 months if the test is positive. Other Measures Tuberculosis in infants and young children is evidence of recent exposure to active infection in an adult, usually a family member or household contact. The source contact (index case) should be identified, isolated, and given treatment to prevent other secondary cases. Exposed tuberculin-negative children should usually receive isoniazid chemoprophylaxis. If a repeated skin test is negative 2­3 months following the last exposure, isoniazid may be stopped. Routine tuberculin skin testing is not recommended for children without risk factors who reside in communities with a low incidence of tuberculosis. Children with no personal risk for tuberculosis but who reside in communities with a high incidence of tuberculosis should be given a skin test at school entry and then again at age 11­16 years. Children with a risk factor for acquiring tuberculosis should be tested every 2­3 years. Children who immigrate into the United States from a country with a high incidence of infection should receive a skin test on entry to the United States or upon presentation to health care providers. Taylor Z et al; American Thoracic Society; Centers for Disease Control and Prevention; Infectious Diseases Society of America: Controlling tuberculosis in the United States. Ethambutol-Because optic neuritis is the major side effect in adults, ethambutol has usually been given only to children whose vision can be reliably tested for loss of color differentiation.


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Any Na in Ca-feldspar of anorthosites pulls these points (triangles) toward the SiO2 apex because the diagram ignores the Na but not its associated SiO2. Also shown for comparison (shaded field) is a range of compositions for typical highland regolith samples, including three lunar meteorites (all regolith breccias), the Luna 20 soil, and average Apollo 16 soil (Warren and Kallemeyn, 1987). The average composition of the upper highland crust presumably plots within this field. The quartz monzodiorite clast in sample 15405 has been the subject of numerous isotopic studies. Unfortunately, it has been heavily shocked and the impact effects have severely disturbed the isotopic systems used for age dating. Data for relatively coarse-grained rocks (samples 15405, 14303, and 15382) are plotted as solid symbols; these samples may be especially subject to errors caused by small sample sizes. Recent analyses of meteorites from the Moon that have been collected in Antarctica. Ferroan Anorthosites the single most common type of pristine highland rock is ferroan anorthosite. It is distinguished from all other highland rocks by the peculiar combination of low-Na plagioclase feldspar with lowMg pyroxene, with or without olivine. The majority of monomict rock types identified from the Apollo 16 site, the only sampled location in a typical highland region, are ferroan anorthosites. Among the lunar meteorites found since 1979 in Antarctica, the majority of pristine rock types identified as clasts Lunar Rocks 221. These data have been obtained mainly from defocused-beam electron microprobe analyses, which are less reliable than most other types of major-element analyses of rocks. If the available Apollo pristine samples are representative, roughly 50% of the outer highland crust consists of ferroan anorthosite (the remainder is mainly Mg-rich rocks; see section 6. The coarse grain size suggests that they are intrusive rocks, formed during slow cooling deep below the surface. The high concentration of plagioclase feldspar suggests that they are also cumulate rocks, produced by the separation of just-formed crystals (in this case, plagioclase feldspar) from the remaining melt. For example, the anorthosite portion (about 100 g) of Apollo 16 breccia 60135 has remnants of original blocky plagioclase crystals up to 4. Although these vestiges of the original igneous texture have survived, 60135 is a severely shocked rock in which most mineral grains have been shock-melted in situ (Warren et al. Other examples of ferroan anorthosites that retain vestiges of former coarse igneous (cumulate) textures include samples 60025 (Ryder, 1982), 62236 (Nord and Wandless, 1983), and 62237 (Dymek et al. The Apollo 15 "Genesis rock" (15415), which is by far the largest (269 g) ferroan anorthosite from a site other than Apollo 16, has a unique texture (Ryder, 1985). Plagioclase makes up about 99% of the rock and occurs as extremely coarse (up to 3 cm across) anhedral or polygonal grains. This unusual texture may have been produced by thermal metamorphism at least a few kilometers deep in the crust after the 222 Lunar Sourcebook. Photomicrographs of typical ferroan and other anorthosites: (a) and (b), severely brecciated and crushed areas in ferroan anorthosite 62236 [note relatively unbrecciated, pyroxene-rich area (gray) in lower left]; (c) and (d), ferroan anorthosite 62237, showing "stringers" of pulverized mafic silicates (gray) among larger plagioclase fragments (white); (e) ferroan anorthosite 15415, showing coarsely crystalline texture; (f) alkali anorthosite 12073c, showing texture resulting from severe crushing followed by thermal annealing. All views in transmitted light and crossed polarizers, except (a) and (c), which are with uncrossed polarizers. Photomicrographs of areas of ferroan anorthosite samples containing mafic minerals (olivine and pyroxene). These minerals show relict cumulate textures produced by accumulation of crystals from a melt, most notably the smooth, arcuate boundaries between coarse pyroxenes (dark gray) and plagioclase. Based on its "ferroan" composition, this clast is thought to be an atypically pyroxene-rich fragment of an anorthosite. Images (c) and (d) show part of sample 62237, in which small pyroxenes are surrounded by large plagioclase crystals. Images (e) and (f) show another clast, composed of plagioclase and low-Ca pyroxene, which is also presumed to be an atypically pyroxene-rich fragment of an anorthosite, from sample 66035.

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The Coombs test is negative, and there is no evidence of chronic renal disease, hypothyroidism, or other systemic disorder. Bone marrow examination shows severe erythroid hypoplasia initially; subsequently, erythroid hyperplasia develops along with reticulocytosis, and the anemia resolves. General Considerations Long considered the most common cause of anemia in pediatrics, iron deficiency has decreased substantially in incidence due to improved nutrition and the increased availability of iron-fortified infant formulas and cereals. Thus, the current approach to anemia in childhood must take into consideration a relatively greater likelihood of other causes. Normal-term infants are born with sufficient iron stores to prevent iron deficiency for the first 4­5 months of life. Thereafter, enough iron needs to be absorbed to support the needs of rapid growth. For this reason, nutritional iron deficiency is most common between 6 and 24 months of life. A deficiency earlier than age 6 months may occur if iron stores at birth are reduced by prematurity, small birth weight, neonatal anemia, or perinatal blood loss or if there is subsequent iron loss due to hemorrhage. Iron-deficient children older than age 24 months should be evaluated for blood loss. Iron deficiency, in addition to causing anemia, has adverse effects on multiple organ systems. Thus, the importance of identifying and treating iron deficiency extends past the resolution of any symptoms directly attributable to a decreased hemoglobin concentration. Differential Diagnosis Transient erythroblastopenia of childhood must be differentiated from Diamond-Blackfan anemia, particularly in infants younger than age 1 year. In contrast to DiamondBlackfan anemia, transient erythroblastopenia is not associated with macrocytosis, short stature, or congenital anomalies, or with evidence of fetal erythropoiesis prior to the phase of recovery. Also in contrast to DiamondBlackfan anemia, transient erythroblastopenia is associated with normal levels of red cell adenosine deaminase. Transient erythroblastopenia of childhood must also be differentiated from chronic disorders associated with decreased red cell production, such as renal failure, hypothyroidism, and other chronic states of infection or inflammation. As with other single cytopenias, the possibility of malignancy (ie, leukemia) should always be considered, particularly if fever, bone pain, hepatosplenomegaly, or lymphadenopathy is present. Confusion may sometimes arise when the anemia of transient erythroblastopenia is first identified during the early phase of recovery when the reticulocyte count is high. In such cases, the disorder may be confused with the anemia of acute blood loss or with hemolytic disease. In contrast to hemolytic disorders, transient erythroblastopenia of childhood is not associated with jaundice or peripheral destruction of red cells. In infants with more severe iron deficiency, pallor, fatigue, irritability, and delayed motor development are common. Laboratory Findings the severity of anemia depends on the degree of iron deficiency, and the hemoglobin level may be as low as 3­4 g/dL in severe cases. The red blood cell distribution width is typically elevated, even with mild iron deficiency. The reticulocyte count is usually normal or slightly elevated, but the reticulocyte index or absolute reticulocyte count is decreased. Iron studies show a decreased serum ferritin and a low serum iron, elevated total ironbinding capacity, and decreased transferrin saturation. These laboratory abnormalities are usually present with moderate to severe iron deficiency, but mild cases may be associated with variable laboratory results. The peripheral blood smear shows microcytic, hypochromic red blood cells with anisocytosis, and occasional target, teardrop, elliptical, and fragmented red cells. Leukocytes are normal, and very often platelet count is increased with normal morphology. The bone marrow examination is not helpful in the diagnosis of iron deficiency in infants and small children because little or no iron is stored as marrow hemosiderin at these ages.

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The mechanism of injury is a forceful, unbalanced muscle contraction that causes avulsion of the muscle tendon insertion. The athlete presents with a history of an acute traumatic incident; often a "pop" is felt and the athlete is immediately unable to bear weight. If a radiograph shows an avulsed fragment is displaced less than 2 mm, a thumb spica cast can be used. If there is no fragment and less than 35 degrees of lateral joint space opening, a spica cast for 6 weeks is indicated. In severe cases the leg can be immobilized in a spica cast until the muscle has a chance to heal. The rehabilitation phase focuses on regaining motion, flexibility training, and pelvic and core strengthening. Progressive return to activity can often be accomplished in 4­6 weeks if full range of motion, full strength, and sport-specific skills have been achieved. The classic scenario is an athlete who suddenly stops play, grabbing the back of the knee. It is particularly important to stretch the hamstring because, as a two-joint muscle, it is more susceptible to injury than other types of muscle. Radiographs in the frog-leg position show widening of the physis and epiphyseal slippage. The physis is weakened during times of rapid growing and is susceptible to shearing failure. Examination shows painful range of motion of the hip, limited internal rotation, and obligatory external rotation when the hip is flexed. Treatment consists of immediate non­weight bearing and urgent referral to an orthopedic specialist for open reduction and internal fixation. Rehabilitation is a component of the postsurgical treatment, and return to activity is progressive over months. Quadriceps Contusion Quadriceps contusion is caused by a direct injury to the muscle, resulting in bruising, swelling, and pain. The anterior and lateral thigh regions are most commonly injured often in contact sports such as football and lacrosse. Two to three days after the injury, range-of-motion exercises may begin in both flexion and extension. Once 120 degrees of motion has been established and movement does not cause pain, the athlete may return to competitive activity. If the muscle remains firm on examination after 2 weeks, then radiographs of the thigh should be obtained to rule out myositis ossificans. Myositis ossificans is an abnormal deposition of calcium in the muscle that may be induced by aggressive stretching of the muscle too early in the clinical course. The injury often occurs from a twisting injury of the hip that tears the fibrocartilaginous ring around the acetabulum. Athletes present with deep anterior hip or groin pain that worsens with activity and is resistant to treatment. Adductor Strain An adductor strain or a groin pull is generally caused by forced abduction as in running, falling, twisting, or tackling. Sports that require quick directional changes place the athlete at risk for these types of injuries. There is often pain with adduction or hip flexion and tenderness over the adductor tubercle. Athletes with this injury classically present with hip flexion, adduction, and internal rotation. Hip dislocations in skeletally mature athletes are almost always associated with acetabular and femoral neck fracture. This is a true on-field emergency, and the athlete should be transported to the nearest facility that has an orthopedic surgeon available. Once reduction has been established in an uncomplicated case, protected weight bearing on crutches for 6 weeks is recommended followed by another 6 weeks of range-of-motion and strengthening exercises.


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The chronological data are much too sparse to establish any systematic differences in age between ferroan and magnesian granulitic rocks. The clast-matrix structure of the granulitic breccias and the meteoroid contamination detected in most granulitic rocks demonstrates that they were derived from even older breccias. These older breccias were metamorphosed and recrystallized by prolonged heating to temperatures of more than 1000° C (Stewart, 1975; Bickel et al. The prolonged heating necessary to produce the observed textures is different from the effects produced by the intense bombardment about 3. The effects in the granulitic breccias could have resulted from burial at a depth of several kilometers, possibly during an earlier period of even higher impact flux, accompanied by increased heat flow from the lunar interior (Warner et al. The chemical and textural characteristics suggest that some of the granulites may have been derived from distinctive anorthositic norite precursors; most, however, are clearly polymict (Lindstrom and Lindstrom, 1986). The bulk chemical compositions of granulites are similar to the average lunar surface 256 Lunar Sourcebook compositions estimated from remotely-sensed data (Taylor, 1982), even more so than the Apollo 16 fragmental breccias. There appears to be no difference in regional distribution between the ferroan and magnesian granulitic rocks, but the available orbital measurements are not adequate to preclude regional differences. The samples generally resemble complex veins or dikes of dark and light components. The dark material is a fine-grained crystalline melt breccia or a nearly clast-free impact melt. The lightcolored material is, in most cases, an anorthositic breccia whose main constituents are crushed and shattered (cataclastic) anorthosite fragments. Dimict breccias cannot be recognized in samples less than a few centimeters across, because the scale of mutual intrusion is on that order. The white portion varies from nearly pure cataclastic ferroan anorthosite to less aluminous breccias (nearly all containing more than 30% Al2O3; McKinley et al. In these large impact events the melt could have been created and the older anorthositic breccia could have been shattered and remobilized at the same time. Available surface exposure ages suggest that all the dimict breccia samples were ejected about 2 m. Most of the contacts between the two lithologies are smoothly curving surfaces; some are shear planes. Not all samples can be shown to be mutually intrusive, and in some specimens the melt phase is perhaps more clearly the host. The dark-colored impact melt lithology is a crystalline melt breccia such as those described in section 6. The melt is fine-grained and consists of lath-shaped plagioclase crystals, generally equant olivine grains, and pyroxene. A glassy mesostasis, producing an intersertal texture, commonly occurs between the crystals. This composition is remarkably constant and is similar to most impact melts found at the Apollo 16 site (Tables A6. The dimict breccias, however, form a tighter compositional cluster than do the other impact melts of roughly similar composition. In addition, the Apollo 16 dimict breccias have Mg/(Mg + Fe) ratios of about 70, and all those analyzed show evidence of contamination from meteoroid siderophile elements. The light-colored lithology is composed dominantly of cataclastic anorthosite, containing more than 95% plagioclase. In their chemistry and mineralogy, these anorthosites are similar to the pristine igneous anorthosites described in section 6. In dimict breccias, the compositional range of the mafic minerals (pyroxene, olivine) extends to more magnesian compositions, however, and this greater range suggests that these light portions are actually polymict. The textures of these anorthosites have been extensively modified by impact processes. The clasts are shattered, and the individual crystals are granulated and have undulatory (strain) extinction under polarized light. The anorthosites have typical low rare earth abundances and lack meteoroid contamination. There are no ages available for the dark crystalline melt breccia phase of dimict breccias, the lithology that offers the best possibilities for age dating. These ages probably date the intense heating and deformation of the anorthosites, i. The original crystallization of the anorthosites presumably took place much earlier.

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From all of the available evidence, it appears that very small quantities of vitamin K cross the placenta from mother to fetus. Indeed, even maternal pharmacologic doses of vitamin K have unpredictable effects on cord blood concentration. Vitamin K­dependent proteins have been identified in nearly all tissues of the body. These include osteocalcin (bone gla protein), matrix gla protein of the skeleton, and kidney gla protein. It is a growth factor with mitogenic and antiapoptotic properties and plays a role in maintaining cells in the G0 phase or rest phase of the cell cycle. All of the activated vitamin K­dependent proteins have in common -carboxyglutamic acid (Gla), the unique amino acid formed by the postribosomal action of the vitamin K­dependent enzyme -glutamyl carboxylase. These Gla residues are located in the amino-terminal domain of the protein, for which there is a high degree of amino acid sequence identity in all vitamin K­dependent proteins. The conversion of a glutamyl residue on a vitamin K­dependent protein (2) to a -carboxyglutamyl (gla) residue (4) by the enzyme glutamyl carboxylase (3), is dependent on the reduced vitamin K (1) and is coupled to the formation of vitamin K epoxide (5). An overview of the current knowledge of the vitamin K­dependent proteins and vitamin K metabolism can be found in more detail elsewhere but will be summarized here. This series of reactions makes up the vitamin K cycle, which results in the continuous regeneration of the coenzyme form of vitamin K (hydroquinone)120-122 (see. This regeneration is important because many vitamin K­dependent proteins have multiple glutamyl residues, and for each glutamyl residue carboxylated, a molecule of vitamin K epoxide is formed. The C-terminal end of the protein is located in the cell cytoplasm and binds warfarin. Thus, without prophylactic vitamin K at birth, the primary source of vitamin K for the term and near-term infant would be intestinal absorption. Vitamin K is absorbed from the intestine into the lymphatic system, requiring the presence of both bile salts and pancreatic secretions. In the neonate, 29% of an oral dose of vitamin K1 is reportedly absorbed from the intestine. Compared with other fat-soluble vitamins, relatively small amounts of vitamin K have been reported in the liver of the neonate. However, vitamin K is found in relatively high concentrations in liver, heart, and bone compared with other tissues. Human milk generally contains less than 10 µg/L of vitamin K, which is found in the milk fat globules. Premature infants on formula or fortified human milk, by 40 weeks postconceptional age, have plasma vitamin K concentrations (5 to 6 ng/mL) and intake (45 to 50 µg/day) comparable to those of term infants on fortified formula. Although this has been an area of controversy, the preferred method of prophylaxis remains the intramuscular route, owing to the need for repeated dosing of oral preparations and its variable intestinal absorption. Premature infants may show an accelerated postnatal maturation toward adult levels compared with term infants. The prothrombin time has a wider range and variability in the newborn at birth (11 to 16 seconds) compared with the adult (11 to 14 seconds), and this persists through the first 6 months of life. In contrast, the activated partial thromboplastin time shows a similar pattern through the first six months of life compared with adults. In newborn infants, its usefulness as a predictor of subclinical vitamin K deficiency remains to be demonstrated. In the United States and Canada, it is not a major concern because nearly all infants receive prophylactic vitamin K at the time of birth. In the United States, the most common scenario for hemorrhagic disease of the newborn is in an exclusively breastfed infant who does not receive vitamin K prophylaxis at birth and who may or may not have another disease that compromises vitamin K absorption, such as biliary atresia or 1-antitrypsin deficiency. In the classic form of the disease, hemorrhage occurs between days 2 and 10 of life, and intracranial hemorrhage is uncommon. Again, this form occurs mostly in breastfeeding infants between 6 weeks and 6 months of life, and the associated intracranial hemorrhage results in devastating neurologic sequelae. High-Dose Vitamin K for Infants and Toxicity Pharmacologic doses of the vitamin are used in the newborn period for prevention of hemorrhagic disease.

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Females may be either homozygous or heterozygous, because they have two X chromosomes. Males, by contrast, have only one X, and a male is said to be hemizygous for any gene on his X chromosome. The severity of any disorder is greater in males than in females (within a specific family). According to the Lyon hypothesis, because one of the two X chromosomes in each cell is inactivated, and this inactivation is random, the clinical picture in females depends on the percentage of mutant versus normal alleles inactivated. The X chromosome is not inactivated until about 14 days of gestation, and parts of the short arm remain active throughout life. X-Linked Recessive Inheritance the following features are characteristic of X-linked recessive inheritance: 1. Males are affected, and heterozygous females are either normal or have mild manifestations. A female carrier has a 50% chance that each daughter will be a carrier and a 50% chance that each son will be affected. Male-to-male transmission is seen in this category, with all sons of affected males being affected and no daughters or females being affected. Studies of twins have proven useful in determining the relative importance of genetic versus environmental factors in the expression of polygenic traits. If genetic factors are of little or no importance, then the concordance between monozygotic and dizygotic twins should be the same. The latter term recognizes that environmental factors such as diet also contribute to these traits. Many disorders and congenital abnormalities that are clearly familial but do not segregate as mendelian traits (eg, autosomal dominant, recessive, etc) show polygenic inheritance. For the most part, these conditions become manifest when thresholds of additive gene actions or contributing environmental factors are exceeded. Many common disorders ranging from hypertension, stroke, and thrombophlebitis to behavioral traits such as alcoholism demonstrate multifactorial (polygenic) inheritance. Some common birth defects, including isolated congenital heart disease, cleft lip and palate, and neural tube defects, also demonstrate polygenic inheritance. Neural tube defects provide a good model illustrating how identification of both environmental and genetic contributions to multifactorial traits can lead to preventive measures. Polygenic or multifactorial inheritance has several distinctive characteristics: 1. The risk is higher for first-degree relatives (those who have 50% of their genes in common) and lower for more distant relations, although the risk for the latter is higher than for the general population (Table 35­2). For example, after one child is born with a neural tube defect, the recurrence risk is 2­3%. If a second affected child is born, the risk for any future child increases to 10­12%. This is in contrast to single gene disorders, in which the risk is the same no matter how many family members are affected. In Hirschsprung disease, another polygenic condition, the longer the aganglionic segment, the higher is the recurrence risk. If a marked discrepancy exists, the recurrence risk is higher if a child of the less commonly affected sex has the disorder. This assumes that more genetic factors are required to raise the more resistant sex above the threshold. If the first affected child is a female, the recurrence risk is higher than if the child is a male. The risk for the offspring of an affected person is approximately the same as the risk for siblings, assuming that the spouse of the affected person has a negative family history. For many conditions, however, assortative mating, "like marrying like," adds to risks in offspring.

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An orthotic that holds the heel in neutral and supports the arch may relieve discomfort if more support is needed. An arch insert should not be prescribed unless passive correction of the arch is easily accomplished; otherwise, the skin over the medial side of the foot will be irritated. Internal rotation amounts to about 20 degrees at birth but decreases to neutral rotation by age 16 months. The deformity is sometimes accentuated by laxity of the knee ligaments, allowing excessive internal rotation of the leg in small children. In children who have a persistent internal rotation of the tibia beyond age 16­18 months, the condition is often due to sleeping with feet turned in and can be reversed with an external rotation splint worn only at night. Talipes Calcaneovalgus Talipes calcaneovalgus is characterized by excessive dorsiflexion at the ankle and eversion of the foot. In rare instances, it may be necessary to use plaster casts to help with manipulation and positioning. This femoral alignment follows a natural history of progressive decrease toward neutral during growth. Studies comparing the results of treatment with shoes or braces to the natural history have shown that little is gained by active treatment. Active external rotation exercises, such as skating or bicycle riding, can be encouraged. Children who have no external rotation of hip in extension are candidates for orthopedic consultation. Cavus Foot this deformity consists of an unusually high longitudinal arch of the foot. It may be hereditary or associated with neurologic conditions such as poliomyelitis, Charcot-MarieTooth disease, Friedreich ataxia, and diastematomyelia. There is usually an associated contracture of the toe extensor, producing a claw toe deformity in which the metatarsophalangeal joints are hyperextended and the interphalangeal joints acutely flexed. Any child presenting with cavus feet should receive a careful neurologic examination and radiographs of the spine. In symptomatic cases, surgery may be necessary to lengthen the contracted extensor and flexor tendons and to release the plantar fascia and other tight plantar structures. The forefeet are mildly pronated or rotated inward, with a slight valgus alignment of the knees. As the child grows and joint laxity decreases, the long arch is better supported and more normal relationships occur in the lower extremities. If the heel cord is of normal length, full dorsiflexion is possible with the heel in the neutral position. As long as the heel cord is of normal length and a longitudinal arch is noted when the child is sitting in a non­weight-bearing position, the parents can be assured that a normal arch will probably develop. There is usually a familial incidence of relaxed flatfeet in children who have no apparent arch. In any child with a shortened heel cord or stiffness of the foot, other causes of flatfoot such as tarsal coalition or vertical talus should be ruled out by a complete orthopedic examination and radiograph. In the child with an ordinary relaxed flatfoot, no active treatment is indicated unless calf or leg pain is present. Bunions (Hallux Valgus) Adolescents may present with lateral deviation of the great toe associated with a prominence over the head of the first metatarsal. This deformity is painful only with shoe wear and almost always can be relieved by fitting shoes that are wide enough in the toe. Surgery should be avoided in the adolescent, because further growth tends to cause recurrence of the deformity. Degenerative arthritis may follow childhood skeletal problems, such as infection, slipped capital femoral epiphysis, avascular necrosis, or trauma, or it may occur in association with hemophilia. Degenerative changes in the soft tissues around joints may occur as a result of overuse syndrome in adolescent athletes.

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These tests are influenced by plasma proteins which are either slowly responding acute phase reactants. Erythrocyte sedimentation rate this commonly used but non-specific test measures the speed of sedimentation of red cells in plasma over a period of 1 hour. The normal range in men is 1­5 mm/hour and in women 5­15 mm/hour but there is a progressive increase in old age. It is useful for diagnosing and monitor- Chapter 28 Haematological changes in systemic disease / 395 (a) (b) Figure 28. High values (>100 mm/hour) have a 90% predictive value for serious disease including infections, collagen vascular disease or malignancy (particularly myeloma). Lower than expected readings occur in polycythaemia vera because of the high red cell concentration. Higher than expected values may occur in severe anaemia because of the low red cell concentration. Plasma viscosity is affected by the concentration of plasma proteins of large molecular size, especially those with pronounced axial asymmetry ­ fibrinogen and some immunoglobulins. Lower levels are found in neonates because of lower levels of proteins, particularly fibrinogen. These include neutrophil leucocytosis especially in bacterial infections, leucoerythroblastic or leukaemoid reactions, and in viral and connective tissue diseases, neutropenia. Eosinophilia occurs with certain infections, particularly parasitic and allergic disease. Platelets may be increased or low in malignant, infectious and other systemic diseases. Disseminated intravascular coagulation is a major cause of thrombocytopenia and fall in coagulation factors. C-reactive protein can be used for nonspecific monitoring of systemic disease for short term (hours or days) and erythrocyte sedimentation rate (or plasma viscosity) over weeks or months. Cryosupernatant is used for plasma exchange in thrombotic thrombocytopenic purpura. Blood group antibodies Naturally occurring antibodies occur in the plasma of subjects who lack the corresponding antigen and who have not been transfused or been pregnant (Table 29. They are usually immunoglobulin M (IgM), and react optimally at cold temperatures (4°C) so, although reactive at 37°C, are called cold antibodies. Immune antibodies develop in response to the introduction ­ by transfusion or by transplacental passage during pregnancy ­ of red cells possessing antigens that the subject lacks. These antibodies are commonly IgG, although some IgM antibodies may also develop ­ usually in the early phase of an immune response. Red cell antigens and blood group antibodies Approximately 400 red blood cell group antigens have been described. The clinical significance of blood groups in blood transfusion is that individuals who lack a particular blood group antigen may produce antibodies reacting with that antigen which Chapter 29 Blood transfusion / 399 Table 29. The A and B genes control the synthesis of specific enzymes responsible for the addition of single carbohydrate residues (N-acetyl galactosamine for group A and D-galactose for group B) to a basic antigenic glycoprotein or glycolipid with a terminal sugar L-fucose on the red cell, known as the H substance. Although there are six possible genotypes, the absence of a specific anti-O prevents the serological recognition of more than four phenotypes (Table 29. The two major subgroups of A (A1 and A2) complicate the issue but are of minor clinical significance. A2 cells react more weakly than A1 cells with anti-A and patients who are A2B can be wrongly grouped as B. The A, B and H antigens are present on most body cells including white cells and platelets. In the 80% of the population who possess secretor genes, these antigens are also found in soluble form in secretions and body fluids. Naturally occurring antibodies (usually IgM, occasionally IgG) to A and/or B antigens are found in the plasma of subjects whose red cells lack the corresponding antigen (Table 29. Each consists of a chain of sugars attached to lipids or proteins which are an integral part of the cell membrane. The A antigen has an additional N-acetyl galactosamine (galnac), and the B antigen has an additional galactose (gal).


  • http://www.med.umich.edu/1libr/Anesthesiology/SacroiliacJointRFA.pdf
  • https://www.aota.org/~/media/Corporate/Files/Publications/CE-Articles/CE-Article-November-2018.pdf
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