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One known risk factor is a family history of African Americans antifungal tube generic 200mg ketoconazole overnight delivery, Native Americans, and Hispanic indi diabetic nephropathy. Dyslipidemia these individuals develop a propensity to hyperkalemia, should also be treated. However, once macroalbuminuria exists, it is are predisposed to radiocontrast-induced nephrotoxicity. Furthermore, many glucose contrast dye should be well hydrated before and after dye lowering medications (sulfonylureas and metformin) are exposure, and the serum creatinine should be monitored contraindicated in advanced renal insuf ciency. Blood pressure should be maintained at <130/80 mmHg in diabetic individuals the optimal therapy for diabetic nephropathy is preven without proteinuria. Atherosclerosis is the lead Intercostal or truncal radiculopathy causes pain over the ing cause of death in diabetic individuals on dialysis, thorax or abdomen. Involvement of the lumbar plexus or and hyperlipidemia should be treated aggressively. Combined pancreas-kidney transplant offers the diabetic polyradiculopathies are usually self-limited and promise of normoglycemia and freedom from dialysis. A vascular etiology has been Diabetic neuropathy occurs in 50% of individuals with suggested, but the pathogenesis is unknown. It may manifest as of the third cranial nerve is most common and is heralded polyneuropathy, mononeuropathy, and/or autonomic by diplopia. All individuals with diabetes should then Autonomic neuropathies affecting the cardiovascular sys be screened annually for both forms of neuropathy. It most frequently presents and anhidrosis of the lower extremities result from sympa with distal sensory loss, but up to 50% of patients do not thetic nervous system dysfunction. Hyperesthesia, paresthe can promote dry skin with cracking, which increases the sia, and dysesthesia also may occur. Autonomic neuropathy may reduce these symptoms may develop as neuropathy progresses. Neuropathic pain develops in some the risk of severe hypoglycemia and complicating efforts of these individuals, occasionally preceded by improve to improve glycemic control. Pain typically involves the lower extremities, is usually present at rest, and wors ens at night. As diabetic neuropathy progresses, the pain Treatment of diabetic neuropathy is less than satisfac subsides and eventually disappears, but a sensory de cit tory. Improved glycemic control should be aggressively in the lower extremities persists. Physical examination pursued and will improve nerve conduction velocity, but reveals sensory loss, loss of ankle re exes, and abnormal symptoms of diabetic neuropathy may not necessarily position sense. Though parasympathetic dysfunction sec confounded by autonomic neuropathy and hypo ondary to chronic hyperglycemia is important in the devel glycemia unawareness. Risk factors for neuropathy such opment of gastroparesis, hyperglycemia itself also impairs as hypertension and hypertriglyceridemia should be gastric emptying. If foot deformities are pre diabetic cystopathy begin with an inability to sense a full sent, a podiatrist should be involved. As bladder con Chronic, painful diabetic neuropathy is dif cult to treat tractility worsens, bladder capacity and the postvoid resid but may respond to antidepressants (tricyclic antidepres ual increase, leading to symptoms of urinary hesitancy, sants such as amitriptyline, desipramine, nortriptyline, or decreased voiding frequency, incontinence, and recurrent imipramine or selective serotonin norepinephrine reup urinary tract infections. Diagnostic evaluation includes take inhibitors such as duloxetine) or anticonvulsants cystometry and urodynamic studies. However, pending which increases in frequency with the age of the patient further study, most recommend beginning with other and the duration of diabetes, may occur in the absence of agents such as a tricyclic antidepressant and switching if other signs of diabetic autonomic neuropathy. Improved glycemic control should be a pri have limited success (udrocortisone, midodrine, cloni mary goal, as some aspects (neuropathy, gastric func dine, octreotide, and yohimbine), but each has signi cant tion) may improve. Nonpharmacologic maneuvers (adequate salt easier to digest (liquid) and low in fat and ber may mini intake, avoidance of dehydration and diuretics, and lower mize symptoms of gastroparesis. Erythromycin interacts with the motilin receptor and may promote gastric emptying. Nuclear tion in women may be improved with use of vaginal medicine scintigraphy after ingestion of a radiolabeled meal lubricants, treatment of vaginal infections, and systemic is the best study to document delayed gastric emptying, but or local estrogen replacement. The Framingham Heart Study revealed a diovascular events in type 2 diabetes are underway. Risk factors for macrovascular betic patients have higher rates of restenosis and lower disease in diabetic individuals include dyslipidemia, hyper long-term patency and survival rates in older studies. Past trepidation about using beta associated with endothelial, vascular smooth-muscle, and blockers in individuals who have diabetes should not pre platelet dysfunction. Aspirin therapy does not have quency of cardiovascular disease is low in children and detrimental effects on renal function or hypertension, young adults with diabetes, assessment of cardiovascular nor does it in uence the course of diabetic retinopathy. Initial risk of hyperglycemia and hyperlipidemia, lipid abnor therapy for all forms of dyslipidemia should include malities should be assessed aggressively and treated as dietary changes, as well as the same lifestyle modi ca part of comprehensive diabetes care (Fig. Non-dihydropyridine calcium channel blockers can be used in patients with diabetes, but high doses (verapamil and diltiazem), rather than dihydropyri (>2 g/d) may worsen glycemic control and increase dine agents (amlodipine and nifedipine), are preferred insulin resistance. Serum potassium and renal function should be individual also has other risk factors. Disordered proprioception slowed progression of nephropathy; (2) in patients with causes abnormal weight bearing while walking and sub type 2 diabetes, hypertension, and microalbuminuria, an sequent formation of callus or ulceration. Autonomic neuropathy results in anhidro tional points of emphasis include: sis and altered super cial blood ow in the foot, which 1. Calcium channel breaks in the skin, allowing them to enlarge and to become blockers, central adrenergic antagonists, and vasodilators infected. Sympathetic inhibitors and adrenergic blockers arterial disease, smoking, history of previous ulcer or may worsen orthostatic hypotension in the diabetic amputation, and poor glycemic control. The possible contribution of vas signs of poor tting footwear or minor trauma, (3) daily cular insuf ciency should be considered in all patients. Peripheral arter consultation with a health care provider if an abnormal ial bypass procedures are often effective in promoting ity arises. Patients at high risk for ulceration or amputa wound healing and in decreasing the need for amputa tion may bene t from evaluation by a foot care special tion of the ischemic limb. Interventions directed at risk factor modi cation A growing number of possible treatments for diabetic include orthotic shoes and devices, callus management, foot ulcers exist, but they have yet to demonstrate clear nail care, and prophylactic measures to reduce ef cacy in prospective, controlled trials. Attention to other risk factors for vascular disease demonstrated ef cacy in diabetic foot wounds: (1) off (smoking, dyslipidemia, hypertension) and improved loading, (2) debridement, (3) wound dressings, (4) appropri glycemic control are also important. Off-loading is the complete avoidance of infection are common and represent a serious problem. Bed rest and a ity ulcers, management of these lesions is multidiscipli variety of orthotic devices or contact casting limit weight nary and often demands expertise in orthopedics, vas bearing on wounds or pressure points. Surgical debride cular surgery, endocrinology, podiatry, and infectious ment is important and effective, but clear ef cacy of diseases. The plantar surface of the foot is the most other modalities for wound cleaning (enzymes, soaking, common site of ulceration. Dressings such as hydrocolloid dress ropathic (no accompanying infection) or may have sur ings promote wound healing by creating a moist environ rounding cellulitis or osteomyelitis. Antiseptic agents should ulceration is also frequent and should be treated with be avoided. Referral antibiotics that provide broad-spectrum coverage, for physical therapy, orthotic evaluation, and rehabilitation including anaerobes. An infected ulcer is a clinical diagnosis, since super Mild or non-limb-threatening infections can be cial culture of any ulceration will likely nd multiple pos treated with oral antibiotics (cephalosporin, clindamycin, sible bacterial pathogens. The infection surrounding the amoxicillin/clavulanate, and uoroquinolones), surgical foot ulcer is often the result of multiple organisms debridement of necrotic tissue, local wound care (avoid (gram-positive and negative organisms and anaer ance of weight bearing over the ulcer), and close surveil obes), and gas gangrene may develop in the absence of lance for progression of infection. Urgent surgical debridement may be ulcer base or from purulent drainage or aspiration of the required.

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In certain circumstances antifungal moisturiser discount ketoconazole online american express, epidemiologic considerations, familial risk factors, results of other screening procedures, exposure to various teratogens, and threatened pregnancy complications may necessitate sonographic evalua tion of the fetus and pregnancy. Detailed sonography often is best performed at referral centers, which fre quently bene t from better equipment and often are staffed with more expe rienced technicians and diagnosticians. American College of Obstetrics and Gynecology: Practice Bulletin: Clinical Management Guidelines for Obstetrician-Gynecologists, 27:2001. Anderson N, Boswell O, Duff G: Prenatal sonography for the detection of fetal anomalies: results of a prospective study and comparison with previous studies. Schroeder B, Langer O: Isolated oligohydramnios in the term pregnancy: is it a clinical entity The routine antenatal diagnostic imaging with ultrasound study: another per spective. Enk L, Wieland M, Hammarberg K, Lindblom B: the value of endovaginal sonography and urinaryhumanchorionicgonadotropintestsfordifferentiationbetweenintrauterineand ectopic pregnancy. Hickey J, Goldberg F: Ultrasound Review of Obstetrics and Gynecology, Philadelphia, Lippincott-Raven, 1996. Lencioni R, Cioni D, Bartolozzi C: Tissue harmonic and contrast-speci c imaging: back to gray scale in ultrasound. Madazli R, Uluda S, Ocak V: Doppler assessment of umbilical artery, thoracic aorta and middle cerebral artery in the management of pregnancies with growth restriction. Mari G, Detti L, Oz U, Zimmerman R, Duerig P, Stefos T: Accurate prediction of fetal hemoglobin by Doppler ultrasonography. Muller T, Nanan R, Rehn M, Kristen P, Dietl J: Arterial and ductus venosus Doppler in fetuses with absent or reverse end-diastolic ow in the umbilical artery: correlation with short-term perinatal outcome. Stefos T, Cosmi E, Detti L, Mari G: Correction of fetal anemia on the middle cerebral artery peak systolic velocity. Porter Obstetric ultrasonography is widely used for both general screening for un derlying anomalies in low-risk infants and for detailed screening of suspected abnormalities. One principle goal is to identify conditions that present oppor tunities to improve the fetal outcome, such as in fetal growth restriction or obstructive uropathy, or that present high risk for adverse fetal outcomes. To achieve these goals, it is necessary to understand how various combinations of sonographic ndings may suggest syndromic fetal abnormalities. To identify the forms of aneuploidy least compatible with life, it is important to be aware of ndings that are characteristic of these syndromes. Infants with trisomy 13 often have structural, such as cardiac, anomalies, midline facial anomalies, microcephaly, holoprosencephaly, polydactyly, rocker-bottom feet, and single umbilical artery. In cases of trisomy 18, structural cardiac anoma lies, growthretardation, cleftlip, singleumbilicalartery, cystichygroma, hydro cephaly, overlapping ngers, androcker-bottomfeetareoftenobserved. Infants with polyploidy often experience severe early-onset asymmetric growth retar dation, molar degeneration of the placenta, cardiac anomalies, central nervous system defects, and oligohydramnios; they may present with early onset se vere preeclampsia. As a result, such infants often are identi ed by abnormal sonographic ndings, and, in common with low baseline prevalence rates, a normal screening sonogram makes such syndromes very unlikely in a given fetus. Certain major structural malformations and ndings place the fetus at very high risk for aneuploidy. Early diagnosis of such conditions allows assessment of the fetal karyotype and offers impor tant help in managing the ongoing pregnancy, especially if a highly morbid karyotype is identi ed. When a condition with an extremely poor prognosis is identi ed, such as trisomy 13 or 18, pregnancy termination may be considered, or cesarean section at term for fetal distress may be avoided (as it will offer little bene t to the fetus and signi cant potential morbidity to the mother). If screening for fetal structural anomalies is elected, it is generally most ef cient to do an initial, broad assessment of fetal anatomy, and then pursue any further anomalous ndings that may have been uncovered. The following sec tions describe differential diagnostic considerations for various fetal anomalies that may be encountered. The image is obtained in a plane showing the medial walls of the cerebral lateral ventricles, the cavum septum pellucida, and the thalamic nuclei. Basic evaluation of the head usually includes a brief evaluation of head shape and of the symmetry of intracranial structures, ensuring that no shift of midline structures is present. The lateral ventricles, thalami, and other mid line structures should be observed. Views of the face, with attention to the mouth and palate (if possible), may be obtained and the posterior fossa evalu ated. If other abnormalities are noted on the sonogram, care should be taken to evaluate organ systems that might result in the abnormal ndings noted. Polyhydramnios, for example, might prompt further evaluation of the tracheo-esophageal disorders or bowel atresias. Assuming proper imaging orientation, shifts of midline structures suggest a local mass effect, perhaps from isolated ventriculomegaly. The cere bral ventricles normally do not exceed 10 or 11 mm in diameter, and values in excess of 11 mm usually indicate ventriculomegaly (Pretorius et al. The proportionality between the lateral ventricles and the hemispheric diam eter can also be used to help identify abnormal ventricular dilation. It is possible for normal brain tissue to give the appearance of ventricu lomegaly (pseudoventriculomegaly) if there is sonographic dropoff (poor acoustic return) posterior to the distal ventricular wall margin. This acous tic loss may give the false impression of excessive ventricular diameter and an abnormally large ventricle. They are never normally oriented at acute angles or perpendicular to the ventricle, and a dangling choroid crossing most of the width of the ventricle strongly suggests ventriculomegaly (Figure 4. Aneuploidy is found in 2% of infants with isolated ven triculomegaly and in 17% if one or more other structural abnormalities are present. Toxoplasmosis may present with ventricu lomegaly and is sometimes treatable in utero with potential salvage of fetal neurologic development. If patients are unwilling to risk pregnancy loss by amniocentesis before 24 weeks gestation, later amniocentesis at about 34 weeks gestation should be considered. Amniocentesis at this time risks only preterm emergency delivery, will usually allow chromosomal determination in time to optimize delivery management, and may facilitate management of the neonate after birth. Choroid cysts appear as single or multiple 2 to 5-mm cysts and may be unilateral or bilateral. Aneuploid karyotypes have been reported in 8% of infants with choroid cysts (1% aneuploidy in cases of isolated cysts but 46% aneuploidy if other anomalies are present). Choroid cysts occur in 47% of infants with trisomy 18, and with lesser frequency in trisomy 21 (8%) and trisomy 13 (2%). As isolated abnormalities, the risk of trisomy 18 for choroid cysts does not exceed 1/280 until the maternal age is 40 or greater (the risk at age 40 is 1/238). If any other single abnormality is identi ed, the risk for trisomy 18 is 1/277 in women 26 years of age, but the risk of trisomy 18 is 1/6 in women 20 years old if two or more abnormalities are present (Snijders 1996). Counseling for patients with fetal choroid cysts varies by maternal age and the ability to accurately detect other sonographic ndings. The potential for falsely low risk assessments due to false negative sonographic screening should be discussed with patients during the process of their evaluation. The most common additional ndings in trisomy 18 are ventricular septal defects and abnormalities of the extremities, which may be subtle and dif cult to detect.

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For physiological reasons certain dipyrroles are also sometimes re It has an estimated Mr of 160 000 fungus gnats in hydro ketoconazole 200mg online. It is synthesized from an a1-microglobulin/ colourless bile pigment, or bilinogen (def. Bilirubin accumulates in the blood bindin a protein of 285 amino acids, Mr 35 000, extracted from the and tissues in jaundice, which may arise from acquired or heredi insoluble granular material of sea-urchin sperm, responsible for the tary causes. H H H H binding the act or process by which one molecule attaches to an N N N N other by noncovalent forces; ligation see ligate (def. Com biocatalyst any agent, present in or obtained from living material, pare biosynthesis. Oxidation of the latter by microorgan biogenesis 1 the synthesis of a substance in a living organism; isms removes dissolved oxygen, hence reducing the ability of the biosynthesis. Biologically active substances are often of bio nuclear magnetic resonance spectrometry, mass spectrometry, fluo logical origin themselves. It has been isolated from queen-bee jelly and is considered a logical system or sample and giving a measure of exposure, effect, growth factor for some insects. O biosynthetic pathway any metabolic pathway effecting biosynthe sis; an anabolic pathway. It is named after the baculovirus, in which it was first discov gineering, and single-cell protein production. Both singlet and triplet species serves as a carrier in a number of enzymic b-carboxylation reac are embraced. In biotin-containing enzymes it is covalently bound at the ac bird flu a disease caused by the avian influenza virus with haemag tive site to the e-amino group of a lysine residue. It benzimidazolyl phenol (Hoechst 33258) or its ethyl ether (Hoechst is present in many human tissues. The protein also has a third activity, that of 3-phosphoglycerate mutase, which catalyses exhibits a Ki of 14 nm for the purified enzyme, but its potency on the reaction: 3-phosphoglycerate = 2-phosphoglycerate. It is inexpensive, stable, and blank (determination) any analytical mixture from which analyte readily crystallizable. A group of (usually) eight bleb 1 a spherical vesicle, about 10 lm in diameter, formed when a bits comprises a byte, which can represent numbers between 0 and chloroplast swells on suspension in very hypotonic medium. It when biuret (carbamoylurea) or compounds containing two or rapidly and reversibly blocks formation of cell blebs. It consists of blades rotating at the bottom of a glass orimetric method for the qualitative or quantitative determination or stainless-steel vessel (originally named a Waring blendor, from a of proteins. The binding of n ligand atoms, ions, or molecules to an acceptor atom, method is undiscriminating and may damage organelle membranes ion, or molecule. Kn are the stepwise formation (stability) cycle in the G2 phase (see cell-division cycle). It is used to induce syn constants of the n complexes; and [L] is the free ligand concentra chrony in cell cultures and as an antineoplastic agent, especially in tion. It is used for evaluating the association con protein of 1417 residues encoded by the locus for Bloom syndrome at stants in a Bjerrum formation function. It contains a 350-residue domain that comprises seven se Bk symbol for berkelium. The current concept of the mechanism has protein of 150 kDa (human), 76 kDa (bovine). In humans 14 different, geneti added to blood plasma, markedly shortens the time required for cally independent blood-group systems are known. The specificities of the blood-group Factor V (or accelerator globulin or proaccelerin) a glycoprotein of antigens arise in some cases from oligosaccharide chains linked to 330 kDa. After activation to factor Va (accelerin), it acts with the protein or lipid (ceramide); antigens that fall into this category are protease factor Xa in activating prothrombin. It is characterized by strong absorption in the visible re cause) that react with these antigens on red blood cells causing them gion owing to coordination of the copper by cysteine sulfur. Only the presence of a blood-group antigen during blue dextran a soluble dextran, of average M 106, conjugated with r fetal life ensures that no antibody against it will be produced. It is useful in gel filtration for checking col if blood from an individual (the donor) who lacks a particular anti umn packing and determining the void volume. Blue oxidases are the most complicated of cop been of interest largely in relation to blood transfusion, and in most per proteins; the blue colour is due to a strong absorption band cases the true physiological function of these substances is un around 600 nm. The Lewis antigens, Lea and Leb, are associated with gly histochemical studies to demonstrate oxidoreductase activity, and cosphingolipids adsorbed from plasma lipoproteins on to adult in the colorimetric assay of some dehydrogenases. Clotting may be prevented by the addition of disodium hy N N drogen citrate which removes ionized Ca2+ by the formation of an + un-ionized complex. Their maturation is de body size, a sun-sensitive erythematous skin rash, characteristic fa termined by processing within the bursa of Fabricius in birds, or cies and head shape, immunodeficiency, and chronic lung dissease. B lymphocytes Heterozygotes have twice the normal risk of developing colorectal may be differentiated from T lymphocytes by their surface markers cancer. It is named from B-cell-specific Moloney murine specific radioactive or fluorescent probes. The substance is placed in a residue and functions in inducer binding and in dimerization. The heat evolved is measured by the rise in temperature of the Bmr transporter see BmrR. They all lyse erythrocytes and lipo effects arising from oxygen-linked acid groups in hemoglobin and somes, release histamine from mast cells, and stimulate phospholi similar oxygen-carrying proteins, and also encompasses similar pase A; their properties are similar to those of melittin. See coordination, dipolar bond, hydrogen fundamental physical constant, of value 9. Red marrow (or myeloid tissue), found in developing duce aldehydes, ketones, and Schiff bases in nonaqueous solvents, bone, ribs, vertebrae, and in parts of the long bones, is actively he and also acids, esters, acid chlorides, and nitriles. In adult mammals, B lymphocytes de borosilicate (glass) a silicate glass containing at least 5% boric velop and differentiate in the bone marrow. Such a material has a high melting point and a low coeffi bone-marrow-derived cell any cell derived from bone marrow tis cient of thermal expansion, and hence is useful for the manufacture sue, including erythrocytes, lymphocytes, granulocytes, etc. It is a powerful blood-vessel dilator, increasing Boyden chamber an apparatus, consisting of two small chambers vascular permeability and causing a fall in blood pressure; it is also separated by a micropore filter, used in the study of chemotaxis. The rat B2 receptor is a seven-transmembrane-domain pro cient in 53Bp1 show growth retardation, immune deficiency, and tein which has been shown on activation to stimulate phosphoinosi sensitivity to irradiation and are cancer prone. It rays of wavelength k strikes the crystal at an angle h, reinforcement may be a receptor for a subset of these proteins and is produced in of the reflected waves occurs when sin h = n k/2d, where n is an inte these plants by a multigene family. Maple-syrup urine disease results from their de fective oxidative decarboxylation. It effects a rapid increase methyl-2-oxobutanoate dehydrogenase (lipoamide)]-phosphatase. Branching enzymes fall into two types: the plant Q-enzymes and the mammalian enzymes, which B region the site of final epoxidation of carcinogenic polycyclic aro are able to produce glycogen, a more highly branched molecule matic hydrocarbons. It is located on the terminal ring of the bay re than the amylopectin produced in plants by Q-enzymes. Such a process may occur brevetoxin any of the highly toxic lipid-soluble polyether com in transcription or in recombination. They occur in algae, ferns, gymnosperms, and angiosperms brevican a proteoglycan that contains linked chondroitin sulfate and induce a broad variety of biological responses. It con 28C steroid) is a plant growth regulator discovered in rape (Brassica tains an N-terminal hyaluronan-binding domain. Several hundred binding sites able to interact with and join a corresponding number mutations in each gene have been reported. Bridging is indicated by the Greek letter mu (l) ap breakage and reunion model the classical and generally accepted pearing before the ligand name and separated by a hyphen.

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Note the presence of septations in both fetuses fungus acne buy cheap ketoconazole 200 mg on line, and also note that the fluid within the septations (asterisk) is clear in A and echogenic, jelly like in B. Ultrasound Findings the presence of cystic masses on ultrasound in the posterolateral aspect of the fetal neck is suggestive of cystic hygroma. The demonstration of the presence of septations is best done in the axial plane of the neck and upper chest (Fig. A thick septum is commonly seen in the posterior midline neck region corresponding to the nuchal ligament (Fig. When multiple septations are present, the ultrasound appearance resembles a honeycomb. Nonseptated cystic hygroma is seen as cystic spaces on either side of the fetal neck, representing dilated cervical lymphatics. Given the common association with other fetal malformations and chromosomal abnormalities, a comprehensive evaluation of the fetus by detailed ultrasound is warranted when a cystic hygroma is diagnosed in the first trimester. Associated Malformations Cystic hygroma is associated with other fetal anatomic abnormalities in 60% of cases. Associated abnormalities commonly include cardiac, genitourinary, skeletal, and central nervous systems, and the majority can be seen on the first-trimester ultrasound. Chromosomal abnormalities are common, with trisomy 21 and Turner syndrome representing the two most common associated chromosomal 59 findings, reported in more than 50% of cases. A typical syndromic condition to be considered is the presence of Noonan syndrome (Fig. Amniotic fluid abnormalities are common, but they are noted in the second and third trimesters of pregnancy. The outcome is usually good when cystic hygroma resolves prenatally in the presence of a normal karyotype. Note in A and B the presence of an enlarged nuchal translucency (asterisks), measuring 7. C and D: A normal four-chamber view and a normal three-vessel-trachea view, respectively. The risk of abnormal neurodevelopmental delay is currently unclear, and controversial observations 65 are reported. In this section, we present essential points and current literature related to this topic. A follow-up fetal echocardiogram is also performed at 16 to 22 weeks of gestation. Please refer to Chapter 11 for a detailed discussion of the evaluation of the fetal heart in the first trimester. However, it is still unclear whether in all reported cases the 65 relationship is causal or accidental. It is possible that in the future, whole genomic sequencing may be offered in these conditions, but the value of this approach has to be proven in large studies before wide implementation. The components of the detailed first trimester ultrasound examination are presented in Chapter 5. A follow-up ultrasound examination at 75 16 weeks of gestation is also warranted in order to reassess fetal anatomy. Evaluation of the nuchal fold in the second trimester is also important because outcome is improved if the nuchal fold is normal (Fig. A detailed second-trimester ultrasound examination at 18 to 22 weeks of gestation along with a fetal echocardiogram is also recommended. This approach will detect the majority of major malformations and syndromic conditions, many of which can be detected in the first and early second ultrasound examinations. Absence of nasal bone in fetuses with trisomy 21 at 11 14 weeks of gestation: an observational study. Prenasal thickness to nasal bone length ratio in normal and trisomy 21 fetuses at 11-14 weeks of gestation. Prenasal thickness, prefrontal space ratio and other facial profile markers in first-trimester fetuses with aneuploidies, cleft palate, and micrognathia. Retronasal triangle: a sonographic landmark for the screening of cleft palate in the first trimester. Absent mandibular gap in the retronasal triangle view: a clue to the diagnosis of micrognathia in the first trimester. Ultrasound evaluation of the length of the fetal nasal bones throughout gestation. Nuchal translucency and other first-trimester sonographic markers of chromosomal abnormalities. Second trimester ultrasound prenasal thickness combined with nasal bone length: a new method of Down syndrome screening. Frontomaxillary facial angle in chromosomally normal fetuses at 11 + 0 to 13 + 6 weeks. Frontomaxillary facial angle in screening for trisomy 21 at 11 + 0 to 13 + 6 weeks. Frontomaxillary and mandibulomaxillary facial angles at 11 + 0 to 13 + 6 weeks in fetuses with trisomy 18. Frontomaxillary facial angle in fetuses with trisomy 13 at 11 + 0 to 13 + 6 weeks. Frontomaxillary facial angle at 11 + 0 to 13 + 6 weeks: effect of plane of acquisition. Maxilla-nasion-mandible angle: a new method to assess profile anomalies in pregnancy. Brains and faces in holoprosencephaly: pre and postnatal description of 30 cases. Prenatal diagnosis of severe epignathus in a twin: case report and review of the literature. Prenatal ultrasonographic diagnosis of cataract: in utero manifestations of cryptic disease. Incidence of cleft lip, cleft palate, and cleft lip and palate among races: a review. Three-dimensional sonographic imaging of fetal bilateral cleft lip and palate in the first trimester. Bilateral cleft lip and palate diagnosed sonographically at 11 weeks of pregnancy. Ultrasonographic features of orofacial clefts at first trimester of pregnancy: report of two cases [in French]. Clinical significance of first-trimester screening of the retronasal triangle for identification of primary cleft palate. Early prenatal diagnosis of orofacial clefts: evaluation of the retronasal triangle using a new three-dimensional reslicing technique. Antenatal detection of cleft lip with or without cleft palate: incidence of associated chromosomal and structural anomalies. Fetal cleft lip and palate: sonographic diagnosis, chromosomal abnormalities, associated anomalies and postnatal outcome in 70 fetuses. Bilateral cleft lip and palate without premaxillary protrusion is associated with lethal aneuploidies. Ultrasonographic diagnosis of glossoptosis in fetuses with Pierre Robin sequence in early and mid pregnancy. First-trimester diagnosis of micrognathia as a presentation of Pierre Robin syndrome. First-trimester septated cystic hygroma: prevalence, natural history, and pediatric outcome. Cystic hygromas, nuchal edema, and nuchal translucency at 11-14 weeks of gestation. Defects and syndromes in chromosomally normal fetuses with increased nuchal translucency thickness at 10-14 weeks of gestation. Genomic microarray in fetuses with increased nuchal translucency and normal karyotype: a systematic review and meta-analysis.

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Clinically a spectrum is encountered that ranges from a limited period of amenorrhea associated with a crash diet antifungal examples discount ketoconazole 200 mg online, to the severely ill patient with the life-threatening attrition of anorexia nervosa. It is a common experience for a clinician to be the first to recognize anorexia nervosa in a patient presenting with the complaint of amenorrhea. It is also not infrequent that a clinician will evaluate and manage an infertility problem due to hypogonadotropism and not be aware of a developing case 198, 199 of anorexia. Anorexia nervosa has been recognized to occur frequently in young white middle to upper class females under age 25, but it is now apparent that this problem occurs 200 at all socioeconomic levels in about 1% of young women. Serious problems may be present within the family, but the parents make every effort to maintain an apparent marital harmony, glossing over or denying conflicts. This brings a sense of power and accomplishment, soon followed by a fear that 201 weight cannot be controlled if discipline is allowed to relax. A reasonable view is to consider anorexia as a mechanism that identifies a generally disturbed family. The symptom pattern is the expression of the various psychological, familial, and cultural factors involved. At puberty, the normal weight gain may be interpreted as excessive, and this can trip the teenager over into true anorexia nervosa. Excessive physical activity can be the earliest sign of incipient anorexia nervosa. They seldom give any trouble, but are judgmental and demand that others live up to their rigid value system, often resulting in social isolation. Patients with eating disorders usually demonstrate delayed psychosexual 202 development marked by sexual experiences occurring at a later age. The cultural value our society places on thinness definitely plays a role in eating disorders. Both occupational and recreational environments that stress thinness put women at greater risk for anorexia nervosa and bulimia. But basically, an eating disorder is a method being utilized to solve a psychological dilemma. Besides amenorrhea, constipation is a common symptom, often severe and accompanied by abdominal pain. The preoccupation with food may manifest itself by large intakes of lettuce, raw vegetables, and low-calorie foods. Hypotension, hypothermia, rough dry skin, soft lanugo-type hair on the back and buttocks, bradycardia, and edema are the most commonly encountered signs. An elevation of the serum carotene is not always associated with a large intake of yellow vegetables, suggesting that a defect in vitamin A utilization is present. Hypercarotenemia should be regarded as a metabolic marker, but not every woman with hypercarotenemia will be amenorrheic or 203 anovulatory. It appears to be a growing problem among young women; however, careful study indicates that although bulimic behaviors may be relatively common, clinically significant bulimia is not (approximately 1. Bulimic behavior is frequently seen in patients with anorexia nervosa (about half), but not in all. Patients with bulimia have a high incidence of depressive symptoms, and a problem with shoplifting (usually food). There is a growing tendency to divide patients with anorexia nervosa into bulimic anorectics and dieters. Bulimic anorectics are older, less isolated socially, and have a higher incidence of family problems. However, the borderline anorectic frequently presents to a gynecologist, pediatrician, or family physician as a teenager who has low body weight, amenorrhea, and hyperactivity (excellent grades and many extracurricular activities). The amenorrhea can precede, follow, or appear coincidentally with the weight loss. The various problems associated with anorexia represent dysfunction of the body mechanisms regulated by the hypothalamus: appetite, thirst and water conservation, 208 temperature, sleep, autonomic balance, and endocrine secretion. Indeed, many of the symptoms can be explained by relative hypothyroidism (constipation, cold intolerance, bradycardia, hypotension, dry skin, low metabolic rates, hypercarotenemia). There appears to be a compensation to the state of undernourishment, with diversion from formation of the active T 3 to the inactive metabolite, reverse T 3. Even though normal gonadotropin secretion may be restored with weight gain, 30% of patients remain 206 amenorrheic, a good sign of ongoing psychological conflict. Patients with anorexia nervosa have persistent low levels of gonadotropins similar to prepubertal children. With full recovery, the 24-hour pattern is similar to that of an adult, marked by fluctuating peaks. Neuropeptide Y cell bodies are located in the arcuate nucleus of the hypothalamus. In response to food deprivation, the endogenous levels of neuropeptide Y increase, and elevated concentrations of neuropeptide Y can be measured in the cerebrospinal fluid of anorexic women. This is consistent with the known actions of leptin, as discussed with full references in Chapter 19. This is one of the rare conditions in which gonadotropins may be undetectable (large pituitary tumors and genetic deficiencies are the others). If necessary, a high plasma cortisol can differentiate this condition from pituitary insufficiency. Adherence to our scheme for the evaluation of amenorrhea is indicated to rule out other pathological processes. A careful and gentle revelation to the patient of the relationship between the amenorrhea and the low body weight is often all that is necessary to stimulate the patient to return to normal weight and normal menstrual function. In an adult weighing less than 100 pounds, continued weight loss requires psychiatric consultation. Some would argue that any patient with an eating disorder requires psychiatric intervention. Going away to school or the development of a relationship with a male friend often are turning points for young women with mild to moderate anorexia. A failure to respond to these life changes is relatively ominous, predicting a severe problem with a protracted course. It is disappointing that despite the impressive studies on anorexia, there is no specific or new therapy available. This only serves to emphasize the need for early 211 recognition to allow psychologic intervention before the syndrome is entrenched in its full severity. The use of serotonin antagonists or uptake blockers is restricted 212 to patients who, as is frequently the case, have the comorbidity of clinical depression. Clinicians (and parents) should pay particular attention to weight and diet in young women with amenorrhea. Even in amenorrheic adolescents of normal or above-normal body weights, disordered eating patterns (fasting and purging) are often 213 present, a sign of an underlying stressful disorder. Late in the 20th century, there was a new awareness that competitive female athletes, as well as women engaged in strenuous recreational exercise and women engaged in other forms of demanding activity, such as ballet and modern dance, have a significant incidence of menstrual irregularity and amenorrhea, in the pattern called hypothalamic suppression. The extent of this problem has perhaps been underestimated 214 because of a lack of attention to anovulatory cycles. As many as two-thirds of runners who have menstrual periods have short luteal phases or are anovulatory. When training starts before menarche, menarche can be delayed by as much as 3 years, and the subsequent incidence of menstrual irregularity is higher. In some individuals, secondary amenorrhea is associated with delayed menarche even though training did not begin until after menarche. It is suggested that some girls with these characteristics may be socially influenced to pursue athletic training.

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She says that the pain usually lasts for a few days and is somewhat relieved by nonsteroidal anti-inflammatory medications antifungal drinks buy cheap ketoconazole 200 mg on-line. Her blood pressure and heart rate are normal for her age and body mass index is at the 80th percentile. Symptoms of imperforate hymen include lack of menses, cyclical abdominal or back pain, urinary retention, constipation, and lower extremity edema. On physical examination, an abdominal mass can be palpated, as well as a bluish bulging mass at the introitus from accumulation of menstrual bleeding. Treatment of an imperforate hymen requires a hymenotomy, a surgical resection of the membrane. However, a low transverse vaginal septum can be distinguished from an imperforate hymen with the Valsalva maneuver. During the Valsalva maneuver, bulging is seen with an imperforate hymen, and not with a low transverse vaginal septum. Vaginal agenesis is typically characterized by absence of the proximal vagina and absence or hypoplasia of the uterus. In addition to those findings, ultrasonography may reveal additional abnormalities such as urinary tract anomalies. Uterine duplication anomalies represent malformations related to failed fusion of the Mullerian duct structures. Uterine duplication anomalies are often asymptomatic unless an obstruction is present. Labial adhesions occur typically in the prepubescent population before the production of endogenous estrogen, which starts at puberty. Her physical examination is remarkable only for several papules located in the left antecubital fossa (Item Q23). It is especially prevalent in children who have atopic dermatitis, with a disrupted skin barrier and impaired cutaneous immunity. Papules vary in number and range in size from 1 to 6 mm in diameter, and can affect most body surfaces, although involvement of the palms, soles, and mucous membranes is rare. It is not known whether this represents a host response to the virus or underlying atopic dermatitis. Molluscum contagiosum is self-limited, therefore no intervention would be a reasonable choice for children who have only a few asymptomatic lesions. Especially in young children who do not tolerate discomfort well, cantharidin (a blister beetle extract) may be applied in the office to individual lesions. Alternative painless topical agents that may be applied at home include salicylic acid and a topical retinoid (eg, tretinoin or adapalene). For children who can tolerate discomfort, cryotherapy and curettage are effective. A less severe cardiovascular condition with a perfusing rhythm is not as likely because he is not breathing. Although a neurologic catastrophe (eg, trauma or spontaneous hemorrhage of a cerebrovascular malformation) should be considered as a possible cause of this event, it is significantly less likely without a supporting history. Appropriate life support responses for children include the algorithms of basic life support, in which it is assumed that there is only 1 responder, and pediatric advanced life support, which takes place in an environment in which many rescuers are involved and actions can be undertaken simultaneously. If no advanced airway, ie, an endotracheal tube or laryngeal mask airway, is present, a 15:2 compression-ventilation ratio should be followed. If an advanced airway is in place, 8 to 10 breaths per minute should be given with continuous chest compressions. Because the boy in the vignette presented with collapse and apnea, he is unlikely to have a perfusing rhythm. Palpation for a pulse in this setting may not be accurate, and could lead to a delay in definitive care. The cause of his collapse is likely cardiac, therefore jaw-thrust or chin-lift maneuvers would not be helpful. The precordial thump is no longer recommended in the latest American Heart Association guidelines. In the absence of trauma, immobilization of the cervical spine is not recommended. On physical examination, he is irritable and has a faint erythematous maculopapular rash principally over the lower extremities. While arboviral infections, including West Nile virus, can present with a nonspecific febrile illness or aseptic meningitis, they are a less common etiology in this age group, as they would require contact with the respective vector. Immunoglobulin M is usually detectable by 3 to 8 days in patients with arboviral infections. However, if an arboviral infection is strongly suspected and testing is negative within 10 days of the onset of illness, convalescent testing is recommended. While herpes simplex virus infection can present as a febrile illness with associated meningoencephalitis, an exanthem, if present, would be expected to be vesicular in nature. An abdominal examination reveals tenderness of the left upper abdomen and a mass on the left side. Complete blood cell count, blood urea nitrogen, serum creatinine, electrolytes, and liver function tests all yield normal results. His urine microscopy shows 10 to 20 red blood cells/high power field, less than 5 white blood cells/ high power field, and no crystals and no bacteria. Other less common presentations include urinary tract infection, hematuria, or failure to thrive. These patients may return to the emergency room with history of recurrent episodes of flank or abdominal pain, and may even have extensive negative evaluations for abdominal pain. It is important to perform an ultrasonographic examination during episodes of acute pain, as this may be normal once the pain subsides. Diuretic renal scan (renal scan along with administration of a furosemide) is used to confirm the diagnosis of urinary tract obstruction. The timed excretion of the radioisotope correlates with the degree of obstruction. Administration of furosemide results in a prompt washout in nonobstructed kidneys, while a half-life greater than 20 minutes to clear the isotope from the kidney is indicative of obstruction. Normally, reflux of urine is prevented by compression of the intravesical ureter by the contracting bladder muscles. Grade V reflux rarely resolves spontaneously, therefore these patients usually require surgical intervention. Multicystic dysplastic kidney is usually suspected based on renal abnormalities detected on antenatal ultrasonography or in neonates with abdominal mass on examination. Classic findings on renal ultrasonography include multiple noncommunicating cysts with intervening dysplastic renal tissue. The classic presentation of Wilms tumor is abdominal swelling with or without associated symptoms, including abdominal pain, hematuria, and hypertension. Physical examination reveals a firm, nontender, smooth mass that usually does not cross the midline. Despite aggressive medical management, she required resection of her ileum, including her ileocecal valve 4 months ago. Stool studies demonstrate normal bacterial flora, negative reducing substances, and are heme negative. In addition to having a chronic disease, the child in this vignette has lost most of her ileum. Absorption of bile occurs in the ileum and malabsorption results in chronic diarrhea, as in the case in the girl in this vignette. Disaccharides (lactose, fructose, sucrose, etc) are digested and absorbed in the duodenum and jejunum. Small bowel inflammation may result in injury to villi, causing a secondary disaccharidase deficiency resulting in diarrhea. Malabsorption of carbohydrates results in increased stool reducing substances, not seen in the child in the vignette.

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There is no evidence Athletes generally use increasing doses of multiple that testosterone replacement causes prostate cancer kingdom fungi definition biology buy ketoconazole 200 mg without a prescription. A majority of ath However, androgen administration can exacerbate preex letes who abuse androgenic steroids also use other drugs isting prostate cancer. Many older men harbor microscopic that are perceived to be muscle-building or performance foci of cancer in their prostates. Elevations of liver enzymes, hepatic neo terone supplementation in androgen-de cient men are plasms, and peliosis hepatis have been reported, mostly generally <0. Upon dis Cardiovascular Risk Assessment the long continuation of exogenous androgen use, the sup term effects of testosterone supplementation on cardio pressed hypothalamic-pituitary axis may take weeks to vascular risk are unknown. During this period when testos depend on the dose (physiologic or supraphysiologic), terone levels are low, the athletes may experience sexual the route of administration (oral or parenteral), and the dysfunction, hot ushes, fatigue, and depressed mood, formulation (whether aromatizable or not). In epi mass and strength without commensurate adaptations demiologic studies, testosterone concentrations are in tendons and other connective tissues may predispose inversely related to waist-to-hip ratio and directly corre to the risk of tendon injuries. These data suggest Accredited laboratories use gas chromatography that physiologic testosterone concentration is corre mass spectrometry or liquid chromatography-mass lated with factors associated with reduced cardiovascu spectrometry to detect anabolic steroid abuse. However, no prospective studies have examined years, the availability of high-resolution mass spectrom the effect on testosterone replacement on cardiovascu etry and tandem mass spectrometry has further lar risk. Ratios above ciency syndromes:An Endocrine Society clinical practice guide 6 suggest exogenous testosterone use but can also line. Orchiopexy should the malignant transformation of primordial germ cells, be performed before puberty, if possible. An abdominal cryptorchid testis that cannot be mediastinum, the retroperitoneum, and, very rarely, the brought into the scrotum should be removed. More commonly, patients present with been observed in Scandinavia and New Zealand than in the testicular discomfort or swelling suggestive of epididymitis United States. Abdominal cryptorchid testes are at a higher testicular malignancy is considered and for persistent or 180 painful testicular swelling. If a testicular mass is detected, testicular tumor, the rst involved lymph nodes are lateral 181 a radical inguinal orchiectomy should be performed. Because the testis develops from the gonadal ridge, its In both cases, further nodal spread is inferior, contralateral, blood supply and lymphatic drainage originate in the and, less commonly, above the renal hilum. An involvement can extend cephalad to the retrocrural, poste inguinal approach is taken to avoid breaching anatomic rior mediastinal, and supraclavicular lymph nodes. If the primary tumor shows no evi median age in the fourth decade, and generally follows a dence for lymphatic or vascular invasion and is limited more indolent clinical course. Radiation therapy is the treatment of through T4), then surveillance should not be offered. The operation removes the lymph nodes ipsilat the more aggressive nonseminoma component. If retroperitoneal nodes are found to be tion is increased only in patients with nonseminoma. Depending on the extent of disease, the postoperative management options include either and hair loss occur in most patients, although nausea 183 surveillance or two cycles of adjuvant chemotherapy. For those who relapse, risk neutropenia with septicemia or bleomycin-induced directed chemotherapy is indicated. For good-risk patients, the goal is to achieve About 2% of patients relapse with supradiaphragmatic maximum ef cacy with minimal toxicity. Surveillance has been proposed as patients, the goal is to identify more effective therapy an option, and studies have shown that about 15% of with tolerable toxicity. Prophylactic supra both anatomy (site and extent of disease) and biology diaphragmatic elds are not used. Approximately 90% of or intermediate risk, based on the absence or presence patients achieve relapse-free survival with retroperi of nonpulmonary visceral metastases. Marker levels play no role in third of patients with bulkier disease relapse, initial de ning risk for seminoma. A complete limited to 9 weeks; myelosuppression with neutropenic response (the complete disappearance of all clinical evi fever is less frequent; and the treatment mortality rate is dence of tumor on physical examination and radiography negligible. In general, residual retroperitoneal disease remission to rst-line cisplatin-containing chemotherapy. Thoracotomy (uni In contrast, if the patient failed to achieve a complete lateral or bilateral) and neck dissection are less fre response or has a primary mediastinal nonseminoma, quently required to remove residual mediastinal, pul then standard-dose salvage therapy is rarely bene cial. Viable Treatment options for such patients include dose tumor (seminoma, embryonal carcinoma, yolk sac intensive treatment, experimental therapies, and surgi tumor, or choriocarcinoma) will be present in 15%, cal resection. The frequency of ter carboplatin (1500 mg/m2) plus etoposide (1200 mg/m2), atoma or viable disease is highest in residual mediasti with or without cyclophosphamide, or ifosfamide, with nal tumors. If necrotic debris or mature teratoma is peripheral blood stem cell support, induces a complete present, no further chemotherapy is necessary. High If the initial histology is pure seminoma, mature ter dose therapy is the treatment of choice and standard of atoma is rarely present, and the most frequent nding is care for this patient population. Spermato nosed mediastinal nonseminoma are considered to have genesis does recur in some patients after chemotherapy. In addi reproductive capacity, semen analysis and cryopreservation tion, mediastinal nonseminoma is associated with hema of sperm in a sperm bank should be recommended to all tologic disorders, including acute myelogenous leukemia, patients before treatment. J Clin fraction that are cisplatin-responsive), con rming their origin Oncol 15:594, 1997 from primitive germ cells. To changes responsible for puberty and adult reproductive achieve these functions in repeated monthly cycles, the function. Normal reproductive function in women requires ovary undergoes some of the most dynamic changes of the dynamic integration of hormonal signals from the any organ in the body. In contrast to testis development, germ cells chapters: menstrual cycle disorders (Chap. This allows the oocyte to be surrounded by a sin gen, progesterone, inhibin) that are critical for pubertal gle layer of attened granulosa cells to form a primordial development and preparation of the uterus for conception, follicle. Granulosa cells are derived from mesonephric cells 186 that invade the ovary early in its development, pushing 187 the germ cells to the periphery or ovarian cortex. Although recent studies have reopened the debate, the weight of evi dence supports the concept that the ovary contains a nonre newable pool of germ cells. The oocyte persists in prophase of the rst meiotic division until just before ovulation, when meiosis resumes.

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Among known Other causes of delayed puberty should be considered causes fungus names order 200 mg ketoconazole amex, familial hypogonadotropic hypogonadism can be when there are associated clinical features or when boys transmitted as an X-linked (20%), autosomal recessive do not enter puberty spontaneously after a year of obser (30%), or autosomal dominant (50%) trait. Those with the most severe defciency have which encodes a nuclear receptor in the adrenal gland 158 and reproductive axis. Adrenal hypoplasia congenita is syndrome is a genomic imprinting disorder caused by characterized by absent development of the adult zone deletions of the proximal portion of paternally derived of the adrenal cortex, leading to neonatal adrenal insuf chromosome 15q, uniparental disomy of the mater fciency. Puberty usually does not occur or is arrested, nal alleles, or mutations of the genes/loci involved in refecting variable degrees of gonadotropin defciency. Although gonadotropin defciency and repro other mutations may alter signal transduction down ductive dysfunction are well documented in these stream of hormone binding. Unlike women, most male runners gonadotropic hypogonadism, although they are rare. Mutations in more than one gene but probably involves a combination of cytokine and/ (digenicity) may contribute to clinical heterogeneity in or glucocorticoid effects. Prader-Willi secretion and alter the sensitivity to feedback inhibition by gonadal steroids. Men who are heavy users of mari Hemochromatosis 159 juana have decreased testosterone secretion and sperm Both the pituitary and the testis can be affected by exces production. Gyneco predominant lesion in most patients with hemochroma mastia observed in marijuana users can also be caused by tosis and hypogonadism. Androgen depri matosis is suggested by the association of characteristic vation therapy in men with prostate cancer has been skin discoloration, hepatic enlargement or dysfunction, associated with increased risk of bone fractures, diabetes diabetes mellitus, arthritis, cardiac conduction defects, mellitus, cardiovascular events, fatigue, sexual dysfunc and hypogonadism. Estradiol levels are higher in obese men than in be associated with impaired spermatogenesis, decreased healthy, nonobese controls because of aromatization of androgen production, or both. Weight loss is of testis development, androgen synthesis, and androgen associated with reversal of these abnormalities, includ action. Weight gain in adult men common chromosomal disorder associated with testicu can accelerate the rate of age-related decline in testos lar dysfunction and male infertility. Testicular histology shows hyalinization rounding gonadotropes by invasion or compression of of seminiferous tubules and absence of spermatogenesis. Treatment with dopamine agonists Although their function is impaired, the number of Ley reverses gonadotropin defciency, although there may be dig cells appears to increase. Fertility lesions affecting gonadotropin and other pituitary hor has been achieved by intracytoplasmic injection of sperm mone production. The presence of diabetes insipidus suggests the pos Cryptorchidism occurs when there is incomplete sibility of a craniopharyngioma, infltrative disorder, or descent of the testis from the abdominal cavity into the other hypothalamic lesions (Chap. The incidence of cryptorchidism is <1% may impair Leydig cell function and cause infertility. Androgens regulate both the the degree of gonadal dysfunction depends on the type transabdominal and inguinoscrotal descent of the tes of chemotherapeutic agent and the dose and duration tes through degeneration of the craniosuspensory liga of therapy. Because of high response rates and the young ment and a shortening of the gubernacula, respectively. Epidemiologic, clinical, and molecular evidence vinblastine, dacarbazine), are less toxic to germ cells. Elevated estradiol and decreased perturbations and are components of the testicular dys testosterone levels may occur in men taking digitalis. The occupational and recreational history should be evaluated carefully in all men with infertility because of the toxic effects of many chemical agents on spermatogen Acquired testicular defects esis. Known environmental hazards include microwaves Viral orchitis may be caused by the mumps virus, echo and ultrasound and chemicals such as nematocide dibro virus, lymphocytic choriomeningitis virus, and group B mochloropropane, cadmium, phthalates, and lead. Orchitis occurs in as many as one-fourth some populations, sperm density is said to have declined of adult men with mumps; the orchitis is unilateral in by as much as 40% in the last 50 years. In some instances, returns to normal for three-fourths of men with uni these antibodies are secondary phenomena result lateral involvement but for only one-third of men with ing from duct obstruction or vasectomy. Trauma, including testicular torsion, tous diseases can affect the testes, and testicular atrophy also can cause secondary atrophy of the testes. Doses Systemic disease can cause primary testis dysfunction >200 mGy (20 rad) are associated with increased in addition to suppressing gonadotropin production. In cirrhosis, a combined testicular and pituitary abnor After 800 mGy (80 rad), oligospermia or azoospermia mality leads to decreased testosterone production inde develops, and higher doses may obliterate the germinal pendent of the direct toxic effects of ethanol. Testicular atrophy and lymphoblastic leukemia have permanently low testoster gynecomastia are present in approximately one-half of one levels. In chronic renal failure, androgen patients undergo radiation treatment or chemotherapy. Testicular atrophy is present in one a normal physiologic phenomenon in the newborn 161 third of men with sickle cell anemia. The defect may be (due to transplacental transfer of maternal and placen at either the testicular or the hypothalamic-pituitary level. Infertility in men with celiac disease is associated but it also can result from pathologic conditions asso with a hormonal pattern typical of androgen resistance, ciated with androgen defciency or estrogen excess. In myotonic dystrophy, alter androgen metabolism or action may also cause small testes may be associated with impairment of both gynecomastia. Spinobulbar increased in men with gynecomastia, although the muscular atrophy is caused by an expansion of the gluta absolute risk is relatively small. Men with spinobulbar muscular atrophy Any cause of androgen defciency can lead to gynecomas often have undervirilization and infertility as a late mani tia, refecting an increased estrogen/androgen ratio, festation. Spinal cord lesions that cause paraplegia can lead as estrogen synthesis still occurs by aromatization of to a temporary decrease in testosterone levels and may residual adrenal and gonadal androgens. Excess estrogen production may be caused by tumors, including Sertoli cell tumors in isolation andRogen insensitivity syndRomes or in association with Peutz-Jegher syndrome or Car ney complex. Increased conversion of androgens to estrogens can associated with variable degrees of defective male phe be a result of increased availability of substrate (andro notypic development and undervirilization (Chap. In some families with this disorder, an inver defcient individual that these testosterone actions are sion in chromosome 15q21. Drugs can cause gyne gynecoMastia comastia by acting directly as estrogenic substances. True Because up to two-thirds of pubertal boys and one gynecomastia is associated with glandular breast tissue half of hospitalized men have palpable glandular tissue that is >4 cm in diameter and often tender. Glandu that is benign, detailed investigation or intervention lar tissue enlargement should be distinguished from is not indicated in all men presenting with gyneco excess adipose tissue: glandular tissue is frmer and mastia (Fig. Gynecomastia occurs as comastia, recent onset, rapid growth, tender tissue, 162 Breast enlargement breast tissue size in over one-half of the patients. The estrogen receptor antagonists tamoxifen and ral oxifen have been reported in small trials to reduce breast True glandular enlargement Increased adipose tissue size in men with pubertal gynecomastia, although com plete regression of breast enlargement is unusual with Breast mass hard or fixed to Mammography and/or the underlying tissue biopsy to exclude the use of estrogen receptor antagonists. Aromatase Recent onset and rapid growth malignancy inhibitors can be efective in the early proliferative phase of the disorder. However, in a randomized trial in men Onset in neonatal or peripubertal period Follow-up with serial with established gynecomastia, anastrozole was no more Causative drugs examinations efective than placebo in reducing breast size. Figure 8-5 the age-related decline in testosterone is due to defects evaluation of gynecomastia. This should include a careful drug suggests that testis dysfunction is the main cause of history, measurement and examination of the testes, declining androgen levels. A karyo discrete time when testosterone concentrations decline type should be obtained in men with very small testes abruptly. In spite of exten In epidemiologic surveys, low total and bioavail sive evaluation, the etiology is established in fewer than able testosterone concentrations have been associated one-half of patients.


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