By P. Silvio. Touro College.
The cause 830 GALE ENCYCLOPEDIA OF GENETIC DISORDERS of an isolated omphalocele is suspected to be multifacto- other health problems purchase prazosin 1mg. Multifactorial means that many factors generic 1 mg prazosin with visa, both genetic may be performed such as a chromosome study discount 1 mg prazosin, which is and environmental discount prazosin 1 mg otc, contribute to the cause. Since the chest cavity genes involved, as well as the specific environmental fac- may be small in an infant born with an omphalocele, the tors are largely unknown. The chance for a couple to have baby may have underdeveloped lungs, requiring breath- another baby with an omphalocele, after they have had ing assistance with a ventilator (mechanical breathing one with an isolated omphalocele is approximately one in machine). During pregnancy, two different signs may cause a Approximately 30% of babies with an omphalocele physician to suspect an omphalocele: increased fluid have a chromosome abnormality as the underlying cause around the baby (polyhydramnios) on a fetal ultrasound of the omphalocele. Babies with chromosome abnormal- and/or an abnormal maternal serum screening test, show- ities usually have multiple birth defects, so many babies ing an elevated amount of alpha-fetoprotein (AFP). The normal num- to screen for various disorders such as Down syndrome, ber of chromosomes is 46; having extra or missing chro- trisomy 18, and abnormalities of the spine (such as spina mosome material is associated with health problems. Other abnormalities can give an abnormal test Babies with an omphalocele may have an extra chromo- result, and an omphalocele is an example. This is because the chance for a chromosome if one has not already been performed. An example is nios, or if she had an abnormal maternal serum screening Beckwith-Wiedemann syndrome, where a baby is test, an amniocentesis may be offered. Dominant means that only one gene is in the amniotic fluid can then be done to test for problems necessary to produce the condition, while recessive such as omphalocele. In addition, a chromosome analysis means that two genes are necessary to have the condition. When the AFP in the amniotic fluid is chance with each pregnancy to have an affected child, elevated, an additional test is used to look for the pres- while with autosomal recessive inheritance. ACHE is present in the amniotic fluid only when a baby has an opening Demographics such as spina bifida or an omphalocele. Not all babies Omphalocele is estimated to occur in one in 4,000 to with an omphalocele will cause the maternal serum one in 6,000 liveborns. Males are slightly more often screening test to be abnormal or to cause extra fluid accu- affected than females (1. Signs and symptoms Treatment and management Anytime an infant is born with an omphalocele, a thorough physical examination is performed to determine Treatment and management of an omphalocele whether the omphalocele is isolated or associated with depends upon the size of the abnormality, whether the sac GALE ENCYCLOPEDIA OF GENETIC DISORDERS 831 KEY TERMS Acetylcholinesterase (ACHE)—An enzyme found in Gastroschisis—A small defect in the abdominal nerve tissue. AFP is also found in abnormally high concen- Gene—A building block of inheritance, which con- trations in most patients with primary liver cancer. Either the fluid itself or cells from Macrosomia—Overall large size due to overgrowth. Multifactorial—Describes a disease that is the product of the interaction of multiple genetic and Autosomal dominant—A pattern of genetic inheri- environmental factors. Polyhydramnios—A condition in which there is too much fluid around the fetus in the amniotic sac. Beckwith-Wiedemann syndrome—A collection of health problems present at birth including an Thoracic cavity—The chest. Ultrasound—An imaging technique that uses sound Chromosome—A microscopic thread-like structure waves to help visualize internal structures in the found within each cell of the body and consists of a body. Changes in either the total number of chromosomes or their Ventral wall defect—An opening in the abdomen shape and size (structure) may lead to physical or (ventral wall). A small omphalocele is usually repaired by closed once all of the organs have been returned to the surgery shortly after birth, where an operation is per- abdomen. Infants are often on a breathing machine (ven- formed to return the organs to the abdomen and close the tilator) until the abdominal cavity increases in size since opening in the abdominal wall. If the omphalocele is returning the organs to the abdomen may crowd the lungs large, where most of the intestines, liver, and/or spleen in the chest area. Initially, sterile protec- tive gauze is placed over the abdominal organs whether The prognosis of an infant born with an omphalocele the omphalocele is large or small.
Clarithromycin (D) is used 566 VI CHEMOTHERAPY as a chemoprophylactic agent for MAC in AIDS SUPPLEMENTAL READING patients discount prazosin 1 mg mastercard. Cycloserine should Targeted tuberculin testing and treatment of latent in- be avoided in patients with psychiatric disorders generic prazosin 1 mg fast delivery. Centers For Disease Control and Pyrazinamide (A) is associated with a hepatic dys- Prevention MMWR 2000;49:1–54 buy prazosin 1 mg without prescription. Nearly all Updated Guidelines for the Use of Rifabutin or patients taking pyrazinamide develop hyper- Rifampin for the Treatment and Prevention of uricemia buy prazosin 2mg online. Tuberculosis Among HIV-infected Patients Taking Aminosalicylic acid (B) is associated with GI intol- Protease Inhibitors or Non-nucleoside Reverse erance, especially acute bleeding, due to severe gas- Transcriptase Inhibitors. Rifampin (A) is known to induce certain Amatic and injection drug user, presents with a cytochrome P-450 enzymes and accelerates the cough, 10-lb weight loss, and general weakness. No genetic oral prednisone 20 mg per day and denies any drug predetermination is involved in this process. Upon examination, he appears to be Isoniazid (B) is acetylated to acetyl isoniazid by N- chronically ill with a low-grade temperature of acetyltransferase present in the liver. His physical examination produced population shows heterogenicity with regard to the benign findings except for bilateral rhonchi over the rate of acetylation. A presumptive diagnosis of pul- ratios of acetyl isoniazid to isoniazid than do slow monary tuberculosis is based on the history and the acetylators. This genetic determination is rarely appearance of right apical infiltrates on the chest ra- important clinically. Four-drug therapy with isoniazid, ri- deaminated by the microsomal drug metabolizing fampin, pyrazinamide, and ethambutol was ordered enzyme pyrazinamide deaminase to form pyrazinoic along with pyridoxine acid. There is no genetic predetermination for this supplements pending the final culture and suscep- process. Orally it is well absorbed and Metabolism of which ONE of the above- distributed, and about 15% is excreted in the form mentioned drugs is genetically predetermined? Viral cores can contain either DNA or RNA; thus, viruses may be classified as DNA viruses or Viruses are obligate intracellular parasites that use RNA viruses. Pathogenic RNA viruses in- clude arborviruses (tick-borne encephalitis, yellow fever); arenaviruses (Lassa fever, meningitis); or- Classification of Viruses thomyxoviruses (influenza); paramyxoviruses (measles, Viruses are composed of one or more strands of a nu- mumps); picornaviruses (polio, meningitis, colds); rhab- cleic acid (core) enclosed by a protein coat (capsid). Although the specific details of replication vary among Infection begins when specific receptor sites on the types of viruses, the overall process can be described as virus recognize corresponding surface proteins on the consisting of five phases: (1) attachment and penetra- host cell. The virus penetrates the host membrane by a tion, (2) uncoating, (3) synthesis of viral components, mechanism resembling endocytosis and is encapsulated (4) assembly of virus particles, and (5) release of the 1 Viral proteins: 3 5 Regulatory proteins 2 4 DNA polymerases and Viral mRNA other enzymes 6 Structural proteins Viral DNA 7 A 8 1 5 6 4 Viral 2 Viral mRNA proteins (+ sense) 3 Viral RNA cRNA (+ sense) (- sense) 7 Viral RNA (- sense) 8 B 9 KEY hemagglutinin M2 protein neuraminidase RNP core = 8 segments RNA + nucleoprotein FIGURE 50. Fusion of the viral envelope with the endosomes membrane, dissociation of the RNP complex, and entry of viral RNA into the nucleus. Next, the chemotherapy of viruses is finding a drug that is se- the protein coat dissociates and releases the viral lectively toxic to the virus. Following the release of its genome, the virus This chapter focuses on agents used to combat non- synthesizes nucleic acids and proteins in sequence. Detailed information on drugs DNA viruses, the first genes to be transcribed are the im- used to treat HIV is found in Chapter 51. These genes code for regulatory proteins that in turn initiate the transcription of the early genes responsible for viral genome replication. After the ANTIHERPESVIRUS AGENTS viral DNA is replicated, the late genes are transcribed and translated, producing proteins required for the assembly The following drugs are used primarily in the treatment of the new virions. The retroviruses genital herpes; varicella zoster virus (VZV), which pro- use viral reverse transcriptase enzymes to produce DNA duces chickenpox and shingles; Epstein-Barr virus using viral RNA as a template. The newly synthesized (EBV), which is the major cause of infectious mononu- DNA integrates into the host genome and is transcribed cleosis; and cytomegalovirus (CMV), which can produce into mRNA and genomic RNA for progeny virions. In certain viruses, such as the poxviruses, multiple mem- Acyclovir (Zovirax) is a guanine nucleoside analogue branes surround the capsid. Release of the virus from most effective against HSV-1 and HSV-2, but it has the host cell may be rapid and produce cell lysis and some activity against VCV, CMV, and EBV.
Because Mitotane (Lysodren) produces selective atrophy of the surgical treatment is not always well tolerated by eld- zona fasciculata and zona reticularis purchase prazosin 1 mg mastercard, which results in a erly patients purchase 1 mg prazosin with mastercard, ketoconazole 200 to 1 purchase prazosin 2mg mastercard,000 mg/day can be a decrease in the secretion of 17-hydroxycorticosteroids purchase prazosin 1 mg without prescription. Direct inhibition of cholesterol side-chain cleavage and Common side effects include pruritus, liver dysfunction, 11 /18-hydroxylase activities has also been demon- and gastrointestinal symptoms. On the other hand, Moreover, more than half of patients relapse following the antiandrogenic effects of ketoconazole may prove cessation of therapy. Hypoadrenalism, nausea, and drowsiness have been reported during prolonged ad- Mifepristone is a progesterone receptor antagonist that ministration of mifepristone. This drug has recently been approved for Dexamethasone use in the United States for the treatment of hypercor- tisolism. The addition of a fluoride group on ring C of corti- glucocorticoid therapy sol to give 9- -fluorocortisol (A) Prompt recovery of the hypothalamic– (A) Will shorten its half-life pituitary–adrenal axis results in restoration of en- (B) Will increase both glucocorticoid and miner- dogenous corticotrophin release. Dexamethasone uted to steroid withdrawal may be difficult to distin- (A) Is adequate replacement therapy in an adrena- guish from reactivation of rheumatic disease. Which one of the following enzymes is required for (B) Has a half-life equivalent to that of cortisol cortisol biosynthesis? Recovery from prolonged steroid therapy is thesis, ketoconazole is frequently used as an anti- slow, and the withdrawal may be unpleasant. Its action is readily reversible and is patient may be reluctant to reduce the dose of used principally for interim management of steroid because of its salutary effects on the psyche. Tapering the dose of steroid is important in steroid Ketoconazole preferentially blocks the C17,20 lyase withdrawal; however, the patient may temporarily reaction that is involved in the synthesis of sex require a dose increase during periods of height- steroids. Management of bone disease in patients ment of a sense of well-being may be attributed to on long term glucocorticoid therapy. Inferior petrosal sinus sampling pro- Jwas admitted to the emergency department in vided a final confirmation of the diagnosis. A previous physical examination tient was prescribed metyrapone 2 g/day and showed hypertension and diabetes mellitus type 2. A physi- tion of a mineralocorticoid, fludrocortisone acetate cal examination revealed prominent ankle edema, a 0. Based upon the history better controlled, congestive failure showed im- and clinical findings, what is your diagnosis and provement, insulin resistance diminished, and bone what treatment do you recommend? In the past, the recommended stances that are essential in small amounts for the regu- dietary allowances (RDAs), which are the levels of in- lation of normal metabolism, growth, and function of take of essential nutrients that are considered to be ade- the human body. Not all of the vitamins can be synthe- quate to meet the known nutritional needs of practically sized in the body, and therefore, some vitamins must be all healthy persons, were the primary reference value for obtained from an external source, such as a proper well- vitamins and other nutrients. RDA, EAR, and AI reference standards define nutri- Deficiency diseases can result from insufficient vitamin tional intake adequacy. Since these recommendations are ingestion, irregular absorption, or impaired metabolic given for healthy populations in general and not for indi- use of these nutrients. The ingestion or administration viduals, special problems, such as premature birth, inher- of excessive quantities of vitamins, also known as hy- ited metabolic disorders, infections, chronic disease, and pervitaminosis, may result in toxicity. This chapter focuses on the pharmacological and Separate RDAs have been developed for pregnant and toxicological properties of vitamins. Vitamin supplementation may be re- quired by patients with special conditions and for those who do not consume an appropriate diet. A varied diet containing a wide range of foodstuffs DIETARY REFERENCE STANDARDS provides adequate intake of vitamins for most people, The Food and Nutrition Board of the Institute of and supplementing these amounts will have no benefi- Medicine (IOM) has been developing reference stan- cial effect and may result in the toxicity associated with dards for vitamins and other nutrients called Dietary hypervitaminosis. The DRI also includes the tolerable 777 778 VII DRUGS AFFECTING THE ENDOCRINE SYSTEM upper intake level (UL) of vitamins. Bone development and growth in children as the highest level of intake of a nutrient that will not have also been linked to adequate vitamin A intake. The UL is an important ref- combines with opsin to produce the visual pigment erence standard, especially with the current promotion rhodopsin. A plant pigment, carotene, is a precursor for vitamin DEFICIENCY DISEASES A and is present in highly pigmented vegetables, such as carrots, rutabaga, and red cabbage.
The release Themusclefibersofadeadbodydonotpro- of ADP from myosin ultimately brings the my- duceanyATP cheap 2mg prazosin visa. The remaining A-M complex (rigor ATPreservesneededtobreakdownstableA-M complex) is stable and can again be trans- complexes are soon depleted cheap prazosin 2 mg online. This results in formed into a weak bond when the myosin stiffening of the dead body or rigor mortis buy prazosin 1mg fast delivery, headsbindATPanew(“softeningeffect”ofATP) buy 2 mg prazosin amex. If a new ATP is bound to myosin, the subsequent weakening of the actin–myosin bond allows the realign- ment of the myosin head from 45! IfthecytosolicCa2+concentrationre- mains "10–6 mol/L, the D1 to D4 cycle will begin anew. Only a portionofthemyosinheadsthatpullactinfila- ments are “on duty” (low duty ratio; see p. The Ca2+ ions released from the sarco- plasmic reticulum (SR) are continuously pumped back to the SR due to active transport by Ca2+-ATPase (! Thus, if the RYR-mediated re- lease of Ca2+ from the SR is interrupted, the cy- tosolic Ca2+ concentration rapidly drops below 10–6 mol/L and filament sliding ceases (resting position;! Work cycle of sliding filaments (isotonic contraction) DHPR with (heart) and with- out (muscle) Ca2+channel Action potential RYR T system Myosin Longitudinal ATP Ca2+ tubule Tropomyosin Actin Troponin Resting position ATP- Pi [Ca2+]i ase [Ca2+]i ADP 1µmol/l = 1–10µmol/l 45° 90° Ca2+ ATP 1 Actin-myosin binding, ATP cleavage 50° 90° 4 Loosening of actin–myosin bond (“softening” effect of ATP), myosin heads erect 2a Myosin heads tilt ATP due to Pi release 45° 50° 3 ATP binding With ATP Without ATP Stable “rigor complex” 65 persists 2b Final head position (rigor mortis) after ADP release Despopoulos, Color Atlas of Physiology © 2003 Thieme All rights reserved. The magnitude of contraction of tonus fibers is Muscle 2+ regulated by variation of the cytosolic Ca con- Action potentials generated in muscle fibers centration (not by action potentials! The contraction force is achieved by variable re- individual contractions cannot be detected be- cruitment of motor units (! When apparently at single stimulus always leads to maximum Ca2+ rest, muscles such as the postural muscles are release and, thus, to a maximum single twitch in this involuntary state of tension. Resting of skeletal muscle fiber if above threshold (all- muscle tone is regulated by reflexes or-none response). There are keep the sliding filaments in motion long different types of muscle contractions. This occurs, for example, at 20Hz tions,musclelengthandforcebothvarysimul- in slow-twitch muscles and at 60–100 Hz in taneously. The muscle tionthatbuildsonanisometriconeiscalledan force during tetanus can be as much as four afterloaded contraction. A resting muscle con- Ca2+ concentration, which decreases to some taining ATP can be stretched like a rubber extent between superpositioned stimuli, re- band. Contracture is not caused by ac- stretch, which keeps the sliding filaments in tion potentials, but by persistent local depolari- the sarcomeres from separating, is influenced zation due, for example, to increased extra- to a small extent by the fascia (fibrous tissue). Muscle strength at increasing and decreasing stimulus frequencies Stimulus Range of summation Single contractions Tetanus 0 2 4 6 8 10 Time (s) B. Types of contractions Isometric Isotonic Resting tension curve 0 0 Length Isotonic, then Auxotonic After- isometric loaded Rest Isometric Rest Isotonic contraction contraction C. Isometric muscle force relative to sarcomere length 100 80 Skeletal muscle 60 Cardiac 40 muscle 20 0 1. Ibandregionareflexibleandfunctionas“elas- force of cardiac muscle at rest is greater than ticbands”thatcounteractpassivestretchingof that of skeletal muscle (! Skeletal muscle normally functions in the plateau region of its length–force curve, The extensibility of titin molecules, which can stretchtouptoaroundtentimestheirnormallength whereascardiacmuscletendstooperateinthe in skeletal muscle and somewhat less in cardiac ascendinglimb(belowLmax)ofitslength–force muscle, is mainly due to frequent repetition of the curve without a plateau (! In very the ventricle responds to increased diastolic strong muscle extension, which represents the filling loads by increasing its force develop- steepestpartoftherestingextensibilitycurve(! Action potentials in cardiac muscle are of The length (L) and force (F) or “tension” of a much longer duration than those in skeletal muscle are closely related (! Since the active force is deter- allows the slow influx of Ca2+, causing the ac- mined by the magnitude of all potential actin- tionpotentialtoreachaplateau. Asaresult,the myosin interactions, it varies in accordance refractory period does not end until a contrac- with the initial sarcomere length (! There- Skeletal muscle can develop maximum active fore, tetanus cannot be evoked in cardiac (isometric) force (F )0 from its resting length muscle. Instead, the stimulus spreads of the thin filaments overlap, allowing only across all myocardial fibers of the atria and forces smaller than F0 to develop (! When subsequently of the ventricles generating an L is 70% of Lmax (sarcomere length: 1. In addition, Incardiacmusclebutnotinskeletalmuscle, a greatly pre-extended muscle (L " Lmax) can the duration of an action potential can change develop only restricted force, because the the force of contraction, which is controlled by number of potentially available actin–myosin the variable influx of Ca2+ into the cell.