By Y. Falk. Madonna University.
New York: Oxford The word amniocentesis is derived from the Greek University Press cheap trandate 100mg free shipping heart attack alley, 1993 words purchase trandate 100 mg without a prescription heart attack american, amnion and kentesis, meaning “lamb” and “punc- Watts, Hugh G. A continuous ultrasound evaluation is PERIODICALS typically used so that the doctor can avoid touching both Froster-Iskenius, Ursula G. They are initially A Review of 100 Cases and a New Rating System for separate but begin to fuse early in pregnancy. PO Box Amniocentesis is usually performed in the second 8923, New Fairfield, CT 06812-8923. Common effects of aneuploidy include an and prevents the fetus, or parts of it, from becoming increased risk for pregnancy loss or, in live borns, for attached to the amnion. Fetal Down syndrome is the most common form of ane- cells, primarily derived from the skin, digestive system, uploidy in live born infants, occurring in approximately and urinary tract, are suspended within the fluid. In women smaller number of cells from the amnion and placenta are who are 35 years old, the risk of having a child with also present. Finally, the fetus produces a number of dif- Down syndrome is higher, or roughly one in 385 at deliv- ferent chemical substances that also pass into the amni- ery. These substances may be used, in some the only chromosome abnormality that may occur. Other higher-risk pregnancies, either to assess fetal lung matu- numerical abnormalities are possible, yielding genetic rity or to determine if the fetus has a viral infection. In the conditions that may be either more or less severe than second trimester of pregnancy, one particular protein, Down syndrome. Thus, a woman is often given a risk, called alpha-fetoprotein, is commonly used to screen for based solely on her age, of having a child with any type certain structural birth defects. At age 35, this total risk is It is possible to perform amniocentesis in a twin approximately one in 200. Amniocentesis in some higher-order pregnan- increased to one in 65, and, at age 45, this risk is one in cies, such as triplets, has also been reported. The dye will temporarily a previous child with, a known genetic condition; abnor- tinge the fluid blue-green. A second needle is inserted mal prenatal screening results, such as ultrasound or a into the next amniotic sac with ultrasound guidance. If blood test; or one parent with a previously identified the fluid withdrawn is pale yellow, a sample from the structural chromosome rearrangement. In the case of may make it more likely for a couple to have a child with monoamniotic (in one amniotic sac) twins or triplets, the a genetic condition. Side effects Women who have had an amniocentesis often Indications for amniocentesis describe it as uncomfortable, involving some mild pres- Amniocentesis has been considered a standard of sure or pain as the needle is inserted. This medicine has no effect on the fetus, that amniocentesis be offered to all expectant mothers but may help the mother feel more comfortable during age 35 and older. An experienced physician can, on average, because advancing maternal age is associated with an perform amniocentesis in approximately one to two increasing risk of having a baby with a numerical chro- minutes. At age 35, this risk is approxi- Common complaints after amniocentesis include mately equivalent to the risk of pregnancy loss associated mild abdominal tenderness at the site of needle insertion with amniocentesis. These usually go away within one to A person normally has a total of 46 chromosomes two days. More serious complications are significantly in each cell of his or her body, with the exception of less common but include leakage of amniotic fluid, vagi- sperm or egg cells, which each have only 23. These complications get older, there is an increased risk of producing an egg are estimated to occur in fewer than 1% of pregnancies. This leads to an egg cell In some women, complications after amniocentesis may with 24 chromosomes rather than the normal 23. Aneuploidy results in a con- out amniocentesis, is approximately 2–3% in her second ceptus (product of conception) with either too much or trimester. This, in turn, leads to abnormal or technician, the risk for an amniocentesis-related preg- 74 GALE ENCYCLOPEDIA OF GENETIC DISORDERS KEY TERMS Amnion—Thin, tough membrane surrounding the Fetus—The term used to describe a developing embryo and containing the amniotic fluid. The term embryo is Anesthetic—Drug used to temporarily cause loss of used prior to the third month. An anesthetic may either be general, associated with a loss of con- Fibroid—A non-cancerous tumor of connective tis- sciousness, or local, affecting one area only without sue made of elongated, thread-like structures, or loss of consciousness.
If the two mutations mutated gene of this type are not completely neu- are identical trandate 100 mg without a prescription hypertension 6 year old, the individual is a homozygote buy trandate 100mg lowest price ocular hypertension. Individuals with one defective NEU1 gene, leading to more severe forms of neu- gene and one normal gene encoding neuraminidase may raminidase deficiency. Demographics All of the offspring of two parents with neu- Neuraminidase deficiency is an extremely rare disor- raminidase deficiency will inherit the disorder. Because of its similarities to many other disorders, it offspring of one parent with neuraminidase deficiency has been difficult to determine its frequency. In the and one parent with a single defective NEU1 gene will United States, it is estimated to occur in one out of every inherit at least one defective NEU1 gene. In Australia, the estimate is one out a 50% chance of inheriting two defective genes and, of 4. Since neuraminidase deficiency is an auto- therefore, developing neuraminidase deficiency. The off- somal rather than a sex-linked disorder, it occurs equally spring of one parent with neuraminidase deficiency and in males and females. The offspring of parents who deficiency requires two copies of the defective gene, one both carry one defective NEU1 gene have a 50% chance inherited from each parent. Thus, neuraminidase defi- of inheriting one defective NEU1 gene and a 25% chance ciency is much more common in the offspring of couples of inheriting two genes and developing neuraminidase who are related to each other (consanguineous mar- deficiency. Finally, the children of one parent with a sin- riages), such as first or second cousins. Type 2 sialidosis seems to occur more frequently defective gene, but will not develop neuraminidase defi- among Japanese. Signs and symptoms Mutations in the NEU1 gene The clinical symptoms of neuraminidase deficiency A number of different mutations that can cause neu- are similar to the symptoms of the mucolipidoses, includ- raminidase deficiency have been identified in the NEU1 ing I-cell disease (mucolipidosis II) and pseudoHurler gene. The type of neuraminidase deficiency, sialidoses polydystrophy (mucolipidosis III). Furthermore, the clin- types I or II, as well as the severity of the symptoms, ical distinctions between sialidoses types I and II may not depends on the specific mutation(s) that are present. Some mutations change one amino acid out of the 415 amino acids that compose a single neuraminidase mole- Sialidosis type I cule. Many of the identified mutations are clustered in The symptoms of sialidosis type I do not appear until one region on the surface of the protein. Infants and children with this result in a sharp reduction in the activity of the enzyme form of neuraminidase deficiency may have a normal 804 GALE ENCYCLOPEDIA OF GENETIC DISORDERS appearance and grow normally until adolescence. At that time, the appearance of red spots in both eyes, known as KEY TERMS cherry-red macules or cherry-red macular spots, may be one of the first symptoms of neuraminidase deficiency. Dysostosis multiplex—A variety of bone and Eventually, color and/or night blindness may develop. Cataracts may occur and vision may deteriorate gradu- Fibroblast—Cells that form connective tissue ally into blindness. Other symptoms of sialidosis type I include Glycoprotein—A protein with at least one carbo- myoclonus. Individuals with this form of neu- raminidase deficiency may have increased deep tendon Homozygote—Having two identical copies of a reflexes and may develop tremors and various other neu- gene or chromosome. There may be a progressive loss of Lipid—Large, complex biomolecule, such as a muscle coordination, called ataxia, and walking and fatty acid, that will not dissolve in water. Lysosome—Membrane-enclosed compartment in The above symptoms also may occur in sialidosis cells, containing many hydrolytic enzymes; where type II. However, in addition to the age of onset, type I large molecules and cellular components are bro- can be distinguished from type II by the absence of skele- ken down. Furthermore, individuals Myoclonus—Twitching or spasms of a muscle or with this form of neuraminidase deficiency have normal an interrelated group of muscles. Sialidosis type II Polysaccharide—Linear or branched macromole- Sialidosis type II has three forms: congenital or cule composed of numerous monosaccharide neonatal, with symptoms present at or before birth; infan- (sugar) units linked by glycosidic bonds. Symptoms of sialidosis type II vary from mild to Sialic acid—N-acetylneuraminic acid, a sugar that severe, but are always more severe than in type I siali- is often at the end of an oligosaccharide on a gly- dosis. Thus, ascites, (called coarse facies), a short trunk with relatively long hepatosplenomegaly, and hernias may develop later.
Sialidosis type I sometimes is referred to as juve- characterized by the accumulation and excretion of these nile sialidosis and type II as infantile sialidosis trusted trandate 100mg blood pressure levels high, in substances trusted trandate 100 mg exforge blood pressure medication. In addition to interfering with the lysosomal break- down of sialic acid compounds, neuraminidase defi- Lysosomal storage diseases ciency can lead to abnormal proteins. Following protein Lysosomes are membrane-bound spherical compart- synthesis, some lysosomal enzymes reach the lysosome ments or vesicles within the cytosol, the semi-fluid areas in an inactive form and require further processing for of cells. One such processing step is the neuramini- enzymes that are responsible for digesting, or hydrolyz- dase-catalyzed removal of sialic acid residues from ing, large molecules and cellular components. Lysosomal hydrolases include proteins, polysaccharides, which are long, linear that require further processing by neuraminidase include or branched chains of sugars, and lipids, which are large acid phosphatase, alpha-mannosidase, arylsulfatase B, insoluble biomolecules that are usually built from fatty and alpha-glucosidase. The smaller breakdown products from the lyso- Under conditions of neuraminidase deficiency, sialy- somes are recycled to the cytosol. These disor- fibroblasts (connective tissue cells), bone marrow cells, ders result from mutations in the genes encoding the Kupffer cells of the liver, and Schwann cells, which form hydrolytic enzymes of the lysosome. Furthermore, proteins some of the macromolecules in the lysosomes cannot be with sialic acid attachments accumulate and can be degraded and they, or their partial-breakdown products, detected in fibroblasts and in the urine. Neuraminidase exists in the lysosome in a high- molecular-weight complex with three other proteins: the Neuraminidase deficiency, particularly sialidosis enzyme beta-galactosidase, the enzyme N-acetylgalac- type II, commonly has been classified as the lysosomal tosamine-6-sulfate sulfatase (GALNS), and a multi-func- storage disease called mucolipidosis type I (ML I), for- tional enzyme called protective protein/cathepsin A merly lipomucopolysaccharidosis. Neuraminidase must be associated with PPCA symptoms of neuraminidase deficiency are similar to var- in order for the neuraminidase to reach the lysosome. However mucolipidoses Once inside the lysosome, PPCA mediates the associa- are characterized by the accumulation of large and com- plex lipid-polysaccharides. In contrast, neuraminidase tion of as many as 24 neuraminidase molecules to form deficiency leads to the accumulation of specific types of active neuraminidase. The active enzyme remains associ- short chains of sugar called oligosaccharides and of cer- ated with PPCA and beta-galactosidase, which appear to tain proteins with oligosaccharides attached to them, be necessary for protecting and stabilizing the neu- called glycoproteins. A distinct lysosomal storage disease, classify neuraminidase deficiency as an oligosaccharide neuraminidase deficiency with beta-galactosidase defi- storage disease, since it leads to the accumulation of ciency, or galactosialidosis, results from mutations in the excess oligosaccharides in various tissues throughout the gene encoding PPCA. GALE ENCYCLOPEDIA OF GENETIC DISORDERS 803 Genetic profile and lead to the rapid degradation of neuraminidase inside the lysosome. Inheritance of neuraminidase deficiency Some mutations in the NEU1 gene lead to a com- Neuraminidase deficiency is an autosomal recessive plete absence of neuraminidase activity, with little or no disorder that can be caused by any one of a number of neuraminidase enzyme present in the lysosomes. These different mutations in the NEU1 gene encoding the lyso- mutations usually result in the severe, infantile-onset, somal neuraminidase. Other mutations result in an inactive the NEU1 gene is located on chromosome 6, rather than protein that is present in the lysosome. The disorder is reces- generally result in juvenile-onset, type II sialidosis, with sive because it only develops when both genes encoding symptoms of intermediate severity. Some mutations sig- neuraminidase, one inherited from each parent, are nificantly reduce, but do not obliterate, neuraminidase defective; however, the two defective NEU1 genes do not activity in the lysosome. If the two mutations mutated gene of this type are not completely neu- are identical, the individual is a homozygote. Individuals with one defective NEU1 gene, leading to more severe forms of neu- gene and one normal gene encoding neuraminidase may raminidase deficiency. Demographics All of the offspring of two parents with neu- Neuraminidase deficiency is an extremely rare disor- raminidase deficiency will inherit the disorder. Because of its similarities to many other disorders, it offspring of one parent with neuraminidase deficiency has been difficult to determine its frequency. In the and one parent with a single defective NEU1 gene will United States, it is estimated to occur in one out of every inherit at least one defective NEU1 gene. In Australia, the estimate is one out a 50% chance of inheriting two defective genes and, of 4. Since neuraminidase deficiency is an auto- therefore, developing neuraminidase deficiency. The off- somal rather than a sex-linked disorder, it occurs equally spring of one parent with neuraminidase deficiency and in males and females. The offspring of parents who deficiency requires two copies of the defective gene, one both carry one defective NEU1 gene have a 50% chance inherited from each parent. Thus, neuraminidase defi- of inheriting one defective NEU1 gene and a 25% chance ciency is much more common in the offspring of couples of inheriting two genes and developing neuraminidase who are related to each other (consanguineous mar- deficiency. Finally, the children of one parent with a sin- riages), such as first or second cousins.
Direct the bevel of the needle parallel to the long axis of the body so that the dural fibers are separated rather than sheared 100 mg trandate amex heart attack 4 blocked arteries. If still no fluid appears quality trandate 100mg arteria3d review, and you think that you are within the subarachnoid space, inject 1 mL of air because it is not uncommon for a piece of tissue to clog the needle. If no air returns and if spinal fluid cannot be aspirated, the bevel of the needle probably lies in the epidural space; advance it with the stylet in place. Increased pressure may be due to a tense patient, CHF, ascites, subarachnoid hemorrhage, infection, or a space-occupying lesion. Decreased pressure may be due to needle position or ob- structed flow (you may need to leave the needle in for a myelogram because if it is moved, the subarachnoid space may be lost). In a traumatic tap, the number of RBCs in the first tube should be much higher than in the last tube. In a subarachnoid hemorrhage, the cell counts should be equal, and xanthochromia of the fluid should be present, indicating the presence of old blood. Instruct the patient to remain recumbent for 6–12 h, and encourage an increased fluid intake to help prevent “spinal headaches. Complications • Spinal headache: The most common complication (about 20%), this appears within the first 24 h after the puncture. It goes away when the patient is lying down and is aggravated when the patient sits up. It is usually characterized by a severe throbbing pain in the occipital region and can last a week. It is thought to be caused by in- tracranial traction caused by the acute volume depletion of CSF and by persistent leakage from the puncture site. To help prevent spinal headaches, keep the patient re- cumbent for 6–12 h, encourage the intake of fluids, use the smallest needle possible, and keep the bevel of the needle parallel to the long axis of the body to help prevent 13 a persistent CSF leak. If the patient suddenly complains of paresthesia (numbness or shooting pains in the legs), stop the procedure. ORTHOSTATIC BLOOD PRESSURE MEASUREMENT Indication • Assessment of volume depletion Materials • Blood pressure cuff and stethoscope T A B L E 1 3 – 4 D i f f e r e n t i a l D i a g n o s i s o f C e r e b r o s p i n a l F l u i d O p e n i n g P r o t e i n G l u c o s e P r e s s u r e ( m g / ( m g / C e l l s C o n d i t i o n C o l o r ( m m H O ) 1 0 0 m L ) 1 0 0 m L ) ( # / m m 3 ) 2 N O R M A L A d u l t C l e a r 7 0 – 1 8 0 1 5 – 4 5 4 5 – 8 0 0 – 5 l y m p h o c y t e s N e w b o r n C l e a r 7 0 – 1 8 0 2 0 – 1 2 0 2 / 3 s e r u m 4 0 – 6 0 l y m p h o c y t e s I N F E C T I O U S V i r a l i n f e c t i o n C l e a r o r N o r m a l o r N o r m a l o r N o r m a l 1 0 – 5 0 0 ( “ a s e p t i c m e n i n g i t i s ” ) o p a l e s c e n t s l i g h t l y s l i g h t l y l y m p h o c y t e s i n c r e a s e d i n c r e a s e d P M N s B a c t e r i a l O p a l e s c e n t I n c r e a s e d 5 0 – 1 0, 0 0 0 I n c r e a s e d, 2 5 – 1 0, 0 0 0 i n f e c t i o n y e l l o w, m a y u s u a l l y 2 0 P M N s c l o t G r a n u l o m a t o u s C l e a r o r O f t e n I n c r e a s e d, D e c r e a s e d, 1 0 – 5 0 0 i n f e c t i o n o p a l e s c e n t i n c r e a s e d b u t u s u a l l y u s u a l l y l y m p h o c y t e s ( T B, f u n g a l ) 5 0 0 2 0 – 4 0 N E U R O L O G I C G u i l l a i n – B a r r é C l e a r o r N o r m a l M a r k e d l y N o r m a l N o r m a l o r S y n d r o m e C l o u d y i n c r e a s e d i n c r e a s e d l y m p h o c y t e s ( c o n t i n u e d ) T A B L E 1 3 – 4 ( C o n t i n u e d ) O p e n i n g P r o t e i n G l u c o s e P r e s s u r e ( m g / 1 0 0 ( m g / 1 0 0 C e l l s C o n d i t i o n C o l o r ( m m H O ) m L ) m L ) ( # / m m 3 ) 2 M u l t i p l e s c l e r o s i s C l e a r N o r m a l N o r m a l o r N o r m a l 0 – 2 0 l y m p h o c y t e s i n c r e a s e d P s e u d o t u m o r c e r e b r i C l e a r I n c r e a s e d N o r m a l N o r m a l N o r m a l M I S C E L L A N E O U S N e o p l a s m C l e a r o r I n c r e a s e d N o r m a l o r N o r m a l o r N o r m a l o r x a n t h o c h r o m i c i n c r e a s e d d e c r e a s e d i n c r e a s e d l y m p h o c y t e s T r a u m a t i c t a p B l o o d y, n o N o r m a l N o r m a l S I i n c r e a s e d R B C = p e r i p h e r a l x a n t h o c h r o m i a b l o o d ; L e s s R B C i n t u b e 4 t h a n i n t u b e 1 S u b a r a c h n o i d B l o o d y o r U s u a l l y I n c r e a s e d N o r m a l W B C / R B C h e m o r r h a g e x a n t h o c h r o m i c i n c r e a s e d r a t i o s a m e a f t e r 2 – 8 h a s b l o o d A b b r e v i a t i o n s : W B C = w h i t e b lo o d c e ll; R B C = r e d b lo o d c e ll; P M N s = p o ly m o r p h o n u c le a r n e u t r o p h i ls. Changes in blood pressure and pulse when a patient moves from supine to the upright position are very sensitive guides for detecting early volume depletion. Even before a person becomes overtly tachycardic or hypotensive because of volume loss, the demon- stration of orthostatic hypotension aids in the diagnosis. If the patient is unable to stand, have the patient sit at the bedside with legs dangling. A drop in systolic BP greater than 10 mm Hg or an increase in pulse rate greater than 20 (16 if elderly) suggests volume depletion. A change in heart rate is more sensitive and occurs with a lesser degree of volume depletion. Other causes include peripheral vascular disease, surgical sympathectomy, diabetes, and medications (prazosin, hy- dralazine, or reserpine). PELVIC EXAMINATION Indications • Part of a complete physical examination in the female • Used to assist in the diagnosis of diseases and conditions of the female genital tract Materials • Gloves • Vaginal speculum and lubricant • Slides, fixative (Pap aerosol spray, etc), cotton swabs, endocervical brush and cervi- cal spatula prepared for a Pap smear • Materials for other diagnostic tests: Culture media to test for gonorrhea, Chlamy- 13 dia, herpes; sterile cotton swabs, plain glass slides, KOH, and normal saline solu- tions, as needed Procedure 1. The pelvic exam should be carried out in a comfortable fashion for both the patient and physician. The patient should be draped appropriately with her feet placed in the stirrups on the examining table. Pre- pare a low stool, a good light source, and all needed supplies before the exam begins. In unusual situations examinations are conducted on a stretcher or bed; raise the pa- tients buttocks on one or two pillows to elevate the perineum off the mattress. Observe the skin of the perineum for swelling, ulcers, condylomata (venereal warts), or color changes. Inspect the vaginal orifice for discharge, or protrusion of the walls (cystocele, rec- tocele, urethral prolapse). Use a speculum moistened with warm water not with lubricant (lubricant will in- terfere with Pap tests and slide studies). Because the anterior wall of the vagina is close to the urethra and bladder, do not exert pressure in this area.