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By E. Deckard. Massachusetts Institute of Technology.

A number of freedom from strain and fatigue; conversely discount 75 mg imipramine free shipping, such ailments different characteristics are used in naming muscles buy imipramine 25mg without a prescription, in- as lower back pain—a common complaint—can be traced cluding the following: to poor body mechanics generic imipramine 25 mg. Body mechanics have special sig- nificance to healthcare workers discount 50mg imipramine fast delivery, who are frequently called ◗ Location, named for a nearby bone, for example, or for on to move patients and handle cumbersome equipment. There are three classes of levers, (oblique) which differ only in the location of the fulcrum (F), the ef- ◗ Number of heads (attachment points) as indicated by fort (E), or force, and the resistance (R), the weight or load. The muscle surrounding each eye is called the to Figures 8-9 and 8-10 as you study the locations and orbicularis oculi (OK-u-li), whereas the muscle of the functions of some of the skeletal muscles and try to figure lips is the orbicularis oris. For example, the levator palpebrae described in the singular, most of the muscles are present (PAL-pe-bre) superioris, or lifter of the upper eyelid, is on both sides of the body. There are a number of scalp ones around the eyes and the lips, called the orbicularis muscles by means of which the eyebrows are lifted or (or-bik-u-LAH-ris) muscles because of their shape (think drawn together into a frown. It is because of these the temporalis (TEM-po-ral-is), which is superior to the many muscles that the tongue has such remarkable flexi- ear, and the masseter (mas-SE-ter) at the angle of the jaw. THE MUSCULAR SYSTEM ✦ 163 8 (Epicranial aponeurosis) Sternocleidomastoid Teres minor Trapezius Deltoid Teres major Latissimus dorsi Triceps brachii (Olecranon (Lumbodorsal of ulna) fascia) Gluteus Gluteus maximus medius (Iliotibial tract) Hamstring group: Biceps femoris Semitendinosus Semimembranosus Gastrocnemius Peroneus longus (Achilles tendon) Posterior view Figure 8-10 Superficial muscles, posterior view. Working alone, each muscle tilts and rotates the head so Muscles of the Neck as to orient the face toward the side opposite that mus- The neck muscles tend to be ribbonlike and extend up cle. If the head is abnormally fixed in this position, the and down or obliquely in several layers and in a complex person is said to have torticollis (tor-tih-KOL-is), or manner (Fig. This strong muscle extends superiorly from located at the posterior of the neck, where it helps hold 164 ✦ CHAPTER EIGHT Epicranial aponeurosis Frontalis Muscles That Move the Shoul- (tendon) Orbicularis der and Arm The position of the Temporalis oculi shoulder depends to a large extent on the degree of contraction of the trapez- ius (trah-PE-ze-us), a triangular mus- Nasalis cle that covers the posterior neck and extends across the posterior shoulder Quadratus labii to insert on the clavicle and scapula superioris (Fig. It originates from the inferioris vertebral spine in the middle and lower back and covers the lower half of the Mentalis thoracic region, forming the posterior portion of the axilla (armpit). The pec- Muscles of the Upper Extremities toralis major flexes and adducts the arm, pulling it across Muscles of the upper extremities include the muscles that the chest. Orbicularis oculi Encircles eyelid Closes eye The deltoid covers the shoulder Levator palpebrae Back of orbit to Opens eye joint and is responsible for the round- superioris (deep upper eyelid muscle; not ness of the upper part of the arm just shown) inferior to the shoulder (see Figs. This muscle is named for Buccinator Fleshy part of cheek Flattens cheek; helps in its triangular shape, which resembles eating, whistling, and the Greek letter delta. Arising Temporalis Above and near ear Closes jaw Masseter At angle of jaw Closes jaw from the shoulder girdle (clavicle and Sternocleidomastoid Along side of neck, Flexes head; rotates head to- scapula), the deltoid fibers converge to to mastoid process ward opposite side from insert on the lateral surface of the muscle humerus. Most of the muscles that move the Trapezius Posterior of neck and Raises shoulder and pulls it hand and fingers originate from the ra- upper back, to clavicle back; extends head dius and the ulna (see Fig. Some and scapula Latissimus dorsi Middle and lower back, Extends and adducts arm of them insert on the carpal bones of to humerus behind back the wrist, whereas others have long Pectoralis major Superior, anterior chest, Flexes and adducts arm tendons that cross the wrist and insert to humerus across chest; pulls shoulder on bones of the hand and the fingers. Muscles that Deltoid Covers shoulder joint, to Abducts arm produce finger movements are the sev- lateral humerus eral flexor digitorum (dij-e-TO-rum) Biceps brachii Anterior arm along Flexes forearm at the elbow and the extensor digitorum muscles. Muscles of the Trunk The muscles of the trunk include the The shoulder joint allows for a very wide range of muscles involved in breathing, the thin muscle layers of movement. The four muscles are the supraspinatus, in- Muscles of Respiration The most important muscle fraspinatus, teres minor, and subscapularis, known to- involved in the act of breathing is the diaphragm. In dome-shaped muscle forms the partition between the certain activities, such as swinging a golf club, playing thoracic cavity superiorly and the abdominal cavity infe- tennis, or pitching a baseball, the muscles of the rotator riorly (Fig. Contraction along the humerus, is the muscle you usually display of the intercostal muscles serves to elevate the ribs, thus when you want to “flex your muscles” to show your enlarging the thoracic cavity from side to side and from strength (Fig. Another flexor of the forearm at the elbow is the bra- chioradialis (bra-ke-o-ra-de-A-lis), a prominent muscle Checkpoint 8-13 What muscle is most important in breathing? Muscles of the Abdomen and Pelvis The wall of The triceps brachii, located on the posterior of the the abdomen has three layers of muscle that extend from arm, inserts on the olecranon of the ulna (Fig. They are the ex- 166 ✦ CHAPTER EIGHT ternal oblique on the outside, the in- ternal oblique in the middle, and the Biceps Triceps brachii transversus abdominis, the inner- brachii most. The connective tissue from Brachioradialis these muscles extends forward and en- closes the vertical rectus abdominis of Extensor carpi the anterior abdominal wall. The fibers radialis longus of these muscles, as well as their con- nective tissue extensions (aponeu- Brachioradialis Extensor carpi radialis brevis roses), run in different directions, re- sembling the layers in plywood and Flexor carpi Flexor carpi resulting in a strong abdominal wall.

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They provide • monitoring lung function prolonged relief and help reduce long-term damage to the • learning how to use prescribed medications lungs buy 75mg imipramine. These devices meas- • maintaining healthy lifestyle by controlling weight ure the amount of air exhaled with each breath discount imipramine 25mg visa. They are gain purchase 50mg imipramine free shipping, salt intake purchase imipramine 50 mg without a prescription, blood pressure, and blood cholesterol used to regularly monitor the severity of asthma symp- levels toms and to evaluate and manage treatment procedures Specific goals of asthma management programs for individual patients. In critical cases, additional medications and oxy- that side effects from medications can be minimized gen may be administered in an attempt to restore normal respiratory activity. Delayed access to emergency treat- With the newer, more effective medications now ment can lead to complete respiratory failure—the available, it is possible to provide patients with good patient simply stops breathing and cannot be revived. Asthma patients use both rescue medications and con- Under diagnosis trollers, which provide long-term control of asthma symptoms. Most asthma patients take their asthma medi- Unfortunately, many asthmatic children receive cine with the aid of metered-dose inhalers. Another device that delivers medication in spray- there was a clear over-dependence on rescue medica- form are “nebulizers,” which are sometimes used by tions. This under-treated population required more fre- younger children and hospitalized patients who are quent emergency hospital visits than those patients who unable to properly manipulate inhalers. Under diagnosis and poor treatment are also major causes of mortality, or Rescue medications include bronchodilators, which death, due to asthma. These medications act Health providers advise coaches and other sporting by relaxing the circular muscles in the bronchial tubes officials to be more aware of emergency treatments, such that connect to the lungs. As the muscles relax, the air as dealing with asthmatic attacks, that may be required ways become wider, making breathing easier. The New England Journal of Medicine 343 “anti-IgE” substances that combine with IgE in the (December 14, 2000): 24. This prevents IgE from stimulating the release of “Day Care, Siblings, and Asthma—Please, Sneeze on My histamine from mast cells. So far, this form of treatment provides Folkerts, Gert, Gerhard Walzl, and Peter J. Division of Lung Diseases, National Heart, Lung and Blood The onset of cerebellar ataxia (unsteadiness and lack Institute. MSC 7952, of coordination) marks the beginning of progressive Bethesda, MD 20892-7952. Tim Clark, Chairman of ation gradually leads to a general lack of muscle control, GINA, 0207-594-5008 Fax: (207) 594-8802. Even reading eventually becomes impossible, as eye movements National Asthma Education and Prevention Program (NAEPP). Soon after the onset of the ataxia, an individual usu- National Center for Environmental Health. Centers for Disease ally exhibits another symptom of the disease: telangiec- Control and Prevention, Mail Stop F-29, 4770 Buford tases, or tiny red spider veins (dilated blood vessels). For these patients, the combination of a weak- ened immune system and progressive ataxia can ulti- Alpha-fetoprotein (AFP)—A chemical substance mately lead to pneumonia as a cause of death. AFP is also found in abnormally high con- the blood circulatory system almost 1,000 times more centrations in most patients with primary liver frequently than the general population. Another characteristic dination caused by a progressive degeneration of of the disease is an increased sensitivity to ionizing radi- the part of the brain known as the cerebellum. Genetic profile Immunoglobulin—A protein molecule formed by mature B cells in response to foreign proteins in Ataxia-telangiectasia is called a recessive genetic disorder because parents do not exhibit symptoms; how- the body; the building blocks for antibodies. The recessive gene Leukemia—Cancer of the blood forming organs may lie dormant for generations until two people with the which results in an overproduction of white blood defective gene have children. Every healthy sibling of Lymphoma—A malignant tumor of the lymph a child with A-T has a 2-in-3 chance (66% risk) of being nodes. Recessive gene—A type of gene that is not The A-T gene (called ATM, or A-T Mutated) was dis- expressed as a trait unless inherited by both parents. The ATM protein Telangiectasis—Very small arteriovenous malfor- is thought to prevent damaged DNA from being repro- mations, or connections between the arteries and duced.

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In these Alteration—Change or mutation in a gene buy imipramine 50 mg, specif- instances purchase imipramine 75mg online, an individual may have other health problems ically in the DNA that codes for the gene discount imipramine 25 mg free shipping. As an example cheap imipramine 50 mg line, Hereditary examination of living tissue for diagnostic pur- Non-Polyposis Colorectal Cancer (HNPCC) is a syn- poses. HNPCC is due to changes in sev- procedure that produces a three-dimensional pic- eral genes including hMLH1, hMSH2, hMSH6, and ture of organs or structures inside the body, such as hPMS2. Laparoscopy—A diagnostic procedure in which a Demographics small incision is made in the abdomen and a slen- der, hollow, lighted instrument is passed through On average, a North American woman faces a life- it. The doctor can view the ovaries more closely time risk of approximately 2% to develop ovarian cancer. The American Cancer Society states Laparotomy—An operation in which the abdomi- that in the year 2000 about 23,100 new cases of ovarian nal cavity is opened up. Specific BRCA alter- Magnetic resonance imaging (MRI)—A technique ations are common in certain ethnic groups, which may that employs magnetic fields and radio waves to make hereditary ovarian cancer more common in these create detailed images of internal body structures populations. Ovarian cancer has no specific signs or symptoms in Transvaginal ultrasound—A way to view the the early stages of the disease. A probe is inserted rience some of the following: into the vagina and the ovaries can be seen. Color doppler imaging measures the amount of blood • Pain or swelling in the abdominal area flow, as tumors sometimes have high levels of • Bloating and general feeling of abdominal discomfort blood flow. This • Close genetic relationships between people with cancer, is why it is important for a physician to be informed right such as parent-child, sibling-sibling away if any of the above symptoms are present. In addition, if a woman has had, or has a family history of breast can- • An individual with bilateral or multi-focal breast cancer cer she may be at an increased risk for ovarian cancer. This is because specific BRCA1 and BRCA2 For women with ovarian cancer who are found to alterations are known to be more common in this group have a BRCA alteration, this now places them at an of individuals. For some women, this may be a new risk they were not aware of before the testing, particularly if they have no family history of Diagnosis breast cancer. If a woman has symptoms of ovarian cancer, a pelvic For all women with a BRCA2 alteration, there may examination is usually conducted to feel the ovaries to be a slightly increased risk for colon and pancreatic can- see if they have enlarged, indicative of a tumor. Additionally, because the testing process and test tests to determine the level of a protein, known as carbo- results are quite complex (and may have strong emo- hydrate antigen 125 (CA-125), may be done. CA-125 tional consequences) everyone should receive proper blood levels can be high when a woman has ovarian can- genetic counseling before pursuing any BRCA1 and cer. Prenatal BRCA testing is available, but (with color Doppler imaging) may be used to get several is rarely performed unless accompanied by extensive views of the ovaries, carefully checking their shape and genetic and psychological counseling. A CT scan may be helpful if the ultrasound is technically unsatisfactory for accurate interpretation. Treatment and management A biopsy and surgery is necessary in order to deter- As with many other cancers, treatment is determined mine the type of tumor, as not all tumors are cancerous. This may require abdomen and a slender, hollow, lighted instrument is a laparotomy procedure in order to remove as much can- inserted through it. If the ovary and fallopian tubes, may also be removed (especially if has suspicious findings on laparoscopy and biopsy, a the cancer has spread there). Chemotherapy, the use of laparotomy (open surgery performed under general anes- strong chemicals to kill cancer cells, is usually done fol- thesia) and removal of that ovary is usually performed. The purpose is to destroy any remaining Large masses are investigated by open surgery. Radiation therapy (using radioactive waves Standard imaging techniques such as Computed to kill cancer cells) is not typically used for ovarian can- Tomography (CT) and Magnetic Resonance Imaging cer because it is not as effective as other treatments. A blood sample is used, • Transvaginal ultrasound with color Doppler imaging and both BRCA genes are studied for alterations. There every six months or yearly, beginning at age 25-35 is also targeted testing for people in high-risk ethnic • Yearly blood CA-125 testing, starting at age 25-35 groups (such as Ashkenazi Jewish) in which only the For women with a BRCA1 or BRCA2 alteration, common BRCA alterations can be tested.

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Chronic stomach rounding a fetus in the womb using a needle) at about 16- and intestine infections are often linked to the parasite 18 weeks of pregnancy or from the chorionic villi (a part Giardia lamblia trusted 50mg imipramine. In some Patients with Bruton agammaglobulinemia can suc- families discount imipramine 50mg otc, a BTK gene change cannot be identified purchase 50 mg imipramine fast delivery. Other cessfully defend themselves against infection from laboratory techniques may be available to these families viruses and fungi because other aspects of the immune such as linkage studies or X chromosome inactivation system are still functional buy generic imipramine 50mg on-line. X rays of the sinuses and chest should be lead to progressive and fatal infections of the brain, obtained at regular intervals to monitor for the early joints, and skin. Lung function tests Diagnosis should also be performed on a regular basis, when the Recurrent infections or infections that fail to respond patient is old enough to cooperate. Patients who have completely or quickly to antibiotics should prompt a ongoing gastrointestinal tract symptoms (diarrhea) diagnostic search for immunodeficiency and Bruton should be tested for the parasite Giardia lamblia. Another helpful clue to a diagno- sis of Bruton agammaglobulinemia is the presence of Treatment and management unusually small lymph nodes and tonsils. Additionally, many patients with this disorder have a history of contin- Current research into a cure for Bruton agamma- uous illness; that is, they do not have periods of well- globulinemia is focusing on the ability of bone marrow being between bouts of illness. The amount of immunoglobulin is measured in a infection effectively, to prevent repeated infections, and small amount of blood from the affected individual by a to prevent the lung damage that may result from repeated technique called immunoelectrophoresis. It should be noted that there maglobulinemia is a lack of immunoglobulins, which are is some difficulty in diagnosing the disease in a young the building blocks of antibodies. Thus, treatment infant or newborn because immunoglobulins from the focuses on replacing immunoglobulin, thereby providing mother are still present in the child during the first few patients with the antibodies they need to fight infection. Immunoglobulin can be obtained from the blood of sev- For those patients in which the exact diagnosis is still eral donors and given to a patient with Bruton agamma- unclear, tests can be performed to determine if there has globulinemia. Treatment with immunoglobulin is given been any response to normal childhood immunizations every three to four weeks and is usually effective in pre- (such as the tetanus, diptheria, and pertussis vaccines). Patients with Bruton agammaglobulinemia are unable to Side effects from or allergic reactions to respond with antibody formation following immuniza- immunoglobulin are infrequent, but about 3-12% of tion. Confirmation of the diagnosis can be made by people will experience shortness of breath, sweating, demonstrating abnormally low numbers of mature B cells increased heart rate, stomach pain, fever, chills, in the blood or by genetic studies that look for mutations headache, or nausea. These symptoms will usually sub- 180 GALE ENCYCLOPEDIA OF GENETIC DISORDERS side if the immunoglobulin is given slowly, or the reac- While current therapy allows most individuals with tions may disappear after receiving the immunoglobulin Bruton agammaglobulinemia to reach adulthood, the several times. Paralysis of the legs may sary to use a special filtering process before giving the result from the poliomyelitis virus. Fatal agammaglobulinemia, antibiotics (medications which brain infections have been reported even in patients kill bacteria) are also given to help fight off the infection. Finally, some patients may develop antibiotics may be given every day, even when there is no leukemia or lymphoma. If chronic diarrhea is experienced by the patient, tests should be performed to look for the parasite Giardia BOOKS lamblia, and proper antibiotics should be given to kill the Ammann, A. Prognosis WEBSITES Without immunoglobulin treatment, 90% of patients “Bruton Agammaglobulinemia Tyrosine Kinase. In most patients who have been diag- nosed early and are receiving immunoglobulin on a reg- ular basis, the prognosis is reasonably good. They should Oren Traub, MD, PhD be able to lead a relatively normal childhood and need not be isolated to prevent dangerous infections. Simpson-Golabi-Behmel syndrome GALE ENCYCLOPEDIA OF GENETIC DISORDERS 181 C Campomelic dwarfism see Campomelic both bone formation and testes development. Every dysplasia developing baby in the womb (fetus), whether genetically male (XY) or female (XX), starts life with the capacity to develop either male or female sex organs. After a few weeks, in an XY fetus, the genitals develop into male genitals if male hormones are present. In the absence of ICampomelic dysplasia male hormones, a female body type with female genitals Definition results. Campomelic dysplasia is a rare, often lethal, genetic In individuals with campomelic dysplasia, the SOX9 condition characterized by multiple abnormalities includ- gene is altered such that it does not work properly.

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It appears that The blood vessels of the fetus and mother are separated Pgp generic 50 mg imipramine amex, the efflux transporter protein generic 75 mg imipramine, also plays a role in by a number of tissue layers that collectively constitute forming this blood-testis barrier discount imipramine 50mg with visa. Drugs that traverse this barrier plays a role in preventing certain chemotherapeutic will reach the fetal circulation cheap imipramine 75mg fast delivery. The placental barrier, agents from reaching specific areas of the testis and thus like the blood-brain barrier, does not prevent transport hinders treatment of the neoplasm. Alterations in gastric reduce the amount of foreign chemicals, such as motility may affect the amount of time a drug drugs, that enter the body. One of the more promi- spends in the region of the gastrointestinal tract, nent of these mechanisms is an efflux transport sys- where it undergoes the most extensive absorption. Finally, system is: changes in drug formulation can alter absorption by (A) Facilitated diffusion changing dissolution rates. P-glycoprotein transporters in the intestinal lu- (C) Cytochrome P450 3A men serve as an efflux transporter for many drugs. All of the following statements concerning the into which they were absorbed and back into the in- blood-brain barrier and the passage of drugs from testinal lumen, reducing absorption. Facilitated dif- the systemic circulation into the cerebrospinal fluid fusion and pinocytosis generally result in drug influx are TRUE EXCEPT: (absorption). The cytochrome P450 3A enzymes (A) Ionized drugs are more likely to cross into the metabolize drugs; therefore, even though they may CSF than un-ionized drugs. Un-ionized drugs cross into the cerebrospinal likelihood that drugs will cross the blood-brain bar- fluid more readily than ionized drugs. Lead can substitute for calcium in the bone crys- (D) P glycoprotein serves to pump drugs back into tal lattice, resulting in bone brittleness. Bone may the systemic circulation from endothelial cells lining become a reservoir for other substances as well. Drugs with extremely high lipid– tial site for drug accumulation of lead that has been water partition coefficients tend to accumulate in fat, ingested? The primary site of absorption is the small intes- Multidrug transporters in prokaryotic and eukary- tine. Because of its large surface area and high otic cells: physiological functions and transport blood perfusion rate, the small intestine is optimal mechanisms. The as the primary cause for the low amounts of orally physician also prescribed diltiazem, a calcium administered cyclosporine reaching the systemic channel blocker used for the treatment of circulation. Since he did not have hypertension, increases the bioavailability of cyclosporine, the patient wondered why this additional drug was reducing the dose of drug needed. Finally, a ANSWER: Cyclosporine is an immunosuppressant drug common adverse effect of cyclosporine therapy is used to prevent transplant rejections. Though an the development of hypertension, and the diltiazem oral formulation is available, it has low somewhat protects the patient from this adverse bioavailability (very little reaches the systemic effect. Tracy Both metabolism and excretion can be viewed as Cytochrome P450 Enzymes processes responsible for elimination of drug (parent The cytochrome P450 (CYP450) enzyme superfamily is and metabolite) from the body. Drug metabolism the primary phase I enzyme system involved in the ox- changes the chemical structure of a drug to produce a idative metabolism of drugs and other chemicals. These drug metabolite, which is frequently but not universally enzymes also are responsible for all or part of the me- less pharmacologically active. Metabolism also renders tabolism and synthesis of a number of endogenous com- the drug compound more water soluble and therefore pounds, such as steroid hormones and prostaglandins. Though it was originally described as the CYP450 en- Drug metabolism reactions are carried out by en- zyme, it is now apparent that it is a group of related en- zyme systems that evolved over time to protect the zymes, each with its own substrate specificity. Enzymes within examples of compounds for which each isoform plays a these categories exhibit some limited specificity in rela- substantial role in their metabolism, are listed in Table 4. For example, the calcium specific hydrolytic enzymes, such as esterases and ami- channel blocking drug verapamil is primarily metabolized dases, have not received much research attention.

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