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A s with other sym pathetic certain other adrenom im etic drugs purchase apcalis sx 20 mg amex erectile dysfunction pump infomercial, that is cheap apcalis sx 20 mg with visa erectile dysfunction best treatment, biotransfor- depressant drugs, tolerance to the antihypertensive ef- m ation and neuronal uptake. D angerously high concen- fects of reserpine can occur, owing to a com pensatory trations of catecholam ines at receptor sites are possible. Reserpine, am itriptyline) and som e phenothiazines block the sym - therefore, should be used in conjunction with a diuretic. Conversely, toms of agitated psychotic states and who may be unable guanethidine com petitively inhibits the uptake of drugs to tolerate therapy with phenothiazine derivatives. Reserpine treat- m ent, therefore, is contraindicated in patients with a his- tory of severe depression. Because of the increased gas- tial invades the sym pathetic nerve term inal, a portion of tric secretion, reserpine is contraindicated for patients 20 Antihypertensive Drugs 235 with peptic ulcer. In patients with little cardiac reserve, The orally effective ganglionic blocking agents in fact reserpine m ust be adm inistered with caution because of are not recom m ended for the treatm ent of prim ary hy- its ability to interfere with sym pathetic stim ulation of pertension. NOREPINEPHRINE SYNTHESIS A m ore com plete description of trim ethaphan and other ganglionic blocking agents can be found in M etyrosine (D em ser) is an exam ple of this class of Chapter 14. The drug blocks the action of tyrosine hydroxylase, the rate- lim iting enzym e in the synthesis of catecholam ines. CENTRALLY ACTING HYPOTENSIVE U nlike -m ethyldopa, m etyrosine is not itself incorpo- DRUGS rated into the catecholam ine synthetic pathway. The ul- tim ate action of the drug is to decrease the production Two im portant antihypertensive agents, -m ethyldopa of catecholam ines. A lthough the details of their actions m ay differ nal tract and is excreted in the urine largely as un- in som e respects, their antihypertensive activity is ulti- changed drug. It is useful for preopera- -M ethyldopa tive treatm ent and for long-term therapy when surgery The spectrum of activity of -m ethyldopa (Aldom et) is not feasible. M echanism of Action GANGLIONIC BLOCKING AGENTS A num ber of theories have been put forward to account for the hypotensive action of -m ethyldopa. Current The basis for the antihypertensive activity of the gan- evidence suggests that for -m ethyldopa to be an anti- glionic blockers lies in their ability to block transm is- hypertensive agent, it m ust be converted to -m ethyl- sion through autonom ic ganglia (Fig. This ac- norepinephrine; however, its site of action appears to be tion, which results in a decrease in the num ber of in the brain rather than in the periphery. System ically ad- im pulses passing down the postganglionic sym pathetic m inistered -m ethyldopa rapidly enters the brain, (and parasym pathetic) nerves, decreases vascular tone, where it accum ulates in noradrenergic nerves, is con- cardiac output, and blood pressure. U nfortunately, Absorption, M etabolism, and Excretion blockade of transm ission in both the sym pathetic and parasym pathetic system s produces num erous untoward A pproxim ately 50% of an orally adm inistered dose of responses, including m arked postural hypotension, -m ethyldopa is absorbed from the gastrointestinal blurred vision, and dryness of m outh, constipation, par- tract. O wing to pressure–lowering effects are observed 2 to 6 hours af- the frequency and severity of these side effects and to ter oral adm inistration. A considerable am ount of un- the developm ent of other powerful antihypertensive changed -m ethyldopa and several conjugated and de- agents, the ganglionic blocking agents are rarely used. Clonidine, however, is not The prim ary hem odynam ic alteration responsible for an -blocker, but is actually an -agonist. Its antihyper- the hypotensive effects of -m ethyldopa rem ains in dis- tensive effectiveness appeared paradoxical until it was pute. W hen the patient is supine, the reduction in blood recognized that clonidine activated central 2-receptors, pressure produced by -m ethyldopa correlates best thus reducing sym pathetic outflow to the periphery. W hen the pa- two drugs with considerable structural sim ilarity to tient is upright, the fall in blood pressure corresponds clonidine. A s occurs with m ost sym - pathetic depressant drugs and vasodilators, long-term M echanism of Action therapy with -m ethyldopa leads to fluid retention, The antihypertensive activity of clonidine can be as- edem a form ation, and plasm a volum e expansion. W hile cribed solely to a decrease in the sym pathetic activity data conflict som ewhat, it is generally thought that - transm itted from the brain to the peripheral vasculature. A fter clonidine adm inistration, direct m easurem ents of sym pathetic nerve activity show that electrical dis- Clinical Uses charge is reduced in a num ber of sym pathetic nerves, in- -M ethyldopa is not generally believed to be suitable cluding the cardiac, splanchnic, and cervical nerves. Because It is generally agreed that clonidine acts in the sam e plasm a volum e increases as the duration of -m ethyl- general area in the brain as does -m ethyldopa, that is, dopa therapy is extended, the drug should be used in som ewhere in the m edulla oblongata. The principal dif- conjunction with a diuretic; this will produce a signifi- ference between clonidine and -m ethyldopa is that cantly greater fall in blood pressure than would occur clonidine acts directly on 2-receptors, whereas - with either drug used alone. Because -m ethyldopa low- m ethyldopa first m ust be converted by synthetic en- ers blood pressure without com prom ising either renal zym es to -m ethylnorepinephrine. H owever, if end-stage renal failure accom panies se- Clonidine is well absorbed after oral adm inistration. Peak plasm a levels occur between 2 and 4 hours after The presence of -m ethyldopa and its m etabolites drug adm inistration and correlate well with pharm aco- in the urine reduces the diagnostic value of urinary cat- logical activity. The plasm a half-life in patients with nor- echolam ine m easurem ents as an indicator of pheochro- m al renal function is 12 hours.

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Carrier testing of individuals without a family history Carrier testing of Canavan disease is only recommended for people of DNA testing is the only means of identifying carri- Ashkenazi Jewish background since they have a higher risk ers of Canavan disease purchase 20 mg apcalis sx overnight delivery erectile dysfunction treatment new delhi. As of 1998 buy apcalis sx 20mg list all erectile dysfunction drugs, both the American College of be first performed on the affected family member. If a Obstetricians and Gynecologists and the American College change in the ASPA gene is detected, then carrier testing of Medical Genetics recommend that DNA testing for can be performed in relatives such as siblings, with an Canavan disease be offered to all Ashkenazi Jewish cou- accuracy of greater than 99%. If the affected relative does ples who are planning children or who are currently preg- not possess a detectable ASPA gene change, then carrier nant. If only one member of the couple is of Ashkenazi testing will be inaccurate and should not be performed. If Jewish background than testing of the Jewish partner DNA testing of the affected relative cannot be performed, should be performed first. If the Jewish partner is a carrier, carrier testing of family members can still be performed than testing of the non-Jewish partner is recommended. GALE ENCYCLOPEDIA OF GENETIC DISORDERS 187 Prenatal Testing Resources Prenatal testing through chorionic villus sampling BOOKS (CVS) and amniocentesis is available to parents who are Scriver, C. PERIODICALS Some parents are known to be carriers for Canavan dis- ACOG committee opinion. Matalon, Reuben, Kimberlee Michals-Matalon, and Rajinder Seizures and irritability can often be controlled through Kaul. Feeding tubes are either inserted ORGANIZATIONS through the nose (nasogastric tube) or through a perma- Canavan Foundation. Fairwood Professional Build- benefit from special education programs and physical ing, New Fairwood, CT 06812. Most people with Canavan disease live into their teens Matalon, Reuben and Kimberlee Michals-Matalon. It is, therefore, impossible to predict the lifespan of a particular individual with Canavan disease. Lisa Maria Andres, MS, CGC 188 GALE ENCYCLOPEDIA OF GENETIC DISORDERS Canavan-VanBogaert-Bertrand disease see mutation in the DNA are called carcinogens. For example, certain hor- Canavan disease mones have been shown to have an effect on the growth or control of a particular cell line. Hormones are sub- stances made by one organ and passed through the blood- stream to affect the function of other cells in another organ. ICancer While there is scientific evidence that both environ- Definition mental and genetic factors play a role in most cancers, Cancer is not just one disease, but a large group of only 5-10% of all cancers are classified as hereditary. This results in a greater risk these cells to spread to distant sites (metastasis). However, if someone has a cancer-related gene, it does not mean they will automatically get cancer. Rather, this person is thought to be “predisposed” to a type of cancer, Description or more likely to get this cancer when compared to the Cancer, by definition, is a disease of the genes. Various cancers are known to have a Genes are formed from deoxyribonucleic acid (DNA) hereditary component in some cases. They carry the hereditary breast cancer, colon cancer, ovarian cancer, skin can- instructions for the cell to make the proteins required for cer and prostate cancer. Proteins are special chemical com- Aside from genes, certain physiological traits that pounds that mostly contain carbon, hydrogen, oxygen, are inherited can contribute to cancers as well. They are required by our bodies to carry out ple, fair skin makes a person more likely to develop skin all the processes that allow us to breathe, think, move, cancer, but only if they also have prolonged exposure to etc. Many the most common types include: genes produce proteins that are involved in controlling the processes of cell growth and division. About 80% of Abnormal cells can start dividing uncontrollably, eventu- human cancers fall into this category. Carcinomas can ally forming a new growth known as a “tumor” or “neo- be subdivided into two subtypes: adenocarcinomas and plasm” (medical term for cancer meaning “new growth”). Adenocarcinomas are can- In a healthy individual, the immune system can recognize cers that develop in an organ or a gland, while squa- the neoplastic cells and destroy them before they get a mous cell carcinomas refer to cancers that originate in chance to divide. A • Sarcomas These are cancers of the supporting tissues of benign tumor is slow growing and does not spread or the body, such as bone, muscle, cartilage, and fat. Once the tumor is removed, it • Leukemias Cancers of the blood or blood-forming usually will not start growing again. Malignant tumors can be network of vessels and nodes that acts as a filter in the removed, but if the cancer cells have spread too much, body. It distributes nutrients to blood and tissue and pre- the cancer becomes very difficult, if not impossible, to vents bacteria and other foreign substances from enter- treat. The most common cancers are skin cancer, lung can- Environmental factors responsible for causing the initial cer, colon and rectal (colorectal) cancer, breast cancer (in GALE ENCYCLOPEDIA OF GENETIC DISORDERS 189 women), and prostate cancer (in men). Some cer of the kidneys, ovaries, uterus, pancreas, bladder, and of these people have been cured of their cancer while oth- blood and lymph node cancer (leukemias and lym- ers are still affected with the disease and are undergoing phomas) are also included among the 12 major cancers treatment.

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Muscles and their output discount apcalis sx 20mg without a prescription erectile dysfunction keywords, force buy apcalis sx 20mg free shipping erectile dysfunction medication south africa, are the obvious control variable for cells in motor cortex. Evarts4,5 was the first to show a relation between motor cortex activity and the force generated by the muscles. Since then, a large number of studies have shown relations between motor cortex and the magnitude, direction, and rate Copyright © 2005 CRC Press LLC of change in force. In addition, other work has demonstrated that the location of the hand, and hence the configuration of the arm, may have a systematic effect on the direction tuning of cell activity during an isometric ramp and hold task,53 in which no actual movements were produced. Despite the influence of arm posture on the activity of single cells in the motor cortex, the direction of the population vector, based on the activity of these cells, has been relatively resistent to changes in arm posture. It is obvious that arm kinematics alone cannot account for the changes in neural activity that have been observed. However, such a conclusion is quite different from stating that the motor cortex codes primarily for the kinetics of motor output. As discussed above, there is clear evidence that movement is first specified in terms of kinematics, but the actual movement is ultimately produced by a weighted activation of groups of muscles (kinetics). The hypothesis underlying successive coordinate transformations is that different motor areas, including several sub-areas of parietal cortex, participate in the various stages of this transformation from kinematics to kinetics. The common wisdom is that the motor cortex would either be involved in the final stage of the kinematic to kinetic transformation or would implement the kinetics on instructions from a “higher” motor area such as the lateral premotor cortex or the supplementary motor area. There is more evidence in favor of the Copyright © 2005 CRC Press LLC motor cortex being instrumental in some kind of kinematic to kinetic transformation, though the form of such a transformation is not at all clear. In other words, the motor cortex primarily codes for the most relevant spatial aspects of motor output, both in the case of movement and during behaviors that are purely isometric. Let us imagine that one is required to make force pulses in different target directions in the presence of opposing forces. The muscle forces exerted will not be in the direction of the targets, because one has to neutralize the opposing forces. Will the activity of motor cortex cells reflect the actual forces produced by the muscle or the resultant force (a combination of the muscle force and the opposing force), which is inevitably in the direction of the target? Using this behavioral paradigm in the monkey, it was shown that both the single cell and population activity in the motor cortex related to the resultant force, which was the most relevant spatial variable, and not to the forces produced by the muscles. If motor cortex codes for the spatial aspects of behavior, in what coordinate framework does this coding occur? It is likely that the coding occurs in the coordinate frame that is most relevant for the behavior. For example, the majority of studies has used reaching movements and it is no surprise that cell activity in those cases reflects an extrinsic reference frame anchored to the hand. If instead, one were to perform the behavior using the elbow as a pointer, this would likely be the reference point. Similarly, manipulation of objects by the hands would be coded in a reference frame that might well be muscle or joint-based relative to the hands. However, a coherent theory of coding in the motor cortex must also account for the clear effect of biomechanical factors on cell activity. The available data suggests that if such a gain field exists, it is comprised of unequal partners, the neural activity relating to the spatial output predominating, but modulated in a systematic way dependent on the biomechanics of the limb. For motor behaviors that are performed in two dimensions — for example, the reaching movements in monkeys — one might conceptualize such a field as a plane with a relatively shallow slope. Of course, we currently lack the type of complete quantitative data that would be necessary in order to construct such putative gain fields accurately, but systematic studies of this issue are currently being conducted. We predict that the slope of such gain fields is likely to be small and that the representation of space by the motor cortex, as in the parietal cortex,56 is likely to be distributed. Bizzi and colleagues57–60 have shown, in experiments in the frog and rat, that a set of “motor primitives,” which could form the basis of activating specific sets of muscles during multiple joint movement, can be elicited through microsimulation of the spinal gray matter. These primitives may form the building blocks for voluntary movement by translating spatial signals from the motor cortex into appropriate muscle output. Recent data from experiments using long trains of intracortical microstimulation suggest that the motor cortex may be able to access such primitives directly. These propriospinal interneurons may participate in the integration of reaching movements at a spinal level, and may effectively translate signals from cells in the motor cortex that relate to the direction of force output of the whole limb55 into appropriate patterns of muscle activation. It is likely that the association between motor cortex cell activity and motor primitive “modules” at another level in the motor system is established through learning and adaptation. Though conceptually attractive, the idea of successive coordinate transforma- tions in frontal motor areas culminating in a muscle or joint based coding of motor output in motor cortex63 does not have strong experimental support and should be abandoned, at least as applied to skilled movements. The search for a direct reflection of the motor periphery in the motor cortex is likely to be as futile as the quest for the representation of the single muscle. The well- defined goal, moving the hand to a spatial location, makes it a popular paradigm for exploring sensorimotor function. This conversion of sensory to motor signals involves many cortical and subcortical regions of the CNS, and a major focus of research is to identify the role played by each of these regions. While cells are unlikely literally to code any engineering- inspired variable, it is nonetheless valuable (and even necessary) to relate neural activity to some features of behavior reflecting sensory, cognitive, or motor aspects of the task.

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Appendix 4•3 Blood Chemistry Tests TEST NORMAL VALUE CLINICAL SIGNIFICANCE Basic panel: An overview of electrolytes generic apcalis sx 20 mg erectile dysfunction questions, waste product management discount apcalis sx 20 mg with mastercard erectile dysfunction drugs walgreens, and metabolism Blood urea nitrogen (BUN) 7–18 mg/dL Increased in renal disease and dehydration; decreased in liver damage and malnutrition Carbon dioxide (CO2) 23–30 mmol/L Useful to evaluate acid-base balance by measuring (includes bicarbonate) total carbon dioxide in the blood: Elevated in vomiting and pulmonary disease; decreased in diabetic acidosis, acute renal failure, and hyperventilation Chloride (Cl) 98–106 mEq/L Increased in dehydration, hyperventilation, and congestive heart failure; decreased in vomiting, diarrhea, and fever Creatinine 0. When elevated, specific fractions (isoenzymes) are tested for Gamma-glutamyl Men: 6–26 U/L Women: 4–18 Used to diagnose liver disease and to test for transferase (GGT) U/L chronic alcoholism Globulins 2. Staphylococcus aureus and other Boils, carbuncles, impetigo, osteomyelitis, staphylococcal pneumonia, cystitis, staphylococci pyelonephritis, empyema, septicemia, toxic shock, and food poisoning. Streptococcus pyogenes, Streptococcus Septicemia, septic sore throat, scarlet fever, puerperal sepsis, erysipelas, streptococ- hemolyticus, and other streptococci cal pneumonia, rheumatic fever, subacute bacterial endocarditis, acute glomeru- lonephritis Bacilli Bordetella pertussis Pertussis (whooping cough). Acute inflammation of the throat with the formation of a leathery mem- branelike growth (pseudomembrane) that can obstruct air passages and cause death by asphyxiation. Acute infection of the intestine characterized by prolonged vomiting and diarrhea, leading to severe dehydration, electrolyte imbalance, and in some cases, death. Untreated syphilis is seen in the following three stages: primary-formation of primary lesion (chancre); secondary-skin eruptions and infectious patches on mucous membranes; tertiary-development of generalized lesions (gummas) and destruc- tion of tissues resulting in aneurysm, heart disease, and degenerative changes in brain, spinal cord, ganglia, and meninges. Also causes inclusion conjunctivitis, an acute eye infection, and trachoma, a chronic infection that is a common cause of blindness in underdeveloped areas of the world. The same organism causes lymphogran- uloma venereum (LGV), a sexually transmitted infection characterized by swelling of inguinal lymph nodes and accompanied by signs of general infection. Diagnosed by antibody tests, decline in specific (CD4) cells, and presenting disease, including Candida albicans infection, Pneumo- cystis carinii pneumonia, Kaposi sarcoma, persistent swelling of lymph nodes (lymphadenopathy), chronic diarrhea, and wasting. A less severe form of measles, but especially dangerous during the first 3 months of pregnancy because the disease organism can cause heart defects, deafness, mental deficiency, and other permanent damage in the fetus. Patients are prone to the development of dangerous complications, such as bronchopneumonia and other secondary infections caused by staphylococci and streptococci. AGENT DISEASE Chronic wasting disease agent Chronic wasting disease in deer and elk Creuzfeldt-Jakob agent Cruetzfeldt-Jacob disease (CJD), a spongiform encephalopathy in humans Kuru agent Kuru spongiform encephalopathy in humans Mad cow agent Mad cow spongiform encephalopathy, or bovine spongiform encephalopathy (BSE) in cows and humans Scrapie agent Scrapie spongiform encephalopathy in sheep Appendix 5•4 Fungal Diseases DISEASE/ORGANISM DESCRIPTION Actinomycosis “Lumpy jaw in cattle and humans. Histoplasmosis (Histoplasma A variety of disorders, ranging from mild respiratory symptoms or enlargement of liver, capsulatum) spleen, and lymph nodes to cavities in the lungs with symptoms similar to those of tuberculosis. APPENDIX ✦ A-13 Appendix 6 Answers to Chapter Checkpoint and “Zooming In” Questions CHAPTER 1 Answers to Checkpoint Questions 1-6 The three central regions of the abdomen are the 1-1 Study of body structure is anatomy; study of body function epigastric, umbilical, and hypogastric regions; the three is physiology. CHAPTER 3 Answers to Checkpoint Questions 3-6 The two types of organelles used for movement are the 3-1 The cell shows organization, metabolism, cilia, which are small and hairlike, and the flagellum, responsiveness, homeostasis, growth, and reproduction. A-14 ✦ APPENDIX 3-13 An isotonic solution is the same concentration as the fluid 3-11 If diffusion were occurring in the body, the net would be within the cell; a hypotonic solution is less concentrated; a the plasma membrane. CHAPTER 4 Answers to Checkpoint Questions 4-6 The basic cellular unit of the nervous system is the 4-1 The three basic shapes of epithelium are squamous (flat neuron and it carries nerve impulses. CHAPTER 5 Answers to Checkpoint Questions 5-9 Microbiology includes the study of bacteria, viruses, 5-1 Disease is an abnormality of the structure or function of fungi, protozoa, and algae. APPENDIX ✦ A-15 5-19 Stains are used to color cells so that they can be 5-9 The term intracellular means that the parasites are inside examined under the microscope. CHAPTER 6 Answers to Checkpoint Questions 6-10 Epithelial and connective tissues repair themselves most 6-1 The skin and all its associated structures make up the in- easily. CHAPTER 7 Answers to Checkpoint Questions 7-10 The three types of joints classified according to the 7-1 The shaft of the long bone is the diaphysis; the end of a material between the adjoining bones are fibrous, long bone is the epiphysis. A-16 ✦ APPENDIX CHAPTER 8 Answers to Checkpoint Questions 8-11 The muscle that produces a movement is called the 8-1 The three types of muscle are smooth muscle, cardiac prime mover; the muscle that produces an opposite muscle, and skeletal muscle. CHAPTER 9 Answers to Checkpoint Questions 9-12 A reflex arc is a pathway through the nervous system 9-1 Structurally, the nervous system can be divided into a from a stimulus to an effector. The cervical spinal nerves (C6,7,8) 9-9 Neurotransmitters are the chemicals used to carry carry impulses from the skin of the anterior hand and information across the synaptic cleft. The parasympathetic division of the autonomic 9-10 In the spinal cord, an H-shaped section of gray matter is nervous system has ganglia closer to the effector organ located internally, and the white matter is located than does the sympathetic system. APPENDIX ✦ A-17 CHAPTER 10 Answers to Checkpoint Questions 10-9 Stroke is the common term for cerebrovascular 10-1 The main divisions of the brain are the cerebrum, the accident. The two lateral ventricles are in the cerebral hemispheres, the Answers to Zooming In Questions third ventricle is in the diencephalon, and the fourth is 10-3 Dural (venous) sinuses are located in the space where between the brain stem and the cerebellum. CHAPTER 11 Answers to Checkpoint Questions 11-11 The organ of hearing is the organ of Corti located in 11-1 Structures that protect the eye include the skull bones, the cochlear duct within the cochlea. CHAPTER 12 Answers to Checkpoint Questions 12-4 The anterior pituitary produces growth hormone (GH), 12-1 Hormones are chemicals that have specific regulatory thyroid-stimulating hormone (TSH), effects on certain cells or organs in the body. Some of adrenocorticotropic hormone (ACTH), prolactin (PRL) their effects are to regulate growth, metabolism, follicle stimulating hormone (FSH) and luteinizing reproduction, and behavior. CHAPTER 13 Answers to Checkpoint Questions 13-14 Blood is commonly separated into its component parts 13-1 Some substances transported in blood are oxygen, by a centrifuge. CHAPTER 14 Answers to Checkpoint Questions beat, and by the heart rate, the number of times the 14-1 The innermost layer of the heart is the endocardium, heart beats per minute. APPENDIX ✦ A-19 Answers to Zooming In Questions 14-10 The AV (tricuspid and mitral) valves close when the 14-1 The left lung is smaller than the right lung because the ventricles contract, and the semilunar (pulmonary and heart is located more toward the left of the thorax. CHAPTER 17 Answers to Checkpoint Questions 17-2 The unbroken skin and mucous membranes constitute 17-1 Factors that influence the occurrence of infection the first line of defense against the invasion of pathogens. CHAPTER 19 Answers to Checkpoint Questions 19-6 The three divisions of the small intestine are the 19-1 Food must be broken down by digestion into particles duodenum, jejunum and ileum.

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