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ATYPICAL NEUROLEPTICS Typical neuroleptics reduce the positive symptoms of schizophrenia at the expense of producing EPSs but the so-called atypical neuroleptics have less tendency to cause EPSs buy ditropan 5 mg visa. Clozapine can even be effective in patients refractory to other neuroleptics ditropan 5 mg. It is clearly a special drug buy ditropan 5mg fast delivery, so special in fact that although it was once withdrawn because it causes agranulocytosis in some patients (2%), it has been reintroduced, alongside careful blood monitoring, for refractory cases. This has been shown by (1) increased DA turnover through DOPAC and HVA production in vitro, (2) augmented DA and DOPAC release by microdialysis in vivo and (3) increased c-fos-like expression. How the atypical neuroleptics achieve this differential effect is less clear but they could achieve some control of schizophrenia without producing EPSs by: (1) Acting primarily on a particular subset of DA receptors (2) Antagonising (or augmenting) some other NT(s) instead of, or in addition to, DA (3) Having a particular but appropriate profile of DA and other NT (antagonistic) effects These possibilities will be considered in turn. Significance of different DA receptors So far we have generally just alluded to the neuroleptics as DA receptor antagonists. Clearly, if the DA released at the terminals of one dopaminergic tract acted on a subset of DA receptors that were different from those found postsynaptically at other tracts then some specificity of antagonist action might be achieved. Unfortunately there is no evidence that different pathways innervate different DA receptor populations and as with the use of agonists in PD, the D2 receptor is dominant. Specific D1 antagonists have no anti- schizophrenic effect and antischizophrenic efficacy increases with neuroleptic affinity (potency) at D2 receptors Ð as unfortunately does the tendency to produce EPSs. Thus there is no great advantage in producing more potent D2 antagonists, other than that less drug needs to be incorporated into long-term release depot preparations. PET studies show that at effective therapeutic plasma concentrations most neuro- leptics occupy some 80% of brain D2 receptors (in the striatum at least) and this is therefore considered to be a requirement for efficacy (Pilowsky, Costa and Eli 1992; Farde 1996). If that is so then clozapine, which occupies only 20±40% of the D2 receptors at a therapeutic concentration, must have some other action which accounts for its therapeutic effectiveness. Its activity at D1 receptors has been put forward as a possibility and although it has a relatively higher affinity for D1 than D2 receptors, compared with typical neuroleptics, it is still a weak antagonist at both and in the absence of evidence for D1 (or D5) receptor involvement in schizophrenia the significance of any D1 antagonism is unclear. K1 (nM) values for clozapine at D2 and D1 receptors are 56 and 141 compared with 0. A relatively strong block of D1 compared with D2 receptors may not be the answer for schizophrenia but it could reduce the tendency to produce dyskinesias, if this depends on D1 receptor activation (see Fig. Among the D2 family of receptors (D2,D3 and D4) the D2 receptor itself seems to be the most important. At a therapeutic concentration, most neuroleptics, except clozapine (and risperidone), should, according to in vitro binding studies, be occupying 50±70% of brain D2 receptors. The picture is similar for D3 receptors but only clozapine (and SCHIZOPHRENIA 365 risperidone and olanzapine) occupy more than 50% of D4 receptors at a therapeutic dose. This relative selectivity of clozapine for D4 receptors with their restricted location, even if it is in small numbers, to the prefrontal cortex has stimulated much interest in their involvement in schizophrenia and the control of negative symptoms.

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The specific name giv- Gubler buy 5 mg ditropan free shipping, 2001) purchase ditropan 2.5 mg overnight delivery, or it may be secondary to en to the meningitis infection is frequent- another infection discount 5mg ditropan with mastercard, such as measles or ly related to its cause or location. Some individuals with en- instance, cerebral meningitis refers to cephalitis may experience severe head- meningitis of the brain, whereas cere- ache, stiff neck, and coma. There is no brospinal meningitis refers to meningitis of adequate treatment for encephalitis, ex- both the brain and spinal cord. Menin- cept for maintaining comfort and prevent- gococcal meningitis (commonly known as ing complications. The symptoms can spinal meningitis) is caused by a bacterium subside in a few weeks, leaving no perma- that settles in the lining of the throat and nent damage; however, the condition can is spread easily through respiratory secre- also be life-threatening. Some individuals Conditions Affecting the Brain 33 develop irreversible neurological changes gunshot wound). At times, functional impair- with compromised immune systems, are ments in open head injury may be more often the most susceptible to more severe extensive if additional damage is sus- manifestations of these diseases. For example, in addition to the trauma to the brain itself, bone fragments Traumatic Brain Injury from the injury may also lacerate and injure the brain, blood vessels, or Traumatic brain injury is broadly defined meninges (lining surrounding the brain). It is not degenerative, cient force that the brain slams against the is not the result of a disease, and is not other side of the skull or twists within the congenital in origin. Damage to the brain skull, causing shearing of blood vessels or occurs from a blow to the head that is nerve fibers throughout the brain. This is hard enough to cause the brain to move called diffuse axonal injury. Injury is caused within the skull, or from an impact that to the brain both from the external force fractures the skull, injuring the brain as well as from movement of the brain directly. The initial impact to the Almost two million people, of all ages, brain is called the coup, and the impact of sustain brain injury each year in the the brain on the opposite side of the skull United States. Functional limi- fects, including physical, cognitive, emo- tations associated with closed head injury tional, and behavioral deficits that impact depend on where and how much shear- every aspect of an individual’s life. This ing occurred in the brain and may be wide range of deficits presents unique more diffuse because of the more exten- challenges to rehabilitation of individuals sive damage to the brain itself. Additional injury may occur as an indi- rect result of edema (swelling) of the Types of Traumatic Brain Injury brain, hemorrhage, or the formation of a hematoma (sac filled with blood) within There are two types of traumatic brain the skull as a direct result of the injury injuries: itself. Bleeding within the cranial vault is referred to as intracranial hemorrhage. Be- • Open or penetrating head injury cause the brain is confined within the • Closed head injury skull, there is no space available for expan- Open (penetrating) injuries refer to injuries sion if swelling or bleeding should occur. The length of unconsciousness these events can cause additional perma- is also used as a predictor of prognostic out- nent brain damage or death. Generally, the longer the period of Bleeding and blood clots compress the unconsciousness, the more severe the in- brain, increasing intracranial pressure.

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Spermatogonia undergo mitotic division to replace themselves and produce a daughter cell that will undergo meiotic division discount 5 mg ditropan amex. Upon completion of the first meiotic division generic ditropan 2.5 mg fast delivery, the daughter cells are called secondary spermatocytes ditropan 2.5 mg visa. No- tice that the four spermatids produced by the meiosis of a primary (c) spermatocyte are interconnected. Male Reproductive © The McGraw−Hill Anatomy, Sixth Edition Development System Companies, 2001 Chapter 20 Male Reproductive System 707 Pseudostratified ciliated columnar epithelium Smooth muscle Sperm in lumen of duct Connective tissue FIGURE 20. The tail is continuous with the beginning por- tion of the ductus deferens; both store spermatozoa to be discharged during ejaculation. The time required to produce ma- SPERMATIC DUCTS, ACCESSORY ture spermatozoa—from meiosis in the seminiferous tubules to storage in the ductus deferens—is approximately 2 months. From here, it penetrates the in- Objective 10 Describe the location and structure of each segment of the male duct system. The histological structure of the ductus deferens includes a Objective 12 Describe the location, structure, and functions layer of pseudostratified ciliated columnar epithelium in contact of the ejaculatory ducts, seminal vesicles, prostate, and with the tubular lumen and surrounded by three layers of tightly bulbourethral glands. Stimulation through these nerves causes peristaltic contractions of the muscular layer, Spermatic Ducts which propel the stored spermatozoa toward the ejaculatory duct. The spermatic ducts store spermatozoa and transport them from Much of the ductus deferens is located within a structure the testes to the urethra. The accessory reproductive glands pro- known as the spermatic cord (see figs. Male Reproductive © The McGraw−Hill Anatomy, Sixth Edition Development System Companies, 2001 708 Unit 7 Reproduction and Development Seminal crypt Smooth muscle FIGURE 20. Glandular epithelium plexus, nerves, the cremaster muscle, lymph vessels, and connec- tive tissue. The portion of the spermatic cord that passes anterior to the pubic bone can be easily palpated. This layer partitions the lumen pierces the capsule of the prostate on its posterior surface and into numerous intercommunicating spaces that are lined by pseu- continues through this gland (see fig. Both ejaculatory dostratified columnar and cuboidal secretory epithelia (referred ducts receive secretions from the seminal vesicles and then eject to as glandular epithelium). The seminal vesicles are innervated by shortly, serves as a passageway for both semen and urine. It nal vesicles, the prostate, and the bulbourethral glands (see is about 4 cm (1. The contents of the seminal vesicles and prostate are immediately below the urinary bladder, where it surrounds the mixed with the spermatozoa during ejaculation to form semen beginning portion of the urethra (see fig.

With respect to the hard palate effective ditropan 2.5mg, which kid brother is convinced of this cheap 2.5mg ditropan mastercard. Explain why there are approximately (a) It is composed of two maxillae and him to change his mind? Identify the bones of (c) The mandible articulates with the sensory organs and list the associated the skull that can be palpated buy 5mg ditropan fast delivery. Explain why a proper balance of vitamins, What are the fontanels, where are they (d) The median palatine suture, incisive hormones, and minerals is essential in located, and what are their functions? What foramina are three of its structural examples of diseases or skeletal conditions structures pass through these openings? Describe where imbalance of any of these three essential immediately these two components articulate. The most common surgical approach to a (b) inferior to the frontal sinus. How are these processes similar, team of archaeologists recently completed (b) the tympanic part and how do they differ? Explain how an examination of 18 skeletons from (c) the mastoid part radiographs can be used to determine people buried under tons of volcanic ash (d) the petrous part normal bone growth. Explain the process of endochondral the scientists were able to determine the which bone? Why is it sex, physical health (including a partial (a) the sphenoid bone important that a balance be maintained medical history), approximate age, and (b) the ethmoid bone between osteoblast activity and osteoclast even the general profession of each of the (c) the palatine bone activity? Describe the curvature of the vertebral examination of a preserved skeleton yield 9. Skeletal System: The © The McGraw−Hill Anatomy, Sixth Edition Appendicular Skeleton Companies, 2001 Skeletal System: The Appendicular Skeleton 7 Pectoral Girdle and Upper Extremity 173 Pelvic Girdle and Lower Extremity 178 CLINICAL CONSIDERATIONS 189 Clinical Case Study Answer 191 Developmental Exposition: The Appendicular Skeleton 192 Chapter Summary 194 Review Activities 194 Clinical Case Study A 12-year-old boy was hit by a car while crossing a street. He was brought to the emergency room in stable condition, complaining of severe pain in his left leg. Radiographs revealed a 4- inch fracture extending superiorly from the distal articular surface of the tibia into the anterior body of the bone. With the radiographs in hand, the orthopedic surgeon went into the waiting room and conferred with the boy’s parents. He told them that this kind of injury was more serious in children and growing adolescents than in adults. He went on to say that future growth of the bone might be jeopardized and that surgery, although recommended, could not guarantee normal growth.

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