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Patients The calcium channel blocking agent nifedipine given magnesium lose patellar reflexes at plasma levels (Procardia; see Chapter 19) generic forzest 20 mg, is one of the more recent greater than 8 to 10 mEq/L buy forzest 20mg overnight delivery. It acts by impairing occur at levels greater than 10 to 12 mEq/L discount forzest 20mg online, with respi- the entry of Ca into myometrial cells via voltage- ratory paralysis and arrest soon after (e cheap 20mg forzest with visa. Toxicity can be avoided by following urine out- studies are needed before its usefulness can be fully as- put and checking patellar reflexes in patients receiving sessed buy forzest 20 mg overnight delivery. Other side effects include sweating, Hydroxyprogesterone has been used prophylacti- warmth, flushing, dry mouth, nausea, vomiting, dizzi- cally for the 12th to 37th week of pregnancy, particularly ness, nystagmus, headache, palpitations, pulmonary in women who are in the high-risk category for prema- edema, maternal tetany, profound muscular paralysis, ture delivery (e. Hydroxy- progesterone as a tocolytic agent requires further eval- Other Agents uation before its routine prophylactic administration Since certain prostaglandins are known to play a role in can be recommended. Atosiban is an analogue of oxytocin that is modified at Indomethacin is given orally or rectally for 24 or 48 positions 1, 2, 4, and 8. Early studies have demonstrated that cerning the use of indomethacin is premature closure of this drug does decrease and stop uterine contractions. Adverse reactions to the prostaglandin analogue sulfate that may be related to its ability to relax carboprost tromethamine include all of the follow- uterine smooth muscle EXCEPT ing EXCEPT (A) Uncoupling excitation–contraction in myome- (A) Diarrhea trial cells through inhibition of cellular action po- (B) Fever tentials (C) Water intoxication (B) Decreasing calcium uptake by competing for (D) Nausea binding sites (E) Dyspnea (C) Activating adenylate cyclase 722 VII DRUGS AFFECTING THE ENDOCRINE SYSTEM (D) Stimulating calcium-dependent ATPase rather than inhibit premature labor. The mechanism of action by which (B) Fetal gastrointestinal bleeding magnesium sulfate causes smooth muscle contrac- (C) Fetal hematuria tion is complex and poorly understood. Magnesium (D) Closure of the fetal ductus arteriosis sulfate uncouples excitation–contraction in myome- (E) Fetal muscular paralysis trial cells through inhibition of cellular action po- tentials. Furthermore, magnesium sulfate decreases ANSWERS calcium uptake by competing for binding sites, acti- 1. Oxytocin is considered the drug of choice for in- vating adenylate cyclase (reducing intracellular cal- ducing labor. All other methods of labor induction cium), and stimulating calcium-dependent ATPase, are compared to oxytocin to establish their efficacy. Indomethacin is a potent prostaglandin synthe- Oxytocin is not as effective for labor induction when sis inhibitor. Closure Another agent, such as misoprostol or dinoprostone, of the ductus arteriosis can lead to fetal heart fail- may be better for women with unfavorable cervices. Also, fetal closure can lead to neona- Both misoprostol and dinoprostone are tal pulmonary hypertension. They cause changes in the domethacin for the treatment of neonatal patent substance of the cervix and uterine contraction. Prostaglandin synthesis inhibitors are the risk of uterine hyperstimulation, prostaglandins associated with bleeding. Although bleeding is well are more likely to cause hyperstimulation in women documented in children and adults, the use of in- with favorable cervices. Furthermore, the current for- domethacin has not been shown to cause hematuria mulations of prostaglandins do not allow for tight or gastrointestinal bleeding in the fetus. There is control of blood levels and rapid clearance of med- some evidence, however, that maternal use of in- ication if hyperstimulation occurs. Methyl ergonovine domethacin may increase the risk of neonatal intra- is an -agonist that causes direct smooth muscle con- ventricular hemorrhage. Carboprost tromethamine is a methylated nor cardiac arrest has been demonstrated in the fe- analogue of prostaglandin F2. Both medica- tions are used for the control of uterine bleeding af- SUPPLEMENTAL READING ter delivery by causing tetanic uterine contractions. Prostaglandins are involved in the pyretic response, Tocolytics for preterm labor: A systematic review. She reports no pain, no their due date are classified as having postterm or labor contractions, no vaginal bleeding, no leaking postdate pregnancy. Women who are postterm have a higher risk plaints, and her medical, surgical, social, and family of cesarean section, trauma from delivery, prolonged histories are all negative. The physical examination bleeding after delivery, and prolonged hospitaliza- you perform produces normal findings. Her creased risk of being pathologically large (macroso- pelvic examination reveals that her cervix is 3 cm mia), birth trauma, intolerance to labor, meconium dilated, 50% effaced, soft in consistency, and midpo- staining, meconium aspiration, and possible subse- sition in the vagina. ANSWER: In this case, the decision to induce labor is Obstetricians traditionally use a scoring system to appropriate. Cervical Cervical Score Dilation (cm) Effacement (%) Station Consistency Position 0 Closed 0–30 3 Firm Posterior 1 1–2 40–50 2 Medium Midposition 2 3–4 60–70 1,0 Soft Anterior 3 5 80 1. Miller DRUG LIST GENERIC NAME PAGE GENERIC NAME PAGE Androgens Stanozolol 731 Danazol 730 Antiandrogens Methyltestosterone 730 Cyproterone acetate 732 Testosterone 724 Finasteride 732 Anabolic agents Flutamide 732 Methandrostenolone 731 Ketoconazole 732 Nandrolone 730 Leuprolide Acetate 732 Oxandrolone 730 Spironolactone 732 Oxymetholone 731 Androgens are steroid hormones that are secreted CHARACTERIZATION OF PLASMA primarily by the testis, and testosterone is the principal ANDROGENS androgen secreted.

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Affected females may have partial or complete fusion of the folds of skin on either side of the vagina (labia) cheap 20mg forzest amex, an abnormally large clitoris buy 20 mg forzest overnight delivery, a malformation of the paired tubes that connect the ovaries to the uterus (fallopian tubes) buy forzest 20 mg without a prescription, and/or an abnormally shaped uterus (bicornate Many infants with Fraser syndrome suffer from uterus) buy forzest 20mg otc. Affected females beyond puberty also may not water on the brain (hydrocephaly) and some cases have have a menstrual cycle discount forzest 20 mg amex. In affected males, one or both been found in which one of the normal cavities within the testicles may fail to descend into the scrotum, the urinary brain (the left ventricle) is not present. Dandy-Walker opening may occur on the underside of the penis rather syndrome, a brain malformation of the fourth ventricle of than at the tip of the penis (hypospadias), the penis may the brain, has also been associated with Fraser syndrome. Another complication of Fraser syndrome is malfor- mations of one or both kidneys. These malformations may include improper development (renal dysplasia), underdevelopment (renal hypoplasia), or the complete The symptoms of Fraser syndrome have been classi- absence of one or both kidneys (unilateral or bilateral fied into four major and eight minor characteristics. The navel can be located lower than nor- of the four major characteristics of the syndrome accom- mal and the nipples are generally wider set. A hairline panied by at least one of the eight minor characteristics that extends forward over the temples is an additional of the syndrome, or by the presence of one major charac- cosmetic symptom of Fraser syndrome. Whistling face Deep-set eyes Clubfoot Wide-set eyes Whistling face Clubfoot Wide-set eyes Scoliosis Small mouth Whistling face Whistling face Small nose Deep-set eyes Scoliosis Clubfoot Small mouth Clubfoot Scoliosis (Gale Group) OMIM—Online Mendelian Inheritance in Man. I KEY TERMS Casein hydrolysate Catalyst Enzyme Galactose Glucose Lactose Metabolic pathway Metabolism Recessive trait Diagnosis GALE ENCYCLOPEDIA OF GENETIC DISORDERS 451 Grabowski, Gregory A. PO Box 2123, Granite Bay, inherited traits were thought to be passed on through a CA 95746-2123. Before the chemical and physical nature of genes were discovered they were defined on the basis of phenotypic expression and algebraic symbols were used “Cerezyme. It can be predicted mathematically, for example, that a single allele pair will Amy Vance, MS, CGC always segregate to give a genotype ratio 1AA:2Aa:1aa, and the phenotype ratio 2A:1aa (where A represents both AA and Aa since these cannot be distinguished pheno- typically if dominance is complete). The molecular structure and activity of genes can be modified by mutations and the smallest mutational unit is now known to be a single pair of nucleotides, also known A gene is the fundamental physical and functional as a muton. In most organisms the nine utilization would be Such strains, known as nucleic acid is deoxyribonucleic acid (), although in arginine auxotrophs, would not be able to grow without a retroviruses the genetic material is composed of ribonu- supplement of arginine. Some genes in a cell are active more or plus or minus actually refer to an operon rather than a less all the time, which means that they are continuously single gene, and finer genetic analysis can be used to transcribed and provide a constant supply of their protein reveal the exact location of the mutated gene. These are the “housekeeping” genes that are The use of mutations in studying genes is well-illus- always needed for basic cellular reactions. Others may be trated in a traditional genetic test called the “cis-trans test” rendered active or inactive depending on the needs and which also gave the gene the alternative name, cistron. This is a complemetntation test that can be used to deter- 1 2 The signal that masks or unmasks a gene can come from mine whether two different mutations (m and m ) occur Polydactyly, which results in extra fingers or toes, is one type of genetic mutation. I Bioethics and Human Population Genetics Research Biology Website References for Students and Teachers Evolution—Population Genetics Human Genome Diversity Project Human Genome Project Talk Origins (Photo Researchers, Inc. The practice of marrying or having children examination of the family history a counselor may be with relatives is infrequent in the United States, but is able to discuss the probability of future occurrence of more common in some countries. In recessive inheritance, each parent of a child affected with a disease carries a single gene In taking a family history, a genetic counselor asks for the disease. People who have a com- ethnic groups that have a higher chance of being carriers mon ancestor are more likely than unrelated people to of some genetic diseases. For instance, the chance that an be carriers of genes for the same recessively inherited African American is a carrier of a gene for sickle cell dis- genes. People of Jewish ancestry are more likely to ground, blood tests can be offered to couples to get be carriers of several conditions including more information about the chance for these conditions, and. Genetic coun- selors discuss inheritance patterns of these diseases, car- rier risks, and genetic screening or testing options. During prenatal genetic counseling, the counselor will ask about pregnancy history. If the patient has taken a medication or has had a harmful exposure (like radia- tion), the genetic counselor can discuss the possibility of Another question a genetic counselor asks in taking harmful affects. Ultrasound is often a useful tool to look a family history is if the couple is related to one another for some affects of exposures. Abnormal formation of body systems and parts, for instance the giantisim of feet, often assists with diagnosis of specific inherited disorders.

In the third stage cheap 20mg forzest with mastercard, stimuli X and Y were presented in occasional unrewarded trials as a probe to test this prediction (Figures 10 purchase forzest 20 mg with mastercard. Also as predicted forzest 20mg fast delivery, the Kamin blocking effect was faithfully reflected in the activity of dopaminergic neurons in the midbrain discount 20mg forzest with visa. Nearly half of these (39 cells) responded to the nonredundant stimulus Y forzest 20 mg, but were not activated by the redundant stimulus X (as in Figure 10. As a population, therefore, dopamine neurons responded much more vigorously to stimulus Y than to X (Figure 10. This finding demonstrated that the dopaminergic cells had acquired stronger responses to the nonredundant stimulus Y, compared to the redundant stimulus X, even though both stimuli had been equally paired with reward during the preceding compound stimulus training. These cells apparently predicted reward in the same way that the monkeys predicted reward. For eye-blink conditioning (and for other protective reflexes), cells in the inferior olivary nuclei compare predicted and received neuronal inputs, probably concerning predictions about the US. One answer is that the cerebellum subserves arbitrary stimulus–response mappings for protective responses, whereas the dopamine system plays a similar role for appetitive responses. This issue has been reviewed recently,58,59 so we will only briefly consider this question here. The central nucleus of the amygdala, the nucleus accumbens of the ventral striatum, and the anterior cingulate cortex appear to be important components of the arbitrary mapping system that underlies certain (but not all) types of Pavlovian approach behavior in rats. Initially neutral objects, when mapped to a positive value, trigger ingestive reflexes, such as those involved in procurement of food or water (licking, chewing, salivation, etc. As reviewed by Baxter and Murray,59 these mechanisms involve different parts of the frontal cortex and amygdala than the typical Pavlovian approach behavior described above: the orbital prefrontal cortex (PF) instead of the anterior cingulate cortex and the basolateral nuclei of the amygdala instead of the central nucleus of the amygdala. These structures, very likely in conjunction with the parts of the basal ganglia with which they are interconnected, underlie the arbitrary mapping of stimuli to their value in a special and highly flexible way. This flexibility is required when neutral stimuli map arbitrarily to food items and the value of those food items changes over a short period of time. Stimuli that map arbitrarily to specific food items can change their current value because of several factors, for example, when that food item has been consumed recently in quantity. Normal monkeys can use this information to choose stimuli that map to a higher current value. This mechanism appears to depend on the basolateral nucleus of the amygdala and the orbital PF: when these structures are removed or their interconnections severed, monkeys can no longer use the stimuli to obtain the temporarily more valued food item. Furthermore, monkeys with those lesions remained perfectly capable of choosing the currently preferred food items. The use of updated stimulus–value mappings allows animals to predict the current, biologically relevant outcome of an action produced in the context of that stimulus. This mechanism permits animals to make choices that lead to the best possible outcome when several possible choices with positive outcomes are available, and to choose appropriately in the face of changing values. As summarized by Shadmehr and his colleagues in this volume,11 in their experiments people move a robotic arm from a central location to a visual target. When, during the course of these movements, the robot imposes a complex pattern of forces on the limb, the movement deviates from a straight line to the target. With practice in countering a particular pattern of forces, the motor system learns to produce a reasonably straight trajectory. There is nothing arbitrary about such IMs; they reflect the physics of the limb and the forces imposed upon the limb. In the experiments that first demonstrated this fact, Rao and Shadmehr62 presented participants with two different patterns of imposed force. They gave each person a cue indicating which of these force patterns would occur on any given trial. This cue could be either to the left or to the right of the target, and its location varied randomly from trial to trial, but in neither case did the cue serve as a target of movement or affect the trajectory of movement directly. Instead, the location of the cue was arbitrary with respect to the forces imposed by the robot. The participants in this experiment learned to use this arbitrary cue to call up the appropriate IM for the pattern of imposed forces associated with that cue location. That is, they could select the motor program needed to execute reasonably straight movements for either of two different patterns of perturbations, as long as an arbitrary visual cue indicated what the robot would do to the limb. Having learned this mapping, the participants in these experiments could transfer this ability to color cues. For example, a red cue indicated that the same forces would occur as when the left cue appeared in the previous condition; a blue cue indicated that the other pattern of forces would occur.

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