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Inhibition of the production pears to offer an advantage over the naturally occurring and effects of inflammatory cytokines (IL-6 and IL- ) hormone in that it has a longer duration of action and by the transcription factors nuclear factor- B and AP-1 lacks the antigenic portion of corticotropin cheap motilium 10 mg online chronic gastritis fever. Although may also contribute to the antiinflammatory effects of the short cosyntropin test is recognized as a valid glucocorticoids buy motilium 10mg fast delivery gastritis symptoms in cats. DRUGS USED IN THE DIAGNOSIS OR TREATMENT OF ADRENOCORTICAL Metyrapone ABNORMALITIES Mechanism of Action Corticotropin Metyrapone (Metopirone) produces its primary phar- macological effect by inhibiting 11- -hydroxylase, Corticotropin (ACTH, Acthar, Cortrophin Gel) is an thereby causing diminished production and release of open-chain polypeptide that consists of 39 amino acid cortisol. The resulting reduction in the negative feed- residues, the first 24 of which are essential for its biolog- back of cortisol on the hypothalamus and pituitary ical activity. The remainder of the amino acids are also causes an increase in corticotrophin release and in the clinically important, since they may be involved in stim- secretion of precursor 11-deoxysteroids. The drug tests the functional com- Corticotropin is rapidly inactivated by gastrointestinal petence of the hypothalamic–pituitary axis when the proteolytic enzymes and therefore must be administered adrenals are able to respond to corticotrophin; that is, parenterally. Moreover, if pituitary corticotrophin is suppressed by an autonomously secret- The rationale for using corticotropin instead of phar- ing adrenal carcinoma, there will be no increase in re- macological concentrations of glucocorticoids stems sponse to metyrapone. On the other hand, if pituitary from the fact that corticotropin provides enhanced corticotrophin secretion is maintained, as occurs in adre- amounts of all endogenously secreted adrenocortical nal hyperplasia, the inhibition of corticoid synthesis pro- hormones, including androgens. However, obvious dis- duced by metyrapone will stimulate corticotrophin secre- advantages are associated with the use of this polypep- tion and the release of metabolites of precursor urinary tide: (1) It must be given daily parenterally. However, the compensa- Adverse Effects tory rise in corticotrophin levels in response to falling Aside from hypersensitivity and allergic reactions, cor- cortisol levels tends to maintain adrenal activity. This re- ticotropin administration has been associated with elec- quires that glucocorticoids be administered concomi- trolyte disturbances and masculinization in women. Although metyrapone interferes with 11 - and 18- hydroxylation reactions and thereby inhibits aldos- Cosyntropin terone synthesis, it may not cause mineralocorticoid de- Cosyntropin (Cortrosyn) is a polypeptide that consists ficiency because of the compensatory increased produc- solely of the first 24 amino acids of corticotropin. Being a lipid-soluble substance, mitotane remains Side effects associated with the use of metyrapone in- stored in body tissues for extended periods. This may clude gastrointestinal distress, dizziness, headache, seda- account for the marked patient-to-patient variability in tion, and allergic rash. When administered primary adrenal carcinoma when surgery or radiation to pregnant women during the second or third tri- therapy is not feasible (see Chapter 56). Its effective- mesters, the drug may impair steroid biosynthesis in the ness in curtailing adrenal activity is due to an action on fetus. Because metyrapone is relatively nontoxic, it is adrenocortical mitochondria to impair cytochrome used in combination therapy with the more toxic amino- P450 steps in steroid biosynthesis. It is Aminoglutethimide (Cytadren) is a competitive in- advised to measure serum mitotane levels and urinary hibitor of desmolase, the enzyme that catalyzes the con- free cortisol excretion to ensure adequate therapeutic version of cholesterol to pregnenolone; it also inhibits concentrations. This drug also reduces estrogen terol by inhibiting cytochrome P450–mediated reac- production by inhibiting the aromatase enzyme com- tions and therefore contributes to the cardiovascular plex in peripheral (skin, muscle, fat) and steroid target events that are a significant cause of mortality in un- tissues. Such a medical adrenalectomy is an efficacious Mitotane, being closely related to the organochlo- treatment for metastatic breast and prostate cancer, rine insecticides, shares its inductive effects on the liver since it diminishes the levels of circulating sex hor- microsomal drug-metabolizing enzyme system, and its mones. Glucocorticoids are administered concomitantly use may therefore alter the requirement for concomi- to suppress enhanced corticotrophin release. Cortisol is tantly administered drugs that are also metabolized by preferable to dexamethasone in this situation because this pathway. Hepatic en- zyme induction may be responsible for the develop- Ketoconazole ment of tolerance to the side effects of aminoglu- tethimide, such as ataxia, lethargy, dizziness, and rashes. Since aminoglutethimide ther- the C17-20 lyase reaction involved in the formation of apy is frequently associated with mineralocorticoid de- sex steroids. Cholesterol Aminoglutethimide and metyrapone are frequently side-chain cleavage and 11 /18-hydroxylase are second- used in combination at lower doses of both drugs as an ary sites of inhibition. Because Mitotane (Lysodren) produces selective atrophy of the surgical treatment is not always well tolerated by eld- zona fasciculata and zona reticularis, which results in a erly patients, ketoconazole 200 to 1,000 mg/day can be a decrease in the secretion of 17-hydroxycorticosteroids. Direct inhibition of cholesterol side-chain cleavage and Common side effects include pruritus, liver dysfunction, 11 /18-hydroxylase activities has also been demon- and gastrointestinal symptoms. On the other hand, Moreover, more than half of patients relapse following the antiandrogenic effects of ketoconazole may prove cessation of therapy. Hypoadrenalism, nausea, and drowsiness have been reported during prolonged ad- Mifepristone is a progesterone receptor antagonist that ministration of mifepristone. This drug has recently been approved for Dexamethasone use in the United States for the treatment of hypercor- tisolism.

There are two forms of the estrogen receptor cheap 10 mg motilium visa gastritis cancer, blood levels of estrogen and progesterone order 10mg motilium amex can gastritis symptoms come go, together ER- and ER-, and two forms of the progesterone re- with FSH and LH, modulate the development of ova, ceptor, PR- and PR-. Gene activation is mediated cycle, estradiol blood levels rise slowly and then fall by the ability of steroid hormone receptor complexes to quite rapidly. Estradiol blood levels peak around mid- recruit nuclear coactivator proteins to the transcription cycle (days 12–14). Gene repression occurs in a ligand-dependent thought to be important in triggering a midcycle surge fashion by the recruitment of nuclear corepressor pro- of LH and FSH secretion. This latter effect is an fect on LH and FSH release, with high levels of estro- important mechanism of action of estrogen antagonism. This ligands proceeds through receptor phosphorylation suppression is mediated by inhibition of GnRH release events. The brief elevation of signaling pathways, ER and PR are activated by phos- the LH level stimulates production of the ovarian cor- phorylation events triggered by such diverse stimuli as pus luteum. The high levels of estradiol and the FSH epidermal growth factor, insulinlike growth factor, pro- surge at midcycle inhibit estradiol biosynthesis by the tein kinase A, and protein kinase C. As a consequence, during the An additional mode of estrogen and progesterone luteal phase, estrogen production is reduced and andro- action is classified as nongenomic effects. The menstrual cycle ends about 14 they are difficult to explain by transcriptional activa- days later with the regression of the corpus luteum and 706 VII DRUGS AFFECTING THE ENDOCRINE SYSTEM a concomitant fall in estrogen and progesterone pro- bleeding ensues. In the event that pregnancy occurs, human chorionic go- Growth and Development nadotropin secretion by the embryo maintains the cor- pus luteum through stimulation of progesterone and es- Estrogens cause the growth of the uterus, fallopian trogen synthesis. Stimulation of proliferation of the vaginal epithelium is checked by the cyclical exposure to progesterone during the luteal phase in the mature Control of Pregnancy female. Estrogens also are responsible for the expres- Ovulation sion of female secondary sex characteristics during pu- During the follicular phase of the menstrual cycle, one berty. FSH and tion of body hair, body contours as determined by estrogens are the most important hormones for this de- subcutaneous fat deposition, and skin texture. Complete follicular maturation development, estrogens stimulate proliferation of the cannot occur in the absence of LH. Progesterone me- follicle follows the midcycle peak of LH and FSH by diates lobuloalveolar development at the ends of these about 24 hours. During the luteal phase of the men- breast cell proliferation occur during the menstrual cy- strual cycle and under the influence of LH, the ovarian cle, with the highest levels of proliferation occurring granulosa cells of the corpus luteum become vacuolated during the luteal phase, when circulating levels of both and accumulate a yellow pigment called lutein. This has led to the idea that progesterone, as well as estrogens, exerts mi- totic effects in adult human breast tissue. The effects of Implantation estrogens and progesterone on breast development are The lining of the uterus, that is, the endometrium, is crit- most noticeable during puberty and pregnancy. The en- Estrogens can stimulate the release of growth hor- dometrium consists of a layer of epithelial cells overly- mone and exert a positive effect on nitrogen balance. Under the These effects contribute to the growth spurt during pu- influence of estrogen and progesterone, the endome- berty. Closure of the bone epiphyses signaling the end trium undergoes cyclical changes that prepare it for the of long bone growth is also estrogen mediated. Estrogens to high concentrations of progesterone and moderate maintain bone mass by inhibiting bone resorption by estradiol levels, the mitotic activity in the endometrial the osteoclasts. The action of progesterone on the tokines by peripheral blood cells and the osteoblasts endometrium converts it from a proliferative state to a that stimulate osteoclast activity. The epithelial cell structure assumes a women, declining estrogen levels give rise to a net in- more glandular appearance. Vascularization of the crease in osteoclast activity and loss of bone mass re- stroma increases, and some stromal cells begin to look sulting in the serious condition osteoporosis. Estriol is produced in high concentrations by Other Actions of Estrogens the placenta in pregnant women. The high levels of estrogens and progesterone associ- Under the influence of high levels of estrogen or pro- ated with pregnancy may alter liver function and glu- gesterone, the physicochemical composition of cervical cose metabolism. High circulating levels of estrogen can mucus may reduce sperm motility and provide a barrier cause mild glucose intolerance. Modifications at positions the formation of high-density lipoproteins and reducing C6 and C7 increase their progestational activity. Reductions in serum albumin Examples of these synthetic progestins include me- and antithrombin III synthesis can occur in the pres- droxyprogesterone and megestrol acetate (Megace). These compounds are metabolized in the same manner In males, estrogens stimulate the growth of the stro- as progesterone and are excreted in the urine.

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By explicitly recognizing cheap 10 mg motilium fast delivery gastritis water, managing order motilium 10mg without a prescription gastritis diet , and supporting this role, clinical entities can more effectively manage their limited resources to insure that consonant information is provided to clients that is more likely to result in positive healthcare outcomes. While often services like the CIS have been viewed as a competitor, it may be better to view it as a complementary/supportive service, especially for government driven healthcare systems. Copying or distributing in print or electronic forms without written permission of Idea Group Inc. While the CIS is organized to serve clients directly, it can also interface with clinical practice by providing referrals, enhancing health literacy, providing second opinions and crucial background, assur- ance to clients from neutral third party. Thus, the CIS is a partial answer to information explosion: for client it acts as synthesizer, translator who can relieve clinical settings of this task and through clients it directly acts to disseminate information to improve clinical practice. This chapter highlights how information providers can interface with clinical practice to form a strategic partnership that advances health outcomes for the public. All this suggests the increasing importance of information as a strategic asset that should be systematically incorporated in the planning of health professionals. Health institutions need to recognize the potential benefit of marketing unique corporate knowledge and expertise to other information seekers and to consider their unique role in a complex information seeking environment. Health professionals also need to lobby the govern- ment to maintain critical information infrastructures. While more and more information can be produced more efficiently, there is a concomitant increase in the costs of consuming (e. Conceptual confusions in knowledge management and knowledge management systems: Clarifications for better KMS development. Copying or distributing in print or electronic forms without written permission of Idea Group Inc. From two-step flow to the Internet: The changing array of sources for genetics information seeking. Journal of the American Society for Information Science and Technology, 55, 660- 669. Building the information-age organization: Structure, control, and information technologies. The knowing organization: How organizations use information to construct meaning, create knowledge, and make decisions. Treatment and clinical trials decision making: The impact of the Cancer Information Service, Part 5. Sense-making theory and practice: An overview of user interests in knowledge seeking and use. Social equity and information technologies: Moving toward infor- mation democracy. Health information and health reform: Understanding the need for a national health information system. Knowledge networks: Emerging knowledge work infrastructures to support innovation and knowledge management. How internet users decide what information to trust when they or their loved ones are sick. Copying or distributing in print or electronic forms without written permission of Idea Group Inc. The emergence, maintenance, and dissolution of structural hole brokerage within consortia. The Cancer Information Service Telephone Evaluation and Reporting System (CISTERS): A new tool for assessing quality assurance. The role of the physician data query on-line cancer system in health information dissemination. Paper presented to the annual convention of the Association for Education in Journalism and Mass Communication, Miami Beach, FL. Copying or distributing in print or electronic forms without written permission of Idea Group Inc. The first 15 years: What has been learned about the Cancer Information Service and the implications for the future.

The ultrasound waves bounce off the The electrocardiograph (ECG or EKG) is used to heart and are recorded as they return purchase motilium 10 mg fast delivery chronic gastritis gastroparesis, showing the heart record electrical changes produced as the heart muscle in action discount 10 mg motilium overnight delivery gastritis symptoms chest pain. In right heart catheteri- Heart specialists employ medical and surgical approaches zation, an extremely thin tube (catheter) is passed to the treatment of heart disease, often in combination. A fluoroscope (flu-OR- Medications o-scope), an instrument for examining deep structures One of the oldest drugs for heart treatment, and still the with x-rays, is used to show the route taken by the most important drug for many patients, is digitalis (dij-ih- catheter. Blood samples muscle contractions, is obtained from the leaf of the fox- 14 are obtained along the way for testing, and pressure glove, a plant originally found growing wild in many parts readings are taken. Slow calcium-channel blockers aid in the treatment Ventricular Atrial of coronary heart disease and hypertension by several repolarization depolarization mechanisms. They may be used to prevent clot formation in patients with damage to heart valves or S blood vessels or in patients who have had a myocardial in- mm time (sec) 0. Aspirin (AS-pir-in), chemically known as acetyl- Ventricular depolarization salicylic (a-SE-til-sal-ih-sil-ik) acid (ASA), is an inexpen- sive and time-tested drug for pain and inflammation that Figure 14-16 Normal ECG tracing. ZOOMING IN ✦ What is the length of A small daily dose of aspirin is recommended for patients the cardiac cycle shown in this diagram with angina pectoris, those who have suffered a myocardial 300 ✦ CHAPTER FOURTEEN infarction, and those who have undergone surgery to open anormal rhythm. The for people with bleeding disorders or gastric ulcers, be- restoration of a normal heartbeat either by electric shock cause aspirin irritates the lining of the stomach. In cases of severe tachy- If the SA node fails to generate a normal heartbeat or there cardia, tissue that is causing the disturbance can be de- is some failure in the cardiac conduction system, an elec- stroyed by surgery or catheterization. A dual chamber pacemaker has a lead in each machine siphons off the blood from the large vessels chamber to coordinate beats between the atrium and ven- entering the heart on the right side, so that no blood tricle. The effectiveness of Tip of lead this procedure diminishes over a pe- lodged in apex riod of years, however, owing to of right ventricle blockage of the replacement vessels. Less invasive surgical procedures Pacemaker placed include the technique of angioplasty beneath skin (AN-je-o-plas-te), which is used to in pectoral region open restricted arteries in the heart and other areas of the body. There, the THE HEART AND HEART DISEASE ✦ 301 Left subclavian artery Internal mammary Vein graft artery Anterior descending branch of the left coronary artery A B Figure 14-18 Coronary artery bypass graft (CABG) (A) This graft uses a segment of the saphenous vein to carry blood from the aorta to a part of the right coronary artery that is distal to the occlusion. Today, researchers are experi- ternal battery connected to it by a thin wire, the VAD pulls blood menting with a new completely self-contained artificial heart from the ventricle and pumps it to the aorta (in the case of a left that uses a wireless rechargeable external battery. If the experiments are successful, total a suitable donor heart could be found, but a permanent model artificial hearts may become a real alternative for patients who has recently been approved for use in the United States. This surgery is done Open stent in specialized centers and is available to some patients with degenerative heart disease who are otherwise in Figure 14-20 Intracoronary artery stent. Diseased valves may become so deformed and scarred Word Anatomy Word Anatomy Medical terms are built from standardized word parts (prefixes, roots, and suffixes). THE HEART AND HEART DISEASE ✦ 303 WORD PART MEANING EXAMPLE Function of the Heart sin/o sinus The sinoatrial node is in a space (sinus) in the wall of the right atrium. Pericardium—sac that encloses the heart (1)Stroke volume—amount pumped with each beat (1) Outer layer fibrous (2) Heart rate—number of beats per minute (2) Inner layers—parietal and visceral serous b. Special features of myocardium atrium (1) Lightly striated (2) Atrioventricular node—between atria and ven- (2) Intercalated disks tricles (3) Branching of fibers (3) Atrioventricular bundle (bundle of His)—at top c. Four chambers side of septum (1) Atria—left and right receiving chambers (ii) Purkinje fibers—branch through my- (2) Ventricles—left and right pumping cham- ocardium of ventricles bers c. Four valves—prevent backflow of blood (1) Autonomic nervous system (1) Right atrioventricular (AV) valve—tricuspid (i) Sympathetic system—speeds heart rate (2) Left atrioventricular valve—mitral or bicus- (ii) Parasympathetic system—slows heart rate pid through vagus nerve (3) Pulmonic (semilunar) valve—at entrance to (2) Others—hormones, ions, drugs pulmonary artery (3) Variations in heart rates (4) Aortic (semilunar) valve—at entrance to (i) Bradycardia—slower rate than normal; less aorta than 60 beats/minute 304 ✦ CHAPTER FOURTEEN (ii) Tachycardia—faster rate than normal; more E. Although whole blood does not leave the vessels, components of the plasma and tis- Pulmonary Pulmonary arterioles venules sue fluids can be exchanged through the walls of the tini- est vessels, the capillaries. Pulmonary Pulmonary The vascular system is easier to understand if you refer arteries veins to the appropriate illustrations in this chapter as the ves- sels are described. When this information is added to what Pulmonary you already know about the blood and the heart, a picture valve Left of the cardiovascular system as a whole will emerge. Right atrium ventricle Left AV Right AV valve ◗ Blood Vessels valve Left Right Blood vessels may be divided into five groups, named ventricle atrium below according to the sequence of blood flow from the Superior Aortic heart: and inferior valve venae cavae Aorta ◗ Arteries carry blood away from the heart and toward the tissues. The pulmonary vessels differ from those in the sys- They continue the transport of blood until it is returned temic circuit in that the pulmonary arteries carry blood to the heart that is low in oxygen, and the pulmonary veins carry blood that is high in oxygen. Figure 15-1 shows trients and oxygen to all the tissues and carry waste ma- the vessels in these two circuits; the anatomic relation of terials away from the tissues for disposal.

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