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By J. Goose. Bard College.

Because acromegaly is characterized by sion of the genes for the and subunits of TSH in excessive GH secretion cheap kamagra oral jelly 100 mg visa, the administration of GH thyrotrophs generic kamagra oral jelly 100mg with visa, and decrease the secretion of TSH by thy- would be inappropriate. Thyroid hormones have no effect on ACTH counter the diabetogenic effects of excess GH, but it release. Galactorrhea is commonly associated thickening, or hypertrophy of the liver. Prolactin is thyroid hormone would stimulate GH release in a situ- important in maintaining breast milk production after ation of high GH. GHRH increases cAMP and stimu- APPENDIX A Answers to Review Questions 731 lates GH synthesis and secretion; somatostatin de- because of the protective actions of the thyroid hor- creases cAMP and inhibits GH synthesis and secretion mone-binding proteins. TRH stimulates TSH secretion the iodination of thyroglobulin to form MIT and DIT, and the synthesis of the and subunits of TSH by precursor molecules for T3. The high TSH rules out a defect in the Chapter 33 hypothalamic-pituitary axis and suggests an unrespon- sive thyroid gland, most likely a result of autoimmune 1. The presence of antibodies to thyroid colloid by the apical membrane of the follicular cell. The absence of a goiter rules out hypothy- somal vesicles to release thyroid hormones. T4 and T3 roidism as a result of iodine deficiency; low serum thy- are stored in thyroglobulin in the colloid, not in secre- roid hormone levels would result in elevated TSH with tory vesicles in the follicular cell. It has no growth of the thyroid in this patient because of the no effect on blood flow to the thyroid gland and no di- autoimmune attack on the gland. TSH stimulates an increase in cAMP, pling of two adjacent iodotyrosine residues in the thy- not an increase in the hydrolysis of this second mes- roglobulin precursor to form iodothyronine and dehy- senger. Thyroid hormones are important for peroxide produced by mitochondria to iodinate tyro- normal development of the CNS and for body growth. Thyroid peroxidase is localized to the apical hormones, as well as the growth of the thyroid gland. The release of thyroid hormone spond to TSH, thyroid hormone production would be is mediated by lysosomal degradation of thyroglobu- decreased, resulting in poor development of the CNS lin. TSH would also not be able to the thyroglobulin molecule to form MIT and DIT. De- stimulate the growth of the thyroid, resulting in a small hydroalanine is derived from the free-radical re- gland. Giving thyroid hormones to the child roid peroxidase forms the free radicals necessary for would improve body growth but not mental ability be- this reaction. Therefore, giving thyroid hor- itary would result in elevated thyroid hormone levels mones after birth would be too late. Graves’ disease is would remain smaller than normal because thyroid characterized by elevated thyroid hormone levels and hormones have no trophic effect on the gland; only anti-TSH receptor antibodies. Uncoupling proteins allow protons to to thyroid hormone action could result in elevated thy- flow down their electrochemical gradient across the roid hormone levels but would not cause symptoms of mitochondrial membrane, uncoupled from the synthe- thyrotoxicosis. The resulting energy generated is released result from a point mutation in the TSH receptor, re- as heat, and ATP is not synthesized. The novel increase thyroid hormones but should result in a re- uncoupling proteins are found in many tissues, includ- duction in TSH. Oxidation of fatty acids result in increased thyroid hormone levels and symp- and glucose is not coupled in mitochondria, and the toms of thyrotoxicosis, but would not be associated uncoupling proteins are not the switch between oxida- with elevated TSH. Uncoupling proteins have Hashimoto’s disease, symptoms of thyrotoxicosis may not been demonstrated to be essential to the mainte- be present, but the absence of antithyroid antibodies nance of body temperature in mammals. UCP-1 is important in the ability of small mammals, such as rodents, to tolerate cold temperatures. T3 is produced from T4by 5 -deiodi- nase (type 2) in the anterior pituitary. Cholesterol esters in LDL are the roid hormone product of the thyroid gland is T4. The most important source of cholesterol for sustaining ad- thyroid hormone receptor (TR) is located in the nu- renal steroidogenesis when it occurs at a high rate over cleus. This cholesterol can be used directly after The half-life of T3 in the bloodstream is about 1 day release from LDL and not stored. De novo synthesis of 732 APPENDICES cholesterol from acetate is a minor source of choles- 6. Cholesterol from the plasma mem- the cells of the zona glomerulosa that signals for al- brane or endoplasmic reticulum is not used for dosterone release. Cholesterol esters in lipid droplets signal for aldosterone synthesis and release. The rate of within adrenal cortical cells would be used first and de- aldosterone secretion would increase in response to an pleted during periods of high adrenal steroid hormone increase in renin release from the kidney. The increase in body weight with lit- giotensinogen to angiotensin II, which is a stimulus for tle linear growth suggests that the patient has Cush- aldosterone synthesis and release. A rise in serum ing’s disease rather than general obesity because linear potassium or renal sympathetic nerve activity, a fall in growth usually continues in obesity syndromes. Labo- blood pressure in the kidney, or a decrease in tubule ratory findings in Cushing’s disease include elevated fluid sodium concentration at the macula densa would ACTH, serum cortisol, urinary cortisol, and serum in- stimulate aldosterone synthesis and release. The first and rate-limiting step in all insulin action in skeletal muscle and adipose tissue). Congenital adrenal hyperplasia is the chain cleavage enzyme, resulting in pregnenolone and result of genetic defects that affect adrenal steroido- isocaproic acid.

More than a quarter century’s experience with California’s Medical Injury Compensation Reform Act (MICRA) statutes pro- vides ample evidence that reforms are well defined and effective purchase kamagra oral jelly 100mg online. In the absence of these reforms cheap kamagra oral jelly 100 mg without prescription, it is predictable that the current crisis will worsen and access to fundamental medical services will be increasingly imperiled. Key Words: Legal reform; tort reform; Medical Injury Compen- sation Reform Act (MICRA); premiums; frequency; severity; “bad” doctor; Harvard Medical Practice Study; Institute of Medi- cine; collateral source; periodic payments; caps; contingency fee; defensive medicine. Many physicians have been forced to curtail their practices, move to other venues, or even retire from the practice of medicine (2–5). The issue has been extensively discussed and debated in the medical and legal press, the media in general, a number of state legislatures, and nationally by both Congress and the president. This chapter reviews the nature and extent of the problem, the relevant attributes of medical malpractice insurance, and the evidence that legal reforms can ameliorate the problem. EXTENT OF THE PROBLEM The expansion of tort law into new arenas of potential liability grew throughout the 20th century, particularly the latter half. But until quite recently it was a backwater of the legal system, of little importance in the wider scheme of things. For all practical purposes, the omnipresent tort tax we pay today was conceived in the 1950s and set in place in the 1960s and 1970s by a new generation of lawyers and judges. In the space of twenty years they transformed the legal landscape, proclaiming sweeping new rights to sue. Some grew famous and more grew rich selling their services to enforce the rights that they themselves invented. But the revolution they made could never have taken place had it not had a component of idealism, as well. Tort law, it is widely and passionately believed, is a public- spirited undertaking designed for the protection of the ordinary con- sumer and worker, the hapless accident victim, the ‘little guy. No other country in the world administers anything remotely like it” (6). Peter Huber, author of a seminal treatise on the expansion of liability law, refers to the attendant costs as the tort tax: “It is one of the most ubiquitous taxes we pay, now levied on virtually everything we buy, sell and use. The tax accounts for 30 percent of the price of a stepladder and over 95 percent of the price of childhood vaccines. It is responsible for one-quarter of the price of a ride on a Long Island tour bus and one-third of the price of a small airplane. It will soon cost large municipalities as much as they spend on fire or sanitation services” (6). Chapter 15 / The Case for Legal Reform 203 Responding to the same issues, Philip Howard has referred to “the death of common sense” (7). He founded an organization named Com- mon Good, which is dedicated to reforming America’s legal system (http://cgood. Common Good has this to say about the expansion of medical liability and the provision of health care in the United States: “The lawsuit culture in modern America is creating a crisis in Ameri- can healthcare. The broad perception that anyone can sue for almost anything has fundamentally altered the practice of medicine, eroding the quality and availability of healthcare. Catherine Crier, lamenting the explosion in litigation wrote: “Trial work has become a major stand-alone business within the legal com- munity. What was once the place for good advice about the worthiness of a claim has become a gristmill for expanding rights and remedies. Tradi- tionally, lawyers were officers of the court who zealously represented clients within legal and ethical boundaries. The interests of justice were paramount, such that intentionally misleading a jury or using discovery simply to wear down an opponent or drain his pocketbook was degrading to the practitioner and unethical as well. Using court pleadings or the media as a litigation tactic to destroy an opponent was unacceptable. Attorneys now regularly solicit clients, conjure up cre- ative and nuisance filing, and delay the trial process, all to line their own pockets” (9). To get a sense of the magnitude of this phenomenon, it is interesting to note that if plaintiff attorneys were employed as members of a single corporation, it would have 50% more annual revenue than Microsoft and would be double the size of Coca-Cola (10). In general, the last decade of the 20th century was a period of rapid change and we, as a society, became accustomed to unprecedented numbers preceded by dollar signs. Mass tort litigation produces judgments of hundreds of billions of dol- lars and attorneys demand and receive billion-dollar fees. Twenty-two- 204 Anderson year-olds who worked very hard for 18 months could find themselves Internet billionaires, and ballplayers could command hundred-million dollar contracts. Thus, the expansion of theories of liability has coin- cided with a significant monetary desensitization of the public mind. Jury verdicts in virtually all areas of the law have reached new heights with each succeeding year (4,10). Medical Context It is not difficult to identify numerous factors affecting contempo- rary medical practice that have exacerbated medical malpractice liability within this broader cultural context. Although ideally it offered the potential of cost sav- ings, efficient medical practice patterns, and enhanced quality assess- ment and assurance, we have arrived at a place where virtually no major constituency is satisfied. Physicians and health care institutions are frustrated by reimbursement limitations, increased paperwork, and interruption of the traditional doctor–patient relationship. Patients decry access restrictions, reduced insurance coverage, and the need for frequent provider changes. Payors are unhappy with the resump- tion of significant increases in costs.

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Baltimore: glands contain mucous cells that secrete mucus and HCO3 University Park Press kamagra oral jelly 100mg with visa, 1982 buy generic kamagra oral jelly 100mg. The cardiac glands are located in a small area ad- jacent to the esophagus and are lined by mucus-producing columnar cells. The pyloric glands are located in a larger area adjacent to the duodenum. They contain cells similar to mu- cous neck cells but differ from cardiac and oxyntic glands in having many gastrin-producing cells called G cells. The oxyntic glands, the most abundant glands in the stomach, a) are found in the fundus and the corpus. The oxyntic glands contain parietal (oxyntic) cells, chief cells, mucous neck cells, and some endocrine cells (Fig. Surface mucous cells occupy the gastric pit (foveola); in the gland, most mucous cells are located in the neck region. The base of the oxyntic gland contains mostly chief cells, along with some parietal and endocrine cells. Mucous neck cells secrete mucus, parietal cells principally secrete hydrochloric acid (HCl) and intrinsic factor, and chief cells secrete pepsinogen. The structure of resting parietal cells is unique in that they have intracellular canaliculi as well as an abundance of mitochondria (Fig. This network consists of clefts and canals that are continuous with the lumen of the oxyn- tic gland. There is also an extensive smooth ER referred to as the tubulovesicular membranes. Hydrochloric acid is se- creted across the parietal cell microvillar membrane and FIGURE 27. In: Johnson entire surface of the gastric mucosa and the openings of the LR, Christensen J, Jackson MJ, et al. A, A nonsecret- the most striking difference is the abundance of long microvilli and ing parietal cell. The cytoplasm is filled with the paucity of the tubulovesicular system, making the mitochondria tubulovesicular membranes, and the intracellular canaliculi have be- appear more numerous. The H /K -ATPase is inhibited by characteristic of a surface mucous cell is the presence of nu- omeprazole. Omeprazole, an acid-activated prodrug that is merous mucus granules at its apex. The number of mucus converted in the stomach to the active drug, binds to two granules in storage varies depending on synthesis and se- cysteines on the ATPase, resulting in an irreversible inacti- cretion. Although the secreted H is often depicted as be- similar in appearance to surface mucous cells. Car- by the presence of zymogen granules in the apical region bonic acid (H2CO3) is formed from carbon dioxide (CO2) and an extensive ER. The zymogen granules contain and H2O in a reaction catalyzed by carbonic anhydrase. The Also present in the stomach are various neuroendocrine CO2 is provided by metabolic sources inside the cell and cells, such as G cells, located predominantly in the antrum. These cells produce the hormone gastrin, which stimulates For the H /K -ATPase to work, an adequate supply of acid secretion by the stomach. Although the mecha- trin secretion, a condition known as Zollinger-Ellison syn- nism is still unclear, there is an increase in K conductance drome, results in gastric hypersecretion and peptic ulceration. The H /K -ATPase recycles K ions back into the cell in exchange for H ions. This raises a question: How does the men through Cl channels, down an electrochemical gra- gastric mucosa protect itself from acidity? This is balanced by an equal amount of HCO3 3 layer covering the surface of the gastric mucosa. The blood coming from the ate trapped in the mucus gel layer neutralizes acid, pre- stomach during active acid secretion contains much venting damage to the mucosal cell surface. The os- motic gradient created by the HCl concentration in the gland lumen drives water passively into the lumen, thereby, Hydrochloric Acid Is Secreted by the Parietal Cells maintaining the iso-osmolality of the gastric secretion. The HCl present in the gastric lumen is secreted by the parietal cells of the corpus and fundus. The mechanism of Gastric Juice Contains Various Electrolytes HCl production is depicted in Figure 27. At a low se- etal cell actively pumps H out of the cell in exchange for cretion rate, gastric juice contains high concentrations of Na and Cl and low concentrations of K and H. When the rate of secretion increases, the concentration of Na Plasma Parietal cell Lumen decreases while that of H increases significantly. Also coupled with this increase in gastric secretion is an increase in Cl concentration. To understand the changes in elec- CO2 CO2 + H2O trolyte composition of gastric juice at different secretion Carbonic anhydrase + rates, it is important to remember that gastric juice is de- H H+ rived from the secretions of two major sources: parietal H2CO3 - ATP cells and nonparietal cells. Secretion from nonparietal cells HCO3 HCO - is probably constant; therefore, it is parietal secretion (HCl 3 ADP+Pi K+ secretion) that contributes mainly to the changes in elec- + + trolyte composition with higher secretion rates. Cl- - K K Cl - Cl- Cl Na+ Gastric Secretion Performs Digestive, Na+ ATP Protective, and Other Functions ADP+Pi + + Gastric juice contains several proteins: pepsinogens, K K pepsins, salivary amylase, gastric lipase, and intrinsic factor. The chief cells of the oxyntic glands release inactive The mechanism of HCl secretion by the pepsinogen. Pepsin also cat- CHAPTER 27 Gastrointestinal Secretion, Digestion, and Absorption 487 160 Cl- Vagal Gastric juice stimulation 140 H+ 120 ACh 2+ K+ 100 Ca Gastric hydrogen ion pump H+ 80 Gastrin cAMP Adenylyl 60 cyclase ATP 40 Histamine FIGURE 27. Chicago: Year 2 ceptors results in an increase in intracellular Ca concen- Book, 1977.

Cytoplasm is also contained in ob- lique indentations buy kamagra oral jelly 100mg on line, the Schmidt–Lanterman incisures (C cheap kamagra oral jelly 100mg visa, F6) (see also p. The mar- gins of the sheath cells define the node of Ranvier at which axon collaterals (E) may branch off or synapses may occur. Ultrastructure of the Myelin Sheath (G) The electron micrograph shows the axon enclosed by a plasma membrane, the ax- olemma; it is surrounded by a series of regu- larly spaced, concentric dark and light lines (period lines). The width of each lamella from one dark line to the next measures 120Å on average (1Å=0. As seen at higher magnification, the light lines are subdivided by a thin irregular Kahle, Color Atlas of Human Anatomy, Vol. Myelin Sheath 37 5 4 2 1 A Nerve fiber (according to von Möllendorff) 5 2 4 B Node of Ranvier, osmium stain (diagram) C Schmidt–Lanterman incisures 5 3 D Perikaryon of a Schwann cell E Axonal branching 5 4 6 4 1 F Internode (according to Cajal) 1 2 7 G Electron-microscopic views of the myelin sheath Kahle, Color Atlas of Human Anatomy, Vol. The groove deep- nates only one axon, an oligodendrocyte (B9) ens and its margins approach each other intheCNSmyelinatesseveralaxonsandwill and finally meet. In this way, a duplication later remain connected with several inter- of the cell membrane is formed, the mesaxon nodes via cytoplasmic bridges. The extent (A3), which wraps around the axon like a and shape of the cell becomes clear when spiral as the Schwann cell migrates around visualizing the internodes as being unfurled the encircled axon. The external mesaxon The term mesaxon is based on the term forms an external bulge (B10) starting from mesenterium, a thin duplication that is the cytoplasmic bridge. The myelin lamellae formed as a suspension band by the peri- terminate at the paranodal region (B11) toneum and encloses the intestine. As seen in the longitudi- ilar way, the Schwann cell forms a duplica- nal section, the innermost lamella termi- tion and envelops the axon. Like all plasma nates first and the outermost lamella covers membranes, the cell membrane of the the remaining endings, terminating directly Schwann cell consists of an outer and an at the node of Ranvier. At the ends of the inner dense layer of protein and a light lipid lamellae, the dense major period lines layer between them. Upon membrane du- widen into pockets filled with cytoplasm plication, the two outer protein layers come (B12). The axon of the central nerve fiber is into apposition first and fuse to form the in- completely exposed in the area of the node traperiod line (A4). There are no Schmidt–Lanter- membrane duplication becomes the five- man incisures in the CNS. With further encir- cling, the inner protein layers of the cell membrane make contact as well and fuse to form the dense major period line (A5). At the end of the process, the start of the duplica- tion lies inside the myelin sheath, the inter- nal mesaxon (AB6), while the end lies out- side, the external mesaxon (7 in A, B). Development of Unmyelinated Nerve Fibers (A) Unmyelinated nerve fibers (A8) are en- veloped by sheath cells, each of which en- circles several axons. The margins of the grooves may also form a membrane dupli- cation (mesaxon) but without fusion of the membrane layers. Myelin Sheath 39 4 6 7 1 3 5 2 8 A Development of the myelin sheath (according to Hamilton, Boyd and Mossman) 9 10 7 6 12 B Central nerve fiber, electron-microscopic diagram (according to Bunge) 11 C Oligodendrocyte with myelin lamellae (according to Bunge) Kahle, Color Atlas of Human Anatomy, Vol. This mode of conduction is much borders on a basal lamina (AB2), which en- faster and requires less energy than the con- velops the entire peripheral nerve fiber. The Schmidt–Lanterman The peripheral nerve fiber is surrounded by clefts (A4) are depicted in longitudinal sec- longitudinal collagenous connective-tissue tionascytoplasmiccrevicesofthemajorpe- fibrils; together with the basal membrane, riod lines. The struction, they appear as spirals in which nerve fibers are embedded in a loose con- the cytoplasm communicates between the nective tissue, the endoneurium (D8). At the node of Ranvier able number of nerve fibers is collected into (B5), the Schwann cell processes (AB6) slide bundles or fascicles (C10) by the perineurium over the paranodal region and over the axon (CD9) which consists mainly of circular (ABD7). The innermost layer of the per- dense envelope around the node of Ranvier. The perineural endothelial cells myelin sheaths in CNS and PNS are il- possess a basal membrane at their per- lustrated in B. They represent a barrier its myelin sheath, the distance between the between nerve and surrounding tissue, sim- nodes of Ranvier, and the conduction ilarly to the endothelial cells of cerebral velocity of a nerve fiber. The mechanical cumference of an axon, the thicker the en- strength of the peripheral nerve is based on closing myelin sheath and the longer the in- its content of circular elastic fibers. When myelinated nerve fibers are nerves of the limbs, the perineurium is rein- still growing (e. The epineurium limbs), the internodes are growing in (CD11) borders on the perineurium; its length. The longer the internodes, the faster inner layers form concentric lamellae as the conduction velocity of the fiber. They change into loose connective tinguish between myelinated, poorly myeli- tissue containing fat cells (D12), blood ves- nated, and unmyelinated nerve fibers, also sels, and lymph vessels. Conductionvelocity is the slowest in the unmyelinatedCfibers (up to 2m/s); we are dealing here with a con- tinuous spread of excitation. By contrast, conduction in myelinated nerves is salta- tory, that is, it takes place in jumps. The morphological basis of saltatory conduction is the alternation of myelinated internodes and unmyelinated nodes of Ranvier; the current inside the axon jumps from one Kahle, Color Atlas of Human Anatomy, Vol. Myelin Sheath and Endoneural Sheath of Peripheral Nerves 41 2 PNS 6 7 CNS 5 B Node of Ranvier of a peripheral nerve fiber (top half) and of a cen- tral nerve fiber (bottom half) (according to Bunge) 3 2 7 6 1 4 10 A Peripheral nerve fiber, electron-microscopic diagram (according to Schröder) 13 7 8 9 11 14 C Peripheral nerve, cross section 9 11 12 12 D Detail of C Kahle, Color Atlas of Human Anatomy, Vol. In the gray matter, they and covering tissue of the CNS and has all the accompany neurons (satellitecells) (B).

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