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It produces a net effect of glycogen breakdown by increasing intracel- lular cAMP levels quality 100mg doxycycline antibiotics for acne permanent, initiating a cascade of phosphorylation Acetyl-CoA α-Glycerol Lipoprotein phosphate events that ultimately results in the phosphorylation of phosphorylase b and its activation by conversion into Lipoprotein phosphorylase a order 100mg doxycycline with mastercard antimicrobial toilet seats. Similarly, glucagon promotes the net lipase Fatty acids breakdown of glycogen by promoting the inactivation of Fatty glycogen synthase (Fig. In addition to promot- ing hepatic glucose production by stimulating glycogenol- FIGURE 35. Insulin promotes the accumulation ysis, glucagon stimulates hepatic gluconeogenesis (Fig. It does this principally by increasing the transcrip- shown by the heavy arrows and inhibiting the processes shown tion of mRNA coding for the enzyme phosphoenolpyru- by the light arrows. Similar stimulatory and inhibitory effects oc- vate carboxykinase (PEPCK), a key rate-limiting enzyme in cur in liver cells. Glucagon also stimulates amino acid CHAPTER 35 The Endocrine Pancreas 629 Glucose Glycogen α-Glycerol phosphate Glycogen Glycogen synthase phosphorylase Triglycerides Glucose Glucose Glucose 6- phosphate Acetyl CoA Fatty Hormone- acids sensitive Ketogenesis lipase Ketones Glycerol LIVER CELL FIGURE 35. Heavy ar- rows indicate processes stimulated by glucagon; light arrows indi- cate processes inhibited by glucagon. Ketones Fatty acids transport into liver cells and the degradation of hepatic proteins, helping provide substrates for gluconeogenesis. The glucagon-enhanced The role of glucagon in lipolysis and keto- FIGURE 35. Glucagon assists in the disposal of processes stimulated by glucagon; light arrows indicate processes ammonia by increasing the activity of the urea cycle en- inhibited by glucagon. Ketones are an important Amino source of fuel for muscle cells and heart cells during times of acids starvation, sparing blood glucose for other tissues that are obligate glucose users, such as the central nervous system. During prolonged starvation, the brain adapts its metabolism to use ketones as a fuel source, lessening the overall need for hepatic glucose production (see Chapter 34). Protein synthesis Gluconeo- The Insulin-Glucagon Ratio Determines genesis Amino Metabolic Status Glucose Protein acids In most instances, insulin and glucagon produce opposing effects. Therefore, the net physiological response is deter- Ammonia Protein mined by the relative levels of both hormones in the blood degradation plasma, the insulin-glucagon ratio (I/G ratio). The I/G ratio Urea may vary 100-fold or more because the plasma concentra- tion of each hormone can vary considerably in different nu- tritional states. After an overnight fast, it may fall to about 2, and with prolonged fasting, it may fall to as low as 0. LIVER CELL The role of glucagon in gluconeogenesis Inappropriate I/G Ratios in Diabetes. Heavy arrows the profound influence of the I/G ratio on metabolic status indicate processes stimulated by glucagon; light arrow indicates is in insulin-deficient diabetes. The specific environmental factors have not been secretion of glucagon is inappropriately elevated. Because the primary defect in type 1 diabetes is the in- ability of beta cells to secrete adequate amounts of insulin, these patients must be treated with injections of insulin. In DIABETES MELLITUS an attempt to match insulin concentrations in the blood Diabetes mellitus is a disease of metabolic dysregulation— with the metabolic requirements of the individual, various most notably a dysregulation of glucose metabolism—ac- formulations of insulin with different durations of action companied by long-term vascular and neurological complica- have been developed. Diabetes has several clinical forms, each of which has a amount of these different insulin forms to match their di- distinct etiology, clinical presentation, and course. Diabetes is the most common endocrine dis- tients are advised to monitor their diet and level of physical order. Some 16 million people may have the disease in the activity, as well as their insulin dosage. Exercise per se, United States; the exact number is not known because many much like insulin, increases glucose uptake by muscle. Symptoms usually include frequent urination, increased thirst, increased food consumption, and weight loss. The Type 2 Diabetes Mellitus Primarily Originates standard criterion for a diagnosis of diabetes is an elevated in the Target Tissue plasma glucose level after an overnight fast on at least two Type 2 diabetes mellitus results primarily from impaired separate occasions. In some cases, it is a permanent, lifelong disorder; in causes, symptoms, and general medical outcomes are vari- others, it results from the secretion of counterregulatory able. Generally, the disease takes one of two forms, type 1 hormones in a normal (e.

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Pietka E purchase doxycycline 200 mg with mastercard bacteria quizlet, Gertych A discount 100 mg doxycycline fast delivery antibiotics for ethmoid sinus infection, Pospiecha Euro Kurkowska S et al (2004) Computer-assisted bone age assessment:graphical user inter- face for image processing and comparison, J Digit Imaging 17(3):175-188 a 8. Nelson DA, Kleerekoper M, Parfitt AM (1988) Bone mass, skin color and body size among black and white women. Jouanny P, Guillemin F, Kuntz C et al (1995) Environmental and genetic factors affecting bone mass. Krall EA, Dawson-Hughes B (1993) Heritable and life-style determinants of bone mineral density. Wynne AG, Van Heerden J, Carney JA, Fitzpatrick LA (1992) Parathyroid carcinoma: clinical and pathological features in 43 patients. Kaplan EL, Yoshiro Y, Salti G (1992) Primary hyperparathy- roidism in the 1990s. Consensus Development Conference Panel: Diagnosis and management of asymptomatic primary hyperparathyroidism: Consensus Development Conference Statement. Davies M (1992) Primary hyperparathyroidism: aggressive or conservative treatment? Davies M, Fraser WD, Hosking DJ (2002) The management of are reduced in density and in height and are biconcave. Clin Endocrinol 57:145-155 The bowing of the limbs causes affected individuals to be 19. Genant HK, Heck LL, Lanzl LH et al (1973) Primary hyper- parathyroidism: A comprehensive study of clinical, biochemi- short in height. There is often premature loss of dentition cal, and radiographic manifestations. Radiology 109:513-524 due to resorption of dentine, with replacement of the pulp 20. Am J Roentgenol 104:884-892 The radiographic features closely resemble those of 21. Genant HK, Baron JM, Strauss FH et al (1975) Osteosclerosis in primary hyperparathyroidism. Am J Med 59:104-113 Paget’s disease, but are diagnostic as they involve the 22. Skelet Radiol, whole skeleton and affect children from the age of 2 18:415-426 years. Wishart J, Horowitz M, Need A, Nordin BE (1990) 40 years, and skeletal involvement is either monostotic or Relationship between forearm and vertebral mineral density in asymmetrically polyostotic. On radionuclide scanning, postmenopausal women with primary hyperparathyroidism. Arch Intern Med 150:1329-1331 there is a generalized increase in uptake, giving a “super 24. Silverberg SJ, Gartenberg F, Jacobs TP et al (1995) Increased scan”, due to excessive osteoblastic activity, with absence bone density after parathyroidectomy in primary hyper- of evidence of renal uptake. Semin Dial 15(4)277- roidism: analysis of 52 cases, including report of new case. Gipstein RM, Coburn JW, Adams JA et al (1976) 28) Salvesen HA, Boe J (1953) Idiopathic hypoparathyroidism. Calciphylaxis in man: A syndrome of tissue necrosis and vas- Acta Endocinol 14:214-226 cular calcification in 11 patients with chronic renal failure. Ryan EA, Reiss E (1984) Oncogenous osteomalacia: Review Pseudohypoparathyroidism - An example of “Seabright- of the world literature of 42 cases. Curr Ther Endocrinol Metab 5:492-495 pseudohypoparathyroidism (PH) and pseudo-pseudohy- 56. Steendijk R, Hauspie RC (1992) The pattern of growth and poparathyroidism (PPH). Differentiation from other syn- growth retardation of patients with hypophosphataemic vita- dromes associated with short metacarpals, metatarsals and min D-resistant rickets: longitudinal study.

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Information and Choice Information about medical errors and provider responsibility com- prises a fourth important category of cutting-edge malpractice reforms safe doxycycline 100mg antimicrobial resistance definition. If patients had perfect information order doxycycline 100mg with mastercard virus living, they would only choose competent physicians with whom they could agree in advance on acceptable criteria for care and for payment. However, in economist Patricia Danzon’s words: “Just as imperfect information undermines the efficient functioning of the mar- ket, imperfect information undermines the efficient functioning of the liability system... Therefore, an alternative is to focus reform on improving information for both providers and patients and on leveling the playing field between them. Informational measures take two common forms: error disclosure requirements involving spe- cific patients, and publicly available information about malpractice judgments and settlements. As the Danzon quote suggests, greater transparency regarding medi- cal errors might eventually open private contractual alternatives to tort liability. The primary objection to private contracting has been that patients are poorly informed and are not in a position to weigh the risks when they are in need of medical care. Private contracting would allow parties to contract out of judicially mandated tort rules and might specify the circumstances for liability, the basis for damages, and the rules and forum for dispute resolution (63). Institutional liability can also be structured around private contracts (64), with managed care plans and patients sharing the savings from cost-reducing contractual change through lower premiums for health insurance. By the end of 2003, eight states had made information about indi- vidual physicians’ malpractice histories publicly available on the Internet. States vary as to whether they disclose claims, settlements, or judgments and as to whether liability insurers or physicians are prima- rily responsible for reporting this information to the government. As with physician “report cards,” the general principal idea behind Web- based malpractice information is to help consumers make better deci- sions about their care. Unfortunately, prior malpractice litigation is a poor indicator of physician quality except in extreme cases and can easily be misunderstood by patients. Physicians also may react per- versely to the threat of formal reporting because they foresee various unpleasant financial and reputational consequences. For example, the federal law that requires malpractice payments on behalf of physicians Chapter 17 / New Directions in Liability Reform 271 to be reported to the National Practitioner Data Bank has been widely evaded, has reduced physicians’ willingness to settle claims, and prob- ably should be abolished. On the other hand, a strong argument exists for prohibiting confidential settlements in high-dollar malpractice cases, particularly if confidentiality allows suboptimal safety practices to con- tinue. For example, the potential harm to patients from overworking young physicians in training came to light in the Libby Zion case (64a) in large part because the case was brought before a criminal grand jury that issued a public statement, rather than being settled out of view. In addition to helping consumers make better decisions about care as a private malpractice claim, information can improve system safety by focusing providers on improvement, support the personhood and dignity of victims and families, and foster public debate about the social risks and benefits of medicine (65). For example, trust and other indicators of interpersonal quality are integral to sound medical therapy (66,67) and can be jeopardized if health care providers vanish or become uncommunicative of an adverse event occurs. Therefore, information is an important form of compensation and justice for indi- viduals who have been harmed by medical errors. As discussed earlier, the search for explanations motivates many malpractice suits, and assigning blame where blame is warranted may be meaningful to patients and families (68). There is a trend toward requiring limited disclosure of medical errors and adverse events. The Joint Commission on the Accreditation of Healthcare Organizations somewhat tentatively requires that “Patients and, when appropriate, their families are informed about the outcomes of care, including unanticipated outcomes” (Standard R01. In Pennsylvania, com- prehensive malpractice reform legislation enacted in 2002 includes a provision stating that “A medical facility through an appropriate designee shall provide written notification to a patient affected by a serious event... Using mediation and other structured approaches to communication can help both providers and patients obtain maximum benefit from disclosure mandates (42). The greatest challenge for informational approaches to malpractice reform is the tension between disclosing 272 Sage information and producing information (69). Indeed, the breakthrough insight of the patient safety movement is that creating a “safe environ- ment” in which information can be shared and analyzed is central to improving complex professional processes. Accordingly, patient safety advocates have criticized the malpractice system for chilling information generation and exchange (70,71). Along these lines, it is eminently reasonable to strengthen peer review protections for safety- related information so that true “near misses” and internal analyses are immune from discovery and use in litigation. However, the line be- tween information that should be shared (at least with individual pa- tients) and information that should be reserved for professional quality improvement will never be easy to draw. Therefore, researchers should explore other ways to generate information about medical errors, in- cluding public subsidies (72).

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