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An anteriorly placed collection of pus below the diaphragm can alternatively be drained via an incision placed below and parallel to the costal margin generic 400mg quibron-t with mastercard. Nowadays discount 400 mg quibron-t fast delivery, intra-abdominal fluid collections can often be drained percuta- neously under ultrasound or CT control buy quibron-t 400mg on line. The gastrointestinal tract The stomach The stomach is roughly J-shaped, although its size and shape vary consid- erably. It tends to be high and transverse in the obese short subject and to be elongated in the asthenic individual; even in the same person, its shape depends on whether it is full or empty, on the position of the body and on the phase of respiration. The stomach has two surfaces— the anterior and posterior; two curvatures — the greater and lesser; and two orifices — the cardia and pylorus (Fig. The stomach projects to the left, above the level of the cardia, to form the dome-like gastric fundus. Between the cardia and the pylorus lies the body of the stomach leading to a narrow portion, immediately preceding the pylorus, which is termed the pyloric antrum. The junction of the body with the pyloric antrum is marked by a distinct notch on the lesser curvature termed the incisura angularis. The junction of pylorus with duodenum is marked by a constriction externally and also by a constant vein (of Mayo) which crosses it at this level. The thickened pyloric sphincter is easily felt and surrounds the lumen of the pyloric canal. The pyloric sphincter is an anatomical structure as well as a physiological mechanism. The cardia, on the other hand, although compe- tent (gastric contents do not flow out of your mouth if you stand on your head), is not demarcated by a distinct anatomical sphincter. The exact nature of the cardiac sphincter action is still not fully understood, but the following mechanisms have been suggested, each supported by some experimental and clinical evidence. The gastrointestinal tract 71 1Mucosal folds at the oesophagogastric junction act as a valve. The lesser omentum is attached along the lesser curvature of the stomach, the greater omentum along the greater curvature. This extensive lymphatic drainage and the technical impossibility of its complete removal is one of the serious problems in dealing with stomach cancer. Involvement of the nodes along the splenic vessels can be dealt with by removing spleen, gastrosplenic and lienorenal ligaments and the body and tail of the pancreas. Lymph nodes among the gastro-epiploic vessels are removed by excising the greater omentum. However, involvement of the nodes around the aorta and the head of the pancreas may render the growth incurable. The anterior nerve lies close to the stomach wall but the posterior, and larger, nerve is at a little distance from it. The posterior vagus gives branches to both the anterior and posterior aspects of the body of the stomach but the bulk of the nerve forms the coeliac branch. This runs along the left gastric artery to the coeliac ganglion for distribution to the intestine, as far as the midtrans- verse colon, and the pancreas. The exact means by which the vagal fibres reach the stomach is of con- siderable practical importance to the surgeon. The gastric divisions of both the anterior and posterior vagi reach the stomach at the cardia and descend along the lesser curvature between the anterior and posterior peritoneal attachments of the lesser omentum (the anterior and posterior nerves of Latarjet). The stomach is innervated by terminal branches from the anterior and posterior gastric nerves and it is, therefore, possible to divide those branches which supply the acid-secreting body of the stomach yet preserv- ing the pyloric innervation (highly selective vagotomy, see below). When divided, in the operation of vagotomy, the neurogenic (reflex) gastric acid secretion is abolished but the stomach is, at the same time, rendered atonic so that it empties only with difficulty; because of this, total vagotomy must always be accompanied by some sort of drainage pro- cedure, either a pyloroplasty (to enlarge the pyloric exit and render the pyloric sphincter incompetent) or by a gastrojejunostomy (to drain the stomach into the proximal small intestine). Drainage can be avoided if the nerve of Latarjet is preserved, thus maintaining the innervation and function of the pyloric antrum (highly selective vagotomy).

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The drug is highly active in the treatment of chronic Cytarabine is rapidly metabolized in the liver generic quibron-t 400 mg, kid- lymphocytic leukemia cheap 400mg quibron-t overnight delivery, with approximately 40% of pa- ney purchase quibron-t 400mg with amex, intestinal mucosa, and red blood cells and has a tients achieving remissions after previous therapy with half-life in plasma of only 10 minutes after intravenous alkylating agents has failed. About 80% of a given contributes to fevers and infections in as many as half of dose is excreted in the urine within 24 hours, with less treated patients. When the drug is given by continuous infusion, doses, with agitation, confusion, and visual disturbances. Pentostatin Cytarabine is used in the chemotherapy of acute myelogenous leukemia, usually in combination with an Pentostatin (Nipent, deoxycoformycin) is a purine iso- anthracycline agent, thioguanine, or both. It is less use- lated from fermentation cultures of the microbe ful in acute lymphoblastic leukemia and the lymphomas Streptomyces antibioticus. It has volves inhibition of the enzyme adenosine deaminase, been used intrathecally in the treatment of meningeal which plays an important role in purine salvage path- leukemias and lymphomas as an alternative to meth- ways and DNA synthesis. Intrathecal administration occasionally pro- leukemia, producing remissions in 80 to 90% of patients duces arachnoiditis or more severe neurological toxicity. Fluorouracil (5-fluorouracil, 5-fluorouracil, Efudex, Cladribine Adrucil) is a halogenated pyrimidine analogue that must be activated metabolically. The active metabolite Cladribine (Leustatin) is a synthetic purine nucleoside that inhibits DNA synthesis is the deoxyribonucleotide that is converted to an active cytotoxic metabolite by 5-fluoro-2 deoxyuridine-S -phosphate (FdUMP). Like the other purine Fluorouracil is selectively toxic to proliferating rather antimetabolites, it is relatively selective for both normal than non-proliferating cells and is active in both the G - 1 and malignant lymphoid cells and kills resting as well as and S-phases. The target enzyme inhibited by 5-fluo- dividing cells by mechanisms that are not completely rouracilfluorouracil is thymidylate synthetase, which understood. Activity has Uridylate thymidylate also been noted in other low-grade lymphoid malignan- (dUMP) (dTMP) cies. The reduced folate cofactor occupies Cytarabine (cytosine arabinoside, ara-C, Cytosar-U)is an allosteric site on thymidylate synthetase, which al- an analogue of the pyrimidine nucleosides cytidine and lows for the covalent binding of 5-FdUMP to the active deoxycytidine. Another action proposed for 5-fluorouracil may in- Cytarabine kills cells in the S-phase of the cycle by com- volve the incorporation of the nucleotide 5-fluorouri- petitively inhibiting DNA polymerase. The cytotoxic 646 VI CHEMOTHERAPY role of these “fraudulent” 5-fluorouracil-containing the two drugs have similar pharmacological and toxico- RNAs is not well understood. Inter- to nucleotides, an increase in the pool of the normal calation results in steric hindrance, hence production of metabolite deoxyuridylic acid (dUMP), and an increase single-strand breaks in DNA and inhibition of DNA in the rate of catabolism of 5-fluorouracil. The en- The drug has been administered orally, but absorp- zyme topoisomerase II is thought to be involved in the tion by this route is erratic. Less than 20% of the parent though cytotoxicity also occurs in other phases of the compound is excreted into the urine, the rest being cell cycle. In addition to the intercalation mechanism de- 5-Fluorouracil is used in several combination regi- scribed, the anthracycline ring of doxorubicin can un- mens in the treatment of breast cancer. It also has pal- dergo a one-electron reduction to form free radicals liative activity in gastrointestinal adenocarcinomas, in- and participate in further electron transfer. These highly cluding those originating in the stomach, pancreas, liver, active substances can then react with tissue macromol- colon, and rectum. This type of interaction suggests an alternative mor effects have been reported include carcinomas of mechanism of cytotoxicity for the anthracyclines. This form of drug resistance is common among Floxuridine (FUDR) is the nucleoside of 5-fluo- the large, heterocyclic naturally derived anticancer rouracil that is readily converted into 5-fluorouracil in agents. It has similar pharmacological effects but is pre- high degree of cross-resistance among the anthracy- ferred to 5-fluorouracil for hepatic arterial infusions be- clines, vinca alkaloids, dactinomycin, and podophyllo- cause it is more extensively metabolized in the liver toxins (see Chapter 55). Doxorubicin is not absorbed orally, and because of The toxicities of 5-fluorouracil vary with the sched- its ability to cause tissue necrosis must not be injected ule and mode of administration.

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Up to 70% of an administered nary blood flow are the negative chronotropic and in- dose is excreted unchanged buy cheap quibron-t 400mg on-line. It is subject to hydrolysis by cytosolic es- blood pressure may also contribute to the reduced coro- terases in red blood cells to yield methanol and an acid nary blood flow cheap quibron-t 400 mg on-line. Only 2% of the administered esmolol is agents on coronary blood flow order quibron-t 400 mg visa, it seems paradoxical that excreted unchanged. Because of its rapid onset and these drugs are useful for the prophylactic treatment of 11 Adrenoceptor Antagonists 115 angina pectoris, a condition characterized by inade- pathetic nerve activity to maintain sufficient cardiac quate myocardial perfusion. The chief benefit of the - output, the -blockers have been shown to be quite use- blockers in this condition derives from their ability to ful in the long-term management of patients with mild decrease cardiac work and oxygen demand. For this purpose, it is best if oxygen demand may also be responsible for the favor- -blocker therapy is instituted soon after the MI and able effects of these agents in the long-term manage- continued for the long term. The release of renin from the juxtaglomerular cells of the kidney is believed to be regulated in part by - Hyperthyroidism receptors; most -blockers decrease renin release. The -blockers significantly reduce the peripheral man- While the drug-induced decrease in renin release may ifestations of hyperthyroidism, particularly elevated contribute to their hypotensive actions, it is probably heart rate, increased cardiac output, and muscle tremors. Nevertheless, - Although the -blockers can improve the clinical status blockers are useful and logical agents to use when treat- of the hyperthyroid patient, the patient remains bio- ing hypertension that is accompanied by high plasma chemically hyperthyroid. The -blockers should not be renin activity, although angiotensin converting enzyme used as the sole form of therapy in hyperthyroidism. They are most logically employed in the management of The glycogenolytic and lipolytic actions of endoge- hyperthyroid crisis, in the preoperative preparation for nous catecholamines are mediated by -receptors and thyroidectomy, and during the initial period of adminis- are subject to blockade by -blockers. Other physiological changes induced by hy- -Blockers can be used topically to reduce intraocular poglycemia, such as tachycardia, may be blunted by - pressure in patients with chronic open-angle glaucoma blockers. Timolol has a sponses to catecholamines are mediated by 2-receptors somewhat greater ocular hypotensive effect than do the and possibly by 3-receptors, 1-selective antagonists available cholinomimetic or adrenomimetic drugs. The such as metoprolol and atenolol may be better choices -blockers also are beneficial in the treatment of acute whenever -blocker therapy is indicated for a patient angle-closure glaucoma. Propranolol increases airway resistance by antago- Anxiety States nizing 2-receptor–mediated bronchodilation. Although the resulting bronchoconstriction is not a great concern Patients with anxiety have a variety of psychic and so- in patients with normal lung function, it can be quite se- matic symptoms. The -blocking agents may -Blockers can reduce intraocular pressure in glau- offer some benefit in the treatment of anxiety. The -blockers may offer some value in the prophylaxis of migraine headache, possibly because a blockade of Clinical Uses craniovascular -receptors results in reduced vasodila- tion. The painful phase of a migraine attack is believed The -receptor blocking agents have widespread and to be produced by vasodilation. Their uses in Adverse Effects and Contraindications these conditions are reviewed in Chapters 16, 17, and 20, respectively. Even though acute administration of The most prominent side effects associated with the ad- -blockers can precipitate congestive heart failure in ministration of the -blockers are those directly attrib- patients who are largely dependent on enhanced sym- utable to their ability to block -receptors. Although 116 II DRUGS AFFECTING THE AUTONOMIC NERVOUS SYSTEM -blockers prevent an increase in heart rate and cardiac Mechanism of Action output resulting from an activation of the autonomic Labetalol produces equilibrium-competitive antagonism nervous system, these effects may not be troublesome at -receptors but does not exhibit selectivity for 1- or in patients with adequate or marginal cardiac reserve. This intrinsic activity, or partial ago- impulses in the heart may be slowed by -blockers, pa- nism, especially at 2-receptors in the vasculature, has tients with conduction disturbances, particularly been suggested to contribute to the vasodilator effect through the atrioventricular node, should not be treated of the drug. Cardioselective -blockers The -blockade produced by labetalol is also of the have less propensity to aggravate bronchoconstriction equilibrium-competitive type. The use of -blockers in hypoglycemic patients is trinsic activity at -receptors, although this action is less therefore dangerous and must be undertaken with cau- than its intrinsic -receptor–stimulating effects. If -blocker therapy is required, a cardioselective Labetalol appears to produce relaxation of vascular -blocker is preferred. In addition, la- riod of greatest danger for asthmatics or insulin- betalol may produce vascular relaxation by a direct dependent diabetics is during the initial period of drug non–receptor-mediated effect. This action, plus its city does not occur during this period, further doses are slight intrinsic activity at -receptors, may account for less likely to cause problems.

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Procedure: While immobilizing the medial forefoot with one hand discount quibron-t 400 mg visa, the examiner grasps the distal portion of one proximal phalanx with the other hand and moves it posteriorly and plantarward relative to the metatarsal head discount 400mg quibron-t with mastercard. Assessment: Motion pain in the metatarsophalangeal joint accompa- nied by signs of instability suggests an increasing deformity of the toe leading to a functional claw toe deformity during weight bearing generic quibron-t 400 mg without a prescription. Pro- Buckup, Clinical Tests for the Musculoskeletal System © 2004 Thieme All rights reserved. In a dislocation of the metatarsophalangeal joint, it will be impossible to reduce the joint in the toe displacement test. The examiner immobilizes the lateral forefoot with the other hand, placing the thumb on its plantar aspect and the fingers on its posterior aspect. The examiner passively plantar flexes, dorsiflexes, and rotates the metatarsophalangeal joint. Assessment: In hallux rigidus, joint motion in every direction will be painful and, primarily in dorsiflexion, restricted. This will be accompa- nied by palpable or audible crepitation as a result of osteoarthritic changes in the joint. Procedure: The examiner immobilizes the metatarsal heads in one plane between the fingers of one hand on the plantar aspect of the foot and the thumb on the posterior aspect. The other hand grasps the toes in a pincer grip, applying medial and lateral compression to the forefoot via the metatarsal heads of the great toe and little toe. It will also often cause pain in a significant splay foot deformity where there is irritation of the joint capsule. Procedure: The patient is supine with the feet hanging over the edge of the examining table. The examiner slightly hyperextends the toes with one hand and taps the metatarsal heads or metatarsophalangeal joints with a reflex hammer held in the other hand. Assessment: In a patient with metatarsalgia due to chronic irritation of the metatarsophalangeal joints, tapping the ball of the foot will exac- erbate the metatarsalgia symptoms. Pain upon tapping that occurs between the metatarsal heads—primarily the third and fourth metatar- sals—with acute episodic pain radiating into the adjacent toes suggests a Morton neuroma (see Mulder click test). Buckup, Clinical Tests for the Musculoskeletal System © 2004 Thieme All rights reserved. Procedure: The patient is prone with the feet projecting past the edge of the examining table. The examiner grasps the calf of the affected leg with one hand and forcefully compresses the musculature. Assessment: Compressing the calf muscles should normally provoke rapid passive plantar flexion of the foot. The response to the compression test is not always unambiguous in patients with partial tears and will depend on the degree of disruption. In an Achilles tendon tear, the patient will be unable to stand on tiptoe, especially when standing only on the injured leg, and the Achilles tendon reflex will be absent. Note: The test can also be performed with the patient prone and the knee flexed 90°. Procedure: The patient is prone with the feet projecting over the edge of the examining table. Assessment: In a chronic Achilles tendon tear, tension in the Achilles tendon will be reduced and the affected foot can be dorsiflexed farther than the contralateral foot. Assessment: Increased pain and loss of plantar flexion (Achilles tendon reflex) are signs of a tear in the Achilles tendon. In the absence of an Achilles tendon reflex, a differential diagnosis should exclude neuro- logic changes.

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