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Thus cheap indocin 75mg mastercard rheumatoid arthritis of spine, weak acids are usually excreted faster in alkaline urine; weak bases are usually excreted faster in acidic urine purchase indocin 25 mg visa arthritis in the knee teenager. Other body fluids in which pH differences from blood pH may cause trapping or reabsorption are the contents of the stomach and small intestine order discount indocin online rheumatoid arthritis labs, breast milk purchase 75mg indocin otc arthritis pain acetaminophen, aqueous humor, and vaginal and prostatic secretions. In the hypothetical case illustrated, the diffusible uncharged form of the drug has equilibrated across the membrane, but the total concentration (charged plus uncharged) in the urine (more than 10 mg) is 25 times higher than in the blood (0. The nitrogen of a neutral amine has three atoms associated with it plus a pair of unshared electrons (see the display that follows). The three atoms may consist of one carbon (designated “R”) and two hydrogens (a primary amine), two carbons and one hydrogen (a secondary amine), or three carbon atoms (a tertiary amine). However, the quaternary amine is permanently charged and has no unshared electrons with which to reversibly bind a proton. Therefore, primary, secondary, and tertiary amines may undergo reversible protonation and vary their lipid solubility with pH, but quaternary amines are always in the poorly lipid-soluble charged form. Many of the drugs within each group are very similar in pharmacodynamic actions and in their pharmacokinetic properties as well. For most groups, one or more prototype drugs can be identified that typify the most important characteristics of the group. This permits classification of other important drugs in the group as variants of the prototype, so that only the prototype must be learned in detail and, for the remaining drugs, only the differences from the prototype. Such discoveries are usually made in public sector institutions (universities and research institutes), and molecules that have beneficial effects on such targets are often discovered in the same laboratories. However, the development of new drugs usually takes place in industrial laboratories because optimization of a class of new drugs requires painstaking and expensive chemical, pharmacologic, and toxicologic research. In fact, much of the recent progress in the application of drugs to disease problems can be ascribed to the pharmaceutical industry including “big pharma,” the multibil-lion-dollar corporations that specialize in drug development and marketing. These companies are uniquely skilled in translating basic findings into commercially successful therapeutic breakthroughs. Such breakthroughs come at a price, however, and the escalating cost of drugs has become a significant contributor to the inflationary increase in the cost of health care. Development of new drugs is enormously expensive, but considerable controversy surrounds drug pricing. Critics claim that the costs of development and marketing are grossly inflated by marketing activities, advertising, and other promotional efforts, which may consume as much as 25% or more of a company’s budget. Finally, pricing schedules for many drugs vary dramatically from country to country and even within countries, where large organizations can negotiate favorable prices and small ones cannot. Some countries have already addressed these inequities, and it seems likely that all countries will have to do so during the next few decades. When a new drug molecule is synthesized or discovered, subsequent steps seek an understanding of the drug’s interactions with its biologic targets. Repeated application of this approach leads to compounds with increased efficacy, potency, and selectivity (Figure 1–6). In the United States, the safety and efficacy of drugs must be defined before marketing can be legally carried out. In addition to in vitro studies, relevant biologic effects, drug metabolism, pharmacokinetic profiles, and relative safety of the drug must be characterized in vivo in animals before human drug trials can be started. With regulatory approval, human testing may then go forward (usually in three phases) before the drug is considered for approval for general use. A fourth phase of data gathering and safety monitoring is becoming increasingly important and follows after approval for marketing. Once approved, the great majority of drugs become available for use by any appropriately licensed practitioner. Highly toxic drugs that are nevertheless considered valuable in lethal diseases may be approved for restricted use by practitioners who have undergone special training in their use and who maintain detailed records. Steps (1) and (2) are often carried out in academic research laboratories, but the costs of steps (3) and (4) usually ensure that industry carries them out. Once a new drug target or promising molecule has been identified, the process of moving from the basic science laboratory to the clinic begins. Drug Screening Drug screening involves a variety of assays at the molecular, cellular, organ system, and whole animal levels to define the pharma-cologic profile, ie, the activity and selectivity of the drug. For example, anti-infective drugs are tested against a variety of infectious organisms, some of which are resistant to standard agents; hypoglycemic drugs are tested for their ability to lower blood sugar, etc. The molecule is also studied for a broad array of other actions to determine the mechanism of action and selectivity of the drug. The selection of compounds for development is most efficiently conducted in animal models of human disease. Where good predictive preclinical models exist (eg, antibacterials, hypertension, or thrombotic disease), we generally have good or excellent drugs. Good drugs or breakthrough improvements are conspicuously lacking and slow for diseases for which preclinical models are poor or not yet available, eg, autism and Alzheimer’s disease. At the molecular level, the compound would be screened for activity on the target, for example, receptor binding affinity to cell membranes containing the homologous animal receptors (or if possible, on the cloned human receptors). Early studies would be done to predict effects that might later cause undesired drug metabolism or toxicologic complications. For example, studies on liver cytochrome P450 enzymes would be performed to determine whether the molecule of interest is likely to be a substrate or inhibitor of these enzymes or to interfere with the metabolism of other drugs. Effects on cell function determine whether the drug is an agonist, partial agonist, inverse agonist, or antagonist at relevant receptors. Isolated tissues would be used to characterize the pharmacologic activity and selectivity of the new compound in comparison with reference compounds. At each step in this process, the compound would have to meet specific performance and selectivity criteria to be carried further. Whole animal studies are generally necessary to determine the effect of the drug on organ systems and disease models. Cardiovascular and renal function studies of new drugs are generally first performed in normal animals. For a candidate antihypertensive drug, animals with hypertension would be treated to see whether blood pressure was lowered in a dose-related manner and to characterize other effects of the compound. Evidence would be collected on duration of action and efficacy after oral and parenteral administration. If the agent possessed useful activity, it would be further studied for possible adverse effects on other major organs, including the respiratory, gastrointestinal, endocrine, and central nervous systems. These studies might suggest the need for further chemical modification (compound optimization) to achieve more desirable pharmacokinetic or pharmacodynamic properties. For example, oral administration studies might show that the drug was poorly absorbed or rapidly metabolized in the liver; modification to improve bioavailability might be indicated. For drugs related to or having mechanisms of action similar to those known to cause physical or psychological dependence, abuse potential would also be studied. The desired result of this screening procedure (which may have to be repeated several times with congeners of the original molecule) is a lead compound, ie, a leading candidate for a successful new drug. A patent application would be filed for a novel compound (a composition of matter patent) that is efficacious, or for a new and nonobvious therapeutic use (a use patent) for a previously known chemical entity. Candidate drugs that survive the initial screening procedures must be carefully evaluated for potential risks before and during clinical testing.

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In the preceding sections of this chapter order indocin 25mg online arthritis in hips for dogs, ly manifested as hypotonia purchase indocin 75 mg overnight delivery rheumatoid arthritis ribbon color, (3) asthenia and in- findings concerning the main cerebellar circuitry creased fatiguability of the muscles quality 25mg indocin rheumatoid arthritis doterra, (4) a proposed were reported discount indocin 25 mg mastercard arthritis medication prescription. Excellent reviews are available and effect on the learning of motor skills (Marr 1969) should be consulted (Holmes 1939; Brown 1949; Dow and in motor adaptation (McCormick 1984; Ito 1989; and Moruzzi 1958; Dow 1969; Eccles et al. The vermal zone, related to fasti- stem anteriorly towards the posterior aspect of the gial nuclei, is responsible for the motor control of cerebellum: posture and locomotion, muscle tone, and equilibri- 1. The intermediate paravermal zone is related to basilar artery just before its superior terminal di- the emboliform and globose nuclei and is concerned vision into posterior cerebral arteries. The around the lateral aspect of the crus cerebri in the lateral zone is related to the dentate nucleus and is lateral wing of the ambient cistern. At its origin it concerned with initiation, planning, and timing as is situated beneath the oculomotor nerve. It is with two branches at the level of the inferior clear that the different parasagittal zones of the cere- colliculi posteriorly. These arteries vascularize bellum differ functionally with regard to their con- the superior aspect of the cerebellar hemispheres nections. Most cerebellar lesions are usually not restrict- ing rise to a labyrinthine branch, and ends at the ed to a discrete anatomic region and the results of flocculus. In its route through the cerebellopontine The Brainstem and Cerebellum 253 cistern, the artery courses along the cochleovesti- climbing fibers of the cerebellum: an experimental study bular and facial nerve roots, frequently visualized in the cat with an autoradiographic tracing method. Springer, New York Berlin Heidelberg Flechsig P (1905) Einige Bemerkungen über die Unter- suchungsmethoden der Grosshirnrinde, insbesondere des Menschen. J Brodal A (1981) Neurological anatomy in relation to clinical Neurophysiol 49:1285–1301 medicine, 3rd edn. J Comp Neurol Jansen J, Brodal A (1940) Experimental studies on the intrin- 140:241–254 sic fibers of the cerebellum. University of Min- Springer, Berlin Heidelberg New York nesota Press, Minneapolis, pp 164–174 Olszeweski J, Baxter C (1954) Cytoarchitecture of the human Kunzle H, Akert K (1977) Efferent connections of cortical brain stem. Lippincott, Philadelphia area 8 (frontal eye field) in Macaca fascicularis: a reinves- Parent A (1986). The cerebellar histology of the cerebellum: the human cerebellum, cer- contribution to higher function. J Physiol (Lond) d’un plan de référence céphalique en imagerie par 202:437–470 résonance magnétique: le plan chiasmato-commissural. J Testut L, Latarjet A (1948) Traité d’anatomie humaine, vol 2: Comp Neurol 330:130–146 Angiologie, système nerveux central, 9th edn. Brain Cogn 14:19–25 Optic Pathway and Striate Cortex 257 9 Optic Pathway and Striate Cortex I Introduction right and left side. However, Galen thought that the canals joined each other at the midline, taking the The visual pathways extend from anterior to posteri- aspect of an “X” before they separated immediately or as the optic nerves, chiasm, optic tracts and optic afterwards. He believed that this kind of exchange at radiations, terminating in the striate or visual cortex the level of the chiasm allowed the pneuma to go to on the medial aspect of the occipital lobes. Along this the opposite eyeball and double its strength if the orbitocranial route, the visual paths maintain a other eye was destroyed. Furthermore, Galen at- roughly axial and horizontal orientation from the tempted to justify the arrangement of the optic eyes to the calcarine fissure. This aim is essential because of the great lation of the scientific and philosophic heritage of an- sensitivity of the visual and the oculomotor systems tiquity. The objective is to achieve max- translations (liber de oculis translatus a Demetrio et imal contrast between the optic pathways and the liber de oculis Constantini africani). Diagnostic algorithms The first representation of the chiasm showing a applicable to specific regional pathology are pro- total crossing over of the optic nerves was in 1266, in posed with the respective clinical correlations. The figure also shows the hollow nerves, experiments on the nervous system of animals in which the visual spirit emanates from the brain. First representation of the chiasm showing a com- plete crossing-over of the optic nerve fibers, attributed to Khalifah (1266), and first realistic representation of the eyes and the anterior optic pathways, annotated in Arabic and in- cluding the chiasma that could be attributed to Ibn Al. A half a century before, Da Vinci, fol- sized that Arabic manuscripts of ophthalmology lowing the concept of total decussation of the optic books contain the oldest representations of the eye, nerves elaborated by the Arabs, was the first to de- the chiasm and the brain. Nonetheless, Arabic anatomy was first book devoted to the optic nerve and demon- not free of the traditional mistakes, such as the un- strated its thalamic origin from the lateral aspect of usually deep posterior chamber of the eye, the loca- the third ventricle (Fig. This had been already tion of the lens lying in the center of the eyeball or reported by Eustache, in 1551, but had not been the canal within the optic nerves. Being very poor, Eustache was unable to In the Renaissance era, the discovery of printing print the plates of his anatomical atlas, which were with moveable type greatly advanced the diffusion edited in 1617 by the physician Lancisi. In 1543, Vesali, (1514–1664) in Bel- a very long search, found this work 50 years after the gium, in the Fabrica, his first textbook of modern author’s death. He also suggested the Descartes (1596–1650), in France, still believed in existence of a cavity inside the optic nerves, except this mechanistic representation of vision, i. However, he persisted in be- optic nerves do not decussate at the level of the chi- lieving that there is no real crossing-over of the asm. Each nerve was thought to originate from a pre- nerves, but rather a simple juxtaposition at the chi- cise region of the lateral ventricle and follow a paral- 1234 Optic Pathway and Striate Cortex 259 Fig. Vesali (1543) shows the first exact reproduction of the inferior surface of the brain and the chiasm (Bibl. Varoli (1573) shows the optic nerves and the chiasm as well as a dissection of the optic radiations (Bibl. Museum National d’Histoire Naturelle, Paris) lel chiasmatic route before terminating in the retina and Vieussens (1641–1715) and showed, in his Traité in a precisely defined manner. Images were thus d’Anatomie et de Physiologie, devoted to the brain, a thought to be transmitted to the pineal gland, sepa- cut of the cerebral hemisphere passing through the rately for each eye, before they were memorized in- optic pathways. These speculations may be obtained presently on magnetic resonance imaging, considered as the preliminary steps in understand- shows the optic nerve junction, the optic tract, the ing regionalization of the retinal projections. He dem- From that time, anatomical knowledge of the vi- onstrated that the optic nerve is composed of fasci- sual pathways progressed quickly and continued cles of nervous fibers, instead of a hollow tube, during the nineteenth century. Willis also discov- later Gratiolet, in 1854, described the continuity of ered the tracts connecting the internal structures to the fibers of the visual tract projecting as terminal the cortex and recognized the existence of higher fibers to the vicinity of the calcarine fissure. The supe- Meynert demonstrated the role of the lateral genicu- rior and inferior colliculi were described as glands. Fi- of the optic tracts and their connections to the thala- nally, Flechsig (1896 1900) was the first to elaborate mi; he also dissected the temporal horns of the later- the time course of myelination in the fetus and al ventricle (Fig. Descartes (1664) established the first diagram con- cerning the brain projection of the retinal images (Bibl. Collins (1685) shows an excellent representation of the optic tracts and their connections to the optic thalami, as well as a dissection of the temporal horns of the lateral ventricles (Bibl. The op- The visual pathways develop from the rostral portion tic stalks contain a circular lumen which is continu- of the neural tube which contribute to form the ous with both cavities, the optic vesicles distally and prosencephalon and the posterior optic pathways in the prosencephalon proximally. A simultaneous in- higher mammals, and the mesencephalon, related to vagination of the lower aspect of the optic vesicles the visual sense in lower vertebrates and to the visuo- and stalks forms the fetal, or choroidal, fissure, motor systems in higher vertebrates including human which will allow penetration of the vascular meso- (Polyak 1957; Hamilton et al. A progressive narrowing, until closure of the Optic Pathway and Striate Cortex 261 choroidal fissure and leaving a small opening to the hyaloid artery, is completed at the 6 weeks stage. Soon after, at the 17 mm stage, the nerve fibers be- gin to grow from the ganglion cells of the retina and reach the optic stalk. Penetrating the stalk, the nerve fibers proceed proximally toward the brain, forming the future optic nerves.

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Strains with high-level resistance have caused hospital- associated outbreaks of staphylococcal infection and colonization order indocin 75 mg overnight delivery arthritis in dogs and walking. Although higher rates of resistance are encountered with intensive use of mupirocin order indocin line arthritis in back muscles, most staphylococcal isolates are still susceptible cheap 75 mg indocin fast delivery how to stop arthritis in fingers naturally. Mupirocin is indicated for topical treatment of minor skin infections order indocin canada rheumatoid arthritis diet in ayurveda, such as impetigo (see Chapter 61). Topical application over large infected areas, such as decubitus ulcers or open surgical wounds, is an important factor leading to emergence of mupirocin-resistant strains and is not recommended. Mupirocin temporarily eliminates S aureus nasal carriage by patients or health care workers, but results are mixed with respect to its ability to prevent subsequent staphylococcal infection. Owing to their significant toxicity with systemic administration (especially nephrotoxicity), polymyxins were, until recently, largely restricted to topical use. Emergence of strains of Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacteriaceae that are resistant to all other agents has renewed interest in polymyxins as parenteral agents for salvage therapy of infections caused by these organisms. Nitrofurantoin At therapeutic doses, nitrofurantoin is bactericidal for many gram-positive and gram-negative bacteria; however, P aeruginosa and many strains of Proteus are inherently resistant. Antibacterial activity appears to correlate with rapid intracellular conversion of nitrofurantoin to highly reactive intermediates by bacterial reductases. It is not known which of the multiple actions of nitrofurantoin is primarily responsible for its bactericidal activity. There is no cross-resistance between nitrofurantoin and other antimicrobial agents, and resistance emerges slowly. As resistance to trimethoprim-sulfamethoxazole and fluoroquinolones has become more common in Escherichia coli, nitrofurantoin has become an important alternative oral agent for treatment of uncomplicated urinary tract infection. In renal failure, urine levels are insufficient for antibacterial action, but high blood levels may cause toxicity. Nitrofurantoin is contraindicated in patients with significant renal insufficiency (creatinine clearance < 60 mL/min). Twenty-five percent is macrocrystalline nitrofurantoin, which has slower dissolution and absorption than nitrofurantoin monohydrate. The remaining 75% is nitrofurantoin monohydrate contained in a powder blend, which upon exposure to gastric and intestinal fluids forms a gel matrix that releases nitrofurantoin over time. A single daily dose of nitrofurantoin, 100 mg, can prevent recurrent urinary tract infections in some women. Neuropathies and hemolytic anemia occur in patients with glucose-6-phosphate dehydrogenase deficiency. Methenamine Mandelate & Methenamine Hippurate Methenamine mandelate is the salt of mandelic acid and methenamine and possesses properties of both of these urinary antiseptics. Mandelic acid or hippuric acid taken orally is excreted unchanged in the urine, in which these drugs are bactericidal for some gram-negative bacteria when pH is less than 5. Methenamine mandelate, 1 g four times daily, or methenamine hippurate, 1 g twice daily by mouth (children, 50 mg/kg/d or 30 mg/kg/d, respectively), is used only as a urinary antiseptic to suppress, not treat, urinary tract infection. Sulfonamides should not be given at the same time because they may form an insoluble compound with the formaldehyde released by methenamine. Persons taking methenamine mandelate may exhibit falsely elevated tests for catecholamine metabolites. Antiseptics are disinfecting chemical agents with sufficiently low toxicity for host cells that they can be used directly on skin, mucous membranes, or wounds. Sterilants kill both vegetative cells and spores when applied to materials for appropriate times and temperatures. Disinfection prevents infection by reducing the number of potentially infective organisms by killing, removing, or diluting them. Disinfection can be accomplished by application of chemical agents or use of physical agents such as ionizing radiation, dry or moist heat, or superheated steam (autoclave, 120°C) to kill microorganisms. Often a combination of agents is used, eg, water and moderate heat over time (pasteurization); ethylene oxide and moist heat (a sterilant); or addition of disinfectant to a detergent. Prevention of infection also can be achieved by washing, which dilutes the potentially infectious organism, or by establishing a barrier, eg, gloves, condom, or respirator, which prevents the pathogen from gaining entry to the host. Hand hygiene is probably the most important means of preventing transmission of infectious agents from person to person or from regions of high microbial load, eg, mouth, nose, or gut, to potential sites of infection. Skin disinfectants along with detergent and water are usually used preoperatively as a surgical scrub for surgeons’ hands. Evaluation of effectiveness of antiseptics, disinfectants, and sterilants, although seemingly simple in principle, is very complex. Factors in any evaluation include the intrinsic resistance of the microorganism, the number of microorganisms present, mixed populations of organisms, amount of organic material present (eg, blood, feces, tissue), concentration and stability of disinfectant or sterilant, time and temperature of exposure, pH, and hydration and binding of the agent to surfaces. Users of antiseptics, disinfectants, and sterilants need to consider their short-term and long-term toxicity because they may have general biocidal activity and may accumulate in the environment or in the body. Disinfectants and antiseptics may also become contaminated by resistant microorganisms—eg, spores, P aeruginosa, or Serratia marcescens—and actually transmit infection. Some of the chemical classes of antiseptics, disinfectants, and sterilants are described briefly in the text that follows. The reader is referred to the general references for descriptions of physical disinfection and sterilization methods. They are rapidly active, killing vegetative bacteria, Mycobacterium tuberculosis, and many fungi, and inactivating lipophilic viruses. They are not used as sterilants because they are not sporicidal, do not penetrate protein-containing organic material, and may not be active against hydrophilic viruses. Alcohol-based hand rubs are ineffective against spores of C difficile, and assiduous handwashing with soap and water is still required for decontamination after caring for a patient with infection from this organism. Therefore, instruments such as tonometers that have been disinfected in alcohol should be rinsed with sterile water, or the alcohol should be allowed to evaporate before they are used. It is active against vegetative bacteria and mycobacteria and has variable activity against fungi and viruses. It strongly adsorbs to bacterial membranes, causing leakage of small molecules and precipitation of cytoplasmic proteins. Chlorhexidine gluconate is slower in its action than alcohols, but, because of its persistence, it has residual activity when used repeatedly, producing bactericidal action equivalent to alcohols. It is most effective against gram-positive cocci and less active against gram-positive and gram- negative rods. However, anionic and nonionic agents in moisturizers, neutral soaps, and surfactants may neutralize its action. Chlorhexidine digluconate formulations of 4% concentration have slightly greater antibacterial activity than newer 2% formulations. The combination of chlorhexidine gluconate in 70% alcohol, available in some countries including the United States, is the preferred agent for skin antisepsis in many surgical and percutaneous procedures. The advantage of this combination over povidone-iodine may derive from its more rapid action after application, its retained activity after exposure to body fluids, and its persistent activity on the skin. Chlorhexidine must not be used during surgery on the middle ear because it causes sensorineural deafness. It is not commonly used because of serious hypersensitivity reactions that may occur and because of its staining of clothing and dressings. An iodophor solution must be diluted according to the manufacturer’s directions to obtain full activity.

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The opposing joint surfaces 50 mg indocin with visa vinegar arthritis pain relieve, on the undersurface of the lateral condyle of the tibia and on the superomedial surface of the head of the fbula discount indocin 50 mg with mastercard climacteric arthritis definition, are flat and circular buy discount indocin 25mg on-line juvenile arthritis diet. Fibular collateral ligament Popliteal fossa The popliteal fossa is an important area of transition between the thigh and leg and is the major route by which structures pass from one region to the other discount indocin 75mg what helps arthritis in back. The popliteal fossa is a diamond-shaped space behind the knee joint formed between muscles in the posterior Anterior ligament compartments of the thigh and leg (Fig. Semimembranosus muscle Biceps femoris muscle Posterior cutaneous (short head) nerve of thigh Femoral vein Adductor hiatus Popliteal Tibial nerve fossa Popliteal vein Plantaris Popliteal artery Common fibular nerve Popliteus muscle Small saphenous vein Posterior cutaneous Small saphenousvein nerve of thigh A B c 616 Fig. Regional anatomy • Thigh • The margins of the smaller lower part of the space are begins as the femoral artery passes posteriorly through the formed medially by the medial head of the gastrocne­ adductor hiatus in the adductor magnus muscle. It descends obliquely through the fossa knee joint and adjacent surfaces of the femur and tibia, with the tibial nerve and enters the posterior compart­ and, more inferiorly, by the popliteus muscle. The popliteal artery is the deepest of the neurovascular structures in the popliteal fossa and is therefore difcult to palpate; however, a pulse can usually be detected by deep Contents palpation near the midline. The major contents of the popliteal fossa are the popliteal In the popliteal fossa, the popliteal artery gives rise to artery, the popliteal vein, and the tibial and common fbular branches, which supply adjacent muscles, and to a series nerves (Fig. Tibial and common fbular nerves The popliteal vein is superfcial to and travels with the The tibial and common fbular nerves originate proximal popliteal artery. It exits the popliteal fossa superiorly to to the popliteal fossa as the two major branches of the become the femoral vein by passing through the adductor sciatic nerve. The most important structure • The tibial nerve descends vertically through the popli­ in the superfcial fascia is the small saphenous vein. This teal fossa and exits deep to the margin of the plantaris vessel ascends vertically in the superfcial fascia on the muscle to enter the posterior compartment of the leg. It ascends to the back of the knee where femoris tendon over the lower lateral margin of the pop­ it penetrates deep fascia, which forms the roof of the pop­ liteal fossa, and continues to the lateral side of the leg liteal fossa, and joins with the popliteal vein. The leg is that part of the lowerlimbbetween the knee joint The tibia is the weight-bearing bone of the leg and is and ankle joint (Fig. Above, it takes part in the formation of the knee joint and below it forms the • Proximally, most major structures pass between the medial malleolus and most of the bony surface for articula­ thigh and leg through or in relation to the popliteal fossa tion of the leg with the foot at the ankle joint. The leg is divided into anterior (extensor), posterior • Distally, structures pass between the leg and foot mainly (flexor), and lateral (fbular) compartments by: through the tarsal tunnel on the posteromedial side of the ankle, the exceptions being the anterior tibial artery • an interosseous membrane, which links adjacent and the ends of the deep and superfcial fbular nerves, borders of the tibia and fbula along most of their length; which enter the foot anterior to the ankle. It articulates superiorly with the inferior aspect of the lateral condyle of the proximal tibia, Muscles inthe anterior compartment ofthe leg dorsiflex but does not take part in formation of the knee joint. Muscles in distal end of the fbula is frmly anchored to the tibia by a the posterior compartment plantarflex the ankle, flex the toes, and invert the foot. Bones Interosseous membrane Shaft and distal end of tibia posterior Theshaf of the tibia is triangular in cross section and has intermuscular anterior, interosseous, and medial borders and medial, septa lateral, and posterior surfaces (Fig. In addition, a vertical line descends down the upper of leg part of the posterior surface from the midpoint of the soleal line. The distal end of the tibia is shaped like a rectangular box with a bony protuberance on the medial side (the Fig. The interosseous border of the fbula riorly and medially onto the posterior surface of the medial faces and is attached to the interosseous border of the tibia malleolus. Shaft and distal end of fbula The posterior surface is marked by a vertical crest The fbula is not involved in weight-bearing. The fbular (medial crest), which divides the posterior surface into shaft is therefore much narrower than the shaft of the two parts each attached to a different deep flexor muscle. Also, and except for the ends, the fbula is enclosed The distal end of the fbula expands to form the spade- by muscles. Here the tibia one at the top and the other at the bottom, for vessels to and fbula are joined together by the distal end of the inter­ pass between the anterior and posterior compartments osseous membrane. The posterior surface of the lateral malleolus is marked The distal ends of the fbula and tibia are held together by a shallow groove for the tendons of the fbularis longus by the inferior aspect of the interosseous membrane, which and fbularis brevis muscles. This expanded end of the interosseous membrane is reinforced Interosseous membrane of leg by anterior and posterior tibiofbular ligaments. This The interosseous membrane of the leg is a tough fbrous frm linking together of the distal ends of the tibia and sheet of connective tissue that spans the distance between fbula is essential to produce the skeletal framework for facing interosseous borders of the tibial and fbular shafts articulation with the foot at the ankle joint. Muscles in theposterior (flexor) compartment of theleg are In theupper leg, theheadsofthegastrocnemius combine organized into two groups, superfcial and deep, separated to form a single elongate muscle belly, which forms much by a layer of deep fascia. Generally, the muscles mainly of the soft tissue bulge identifed as the calf plantarfex and invert the foot and flex the toes. The superfcial group of muscles in the posterior compart­ The gastrocnemius plantarflexes the foot at the ankle ment of the leg comprises three muscles-the gastrocne­ joint and can also flex the leg at the knee joint. As a unit, these muscles Plantaris are large and powerful because they propel the body The plantaris has a small muscle belly proximally and a forward off the planted foot during walking and can elevate long thin tendon, which descends through the leg and the body upward onto the toes when standing. The muscle takes muscles (gastrocnemius and plantaris) originate on the origin superiorly from the lower part of the lateral supra­ distal end of the femur and can also flex the knee. Gastrocnemius The short spindle-shaped muscle body of the plantaris The gastrocnemius muscle is the most superfcial of the descends medially, deep to the lateral head of the gastroc­ muscles in the posterior compartment and is one of the nemius, and forms a thin tendon, which passes between largest muscles in the leg (Fig. It originates fom two the gastrocnemius and soleus muscles and eventually fuses heads, one lateral and one medial: with the medial side of the calcaneal tendon near its attachment to the calcaneus. The soleusmuscle, together withthe gastrocnemius and plantaris, plantarflexes the foot at the ankle joint. In the clinic Achilles tendon rupture Flexor longus Rupture of the Achilles tendon is ofen related to Origin of flexor sudden or direct trauma. Among these conditions are tendinopathy (due Medial Lateral to overuse, or to age-related degenerative changes) and previous Achilles tendon interventions such as injections of pharmaceuticals and the use of certain Groove on Groove on posterior antibiotics (quinolone group). The patient malleolus typically complains of "being kicked" or "shot" behind Groove on inferior the ankle, and clinical examination ofen reveals a gap surface of sustentaculum Tuberosity of in the tendon. It unlocks the extended knee at the initiation of fexion and stabilizes the knee by resisting lateral (external) rotation of the tibia on the femur. It is par­ is inserted into a broad triangular region above the soleal ticularly active during the toe-off phase of walking when line on the posterior surface of the tibia. It aspect of the knee and originates from a tendon, which can also contribute to plantarflexion of the foot at the penetrates the fbrous membrane of the joint capsule of the ankle joint and is innervated by the tibial nerve. The tendon ascends laterally around the joint where it passes between the lateral meniscus and the fbrous Flexor digitorum longus membrane and then into a groove on the inferolateral The flexor digitorum longus muscle originates on the aspect of the lateral femoral condyle. The tendon attaches medial side of the posterior compartment of the leg and to and originates from a depression at the anterior end of inserts into the lateral four digits of the foot {Fig. The popliteus muscle is forms a tendon, which crosses posterior to the tendon of innervated by the tibial nerve. The tendon continues inferiorly in a shallowgroove behind the Flexor hallucis longus medial malleolus and then swings forward to enter the sole The flexor hallucis longus muscle originates on the lateral of the foot. It crosses inferior to the tendon of the flexor side of the posterior compartment of the leg and inserts hallucis longus muscle to reach the medial side of the foot into the plantar surface of the great toe on the medial side and then divides into four tendons, which insert on the of the foot {Fig. The muscle fbers of the flexor hallucis longus converge It is involved with gripping the groundduring walking and inferiorly to form a large cord-like tendon, which passes propelling the body forward off the toes at the end of the behind the distal head of the tibia and then slips into a stance phase of gait. The tendon curves anteriorly Tibialis posterior frst under the talus and then under a shelf of bone (the The tibialis posterior muscle originates from the interosse­ sustentaculum tali), which projects medially from the cal­ ous membrane and the adjacent posterior surfaces of the caneus, and then continues anteriorly through the sole of tibia and fbula {Fig.