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Potassium channels have a tetrameric structure in which four identical protein subunits associate to form a fourfold symmetric (C4) complex arranged around a central ion-conducting pore (a homotetramer) generic 100 mg aurogra with visa erectile dysfunction treatment in thailand. Alternatively buy aurogra visa erectile dysfunction pre diabetes, four related but not identical protein subunits may associate to form a heterotetramer with pseudo C4 symmetry discount aurogra 100 mg on line erectile dysfunction causes and solutions. All potassium-channel subunits have a distinctive pore-loop structure that lines the top of the pore and is responsible for potassium-selective permeability. Theα1 subunit forms the ion- conducting pore, while the associated subunits have several functions, including modulation of gating. It can manifest as an alteration in mental state, tonic or clonic movements and convulsions. The medical syndrome of recurrent, unprovoked seizures is termed epilepsy, but seizures can occur in people who do not have epilepsy. Such events are called strokes; they are the third most common cause of death in developed countries. Degenerative Although degenerative diseases generally affect mental capacity, some only affect motor capacity, for example Fiedreich’s ataxia and amy- otrophic lateral sclerosis. Demyelinating Multiple sclerosis (together with other idiopathic inflammatory demyelinating diseases) is an autoimmune and multifactorial disorder. Movement Parkinson’s disease is caused by the premature degeneration of the dopaminergic neurons of the substantia nigra. Huntington’s disease is known to be an inherited disorder with an autosomal dominance pattern. Dementias Dementias cause a loss of previously normal intellectual functions (in mental retardation such functions are not attained). Major causes of dementia are Alzheimer’s disease and multiple strokes or infarcts. Mental retardation Generally defined as a non-progressive intellectual deficit; frequently the result of processes that begin in utero. Metabolic Can include a variety of effects, but neurodegenerative disorders are pri- marily hereditary in nature (in-born errors of metabolism), for example lysosomal storage diseases. Fluoxetine is approved for the treatment of major depression (including pediatric depression), obsessive-compulsive disorder (in both adult and pediatric populations), bulimia nervosa, anorexia nervosa, panic disorder and premenstrual dysphoric disorder. Only one metabolite of fluoxetine, norfluoxetine (demethylated fluoxetine), is biologically active. These are metallo-proteases that enter nerve cells and block neurotransmitter release via zinc- dependent cleavage of protein components of the neuroexocytosis apparatus. Tetanus is characterised by a prolonged contraction of skeletal muscle fibres; the neu- rotoxin responsible is from Clostridium tetani. Here it attaches to gangliosides at the presynaptic inhibitory motor nerve endings and is taken up into the axon by endocytosis. The effect of the toxin is to block the release of inhibitory neurotransmitters (glycine and gamma-amino butyric acid), which are required to check the nervous impulse, leading to the generalised muscular spasms characteristic of tetanus. Botulinum toxin is produced by the bacterium Clostridium botulinum; it is the most toxic protein known. All known prion agents appear to propagate by transmitting a misfolded protein state; the protein itself does not self-replicate and the process is dependent on the presence of the normal polypeptide in the host organism. All known prions induce the formation of an amyloid fold, in which the protein polymerises into an aggregate consisting of tightly packed β-sheets. Amyloid is characterised by a cross-β-sheet-quaternary structure; the β-strands of the stacked β-sheets come from different protein monomers and align perpendicular to the axis of the fibril. The protein that prions are made of (referred to as PrPc) is normally found throughout the body. Several topological forms exist, including a membrane-bound form that is anchored by a glycolipid and two transmembrane forms. There is evidence that it might function in cell–cell adhesion of neural cells and/or be involved in cell–cell signalling in the brain. All prion diseases affect the structure of the brain or other neural tissue, and all are currently untreatable and always fatal. The reason for amyloid plaque (aggregates) association with such diseases is unclear. An emerging consensus implicates pre- fibrillar intermediates, rather than mature amyloid fibres, in causing cell death. Studies have also shown that amyloid deposition is associated with mitochondrial dysfunction, which can initiate a signalling pathway leading to apoptosis. Nicotinic receptors are made up of five subunits, arranged symmetrically around a central pore. Of these α2–7 and β2–4 have been cloned in humans; the remaining genes have been identified in chick and rat genomes. Agonists of acetylcholine include nicotine, epibatidine and choline (an agonist mimics the response of the normal ligand, an antagonist opposes the response), Figure 17. Agonist binding causes a conformational change resulting in channel opening (a pore of about 0. Opening of the channel allows positively charged ions to move across it; in particular, Na+ enters and K+ exits, with a net flow of positively charged ions inward. First, movement of cations through the channel causes a depolarisation of the plasma membrane (which results in an excitatory postsynaptic potential in neurons), as well as the activation H O N N+ O N acetylcholine nicotine Figure 17. Second, entry of Ca2+ through the channel may directly or indirectly initiate intracellular cascades, leading, for example, to gene regulation or release of neurotransmitters. Given that each nicotinic receptor is a pentamer, there is an immense potential of types, with highly variable kinetic, electrophysiological and phar- macological properties. The current consensus is that nicotine is the psychoactive drug primarily responsible for the addictive nature of tobacco use. Addiction is a complex behavioural phenomenon with causes and effects that range from molecular mechanisms to social interactions. Ultimately the process of drug addiction begins with molecular interactions which alter the activity and metabolism of the neurons that are sensitive to that drug. Over time this alters the properties of individual neurons and circuits, leading to complex behaviours such as dependence, tolerance, sensitisation and craving. Important functional properties of these receptors that contribute to their physiological effects include activation, desensitisation and up-regulation following nicotine exposure. There is considerable diversity in the sensitivity of different receptor subtypes to nicotine. In vitro experiments demonstrate that chronic exposure to nicotine can ‘desensitise’ these receptors, making them less sensitive to the natural neurotransmitter acetylcholine. It is thought that the up-regulation of binding sites might reflect an increased number of receptors that compensate for nicotine-induced desensitisation. Physiologically relevant nicotine concentrations have been shown to up-regulate α4-β2-containing receptors. Up-regulation of other receptor subtypes can occur with higher nicotine concentrations in some cells.

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The prevalence of post-stroke no initiative or decisions and little spontaneous Chapter 12: Behavioral neurology of stroke speech or actions generic 100mg aurogra visa erectile dysfunction levitra. Responses are either absent buy aurogra 100 mg mastercard erectile dysfunction treatment options exercise, Neglect is an inability to attend to purchase aurogra cheap impotence causes cures, orient or delayed or slow. A key feature is the dissociation explore the hemispace contralateral to a brain between impaired self-activation and preserved lesion, usually of the right hemisphere. Amnesia can result from thrombosis or response to other people, and lack of complaining. Relatives are more worried than the choroidal artery and anterior cerebral and anter- ior communicating arteries. Stroke in anatomical locations that interrupt Prefrontal lobe deficits: the cingulate-subcortical thalamo-striate loop can executive deficits (showing difficulty decid- produce apathy. These include anterior thalamic, ing, leaving decisions to proxy and being medial thalamic, caudate, inferior capsular genu, stubborn or rigid), corresponding to the bilateral palidal, uni- or bilateral anterior cerebral dorsolateral prefrontal lobe artery and baso-frontal strokes. Visual agnosias are disorders of visual recogni- survivors detected apathy in 20–40% of the patients tion (for classification see Table 12. Apathy was associated with one of the clinical manifestations of posterior cognitive impairment (defects in attention, concen- cerebral artery infarcts and occipito-temporal tration, working memory and reasoning) with deficits hemorrhages. Apathy was associated with Delirium often complicates acute stroke and is a right-sided lesions involving subcortical circuits, bad prognostic sign. Predictors are a vulnerable which comprised the ipsilateral frontal white matter, patient, the type of stroke and precipitating anterior capsule, basal ganglia and thalamus. Lesion: rostral brainstem and thal- Persistent personality changes (aggressive, disin- amic and partial occipital. Other reasons: hibited, paranoid, labile and apathetic) are frequent sensory deprivation or delirium or substance and for the caregiver one of the most annoying withdrawal. All stroke types are similarly prone to depression, but higher lesion volumes, cerebral atrophy, Chapter Summary silent infarcts and white matter lesions are asso- ciated with a higher risk. Persistent personality changes are most Aphasia occurs following middle cerebral artery annoying for caregivers of patients after stroke. Cardinal tests: (1) confrontation naming; (2) analysis of speech (fluent and nonfluent); (3) verbal auditory comprehension; (4) repetition of words, pseudo- words and sentences. Predictors of cognitive dysfunction after Study Group on Assessment of Unilateral Neglect subarachnoid hemorrhage. Posterior cerebral artery territory infarcts: clinical features, infarct topography, causes and outcome. Clinical, neuropsychological and electrophysiological findings in four anatomical 26. Aggressive behavior in patients with stroke: association with psychopathology and results of 45. Frequency of depression after stroke: a systematic review of observational studies. Stroke is the leading cause of physical not necessarily severe enough to induce dementia disability in adults: of one million inhabitants, 2400 when isolated). The term Even in stroke survivors who are independent, slight VaD cannot be used for all patients who have had cognitive or behavioral changes may have conse- a stroke and are demented, because many of them quences for familial and professional activities [5]. Therefore, the This chapter will not cover: (i) cognitive impair- economic burden of dementia is important. The prevalence of stroke and of ably of vascular origin that occur in the absence of dementia is likely to increase in the coming years, clinical symptoms of stroke or transient ischemic because of the decline in mortality after stroke [8] attacks. Therefore, our review will focus only on and the aging of Western populations [9]. Therefore, dementia that occurs – or was already present – in the burden of stroke-related dementia is also likely to patients who have had clinical symptoms of stroke. A study where stroke was not associated between stroke onset and cognitive assessment, and with an increased risk of dementia [30] was actually criteria used for the diagnosis of dementia [5, 12]. The incidence of dementia after stroke depends on whether the study excluded Stroke doubles the risk of dementia; the attribut- patients with pre-existing cognitive decline or demen- able risk is the highest within the first year after tia or not. In a community-based study of dementia after stroke conducted over a 25-year period, the cumulative inci- Determinants of post-stroke dementia that have been dence of dementia after stroke was 7% after 1 year, found in at least two independent studies, or have 10% after 3 years, 15% after 5 years, 23% after 10 years been identified recently, are listed in Table 13. In hospital-based studies, the incidence of dementia after stroke ranged from Demographic and medical 9% [23] to 16. In the Lille Stroke/ The most important demographic predictors of Dementia cohort after exclusion of patients who were dementia after stroke, in sufficiently powered studies, demented at month 6, only 6% of survivors developed are increasing age and low education level, but not really “new-onset” dementia after 3 years [25]. The risk of dementia after stroke is higher in patients who Incidence of dementia after stroke is 7% after 1 year, 10% after 3 years, 15% after 5 years, 23% were already dependent before stroke [5]. Relative risk of dementia after stroke Diabetes mellitus, atrial fibrillation and myocar- In the Rochester study, the relative risk of dementia dial infarction were also independent risk factors for (i. Arterial by the risk of dementia in stroke-free controls) was hypertension, a risk factor for vascular dementia 8. In the Epileptic seizures [33], sepsis, cardiac arrhythmias Framingham study, the results were similar 10 years and congestive heart failure are independently associ- after stroke, after adjustment for age, gender, educa- ated with an increased risk of dementia after stroke 195 tion level and exposure to individual risk factors for [5]. However, the statistical relationship found Section 3: Diagnostics and syndromes Table 13. The same study may appear several times if several assessments were performed at different time intervals after stroke. This table between these disorders and dementia does not mean includes only determinants of dementia after stroke that have a causal relationship: it is also possible that dementia been found in at least two independent studies or identified recently. A few determinants may not have been confirmed increases the risk of such events [5]. The influence of hyperlipidemia, hyperhomocys- References to the studies cited in this table and published teinemia, alcohol consumption and cigarette smoking before 30 April 2005 can be found in Leys et al. The Demographic and medical characteristics of the patient results concerning cigarette smoking should be inter- Demographic variables preted with caution, because smoking influences mor- tality and stroke recurrence. ApoE4 genotype is Increasing age associated with an increased risk of dementia after Low education level stroke [34]. Pre-stroke dependency Risk factors for dementia after stroke include Dependency increasing age, low education level, diabetes Pre-stroke cognitive decline mellitus, atrial fibrillation, myocardial infarction, epileptic seizures, sepsis, cardiac arrhythmias and Pre-stroke cognitivedecline without dementia[32,50] congestive heart failure. Vascular risk factors Diabetes mellitus Atrial fibrillation Pre-existing silent brain lesions Myocardial infarction in stroke patients ApoE4 genotype [34] Silent infarcts, i. Their Sepsis influence is more important when the follow-up is longer: in the Lille study, silent infarcts were associ- Cardiac arrhythmias ated with dementia after stroke at year 3 [25] but not Congestive heart failure at year 2 and in the Maastricht study silent infarcts Silent brain lesions were independently related to dementia after 12 Silent infarcts months, but not after 1 or 6 months [35]. Stroke patients with associated silent infarcts seem to have Global cerebral atrophy a steeper decline in cognitive function than those Medial temporal lobe atrophy [36] without, but this decline might be confined to those Leukoaraiosis with additional silent infarcts after base-line. Global cerebral atrophy is associated with a higher Stroke characteristics risk of dementia after stroke [5]. However, the question of their influence on Stroke characteristics, such as severity of the clinical deficit or stroke localization, influence the risk of the risk of post-stroke dementia has never been sys- dementia after stroke. The risk of dementia and its severity 10 years younger than in all other studies, and patients are not influenced by the type of stroke (ischemic or who were lost to follow-up at the 3-month evaluation hemorrhagic) [5]. However, differences in survival were more cognitively impaired at the acute stage, and rates between stroke subtypes make the results diffi- in the other [21] the diagnosis of VaD was based on the cult to interpret. In other studies, the risk tia after stroke: (i) in stroke patients who are too of dementia after stroke was lower in patients with young to have Alzheimer lesions, and became demen- small-vessel disease [5].

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Scaling the in vitro intrinsic clearance oxidatively metabolized cheap aurogra 100 mg online impotence causes, then liver microsomes will to hepatic Cl using the rat-validated method order aurogra 100mg online erectile dysfunction treatment high blood pressure, in be sufficient discount aurogra amex psychological erectile dysfunction wiki. However, if the potential for non- conjunction with allometric scaling of renal Cl, microsomal biotransformation exists, then a differ- resulted in a five-fold underprediction of total or ent in vitro system, such as hepatocyte suspensions, systemic clearance in vivo. In the illustration above, it turned olism studies in the dog in vivo revealed that out, as far as clearance of Compound X is con- Compound X undergoes significant additional bio- cerned, man is specifically like a rat, and unlike transformation, particularly N-methylation, which a dog. Oxidative metabol- detected by our initial microsomal studies because ism (seen in vivo and in microsomal enzymes), and there are no N-methyl transferases in microsomes. Had we used a single donor microsomal scaling tactics did eventually teach us about a new sample, rather than pooled liver microsomes (a pool clearance mechanism, and how important this consisting of at least eight individual donors), to was for the systemic clearance of Compound X in scale in vitro data to in vivo hepatic clearance, we the dog. For example, a lipophilic drug may penetrate lipo- philic organs such as brain, and, obviously, brain Elementary Aspects of Oral Bioavailability sampling simply for pharmacokinetic purposes is The oral bioavailability (F ) of a drug is dependent usually possible only in animals. The opposite effect would described as the fraction of the total oral dose for require the drug to be restricted to a fraction of the which systemic exposure is achieved. It is a meas- compartment that is sampled, essentially suggest- urement of extent of exposure, and contrasts with ing that too few compartments have been postu- the rates of absorption or elimination discussed lated, and is almost never encountered. Curry (1980) or Benet et al (1996) for expansion Clinically, F is found by comparing the systemic of these elementary aspects of volume of distribu- exposures that result after intravenous and oral tion. Note that this comparison need not be for doses of the same size (an import- Prediction of Human Volumes of Distribution ant consideration when the pharmaceutical phys- The free (not plasma protein-bound) volume of ician assesses the tolerability aspects of a proposed distribution of experimental drugs is generally con- normal volunteer study). These studies through the intestinal lining, Cl is the hepatic clear- are usually conducted under standard conditions, ance (predicted from in vitro studies, see earlier section) and Q is the hepatic blood flow in man and using crossover protocols, although, occasion- (see, for example, Rane etal. With very rare exceptions, the Fa and Caco-2 cell permeability, expressed as the intravenous administration of a dose is assumed to apparent permeability constant (Papp), as follows: be 100% bioavailable. However, assess- The use of Caco-2 cell permeability studies has ing the bioavailability of these drugs by any other resulted in more accurate oral bioavailability pre- route of administration is usually pointless, unless dictions. Allometric scaling is based on area and species body weight then allows for a similarities among species in their physiology, simple conversion of drug doses across species anatomy, and biochemistry, coupled with the ob- (Figure 10. With the assumption of 100% systemic can use data from a single species (the rat) to absorption, the expected plasma Cmax at this dose successfully predict the pharmacokinetics of Com- was 2000 ng/ml. This method could be cant reduction (greater than 30%) in cortical infarct expected to save time and money in the drug dis- volume, compared with saline controls, when the covery process by enabling us to: drug was given at the time of occlusion and at 0, 0. The selection of the wrong dose in expected to achieve a neuroprotective plasma con- an animal model, especially in a model in a centration of 1500 ng/ml. To do this, we predicted larger species such as cat, could lead to invalid the volume of distribution (V1cat) using data col- results, either through toxicity (if the dose is lected from the volume of distribution in rat (V1rat). The whole brain concentrations of this compound are in equi- By substituting back into the formula and using a librium with plasma concentrations within 5min cat weight of 4 kg, we found: after dosing, and it is also eliminated from the brain in equilibrium with the declining plasma con- V1cat ˆ 4:8 l or 1:21 l=kg: centration. We also know that Compound X is $80% orally bioavailable in rats and dogs (see Our formula for calculating the dose to be adminis- above), and has linear (first-order elimination) tered was: and predictable pharmacokinetics in animals. Next, this compound was tested in a model of Dosecat ˆ Doserat(V1cat=V1rat) excitotoxicity, in which the neurotoxin malonate was injected into the striatum of rats. A subcutane- The formula for predicting the plasma half-life was: ous injection of compound X at 9 mg/kg caused an yÀx 80% reduction in the lesion activity produced by T1=2cat ˆ T1=2rat Wcat=Wrat malonate. As 103 with the cat we made our predictions prospectively, by assuming, as stated earlier, that for the formula b 102 Y ˆ aW , the value of the power function b (or slope of the line from a log vs. We estimated the pharmacokinetic parameters for humans by substi- tuting the calculated intercept function back into again showing very good scaling between rat and the formula and solving for Y for a 70 kg human. Ideally, ing was the same in rats and in humans and that the allometric scaling should be done using pharmaco- metabolism of Compound X was similar in both kinetic data from at least four species, even though species. If possible, information about differ- The values estimated by allometric scaling were ences in metabolism among species should be con- compared with those observed in the single-dose sidered when making predictions. Brodie and colleagues had shown and equal to the ratio of observed maximal effect/ even earlier how complicated the relationships are maximal effect for an agonist with efficacy ˆ 1 (we when drugs with multicompartment distribution call these partial agonists or agonist±antagonists). Some agonists need occupy only a subset of the Lasagna and colleagues, using diuretics, found available receptors, in order to achieve Emax, and that depending on whether a cumulative effect these have efficacy greater than unity. Thus, the relationship tween observed concentration and effect size, as between effect size and concentration of drug in examples from a considerable volume of literature. Smolen 1971; The objectives of modern analysis of drug action Gibaldi and Perrier 1982, Dayneka et al 1993; are to delineate the chemical or physical interactions Levy 1993; Lesko and Williams 1994; Colburn between drug and target cell and to characterize the 1995; Derendorf and Hochhaus 1995; Gabrielsson fullsequence andscopeofactionsofeachdrug(Ross and Weiner 1997; Sharma and Jusko 1997). A more general form of the equation is tration range, the relationship between effect and the sigmoid curve: concentration is often observed to be curvilinear. This log-transformation of the concentration axis facili- where, by addition of a single parameter (n) to the tates a graphical estimation of the slope of the Emax model, it is possible to account for curves apparently linear segment of the curve: which are both shallower and steeper than when n ˆ 1 (i. Note E ˆ m Á ln(C C0) that the sigmoidicity parameter (n) does not neces- sarily have a direct biological interpretation and where m and C0 are the slope and the hypothetical should be viewed as an extension of the original baseline concentration (usually zero, but not for Emax model to account for curvature. An exponent less than unity (< 1) sometimes indicates active metabolites and/or mul- As mentioned earlier, for functional data based tiple receptor sites. These models make no al- There are various forms of this function for agonist lowance for time-dependent events in drug re- (stimulatory) and antagonist (inhibitory) effects. They developed a theoretical basis for able by the following expression after the intraven- À1 the performance of this analysis from data ous bolus dose, with C0 ˆ 45:0andK ˆ 0:50h : obtained from the observation of the time course of pharmacological response, after a single dose of À0:50t C ˆ 45:0e drug, by any route of administration. Considering such a model, assuming (a) first- example, a chain of biochemical events triggered by order input/output processes and (b) extravascular the presence of drug (e. The con- At equilibrium, C will be equal to Ce=Kp by defin- centration of drug in the effect compartment, Ce,is ition, and thus: obtained by dividing Ae by the effect compartment volume, Ve: ke0D  ÀKt Àk tà C ˆ e À e e0 e V1(ke0 À K ) kle D  ÀKt k tà C ˆ e À e e0 e Ve(ke0 À K ) This is how the link-model relates the kinetics in plasma to the kinetics of drug in the effect com- At equilibrium, the rates of drug transfer between partment. It can also be thought of in terms of the rate of presentation of a drug to a specific and the equation for the turnover of clotting factor tissue, determined by, for example, tissue perfusion [P] was: rate, apparent volume of the tissue, and eventual P Q diffusion into the tissue. This con- out often a delay between occurrence of maximum stant can be obtained experimentally from the slope drug concentration in the effect compartment and of a ln (P) vs. Setting the baseline value of clotting factor activity in the absence of warfarin (P0)toa fixed mean of three predose measurements, the pro- 140 gram can estimate that parameter. The use of intrinsic clearance in vitro permits predictions between species for the particu- As stated before, the intensity of a pharmaco- lar enzyme/route of metabolism concerned. Rather, it may be the net tabolism for any particular compound, then this result of several processes only one of which is will weaken the predictive value of the in vitro influenced by the drug. Similarly, allometric scaling works enced by the drug must be identified and an at- best for compounds with a high component of tempt made to relate plasma drug concentration to non-enzymatic elimination, such as our model changes in that process. This prediction weakens as vari- binemic) effect is an inhibition of the synthesis of ations in rates of enzymatic reactions become more certain vitamin K-dependent clotting factors. Unlike the flow chart of a computer pro- gram, after which the diagram is modeled, most of Prospectus the decisions are made in discussions among com- mittee members, and may not necessarily be based In the future, models will exist which will link on hard and fast criteria. Phase I study in humans, we have used the symbol In the shorter term, what can we now do to 1 to represent work that can be expedited by good expedite the drug selection process? The symbol 2 represents represents a flow chart illustrating one form of the tasks that can be expedited by on-line pharma- metabolism/pharmacokinetics input into the drug cokinetic modeling.

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Tibia Shaft Fractures • There are multiple classification systems used to identify tibial shaft fractures and their treatment aurogra 100mg mastercard erectile dysfunction treatment fort lauderdale. Johner and Wruhs report a system by Muller based on the mechanism of injury buy discount aurogra 100 mg line erectile dysfunction quad mix, comminution order aurogra 100mg mastercard erectile dysfunction in teenage, soft-tissue injury and displacement of the fracture. Proximal Fibula Fractures • Isolated uncomplicated fibula fractures can be treated with ice, elevation and analgesia. Complications • Tibia fractures, as mentioned previously, have a higher incidence of malunion, de- layed union and nonumion. Management Prehospital Care • Ankle injuries are commonly isolated injuries, but can be assosciated with multisys- 8 tem trauma. History • Understanding the mechanism and position of the ankle at the time of injury can help understand the fracture or sprain pattern. Physical Exam • Examination of the ankle must include the foot and proximal tibia and fibula. Orthopedic Emergencies 195 An ankle radiographic series is only required if there is any pain in malleolar zone and any of these findings: 1. A foot radiographic series is only required if there is any pain in midfoot zone and any of these findings: 1. Ottawa ankle rules for foot and ankle radiographic series in acute ankle in- jury patients (adapted from Stiell et al). Classification and Treatment Ankle Fracture • There are several classification systems for ankle fractures, however the Danis-Weber and the Lauge-Hansen are the most commonly used (Table 8. The two most commonly used classification systems for ankle fractures Lauge-Hansen Danis Weber Treatment Supination-adduction Type A: Fibula fracture below tibotalar joint Stage I: Transverse fracture A1: isolated Cast for 6-8 wk, of the lateral malleolus at level 3 wk nonweight- below joint or lateral collateral bearing, close ortho ligament tear. Pronation-abduction Stage I: Transverse fracture of medial malleolus or deltoid ligament rupture. Stage I: Transverse fracture of medial C1: Diaphyseal fracture malleolus or deltoid ligament rupture. Orthopedic Emergencies 197 • If there is associated tenderness over the deltoid ligament orthopedic consult is recom- mended. Ankle Sprains • As discussed previously, the ankle is supported by the syndesmotic, lateral, and medial ligaments. Tendon Rupture • Achilles tendon ruptures are commonly occur in middle-aged men during physical activity. If the movement is decreased when compared to the opposite or ankle, or absent, then an Achilles tendon rupture is present. Foot Anatomy and Function • The foot is comprised of the hindpart (seven tarsal bones including the calcaneus and the talus), the midfoot (navicular, cuboid, and three cuneiform bones), and the forepart (five metatarsals, two phalanges of the great toe, and three phalanges of each of the lateral four toes). Management Prehospital Care • Foot injuries are commonly isolated injuries, but can be associated with multisystem trauma. History • The history of a patient should include age, job, recent events, mechanics of the in- jury, nature of the pain, and functional loss. Radiographs • Three basic plain film views are indicated for foot injury—anateroposterior, lateral and obliques. Complications Talar Fractures • The talus can be divided into the head, body and neck. Nondisplaced fractures can be treated with a short-leg walking cast for 6 wk while displaced fractures require imme- diate reduction and emergent orthopedic consultation. Calcaneal Fractures • A twisting mechanism or a fall commonly results in calcaneal fractures. Midfoot Fractures • Nondisplaced navicular and cuboid fractures can be treated with immobilization in a short leg walking cast for 6 wk. Forefoot 8 • Displaced metatarsal fractures (>3 mm or 10 degrees angulation) require orthopedic consultation and open reduction. The Shoulder Girdle Anatomy and Function • The shoulder girdle is a complex structure comprised of the clavicle, the scapula and the humerus articulating at the glenohumeral, acromioclavicular and the sternoclav- icular joints. Orthopedic Emergencies 201 • The sternoclavicular joint is a fibrocartilagenous joint between the sternum and the clavicle. Sup- port is provided by the joint capsule, an articular disc, the sternoclavicular ligament and the costoclavicular ligament. The sternocalvicular joint is highly mobile and moves along with upper extremity motion; it is capable of elevation, forward and backward movement and rotation. The coracoclavicular ligament (extracapsular), the acro- mioclavicular ligament (intracapsular), the joint capsule and the intra-articular disc help stabilize the joint. Mangement Prehospital Care • Immobilization, ice and elevation are important prior to transport to the hospital. The axillary view may be difficult to obtain secondary to the patient’s injury and limited range of motion. Classification Treatment Disposition Complications Fractures • Clavicle—Clavicle fractures are common and can be classified by location of the frac- ture: medial, middle and lateral third. Open fractures, fractures resulting in skin tenting or neurovascular injury require immediate orthopedic consultation. Figure-of-eight splints and clavicular spica casts have been recommended for reduction of the clavicle. If fracture is displaced >20 mm, then orthopedic evaluation within 72 h is recommended. Proximal humeral fractures involve either the ana- tomic neck, the surgical neck, the greater tuberosity or the lesser tuberosity. Orthopedic Emergencies 203 • Nondisplaced fractures are those fracture fragments that are displaced <1 cm or angulated <45 degrees. Nondisplaced fractures can be treated by immobilization with sling and swathe, ice, rest and analgesia. The system de- scribes the fracture fragments by the number of parts, involvement of the articular surface and dislocation if present. Two-part, three-part, four-part fractures and those involving the articular surface (including fracture dis- locations) require immediate orthopedic consultation. Complications include adhesive capsulitis, avascular necrosis of the humeral head, myositis ossificans and neurovascular injuries. Dislocations/Separations • Glenohumeral Dislocation—There are four types of glenohumeral dislocations: ante- rior, posterior, inferior (luxatio erecta) and superior. Posterior dislocations are second most common; inferior and superior dislocations are rare. All dislocations require immediate neurovascular exam and radiographic studies to document the type of injury. Reduction is most successful when the patient has adequate analgesia and muscle relaxation.