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Therefore ethambutol 800 mg mastercard antibiotics joint replacement dental work, decisions must be made regarding the most effective combinations of factors for the neurons/neurological disorder in question order 800 mg ethambutol free shipping virus noro. The identification and characterization of each neurotrophic molecule has been followed by the establishment of transgenic (knock-out) mice that do not produce that factor or the associated receptor components to help unravel the physiological function of these molecules and to assess their contribution to the survival of dif- ferent neuronal types cheap ethambutol 800mg line antibiotic ladder. It should be pointed out purchase ethambutol 800mg antimicrobial treatment, however, that we do not know if neurotrophic gene defects in humans are associated with any aspect of neurologi- cal dysfunction. Extensive research has focused on the beneficial effects of delivering neu- rotrophic factors in the animal models of neurodegeneration and this research has set the foundation for a number of clinical trials (discussed later). The extent of the nervous system damage, the available concentration of neurotrophic factors, and the time at which the factor is released are key parameters in relation to the effective- ness of these molecules to rescue neurons from death. It should be realized that the precise roles of neurotrophic factors and their therapeutic potential in degenera- tion disorders remains to be elucidated. The in vivo method involves direct administration of the virus to the nervous system. For this approach, viral vectors are injected into specified locations of the brain or spinal cord. In the case of ex vivo gene transfer, new genes are first introduced into cells in a tissue culture environment, and then the cells are stereotaxically transplanted into desired regions of the nervous system. The types of viruses and cells that have been used for gene delivery in the nervous system are shown in Figure 9. Now, viral vectors and cells are used together and certain combinations show real promise and benefits over the gene and cell replace- ment procedures used just a few years ago. As each neurotrophic factor is identi- fied, cells are genetically modified to secrete the factor and then tested in animal models for effects on neuronal survival and animal behavior (Table 9. The purpose of this section is to provide some examples of the streams of gene therapy used in the animal models for the neurodegenerative disorders described in this chapter. To model Alzheimer’s, animals are used that show cholinergic neuron loss, the formation of neurofibrillary tangles plaques, or the generation of the amyloid pre- cursor protein. In mammals, transection of the fimbria-fornix pathway (connection between the hippocampus and medial septum) produces significant death (approx- imately 50%) of cholinergic neurons in the medial septum, paralleled by a loss of cholinergic inputs to the hippocampal formation. The possibility of supplying a neurotrophic factor to the brain via genetically engineered cells was first demonstrated by Fred Gage and co-workers in 1988. In addition to gene therapy with neurotrophic factors, strategies that use regula- tory proteins of cell death have been examined. Antiapoptotic factors like Bcl-xL is one of three isoforms of Bcl-x that protects cells from the damaging effect of re- active oxygen molecules. These antiapoptotic factors are being evaluated by gene therapy in animal models of neural degeneration (see section on programmed cell death and neurodegeneration). This treatment results in a loss of dopamine and causes a circling behavior in the animals when they are given a dopamine agonist (e. The circling tendencies can be reduced when the enzyme tyrosine hydroxylase (rate-limiting enzyme for dopamine production) is made available to neurons in the striatum. Initial ex vivo gene therapy experiments in consideration of Parkinson’s used cell lines of fibroblasts genetically modified in culture to express the gene for tyrosine hydroxylase. In this case, the function of the implanted fibroblasts was monitored by observing reductions in the circling behavior of the recipient host rats. It should also be pointed out that fibroblasts as well as other non-neuronal cell types do not make connections with the host brain circuitry but still produce strong functional effects when producing the transgene product. A primary drawback when using fibroblast cell lines has been the continued expan- sion of the fibroblast cell mass within the brain. To prevent tumor formation by these cell lines, the cells can be encapsulated by materials that allow for the exchange of the transgene product between the cells and the host tissue. Although we do not know why neurons that contain dopamine preferentially die in Parkinson’s, neurotrophic factors that enhance the survival and function of these dopamine neurons are the center of attention for gene therapy possibilities with the hope of preventing the death of these neurons. This molecule, discovered in the culture supernatants of a glial cell line by Leu-Fen Lin in the laboratory of Frank Collins in 1993 was shown to have potent effects on the survival of dopamine neurons. Host immune reactions to adenovirus and down-regulation of the viral promoters are common problems observed with adenoviral injections in the brain. Next generation Ad vectors will be designed to minimize the immune reac- tions and extend gene expression. It is a potent survival factor for motor neurons in the spinal cord and for Purkinje neurons in the cerebellum. Another technique to prevent neuronal degeneration has been to transplant support cells with fetal neurons. In this situation, referred to as a co-grafting strat- egy, the support cells assist with the survival of the transplanted neurons. The fibroblasts not only help to maintain the population of trans- planted neurons but also help to reduce the need for large numbers of fetal cells when dissected from embryonic brains. Monkeys given an injection of quinolinic acid show features of neurodegeneration that are character- istic of Huntington’s disease. It should be noted that the vectors are designed to eliminate viral gene expres- sion to avoid cytotoxic and immunological effects. The exclusion of these genes, however, often reduces the efficiency and length of transgene expression. There are intense efforts to develop gene regulatory elements that offer cell-specific (spatial) expression and/or drug-dependent (temporal) expression of the desired therapeutic gene. Potential transgene promoter/regulatory elements to guide neuronal expression include the light neurofilament subunit, a-tubulin, neuron-specific enolase, and tyrosine hydroxylase. Promoters for glial fibrillary acidic protein and myelin basic protein have been constructed to drive transgene expression in astrocytes and oligodendrocytes, respectively. A common inducible (temporal) transgene system uses tetracycline or tetracycline derivatives as con- trolled promoters. Neurons in the nervous system reside in a nondividing state and therefore potential virus vectors for gene therapy must be capable of infecting postmitotic cells. Lentiviruses (from the Latin word lentus meaning slow) cause slow chronic and progressive degenerative diseases of the nervous, hematopoietic, musculoskeletal, and immune systems. These viruses are the only retroviruses able to integrate into the chromo- somes of cells that are not mitotically active. The efficiency of gene transfer is high and reports indicate that lentiviral vectors injected into the adult rat brain stably transduce terminally differentiated cells in vivo, without a decrease in transgene expression or toxicity for at least 6 months in vivo. These genes and their products show homology throughout the animal kingdom from the nematode to the primates. The products of the Bcl-2 family of protooncogenes have been extensively characterized as proteins that regulate cell death. A possible ther- apeutic approach to preventing neuronal degeneration may be via the modula- tion of apoptosis by members of the Bcl-2 family, including bcl-xl and bax. In Alzheimer’s, levels of Bcl-2 protein are significantly higher than aged-matched adult brain, and this protein is predominantly localized to activated astrocytes rather than neurons. Thus, overex- pression of Bcl-2 may prevent the degeneration of motor neurons by inhibiting free radical mediated damage. Poor survival of grafted neurons has been a major issue in neural transplanta- tion. Attempts to increase the survival of grafted neurons have been made by expressing the Bcl-2 gene in cells before transplantation. This concept has been tested with a cell line generated from the substantia nigra. In the rodent fimbria-fornix lesion model of cholinergic neuron degeneration, neuroprotective effects have been demonstrated by the Bcl-xL gene.

The client should also the clinic and recommended emergency clinic cheap ethambutol 600mg on line antibiotics that cover mrsa, sam- bring previous medical records purchase ethambutol 400 mg with mastercard antibiotic resistance concept map, samples of the nor- ples of recommended avian foods and subscription mal diet and samples of any abnormal discharges buy ethambutol 800mg on line virus 68 colorado. Hospitalization Protocol Clients apprehensive about hospital- izing their birds may feel more at ease if they are introduced to the staff members who will be caring for the bird and shown where their bird will be housed buy cheap ethambutol 800 mg line bacteria nintendo 64. Additionally, birds being provided such as heat, light, music transported from one area of the hospital to another should be placed back in an enclosure and visibility of humans. Visitation to prevent accidental releases and injuries (right) (courtesy of Cathy Johnson-Delaney). This helps emphasize the clinic’s com- to its family and becomes depressed when separated mitment to personalized attention for each patient. On the other hand, if the The medical record system used in most small ani- bird has a contagious disease or is recovering from a mal clinics can be modified for avian patients. A serious injury or surgical procedure, the excitement problem-oriented checklist works well for avian and activity associated with a visit may be contrain- cases. In any case, clients should be encouraged to form should be included in the folder sent home with call during specified times to receive updates on the the client. Two copies Before a bird is discharged from the hospital, the should be made so that one remains in the clinic technician should instruct the client on how to ad- records and the other goes with the client. It is usually advisable that written small animal practices can be easily adapted for home care instructions, the hospital bill and the avian patients, including modifying reminder forms recheck appointment be discussed prior to reuniting to list avian procedures. Diagnostic software pack- the bird and the client to prevent the client from ages for the avian patient are under development. Another proven way to maintain a positive client A phone call the day after discharge allows the vet- relationship is by communicating with them through erinarian to evaluate the patient’s condition and the use of “Welcome to the practice” cards, sympathy gives the client an opportunity to ask questions. The survey should potential problems with diet and husbandry to daily be short and include multiple choice questions and assessment of a hospitalized bird’s condition, com- space for written comments regarding clinic facili- munication with the client is essential. If a bird must ties, staff, telephone courtesies, pricing and medical be hospitalized, the client should be given a written treatment. A return envelope will encourage client estimate of the medical plan and costs, and a hospital participation. Occasionally clients will request health certificates in order to transport birds between states or coun- Birds that are boarded at a veterinary clinic must be tries. Most airlines are now refusing to transport kept isolated (different air space with different care- wild-caught birds, and many domestic carriers are takers) from ill birds as well as from other boarding refusing to ship companion birds on the grounds that birds from different households. Clinics with limited it is difficult to differentiate between domestically space may board birds from a single household at one raised and imported birds. Establishing a bird-sitting service using clinic companion birds within the United States will spec- staff or outside individuals works well and decreases ify the type of carrier they will accept and the condi- the risk of exposing birds to infectious agents. If tions of release from liability that must be author- bird-sitters visit more than one household a day, they ized. According to aircraft manufacturers and airline must take precautions to prevent disease transfer engineers, temperature ranges in the cargo bins, between homes. Newer-generation jets (eg, 757s) generally have warmer temperatures in the cargo bins and therefore Accommodating the Avian are more comfortable for animals. Patient Carrier specifications for international shipment are set by the International Air Transport Association, and many airlines use these standards for domestic flights as well. It is advisable to be familiar with In order to transform a traditional small animal these carrier specifications and to contact the state clinic into an “avian friendly” clinic, a number of veterinarian regarding what is considered a properly modifications should be considered. Use of a “Certificate of Veterinary ception and exam room chairs should be of varnished, Inspection” to accompany the state regulatory form metallic or plastic finishes. An evaluation does not guaran- backs and seats of director’s-style chairs can be easily tee that a bird will remain healthy following trans- washed and disinfected and come in many colors and portation. If a client plans to take a bird traveling by car, it is Safety Considerations recommended that the bird first be given a full ex- amination to detect subtle problems that might The areas of the hospital where birds will be handled manifest during the stress of traveling. When possi- outside of their enclosures should be bird-proofed, ble, it is advantageous to place the bird in a familiar and appropriate nets for catching birds should be enclosure for travel. Ceiling fans are not recommended for be carried, as not all diets are available in all areas. Wall fans, radiators, baseboard Clients should also consider weather, potential haz- heaters, light fixtures and other electrical equipment ards (eg, animals, children) in homes or camp- must be shielded from direct contact. Open windows grounds where they will be staying, policies of hotels should be securely screened and be covered with and motels, and if the disruption in daily routine will blinds or draperies. For some birds, it is less may be viewed as perches by free-flying, frightened stressful to be left at home or boarded. The Equipment in the exam room, including a gram scale, staff member who feeds, cleans and interacts with an auxiliary light source, a magnifying head loop, the bird should not be the same person who provides speculums, towels or restraint cloths, oxygen, heat- “threatening” medical treatment. The bird is less ing pad, lamp and diagnostic and first-aid equipment likely to be defensive around a non-threatening per- should all be within easy reach. Furniture should be son, and a more accurate assessment of changes in minimal, including chairs for the clients, sufficient its daily condition can be made. Areas with minimal furniture are Preventing the Spread of Disease more secure and easier to keep clean. Many avian pathogens can be spread through aero- Housing sol and feather particulates, and an efficient ventila- tion system of laminar flow design will minimize Appropriate enclosures for avian patients must also hospital contamination. A separate avian housing area that of the room, it passes across the examination area can be maintained at 80-85°F is preferable, but not and is pulled outside by exhaust fans with vents essential. Birds may be housed in aquariums with placed approximately two feet above floor level in the screened covers, intensive care units or converted opposite wall from the fresh air vent. Aquariums are relatively systems (purifiers) designed to decrease particulates inexpensive and easy to clean and disinfect. Heating pads placed under or along one feathers, dust and contagions that would otherwise side of the aquarium can raise the interior ambient accumulate in the environment. Surgical drapes or clean ing a hospital, areas with separate air flow systems towels can be used to cover portions of the aquarium should be incorporated to allow for the separation of to retain additional heat and allow the bird a more patients that require routine care from those that private convalescent area. Hospital suites for hous- works well for small birds, a ten-gallon size for me- ing sick birds should be divided into small, easily dium-sized birds and a twenty-gallon size for larger cleaned areas that also have separate air flow systems. Commercial and custom-designed aquariums heated with warm water make excellent housing units for sick birds. Some hospitals use avian isolation units, complete with separate heat and ventilation. Existing small animal kennels can be converted by installing a removable perch and lining the enclosure with brown wrapping paper or butcher paper. Heating pads or clamp-lamps provide supplemental heat, and towels, plastic wrap, acrylic or plexiglass sheets can be placed over the front of the enclosure to retain heat (Figure 7. Enclosure doors should be removed, scrubbed and soaked in disinfectant after each bird. Plastic curtain rod holders are glued to the sides of the enclosure to hold removable perches. It should be frequently to prevent the accumulation of feathers, stressed that all disinfectants are toxic and must be dander and foodstuffs. Because vacuum cleaners, handled with care to prevent problems in hospital electric brooms and small portable cleaners tend to premises or patients. No disinfectant can work effec- scatter viruses into the air, it is advisable to spray the tively in the presence of organic material (see Chap- bags prior to, during and after use with a disinfec- ter 2). In vacuums that do not use bags, the intake perches and other enclosure accessories should be pieces, brush attachment and collection chambers free of food and excrement prior to being soaked for must be disinfected thoroughly after each use.

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There would be time enough to trigger vestibu- lospinal responses in leg muscles; a vestibular afferent volley would result ethambutol 800mg line antibiotics and sun, which would elicit vestibulospinal responses in leg muscles (41) 600mg ethambutol mastercard antibiotic resistance process. Actually generic ethambutol 800mg amex antibiotic resistance and infection control journal, in patients with complete bilateral vestibular deficit the responses in the tibialis anterior muscle during toe-up rotation of the supporting platform still occur albeit at a reduced amplitude (40) purchase ethambutol 600mg without a prescription infection you get from the hospital. That means that vestibu- lospinal input is important for modulating the amplitude of but not trig- gering postural responses. These findings suggest that posture is organised with respect to a ‘body schema’, to the construction of which neck input contributes to- gether with signals from vestibular, eye and limb muscles. Most likely, the posterior parietal cortex contributes to the egocentric representation of space, since many of its areas receive signals from neck muscles and from the labyrinth (42). Therefore, it seems that postural corrections do not depend strictly on stretch reflexes evoked by lengthening of ankle muscles. Neverthe- less, proprioceptive input from leg muscles does play a major role in pro- viding important information for the postural control system. Minimal ankle stiffness is required to stand, and reflexes driven by muscle afferents significantly contribute to balance-related ankle stiffness regulation (45). Visual, vestibular and lower limb sensorimotor reflexes each contribute to ankle stiffness; however, the local proprioceptive reflexes alone are suffi- cient to stand under certain circumstances (46). The contribution of the afferent input from muscle spindle to the regulation of postural body ori- entation in standing subjects has been assessed by the use of mechanical vibration, which almost selectively induces a train of action potentials in the primary endings connected to the large-diameter group Ia afferent fibers, i. Depending on the site of vibration, the body changes its inclination in a reproducible way (Fig. As for leg muscle, vibratory stimulation has been used to test the integration of neck af- ferent input into the postural control scheme. Contrary to leg muscle, vibra- tion of either lateral or dorsal neck re- gion induces a prominent body sway in the direction opposite to the stimulated site (50). Effects of vibration of ent fibres in balance control has been Achilles tendon or dorsal neck muscles on suggested from results obtained in body inclination with respect to gravity. Several studies suggest, how- ever, that during quiet standing a subject does not only rely on a continu- ous feedback to control balance. On the contrary, the subject initially utilises open-loop control where there is no feedback to control balance (53). After approximately one second, open-loop control changes to closed-loop control, and the subject then relies on continuous feedback to maintain balance. Improved parametrisation techniques for the extrac- tion of stochastic parameters from stabilograms have been proposed (54). Postural reactions to body displacements can be easily induced by surface translation: they are triggered at about 100 ms by somatosensory signals, are direction-specific and show a distal to proximal sequence of muscle activation (55) named ‘ankle strategy’. The different peripheral and central organisation of the two responses was suggested by several evidences summarised in a series of papers from our laboratory (56, 57, 58, 59, 60). Postural responses can be affected by changes of posture and repetition of perturbation. Functional habituation of postural reflexes induced by toe-up rotations of a supporting platform con- sists of a rapid attenuation of postural responses in the triceps surae muscle between the first and second perturbation as early as the second repetition, followed by slower habituation across the ensuing trials (65). A major role of proprioceptive input in triggering balance corrections has been recently questioned (see 69 for a review). It has been suggested that postural and gait movements are centrally organised at two levels. The first one involves the generation of the basic directionally-specific re- sponse pattern based primarily on hip or trunk proprioceptive input and secondarily on vestibular inputs. The second level is involved in the shaping of centrally-set activation patterns on the basis of multi-sensorial afferent input (includ- ing proprioceptive input from all body segments and vestibular sensors) in order that movements can adapt to different task conditions. Movement-induced perturbations During a voluntary movement performed under upright stance, movement itself is destabilising. In the parallel mode of control of pos- turo-kinetic coordination, an almost symultaneous contraction of the pos- tural and focal muscles is obtained. It is hypothesised that nervous path- ways to control voluntary movement would affect activity of postural muscles through collateral pathways. This type of coordination is observed when a subject performs rapid voluntary upper limb movement. A potential loss of balance follow- ing the movement is prevented by postural muscle activity prior to the on- set of focal muscle activity (70). It has been proposed a model according to which the precise coordination between posture and movement have the follow- ing basic requirements (73): the coupling of postural muscles, the amount of support or the instability prior to the task, and the correct coupling be- tween the postural and focal muscle activity. Posture and cognition It has been suggested that maintaining postural stability does require some degree of attention (80, 81). Ageing and performance of tasks requiring sensory reweighting and integration further requires attentional demands for pos- tural control (82, 83). These studies have used cognitive measures such as memory tests and reaction time tests to imply the attentional demands of postural con- trol. More specifically, there is a progressive increase in the atten- tional demands when moving from sitting to standing to walking (80). Other studies have used more typical postural measures to assess the at- tentional demands of postural control. Results similarly suggest a decline in postural stability associated with demanding cognitive tasks (84, 85, 86). Dual task interference on postural control can be observed in Parkin- sonian patients during performance of cognitive as well as motor tasks (87); the balance deterioration during dual task performance was signifi- cantly enhanced in patients with history of prior falls. Simultaneously, the tensor fasciae latae is inhibit- ed on the stance limb and activated on the swing limb. This pattern would increase the swing hip abductor moment and decrease the stance hip ab- ductor moment, resulting in a momentary loading of the swing limb and unloading of the stance limb. After gait initiation and when walking in normal conditions (no actu- al constraints), adult subjects exhibit a particular stable gait pattern, which is very reproducible from stride to stride, trial to trial but also over days. This rhythmic pattern implies the alternative, out of phase movement of the two legs. The gait cycle is the walking unit defined as the time interval between two successive identical body configurations, in general heel con- tact or heel strike. The gait cycle is divided in two phases: a stance phase – simple or double stance – and a swing phase. Stance and swing durations last about 60% and 40% of the cycle duration, respectively. With increase in body velocity, the stance duration substantially decreases whereas the swing du- ration hardly changes. As a consequence, the duration of the double stance phase significantly decreases with speed increment and even vanishes when switching from walking to running. The stride length linearly increas- es with speed increment until the speed of 2 m/s. Contrary to most mammals, which walk on four legs with the trunk roughly parallel to the ground, humans walk erect on two legs. A pen- dulum-like movement results, which converts ki- netic energy (Ec) into gravitational potential en- ergy (Ep), and inversely, thereby increasing gait efficiency (95, 96) (Fig. Interestingly, model- based studies demonstrated that the human biomechanical system shows a natural propen- sity for locomoting on earth (97). Pendulum-like bipedal locomotor movements are naturally un- movement of the body during stable, in particular in the medio-lateral plane gait. Balance of the trunk and swing leg about the supporting hip is maintained by an active hip abduction moment, which recognises the contribution of the passive accelerational moment, and counters a large destabilizing gravitational moment. Furthermore, bipedal compared to quadrupedal walking implies a dramatic re-organization of patterns of muscle action in order to propel the two-legged body forward while ensuring equilibrium. The motor pat- tern for quadrupedal locomotion consists in a basic alternative activation of extensor (stance) and flexor (swing) muscles. In turn, during human walking, a mixture of extensor and flexor muscles is activated, in particu- lar around the time of heel contact to stiffen the leg and roll over the stance foot.

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Smooth-Bore Weapons Shotguns ethambutol 400 mg visa antibiotics and period, which fire a large number of small projectiles ethambutol 800 mg amex antibiotic treatment for acne, such as lead shot generic 600mg ethambutol bacteria 5 kingdoms, are the most common type of smooth-bore weapons purchase 800mg ethambutol overnight delivery antibiotic jobs. They are commonly used in sporting and agricultural activities and may be either single or double- barreled. The ammunition for these weapons consists of a plastic or cardboard cartridge case with a brass base containing a percussion cap. Inside the main part of the cartridge is a layer of propellant, plastic, felt, or cardboard wads and a mass of pellets (lead shot of variable size) (see Fig. In addition to the pellets, the wads and/or cards may contribute to the appearance of the wounds and may be important in estimating range and possible direction. Rifled Weapons Rifled weapons are characterized by having parallel spiral projecting ridges (or lands) extending down the interior of the barrel from the breach to the muzzle. The rifling also leaves characteristic scratches and rifling marks that are unique to that weapon on the bullet surface. There are three common types of rifled weapons: the revolver, the pistol, and the rifle. The Injury Assessment 145 revolver, which tends to have a low muzzle velocity of 150 m/s, is a short- barreled weapon with its ammunition held in a metal drum, which rotates each time the trigger is released. In the self-loading pistol, often called “semi-automatic” or erroneously “automatic,” the ammunition is held in a metal clip-type maga- zine under the breach. Each time the trigger is pulled, the bullet in the breach is fired, the spent cartridge case is ejected from the weapon, and a spring mecha- nism pushes up the next live bullet into the breach ready to be fired. The rifle is a long-barreled shoulder weapon capable of firing bullets with velocities up to 1500 m/s. Most military rifles are “automatic,” allowing the weapon to continue to fire while the trigger is depressed until the magazine is empty; thus, they are capable of discharging multiple rounds within seconds. Shotgun Wounds When a shotgun is discharged, the lead shot emerges from the muzzle as a solid mass and then progressively diverges in a cone shape as the distance from the weapon increases. The pellets are often accompanied by particles of unburned powder, flame, smoke, gases, wads, and cards, which may all affect the appearance of the entrance wound and are dependent on the range of fire. Both the estimated range and the site of the wound are crucial factors in deter- mining whether the wound could have been self-inflicted. If the wound has been sustained through clothing, then important resi- dues may be found on the clothing if it is submitted for forensic examination. It is absolutely essential that the advice of the forensic science team and crime scene investigator is sought when retrieving such evidence. When clothing is being cut off in the hospital, staff should avoid cutting through any apparent holes. The entrance wound is usually a fairly neat circular hole, the margins of which may be bruised or abraded resulting from impact with the muzzle. In the case of a double-barreled weapon, the circular abraded imprint of the nonfiring muzzle may be clearly seen adjacent to the contact wound. The wound margins and the tissues within the base of the wound are usually blackened by smoke and may show signs of burning owing to the effect of flame. Because the gases from the discharge are forced into the wound, there may be subsid- iary lacerations at the wound margin, giving it a stellate-like shape. This is seen particularly where the muzzle contact against the skin is tight and the skin is closely applied to underlying bone, such as in the scalp. Carbon mon- oxide contained within the gases may cause the surrounding skin and soft 146 Payne-James et al. Con- tact wounds to the head are particularly severe, usually with bursting ruptures of the scalp and face, multiple explosive fractures of the skull, and extrusion or partial extrusion of the underlying brain. Most contact wounds of the head are suicidal in nature, with the temple, mouth, and underchin being the sites of election. In these types of wounds, which are usually rapidly fatal, fragments of scalp, skull, and brain tissue may be dispersed over a wide area. At close, noncontact range with the muzzle up to about 15 cm (6 in) from the skin, the entrance wound is still usually a single circular or oval hole with possible burning and blackening of its margins from flame, smoke, and unburned powder. Blackening resulting from smoke is rarely seen beyond approx 20 cm; tattooing from powder usually only extends to approx 1 m. Up to approx 1 m they are still traveling as a compact mass, but between approx 1–3 m, the pellets start to scatter and cause variable numbers of individual satellite punc- ture wounds surrounding a larger central hole. At ranges greater than 8–10 m, there is no large central hole, only multiple small puncture wounds, giving the skin a peppered appearance. Exit wounds are unusual with shotgun injuries because the shot is usu- ally dispersed in the tissues. However, the pellets may penetrate the neck or a limb and, in close-range wounds to the head, the whole cranium may be dis- rupted. Rifled Weapon Wounds Intact bullets penetrating the skin orthogonally, that is, nose-on, usually cause neat round holes approx 3–10 mm in diameter. Close examination reveals that the wound margin is usually fairly smooth and regular and bordered by an even zone of creamy pink or pinkish red abrasion. A nonorthogonal nose-on strike is associated with an eccentric abrasion collar, widest at the side of the wound from which the bullet was directed (see Fig. Atypical entrance wounds are a feature of contact or near contact wounds to the head where the thick bone subjacent to the skin resists the entry of gases, which accumu- late beneath the skin and cause subsidiary lacerations to the wound margins, imparting a stellate lacerated appearance. Contact wounds elsewhere may be bordered by the imprint of the muzzle and the abraded margin possibly charred and parchmented by flame. Punctate discharge abrasion and sooty soiling are usually absent from the skin surface, but the subcutaneous tissues within the depth of the wound are usually soiled. The effects of flame are rarely seen beyond 10 cm (4 in), with sooty soiling extending to approx 20 cm (8 in). Punctate discharge abrasions, which may be particularly heavy with old revolver ammunition, are often present at ranges up to approx 50 cm (20 in). It is impor- tant to remember that sooty soiling of the skin surrounding a wound is easily removed by vigorous cleaning carried out by medical or nursing staff. The soiling of contact close-range entrance wounds may be absent if clothing or other material is interposed between the skin surface and the muzzle of the weapon. Bullet exit wounds tend to be larger than entrance wounds and usually consist of irregular lacerations or lacerated holes with everted, unabraded, and unbruised margins. When the skin at the site of an entrance wound has been supported by tight clothing, eversion of the margins of the wound may be absent and the margins may even be abraded, albeit somewhat irregularly, but nevertheless making differentiation from entrance wounds more difficult. Entrance wounds caused by damaged or fragmented bullets may be so atypical that it may not be possible to offer a useful opinion as to their nature. It is inappropriate to offer an opinion on the caliber of a bullet based on the size of an entrance wound, and it is not possible to state whether the bullet was fired from a revolver, pistol, or rifle by only the appearance of the wound. These inju- ries typically are seen when an individual has tried to defend himself or herself against an attack and are the result of instinctive reactions to assault. When attacked with blunt objects, most individuals will attempt to protect their eyes, head, and neck by raising their arms, flexing their elbows, and covering their head and neck. Thus, the extensor surface of the forearms (the ulnar side), the lateral/ posterior aspects of the upper arm, and the dorsum of the hands may receive blows. Similarly, the outer and posterior aspects of lower limbs and back may be injured when an individual curls into a ball, with flexion of spine, knees, and hips to protect the anterior part of the body. In sharp-blade attacks, the natural reaction is to try and disarm the attacker, often by grabbing the knife blade.

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