By P. Merdarion. Rice University.

A vaccination program was initiated avian sinuses are not restricted laterally by in the flock buy toradol 10 mg otc. A herpesvirus that is serologically distinct from Pacheco’s disease virus has been iso- Color 22 order toradol. In this case buy toradol 10 mg without prescription, the pharyngeal chronic sinusitis is associated with an in- mucosa is covered with necrotic tissue. Conjunctival scrap- provide supportive care, the client passed a ings collected for cytology and culture are feeding tube and delivered a liquid-based most useful in identifying an etiologic product. The client had passed the tube into long-term treatment with tylosin eye wash the trachea instead of the esophagus, re- and lincomycin/spectinomycin in the drink- sulting in asphyxiation (courtesy of Brett ing water or an ophthalmic solution con- Hopkins). The bird was in excel- ing over-the-counter medications in the lent overall condition and had blood-tinged water for ten days. The lungs were edema- and mucopurulent rhinitis were noted on tous and hemorrhagic. Cytol- ious gases and fumes from non-stick cook- ogy of samples collected from the masses ing surfaces can cause similar gross lesions indicated an accumulation of mixed gram- in the lung. This fungal infection was secon- (h), liver (l), ventriculus (v), cranial thoracic dary to aspiration of ingesta. Note kernels air sac (cr), caudal thoracic air sac (ca), of corn (courtesy of Brett Hopkins). Colo- new methylene blue revealed branching nies in the oxygen-rich areas of the lungs septate hyphae characteristic of Aspergil- and air sacs frequently produce charac- lus spp. The bird was anesthetized with isoflurane and an air sac tube was placed not responsive to antibiotic therapy. Radiographs indi- cated a soft tissue mass in the right thora- depressions in the lung (costal sulci) repre- sent the areas where the lung folds around coabdominal cavity. A two-year-old cated bacterial pneumonia and air sacculi- ostrich hen with a history of respiratory tis. Ingesta was also noted, confirming a disease had fibrinonecrotic pharyngitis diagnosis of aspiration pneumonia. Surfactants in the parabronchi func- tion to keep fluids from entering the air capillary area and prevent tran- sudation. These functions combine to maintain the integrity of the delicate blood gas barriers. Radiographs revealed a soft tissue mass at the non-vagal and can be relaxed with level of the syrinx (arrows). From a functional standpoint, the avian lung is divided into a pa- leopulmo (which all birds have and which constitutes The cranial air sacs are composed of the cervical, at least 75% of the lung) and the neopulmo (which clavicular and cranial thoracic air sacs; the caudal air some birds have and which makes up no more than sacs are composed of the caudal thoracic air sac and 30% of the lung). The cranial thoracic air sacs re- guins, minimally developed in emus, further devel- ceive air via the medioventral parabronchi and are oped in ducks and psittacine birds and maximally physiologically components of the paleopulmonic air developed in pigeons and gallinaceous and passerine sac system. The reasons for this division have not been hand, gets its air from lateroventral parabronchi clearly established, but it has been determined that and, along with the abdominal air sacs, is part of the neopulmonic air sac system. The cervicocephalic air sacs are not connected to the lung and are divided into cephalic and cervical por- tions; they connect to caudal aspects of the infraorbi- Air Sacs tal sinus (see Anatomy Overlay). Extensive cervico- cephalic air sac development has been noted in Pulmonary budgerigars, cockatiels, conures, Amazon parrots, Most birds have four paired and one unpaired pulmo- macaws and cockatoos. This air sac is absent in nary air sacs that connect to the lung and create a diving birds, partially developed in ratites, pigeons large respiratory capacity (see Anatomy Overlay). Most birds, including Psittaciformes, are be- tion as insulating air layers for the retention of heat, lieved to have four paired air sacs that include the to control buoyancy, to reduce the force of impact with cervical, cranial and caudal thoracic and abdominal the water in fish-eating birds and to support the head air sacs. The in- In some species, the cephalic portion is large, and in trathoracic component surrounds the great vessels, others it is minimally developed. Studies involving esophagus and syrinx with diverticula into the ster- budgerigars, conures and cockatiels suggest that the num and sternal ribs. The extrathoracic component cephalic air sacs arise from the infraorbital sinus and represents diverticula into the thoracic girdle (see extend dorsally to cap the dorsum of the skull. No direct connection has been found between the cervicocephalic air sac system and any of the pulmo- nary air sacs. The air sacs of a normal bird are com- pletely transparent (appear similar to clear plastic wrap) (Color 22. The presence of blood vessels in the air sacs may be an indication of early inflammation. Blood vessels that transverse inflamed abdominal air sacs must be avoided during surgical procedures. The trachea, primary bronchi and larger secondary bronchi are lined with pseudostratified or simple columnar ciliated epithelium, whereas the air sacs distal to the connection with the lungs are lined with a single layer of simple squamous epithelial cells. The area of the air sacs near the lung may contain simple cuboidal and columnar ciliated epithelium. The sternum and sternal ribs are pneuma- tized through the intrathoracic diverticula that lie between the coracoid bones. The femur may be pneumatized through a con- nection with the air sac (see Anatomy Overlay). The barium could not be detected in the respiratory system on a Birds have no functional diaphragm. The breathe by using the six inspiratory muscles (princi- cervical portion extends bilaterally dorsolaterally in pally the external intercostales) to pull the ribs cra- the neck from the head to the distal neck (Figure nially, laterally and ventrally and to move the ster- 22. The nine expiratory muscles (principally the internal intercostals and abdominals) pull the ribs caudally, raising the sternum and pulling the ribs inward, causing expiration by creating increased internal pressure within the air sacs. This forces air out of the air sacs and back through the parabronchi (caudal air sacs) or trachea (cranial air sacs). The rapid influx of inspired air into the caudal air sacs and the similar- ity of this air to environmental air have been used to explain the apparent prevalence of air sac infections and pathology in the caudal air sacs versus the cra- nial air sacs; however, it should be noted that half the inspired air enters the lungs. The prevalence of cau- dal air sacculitis may be a reflection of the air layer- ing that occurs in this location. In pigeons, barely detectable tail movements have been shown to be associated with inspiration (mini- mally) and expiration. The tail muscles seem to be most involved in respiration when a bird is resting on its keel, or the sternum is fixed in position. This can occur with an overly aggressive restraint or by the surgeon resting his hands on the body cavity during surgery. Radiographs indicated gase- ing, particularly if they are wrapped tightly around ous distension of the cervical air sac with no other evidence of the caudal portion of the sternum or ribs. A permanent opening (stent) was created in the air sac to resolve the problem (courtesy of Marjorie McMillan). The air that is already in the lungs enters the Obesity Severing of vagus nerve(s) cranial air sacs. On expiration, the ambient air that Pain Air sac oxygen administration is in the caudal air sacs enters the lungs. Although Exercise Sleep not clearly stated in any physiology reference, the air that is in the lungs must exit through the trachea arranged so that blood flows perpendicular to the air along with the air that is in the cranial air sac. The efficiency volume of air that enters the air sacs to move totally of gas exchange is thus greater. Superficially, tion and its associated inflammation, a greater ven- this would appear to be relatively inefficient, but in tilation perfusion mismatch can occur.

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Disadvantages include the fact that an immune response to the vector will preclude gene transfer in some patients and will limit the duration of gene expression buy toradol 10 mg otc. Baculoviruses can transfer genetic information into hepatocytes but do not express the baculoviral genes order 10 mg toradol visa, which require transcription factors that are only present in insect cells discount 10 mg toradol amex. Baculoviral vectors have been used to express genes in hepa- tocytes in vitro and have been delivered to intact livers using an isolated perfusion system. Advantages of baculoviral vectors include the ability to accept large amounts of genetic material and the absence of expression of baculoviral proteins in mammalian cells. Disadvantages include the transient gene expression and the sensitivity of the vector to complement. Oligonucleotides act by altering expression of endogenous genes in cells by a variety of mechanisms (see Figure 4. There are three important factors regarding nonviral vectors that can be ampli- fied in prokaryotic or eukaryotic cells for gene therapy: (1) the size of the insert accepted, (2) how to get the genetic material into cells efficiently, and (3) how to maintain the genetic material inside the cell in order to achieve long-term expression. Nonviral vectors are any type of vector that does not involve a viral particle that can alter gene expression in a cell. They generally contain a promoter and coding sequence that results in expression of a therapeutic protein. Oligonucleotides, or more stable analogs such as phosphorothioates, contain 10 to 25 bases. Size of Insert The size of the insert accepted varies considerably among the different nonviral vectors that replicate in cells. Bacteria can amplify plasmids, bacteriophage, cosmids, or bacterial artificial chromosomes. More recently, the production of a human artificial minichromosome was reported, although its transfer into cells was very inefficient. For ex vivo transfer, genes are usually transferred into the cell by using calcium phosphate co-precipitation, electroporation, cationic lipids, or liposomes. Efficient in vivo transfer is somewhat more difficult to achieve than ex vivo gene transfer. Selective delivery (targeting) of a nonviral vector to a specific organ or cell type would be desirable for some applications. Stabilization of Nonviral Vectors in Cells A major problem with nonviral vectors is transient gene expression, since the genetic material transferred into the cell is unstable. Some investigators have placed origins of replication derived from viruses into nonviral vectors. Plasmids must be engineered to express any proteins necessary to activate the origin of repli- cation. Plasmids containing these replication origins and relevent appropriate proteins activating origins are main- tained longer in cells in vitro and in vivo than plasmids that do not contain these sequences. Artificial chromosomes have elements that stabilize genetic material in a cell and should not have problems of instability. If difficulties in amplifying and transferring artificial chromosomes into cells can be overcome, such vectors should be maintained stably in a cell. There is little quantitative data regarding the efficacy of expression from different promot- ers in vivo. Gene therapy with plasmid vectors has been used to attempt to treat cystic fibrosis (see Chapter 3) and cancer in humans (see Chapter 10). A major advantage of using nonviral vectors is the lack of risk of generating a wild-type virus via recombination. In addi- tion, episomal plasmids do not pose the risk of insertional mutagenesis since they do not integrate into the chromosome. However, some plasmids can integrate into the genome particularly when a procedure is used to select clones exhibiting long- term expression. A second potential risk for nonviral vectors is that certain compounds can facilitate entry into a cell and exert a toxic effect in vivo. For example, many cationic lipids have considerable toxicity when administered at high doses to cells in vitro. It will be necessary to assess the toxicity of such compounds care- fully in vivo. Summary: Nonviral Vectors Nonviral vectors can be amplified to high copy numbers in bacterial cells as well as readily engineered to express a therapeutic gene from a mammalian promoter. These plasmids can be efficiently introduced into cells ex vivo and introduced some- what less efficiently into cells in vivo. Their major advantages are the ease of production and that they cannot recombine to generate replication-competent virus. They can, however, integrate at a low frequency into the chromosome and, therefore, do pose some risk of insertional mutagenesis. This binding can block access of transcription factors, thus inhibiting transcription of a gene. The triplex-forming oligodeoxynucleotide binds to the purine-rich strand of the double helix via Hoogsteen hydrogen bonds. Potential target sites for triplex formation are limited to regions that contain homopurine on one strand. The relatively weak binding affinity and the instability of oligodeoxynu- cleotides in cells results in a transient effect. A third mechanism by which oligodeoxynucleotides can alter gene expression is to bind transcription factors, which prevents them from associating with endogenous genes. Natural antisense oligodeoxynucleotides consist of phosphodiester oligomers, are sensitive to nucleases, and have a half-life in serum of 15 to 60min. Modifications to the backbone have increased the stability of oligonucleotides to allow a pro- longed biological effect on targeted cells in vivo. Substitution of a nonbridge oxygen in the phosphodiester backbone with a sulfur molecule results in phosphorothioate nucleotides, which are resistant to nucleases. Substitution of a nonbridge oxygen with a methyl group results in methylphosphonate nucleotides. Modified oligonucleotides are stable in culture and serum and have resulted in prolonged biological effects. Use and Safety of Oligonucleotides for Gene Therapy Oligonucleotides have been administered in vivo for gene therapy. Oligonucleotides that served as a decoy for a transcription factor have been used to inhibit proliferation of smooth muscle cells in blood vessels in vivo. Antisense oligonucleotides have blocked expression of oncogenes, slowed replication in cells in vitro, and had a modest but transient effect upon growth of tumor cells in vivo. The major toxicity of oligonucleotides relates to the administration of large doses to achieve a clinical effect.

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Incised wounds may be a feature of suicide or attempted suicide (see Subheading 3 toradol 10mg on-line. They are usually located on the wrists toradol 10 mg line, forearms purchase on line toradol, or neck, although other accessible areas on the front of the body may be chosen. The incisions usually take the form of multiple parallel wounds, most of them being tentative and superficial; some may be little more than simple linear abrasions. Stab Wounds Stab wounds are caused by sharp or pointed implements and wounds with a depth greater than their width or length. They are usually caused by knives but can also be inflicted with screwdrivers, pokers, scissors, etc. Although the external injury may not appear to be particularly serious, damage to vital struc- tures, such as the heart, liver, or major blood vessels, can lead to considerable morbidity and death, usually from hemorrhage. In those individuals who survive, it is common for little information to be present about the forensic description of the wound because the priority of resuscitation may mean that no record is made. If operative intervention is undertaken, the forensic signifi- cance of a wound may be obliterated by suturing it or using the wound as the entry for an exploratory operation. In such cases, it is appropriate to attempt to get a forensic physician to assess the wound in theatre or subsequently. Stab wounds are rarely accidental and occasionally suicidal, but usually their infliction is a result of criminal intent. In the case of suicide, the wounds are usually located on the front of the chest or upper abdomen and, as with self- inflicted incisions, may be associated with several superficial tentative punc- ture wounds (see Subheading 3. When deliberately inflicted by an assailant, stab wounds may be associated with defense injuries to the arms and hands. The appearance of the skin wound will vary depending on the weapon used and can easily be distorted by movement of the surrounding skin. If the blade is double- edged, such as that of a dagger, the extremities of the wound tend to be equally pointed. A stab wound from a single-edged blade, such as a kitchen knife, will usually have one extremity rounded, squared-off, or fish-tailed (caused by the noncutting back of the blade). When blunt weapons are used—a pair of scissors, for example—the wound tends to be more rounded or oval, with bruising of its margins (see Fig. Scissor wounds can sometimes have a cross-shape caused by the blade screws or rivets. Notched wounds are often caused by the blade of the weapon being partially withdrawn and then rein- troduced into the wound or twisted during penetration. It is rarely possible from an inspection of the skin wound alone to com- ment usefully on the width of the blade because the skin retracts and the knife is unlikely to have been introduced and removed perfectly perpendicularly. Deliberate Self-Harm Deliberate self-harm refers to any attempt by an individual to harm him- self or herself. When assessing injuries, it is important to understand which factors may indicate the possibility that an injury was caused by deliberate Injury Assessment 143 Table 4 Indicators of Possible Deliberate Self-Harm Injuries • Must be on an area of body accessible to the person to injure themselves. Individuals injure themselves for numerous reasons, including psy- chiatric illness and others, such as attempting to imply events took place that did not or for motives of gain. Self-inflicted injuries have several characteris- tics, which are not diagnostic but that together may give an indication of self- infliction. Table 4 lists features that may assist in the recognition or suspicion that cuts or other injury, such as scratches, are self-inflicted—all or some may be present—their absence does not preclude self-infliction nor does their pres- ence necessarily imply self-infliction (2). As with all injuries within the forensic setting it is essential in these nonfatal cases that the initial appear- ances of the injuries be accurately described and the wounds photographed. This is particularly important because subsequent surgical treatment may dis- tort or completely obliterate the wound characteristics. Furthermore, any frag- ments, bullets, or pellets found within the wounds must be carefully removed and handed over to the appropriate authorities. Smooth-Bore Weapons Shotguns, which fire a large number of small projectiles, such as lead shot, are the most common type of smooth-bore weapons. 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.