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In addition to hypoxemia cheap duetact 16 mg without prescription, what condition must be considered earliest in the management of this patient? She is speaking but com- plains of progressively worsening shortness of breath and hemoptysis order duetact 17 mg on line. On extremity examination duetact 17 mg on-line, the right foot is pale and you cannot palpate a distal pulse but can locate the dorsalis pedis by Doppler order duetact 17mg on line. As you open her eye lids, you notice that her right pupil is 8 mm and nonreactive and her left is 4 mm and minimally reactive. Supine chest radiograph reveals a hazy appearance over the entire right lung field. You place a 36F chest tube into the right thoracic cavity and note 1200 cc of blood in the chest tube drainage system. The patient was the front-seat passenger of the car and was not wearing a seat belt. The patient was wearing a seat belt in the back seat of a car that was struck in the front by another car. Her airway is patent, breath sounds equal bilaterally, and skin is warm with 2+ pulses. He states that the pain started on the left side of his lower back and now involves the right and radiates down both legs. He has a medical history of chronic hypertension and underwent a “vessel surgery” many years earlier. Upon arrival, she does not open her eyes, is verbal but not making any sense, and withdraws to painful stimuli. As you prepare to intu- bate the patient, a colleague notices that her left pupil has become dilated compared to the right. The man tells you his name and complains of right-sided chest pain and difficulty breathing. On primary survey, his airway is patent and his oropharynx has no blood or displaced teeth. He is breathing at 32 beats per minute with retractions and an oxygen saturation of 88% on 15 L of oxygen. These individuals are often amnestic to the event and frequently ask the same questions over and over again (perseverations). Headache with or without vomiting is generally present; however, there are no focal neurologic findings on examination. Diffuse axonal injury (b) is caused by microscopic shearing of brain nerve fibers. Patients typically present unconscious and remain in a coma for a prolonged period of time. The clinical features of a cerebral contusion (c) are similar to those of a concussion except neuro- logic dysfunction is more profound and prolonged and focal deficits may be present if contusions occur in the sensorimotor area. Posttraumatic epilepsy (d) is associated with intracranial hematomas and depressed skull fractures. Some scientists believe that head trauma predis- poses to Alzheimer disease (e); however, this would take years to develop. Although they are all associated with potentially fatal complications, they should be viewed clinically as a continuous spec- trum of myocardial damage: concussion (no permanent cell damage), contu- sion (permanent cell damage), infarction (cell death), tamponade (bleeding into the pericardium), and rupture (exsanguination). The mechanism of injury in a cardiac contusion involves a high-speed deceleration, which causes the heart to move forward, forcibly striking the sternum. In addition, the direct force of hitting an object (eg, the steering wheel) also can damage 148 Trauma Answers 149 the heart. The right ventricle is the most commonly injured because it is the most anterior aspect of the heart and is closest to the sternum.

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Rather than both contracting and conducting impulses as other cardiac muscle does cheap 17mg duetact fast delivery, these structures specialize in conduction alone buy duetact 16 mg, setting the pace for the rest of the heart 16mg duetact with amex. Following is a bit more information about each one: Sinoatrial node: This node really is the pacemaker of the heart buy 17mg duetact with mastercard. Located at the junction of the superior vena cava and the right atrium, this small knot, or mass, of specialized heart muscle initiates an electrical impulse that moves over the musculature of both atria, causing atrial walls to contract simultaneously and emptying blood into both ventricles. Atrioventricular node: The impulse that starts in the S-A node moves to this mass of modified cardiac tissue that’s located in the septal wall of the right atrium. Also called the A-V node, it directs the impulse to the A-V bundles in the septum. Atrioventricular bundle: From the A-V node, the impulse moves into the atri- oventricular bundle, also known as the A-V bundle or bundle of His (pronounced “hiss”). The bundle breaks into two branches that extend down the sides of the interventricular septum under the endocardium to the heart’s apex. Purkinje fibers: At the apex, the bundles break up into terminal conducting fibers, or Purkinje fibers, and merge with the muscular inner walls of the ventricles. The pulse then stimulates ventricular contraction that begins at the apex and moves toward the base of the heart, forcing blood toward the aorta and pulmonary artery. One of the best ways to detect cardiac tissue under a microscope is to look for undu- lating double membranes called intercalated discs separating adjacent cardiac muscle fibers. Gap junctions in the discs permit ions to pass between the cells, spreading the Chapter 10: Spreading the Love: The Circulatory System 171 action potential of the electrical impulse and synchronizing cardiac muscle contrac- tions. Potential problems include fibrillation, a breakdown in rhythm or propagation of the impulses that causes individual fibers to act independently, and heart block, an interruption that causes the atria and ventricles to take on their own rates of contrac- tion. Left atrium Sinoatrial node (pacemaker) Purkinje fibers Atrioventricular node Figure 10-4: Right atrium The conductive Purkinje fibers system of the heart. Wolters Kluwer Health — Lippincott Williams &Wilkins A healthy heart makes a “lub-dub” sound as it beats. The first sound (the “lub”) is heard most clearly near the apex of the heart and comes at the beginning of ventricu- lar systole (the closing of the atrioventricular valves and opening of the semilunar valves). It’s lower in pitch and longer in duration than the second sound (the “dub”), heard most clearly over the second rib, which results from the semilunar valves clos- ing during ventricular diastole. Defects in the valves can cause turbulence or regurgita- tion of blood that can be heard through a stethoscope. S-A node → Purkinje fibers → Bundle of His → A-V node Riding the Network of Blood Vessels Blood vessels come in three varieties, which you can see illustrated in Figure 10-5: Arteries carry blood away from the heart. Small ones are called arterioles, and microscopically small ones are called metarterioles. Veins carry blood toward the heart; all veins except the pulmonary veins contain deoxygenated blood. Microscopically small capillaries carry blood from arterioles to venules, but sometimes tiny spaces in the liver and elsewhere called sinusoids replace capillaries. The walls of arteries and veins have three layers: the outermost tunica externa (some- times called tunica adventitia) composed of white fibrous connective tissue, a central “active” layer called the tunica media composed of smooth muscle fibers and yellow elastic fibers, and an inner layer called the tunica intima made up of endothelium that aids in preventing blood coagulation by reducing the resistance of blood flow. Arterial walls are very strong, thick, and very elastic to withstand the great pressure to which the arteries are subjected. In elastic arteries, found prima- rily near the heart, the tunica media is composed of yellow elastic fibers that stretch Chapter 10: Spreading the Love: The Circulatory System 173 with each systole and recoil during diastole; essentially they act as shock absorbers to smooth out blood flow. In muscular arteries, the tunica media consists primarily of smooth muscle fibers that are active in blood flow and distribution of blood. The larger blood vessels have smaller blood vessels, the vasa vasorum, that carry nourish- ment to the vessel wall. Venule Vein Capillaries Blood flow Figure 10-5: Arteriole The capillary Artery exchange. While larger in diameter than arteries, veins have thinner walls and are less distensible and elastic. Veins that carry blood against the force of gravity, such as those in the legs and feet, contain valves to prevent backsliding into the capillaries. Normally the blood that veins are returning to the heart is unoxygenated (contains carbon dioxide); the one exception is the pulmonary vein, which returns oxygenated blood to the heart from the lungs.

As a result purchase duetact 17 mg overnight delivery, it is possible to generalize about some of the changes caused by the introduction of a particular group into a structure (see Table 4 order duetact 17 mg on line. However generic duetact 17mg with amex, the choice of substituent will ultimately depend on the properties that the development team decide to enhance in an attempt to meet their objectives discount duetact 17 mg with amex. Moreover, it should be realized that the practical results of such a structural change will often be different from the theoretical predictions. In addition, it may introduce a chiral centre, which will result in the formation of stereoisomers, which may or may not have different pharmacological activities (Table 2. Alternatively, it may impose conformation restrictions on some of the bonds in the analogue (Figure 4. The introduction of a new group may result in an increased rate of metabol- ism, a reduction in the rate of metabolism or an alternative route for metabolism (see Chapter 9). These changes could also change the duration of action and the nature of any side effects. Fluorine and Increased Decreased water Used to improve ease of chlorine lipophilic solubility. Hydroxy Decreased Increased water Provides a new centre for lipophilic solubility. The presence of the hydroxy group could result in an increase in the rate of elimination of the drug by a new metabolic pathway and/or excretion. Amino groups Decreased Increased water Provides a new centre for lipophilic solubility due to hydrogen bonding, which could character salt formation. Carboxylic and Decreased Increased water Water solubility may be enhanced sulphonic groups lipophilic solubility due to by in vivo salt formation. Carboxylic solubility acid group introduction into small lead molecules may change the type of activity of the analogue whilst sulphonic acid group incorporation does not normally change the type of activity. It is believed that this prevents the molecule from adopting the conformation necessary for antihistamine activity reduced hepatotoxicity. It is believed that this reduction is due to the methyl groups preventing metabolic hydroxylation of these ortho positions. In one position the new group will lead to an enhancement of activity, while in another position it will result in a reduction of activity. For example, the antihypertensive clonidine with its o,o’-dichloro substitution is more potent than its m,p-dichloro analogue (Figure 4. Classical isosteres were originally defined by Erlenmeyer as atoms, ions and molecules with identical shells of electrons. As a result, they may exhibit similar pharmacokinetic and pharmacodynamic properties. In other words, the replacement of a substituent by its isostere is more likely to result in the formation of an analogue with the same type of activity as the lead than the totally random selection of an alternative substituent. However, luck still plays a part, and an isosteric analogue may have a totally different type of activity from its lead (see section 2. These param- eters are used to represent properties such as lipophilicity, shape and electron distribution, which are believed to have a major influence on the drug’s activity. They are normally defined so that they are in the form of numbers, which are derived from practical data that is thought to be related to the property the parameter represents. This makes it possible to either to measure or to calculate these parameters for a group of compounds and relate their values to the biological activity of these compounds by means of mathematical equations using statistical methods such as regression analysis (see Appendix 6). These equations may be used by the medicinal chemist to make a more informed choice as to which analogues to prepare. For example, it is often possible to use statistical data from other compounds to calculate the theoretical value of a specific parameter for an as yet unsynthesized compound. Substituting this value in the appropriate equation relating activity to that parameter, it is possible to calculate the theoretical activity of this unknown compound. Alter- natively, the equation could be used to determine the value ‘x’ of the parameter ‘y’ that would give optimum activity. As a result, only analogues that have values of y in the region of x need be synthesized. The main properties of a drug that appear to influence its activity are its, lipophilicity, the electronic effects within the molecule and the size and shape of the molecule (steric effects).

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Alcoholic preparations are best suited for this purpose discount duetact 17 mg line, although they are not sporicidal and have only a brief duration of action order 17mg duetact with mastercard. Principles of Sterilization and Disinfection 41 Alcohols are therefore often combined with other disinfectants (e generic duetact 16 mg with amex. Alcohols and/or iodine compounds are suitable for disinfecting patient’s skin in preparation for surgery and injections duetact 17 mg on line. Strong-smelling agents are the logical choice for disinfection of ex- cretions (feces, sputum, urine, etc. Con- taminated hospital sewage can also be thermally disinfected (80–100 8C) if necessary. Suitable agents include aldehyde and phenol derivatives combined with surfactants. Instrument disinfection is used only for instruments that do not cause inju- ries to skin or mucosa (e. Laundry disinfection can be done by chemical means or in combination with heat treatment. The substances used include derivatives of phenols, alde- hydes and chlorine as well as surfactant compounds. Chlorine is the agent of choice for disinfection of drinking water and swimming-pool water. Final room disinfection is the procedure carried out after hospital care of an infection patient is completed and is applied to a room and all of its furnish- ings. Evaporation or atomization of formaldehyde (5 g/m3), which used to be the preferred method, requires an exposure period of six hours. This proce- dure is now being superseded by methods involving surface and spray dis- infection with products containing formaldehyde. Hospital disinfection is an important tool in the prevention of cross-infec- tions among hospital patients. Zinkernagel 2 Introduction & Resistance to disease is based on innate mechanisms and adaptive or acquired immunity. Acquired immune mechanisms act in a specific manner and function to supplement the important nonspecific or natural resistance mechanisms such as physical barriers, granulocytes, macrophages, and chemical barriers (lysozymes, etc. The specific immune mechanisms constitute a combination of less specific factors, including the activation of macrophages, complement, and necrosis factors; the early recognition of invading agents, by cells exhibiting a low level of specificity, (natural killer cells, cd [gamma-delta] T cells); and systems geared toward highly specific recognition (antibodies and ab [alpha-beta] T cells). Many components of the specific immune defenses also contribute to nonspecific or natural defenses such as natural antibodies, complement, interleukins, interferons, macrophages, and natural killer cells. For example, a person who has had measles once will not suffer from measels a second time, and is thus called immune. However, such spe- cific or acquired immune mechanisms do not represent the only factors which determine resistance to infection. The canine distemper virus is a close relative of the measles virus, but never causes an infection in humans. Our immune system recognizes the pathogen as foreign based on certain surface structures, and eliminates it. Humans are thus born with resistance against many microorganisms (innate immunity) and can acquire resistance to others (adaptive or acquired im- munity; Fig. Activation of the mechanisms of innate immunity, also known as the primary immune defenses, takes place when a pathogen breaches the outer barriers of the body. Specific immune defense factors are mobilized later to fortify and regulate these primary defenses. Responses of the adaptive immune system not only engender immunity in the strict sense, but can also contribute to pathogenic processes. The terms immuno- pathology, autoimmunity, and allergy designate a group of immune Kayser, Medical Microbiology © 2005 Thieme All rights reserved. The latter comprises cellular (T-cell responses) and humoral (anti- bodies) components. Specific Tcells, together with antibodies, recruit non-specific effector mechanisms to areas of antigen presence.

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