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By L. Zarkos. University of the Incarnate Word.

Graft copolymers of poloxamers and either poly(acrylic acid) or chitosan change from a sol to a gel at temperature above 37 °C buy cheap malegra fxt 140 mg on-line. The appearing gel forms a stable matrix that can retain a drug for its sustained release buy cheap malegra fxt 140 mg on line. At room temperature, gellation is followed by a further increase in the polymer concentration due to packing of the micelles. Interestingly, the gel is changed into a sol at an elevated temperature such as 45 °C. Upon subcutaneous injection of the polymeric solution into the body (37 °C), a gel is formed immediately. If a drug is dissolved in the polymeric solution prior to the injection, the gel would function as a sustained release matrix for the entrapped drug. The critical gel-sol transition temperature is conveniently modified by varying the length of each block and molecular weight of the triblock polymer. An application of such technology has been in the development of biomimetic secretory granules for drug delivery applications. Secretory granules within certain cells consist of a polyanionic polymer network encapsulated within a lipid membrane. The polymer network, which contains biological mediators such as histamine, exists in a collapsed state as a consequence of the internal pH and ionic content which is maintained by the lipid surrounding the granule. Release of histamine from such granules is initiated through the fusion of the granule with the cell membrane exposing the polyanionic internal matrix to the extracellular environment. The change in pH and ionic strength results in ion exchange and swelling of the polyanionic network which in turn causes release of the endogenous mediators. An environmentally responsive, hydrogel microsphere coated with a lipid bilayer has recently been shown to act as a secretory granule mimic (Figure 16. Disruption of the lipid bilayer by electroporation was shown to cause the microgel particles to swell and release their drug. The use of these systems in conjunction with temperature-sensitive lipids offers potential to target drugs to areas of inflammation or to achieve site-specific, pulsatile drug delivery through the localized external application of ultrasound or heating to disrupt the lipid bilayers. This concept may be visualized by an example of an electrical stimulus-sensitive hydrogel. If it is fabricated into a porous membrane of which edges are fixed in place, the presence and removal of the stimulus would start and stop the exchange of a drug with body fluids. For example, if the implant is exposed to the stimulus, pores in the hydrogel membrane would become wide-open to turn on the chemical valve. Subsequently, the contents of the implant are discharged at the site of implantation. The removal of the stimulus turns off the valve to contract the membrane pores, thereby stopping the flow of the contents. The release of a drug from such an implant, therefore, is at the operator’s control. Such implants have potential to release a drug in a 387 pulsatile manner, according to patients’ biological needs. The focus of such research has been towards the delivery of insulin in response to changes in glucose levels. Preparation of glucose-sensitive phase-reversible hydrogels demands two fundamental requirements: glucose-specificity and reversible cross-linking (i. A highly specific interaction between glucose and concanavalin A (Con A) was used to form physical cross-links between glucose-containing polymer chains. Since Con A exists as a tetramer at physiological pH and each subunit has a glucose binding site, Con A can function as a cross-linking agent for glucose- containing polymer chains. Because of the non-covalent interaction between glucose and Con A, the formed cross-links are reversible (Figure 16. Individual free glucose molecules can compete with the polymer- attached glucose molecules. Thus, the maintenance of the cross-links depends on the relative concentration of free glucose in the environment. The gel is formed by mixing glucose-containing polymers with Con A in the absence of external glucose. In the presence of elevated glucose levels in solution, however, the gel becomes a sol (i. As the environmental glucose level decreases again, the competition of free glucose against the polymer-bound glucose decreases and thus the gel is formed again. It has been shown that diffusion of insulin is much slower in the gel state than in the sol state, and insulin release can be controlled as a function of the glucose concentration in the environment.

Norepinephrine is becoming an earlier choice as a pressor agent used for septic shock generic malegra fxt 140mg with amex, once adequate intravascular volume has been restored generic malegra fxt 140 mg amex. In Case 2, despite adequate fluid resuscitation guided by pulmonary artery, broad-spectrum antibiotics, and surgical drainage of appendiceal abscess, the patient remains hypoperfused. Extensive microvascular endothelial damage leads to liberation of inflammatory mediators, with subsequent microvascular ischemia, increased permeability, decreased intravascular volume, and hypoperfusion. Mortality ranges from 30% to 50% with single organ failure and increases to 80% with three-organ dysfunction. Recently, activated protein C (Xigris, Eli Lilly) has been approved for the treatment of severe sepsis. It is the first agent to demonstrate a mortality reduction in patients with severe sepsis. Activated protein C modulates coagulation, fibrinolysis, and inflammation, thus reinstating homeostasis between the major processes driving sepsis. In certain patient populations, risk of bleeding is elevated, and careful attention to patient selection should be given. Therapy is directed toward minimizing any stimulus of ongoing infection, ischemia, necrosis, fracture, or other tissue injury. Supportive care includes ensuring adequate oxygenation, ensuring organ perfusion, and reducing the duration of shock. Generally accepted cri- teria of adequate perfusion—end points of resuscitation—are summa- rized in Table 7. Summary Shock, by definition, is a clinical syndrome that develops due to inad- equate tissue perfusion. Hypoperfusion results in insufficient delivery of oxygen and nutrients for metabolism, leading to severe vital organ dysfunction. Patients enter into the shock state due to hypo- volemia, trauma, sepsis, cardiac dysfunction, or severe neurologic compromise. The physician’s role in patient management is to ensure adequate hemodynamic support first (airway, breathing, circulation), followed by an aggressive search for the etiology of shock. Hemodynamic responses to shock in young trauma patients: the need for invasive monitoring. Pumonary artery catheterization: narrative and sys- tematic critique of randomized controlled trials and recommendations for the future. Human albumin administration in critically ill patient: sys- tematic review of randomized controlled trials. To describe the differential diagnosis: • To differentiate between surgical and nonsurgi- cal causes of bleeding. To describe factors that can lead to abnormal bleed- ing postoperatively and to discuss the prevention and management of postoperative bleeding: • Inherited and acquired factor deficiencies. Case You are asked to evaluate a 70-year-old woman who has had a femoral- peroneal artery bypass with in-situ saphenous vein because of brisk bleeding from the incision. Surgical Bleeding and Hemostasis 137 • Phase I (vasoconstriction): Vascular injury results in the constriction of vascular smooth muscle and the early decrease in local blood flow. Hemostasis and fibrin clot forma- tion work through the intrinsic and/or extrinsic pathways. Both pathways lead to a common enzyme, factor Xa, that then is followed by the common pathway (Fig. When first evaluating a bleeding patient, two crucial questions must be addressed: 1. Whether or not the patient is hemodynamically stable can be deter- mined quickly by looking at the patient’s general appearance and by obtaining a set of vital signs. In the case presented at the beginning of this chapter, hemodynamic instability (a heart rate of 109 and blood pressure of 89/45) is caused by hypovolemia, which can be corrected with intravenous fluids. Airway The patient’s ability to maintain a patent airway should be evaluated, and rapid endotracheal intubation should be considered if the patient is unconscious or otherwise unable to maintain a clear airway. The patient in our case was “anxious,” which also means conscious, prob- ably communicative, and able to protect her airway. Breathing Adequate breathing should be confirmed by physical exam and pulse oximetry. Circulation Heart rate and blood pressure are good indicators of circulatory volume. Loss of less than 15% of blood volume may result in no change in blood pressure or heart rate. Hemorrhage of 15% to 30% of blood volume results in a decreased pulse pressure and tachycardia. Loss of greater than 30% will result in a decrease in systolic pressure, reflex 138 G. The central pathway involves the activation of factors X to Xa and prothrombin to thrombin. Subsequently, Xa assembles on the platelet phospholipid membrane to form the prothrombinase complex, which converts prothrombin to thrombin.

In patients who are severely malnourished proven malegra fxt 140mg, aggressive nutritional support may be of some benefit malegra fxt 140 mg online, with most of the benefit occurring in the early postoperative period. Hematologic An obvious concern for a surgeon who is about to induce iatrogenic injury to a patient is that of bleeding and the patient’s inherent ability to form clots. On the one hand, the surgeon depends on it so that the patient does not exsanguinate from the intervention (fortu- nately, an exceedingly rare event). Conversely, a patient in a hyper- coaguable state may suffer from a thromboemblic event that could be life threatening. In addition, a growing number of patients requiring surgical intervention are chronically anticoagulated for a number of reasons, e. Historical information of importance includes whether the patient or a family member has had a prior episode of bleeding or a throm- boembolic event, and whether the patient has a history of prior 1. Perioperative Care of the Surgery Patient 13 transfusions, prior surgery, heavy menstrual bleeding, easy bruising, frequent nosebleeds, or gum bleeding after brushing teeth. If the history is negative and the patient has not had a previous significant hemostatic challenge, then the like- lihood of a bleeding or thrombotic event is exceedingly rare and the value of preoperative coagulation testing is low. This underscores the importance of adopting a rea- sonable strategy of ordering only those diagnostic tests indicated by the patient’s history. If a clinically important coagulopathy is identi- fied, therapeutic strategies for management of various coagulation dis- orders in preparation for surgery are listed in Table 1. A good deal of the planning hinges upon how urgently the surgery needs to be performed and the indication for the anticoagula- tion. Most patients who take warfarin and who are to undergo ambu- latory or same-day admission elective surgery can be managed simply by having them discontinue their warfarin for several days prior to surgery. If there is concern that the patient should not be without anticoagulation, the patient can be systemically anticoagulated with unfractionated intravenous heparin. The heparin infusion is discon- tinued approximately 4 hours prior to surgery (the half-life of heparin is about 90 minutes), and surgery proceeds with good hemostasis. Antibiotic Prophylaxis This topic is discussed in greater detail in future chapters. Suffice it to say that surgery is an insult to the body’s immune system and infection is frequently an unwanted side affect. Antibiotic therapy must be used judiciously so as to avoid overuse and selection of resistant strains of bacteria. A type and screen or type and crossmatch should be requested for operations where blood transfusions are likely (Table 1. Levels should be maintained for 5–7 (moderate injury) or 7–14 days (severe injury), as delayed bleeding is typical. Levels should be maintained for 5–7 (moderate injury) or 7–14 days (severe injury), as delayed bleeding is typical. Tachyphylaxis can be restored by a 24-h drug holiday to allow repletion of endothelial stores. Platelet abnormalities Thrombocytopenia Transfuse platelets <50,000 if bleeding or invasive procedure is anticipated; <20,000 otherwise. Platelet infusion after ligation of the splenic artery during splenectomy if the response to immune globulin is poor. Transfuse platelets only if surgery cannot be delayed to allow spontaneous recovery. Summary of evidence-based guidelines for the prevention of surgical site infec- a tion (wound infection). Preparation of the patient Level I: Identify and treat all infections remote to the surgical site before elective operations. Do not remove hair preoperatively unless hair at or near the incision site will interfere with surgery. If hair is removed, it should be removed immediately beforehand, preferably with electric clippers. Indicated blood transfusions should not be withheld as a means to prevent surgical site infection. Patients should shower or bathe with an antiseptic agent at least the night before surgery. Scrub the hands and forearms up to the elbows for at least 2–5min with an appropriate antiseptic. Antimicrobial prophylaxis Level I: Administer antibiotic prophylaxis only when indicated. Administer the initial dose intravenously, timed such that a bactericidal concentration of the drug is established in serum and tissues when the incision is made. Maintain therapeutic levels of the agent in serum and tissues for the duration of the operation.

When blood cells are removed cheap malegra fxt 140mg with amex, alized defence and respond whenever a plasma appears as a thin buy generic malegra fxt 140mg on-line, almost colorless fluid. It is potentially dangerous or abnormal cell is composed of about 92% water and contains such encountered. They “kill” by releasing products as plasma proteins (albumins, globulins, potent chemicals that rupture the cell and fibrinogen), gases, nutrients, salts, hormones, membrane of abnormal cells. Plasma makes possible the highly effective against cancer cells and chemical communication between body cells by cells harboring pathogens. If a blood sample clots in a test tube, the resulting Platelets fluid that remains after the clot is removed is Platelets are the smallest formed elements found serum, because fibrinogen and other clotting ele- in blood. Platelets initiate blood clotting (hemostasis) Human blood is divided into four groups, A, B, when injury occurs. These Table 9-1 Protective Actions of White Blood This chart lists the two main categories of white blood cells along with their cellular components and their protective actions. As extra or develop shortly after birth even though there cellular fluid moves through tissues, it also collects has been no previous exposure to the antigen. In the node, macrophages Blood groups are medically important in trans- phagocytize bacteria and other harmful material fusions, transplants, and maternal-fetal incompati- while T cells and B cells exert their protective bilities. When a local infection exists, the num- more than 300 different blood antigens, most of ber of bacteria entering a node is so great and the these are not of medical concern. This duct drains Lymph System into the (5) right subclavian vein, a major vessel The lymph system consists of a fluid called lymph in the cardiovascular system. Lymph from all other (in which lymphocytes and monocytes are sus- areas of the body enters the (6) thoracic duct and pended), a network of transporting vessels called drains into the (7) left subclavian vein. Lymph is lymph vessels, and a multiplicity of other struc- redeposited into the circulating blood and becomes tures, including nodes, spleen, thymus, and tonsils. Functions of the lymph system include: The (8) spleen resembles lymph nodes because it acts like a filter removing cellular debris, bacteria, • maintaining fluid balance of the body by parasites, and other infectious agents. The (9) thymus is locat- • transporting lipids away from the digestive ed in the upper part of the chest (mediastinum). It organs for use by body tissues partially controls the immune system by transform- • filtering and removing unwanted or ing certain lymphocytes into T cells, the lymp- infectious products in lymph nodes. They act as filters to protect the upper in tissue spaces and terminate at the right lym- respiratory structures from invasion by pathogens. As whole blood circulates, a small amount of Immune System plasma seeps from (1) blood capillaries. This fluid, now called extracellular (interstitial or tissue) Although exposed to a vast number of harmful fluid, resembles plasma but contains slightly less substances, most people suffer relatively few dis- protein. Anatomy and Physiology 235 defenses called resistance work together to protect encounter with its specific antigen, the B cell pro- against disease. Plasma ers (skin and mucous membranes) and chemical cells produce highly specific proteins called anti- and cellular barriers (tears, saliva, gastric juices, and bodies. Another encounters its specific antigen, it attaches to it and form of resistance called the acquired immune forms an antigen-antibody complex. This form of resist- antigen-antibody complex is formed, the antigen is ance is by far the most complex in structure and inactivated, neutralized, or tagged for destruction. It continuously develops throughout life After all antigens have been destroyed, memory as a result of exposure to one disease after another. B cells migrate to lymph tissue and remain avail- With each exposure, the immune system of an able for immediate recall if that same antigen is immunocompetent individual identifies the encountered again. In the event of a second encounter by the same invader, Cellular immunity is the component of the specific the immune system is armed and ready to destroy immune system that protects primarily against intra- it before it can cause disease. The enter tissue spaces and become highly phagocytic cytotoxic T cell is the cell that actually destroys the macrophages. It determines the antigen’s specific numbers of pathogens, including bacteria and weakness and uses this weakness as a point of attack viruses. The helper T cell is essential to the process it in such a way that the highly specific proper functioning of both humoral and cellular antigenic properties of the pathogen are placed on immunity. If the number of helper phocyte capable of responding to that specific T cells is deficient, the immune system essentially antigen. When this occurs, the specific immune shuts down and the patient becomes a victim of even system begins the operations required for the sys- the most harmless organisms. When infec- tion resolves, the suppressor T cell “shuts down” the Lymphocytes immune response. Finally, like the humoral response, Two types of lymphocytes, T cells and B cells, are the cellular response also produces memory cells. These memory T cells find their way to the lymph Each cell type mediates a specific type of immuni- system and remain there long after the encounter ty, either humoral or cellular. Memory B and T cells Humoral immunity is the component of the spe- are able to “recall” how they previously disposed of cific immune system that protects primarily against a particular antigen and are able to repeat the extracellular antigens, such as bacteria and viruses process.

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