Martin K. Rutter MD, FRCP
Almost every educated man of our time was a mason by profession and infallible in the matter of laying foundations menstrual calendar android estrace 1mg generic. That breast cancer 2014 game buy genuine estrace online, however pregnancy quotes tumblr order cheap estrace line, was not what our scholar was concerned to prove; for he maintained that the Great Wall alone would provide for the first time in the history of mankind a secure foundation for a new Tower of Babel menopause xerostomia buy generic estrace line. How could the wall, which did not form even a circle, but only a sort of quarter or half-circle, provide the foundation for a tower But in that case why build the actual wall, which after all was something concrete, the result of the lifelong labor of multitudes of people Human nature, essentially changeable, unstable as the dust, can endure no restraint; if it binds itself it soon begins to tear madly at its bonds, until it rends everything asunder, the wall, the bonds, and its very self. It is possible that these very considerations, which militated against the building of the wall at all, were not left out of account by the high command when the system of piecemeal construction was decided on. We and here I speak in the name of many people did not really know ourselves until we had carefully scrutinized the decrees of the high command, when we discovered that without the high command neither our book learning nor our human understanding would have sufficed for the humble tasks which we performed in the great whole. In the office of the command where it was and who sat there no one whom I have asked knew then or knows now in that office one may be certain that all human thoughts and desires revolved in a circle, and all human aims and fulfillments in a countercircle. And through the window the reflected splendors of divine worlds fell on the hands of the leaders as they traced their plans. And for that reason the incorruptible observer must hold that the command, if it had seriously desired it, could also have overcome those difficulties that prevented a system of continuous construction. There remains, therefore, nothing but the conclusion that the command deliberately chose the system of piecemeal construction. In those days many people, and among them the best, had a secret maxim which ran: Try with all your might to comprehend the decrees of the high command, but only up to a certain point; then avoid further meditation. A Page 271 very wise maxim, which moreover was elaborated in a parable that was later often quoted: Avoid further meditation, but not because it might be harmful; it is not at all certain that it would be harmful. It rises until it grows mightier and nourishes more richly the soil on the long stretch of its banks, still maintaining its own course until it reaches the sea, where it is all the more welcome because it is a worthier ally. But after that the river overflows its banks, loses outline and shape, slows down the speed of its current, tries to ignore its destiny by forming little seas in the interior of the land, damages the fields, and yet cannot maintain itself for long in its new expanse, but must run back between its banks again, must even dry up wretchedly in the hot season that presently follows. Now though this parable may have had extraordinary point and force during the building of the wall, it has at most only a restricted relevance for my present essay. My inquiry is purely historical; no lightning flashes any longer from the long since vanished thunderclouds, and so I may venture to seek for an explanation of the system of piecemeal construction which goes farther than the one that contented people then. The limits that my capacity for thought imposes upon me are narrow enough, but the province to be traversed here is infinite. We read of them in the books of the ancients; the cruelties they commit in accordance with their nature make us sigh in our peaceful arbors. The faithful representations of the artist show us these faces of the damned, their gaping mouths, their jaws furnished with great pointed teeth, their half-shut eyes that already seem to be seeking out the victim which their jaws will rend and devour. When our children are unruly we show them these pictures, and at once they fly weeping into Page 272 our arms. We have not seen them, and if we remain in our villages we shall never see them, even if on their wild horses they should ride as hard as they can straight toward us the land is too vast and would not let them reach us, they would end their course in the empty air. Why, then, since that is so, did we leave our homes, the stream with its bridges, our mothers and fathers, our weeping wives, our children who needed our care, and depart for the distant city to be trained there, while our thoughts journeyed still farther away to the wall in the north They, absorbed in gigantic anxieties, know of us, know our petty pursuits, see us sitting together in our humble huts, and approve or disapprove the evening prayer which the father of the house recites in the midst of his family. Far rather do I believe that the high command has existed from all eternity, and the decision to build the wall likewise. During the building of the wall and ever since to this very day I have occupied myself almost exclusively with the comparative history of races there are certain questions that one can probe to the marrow, as it were, only by this method and I have discovered that we Chinese possess certain folk and political institutions that are Page 273 unique in their clarity, others again unique in their obscurity. The desire to trace the cause of these phenomena, especially the latter, has always intrigued me and intrigues me still, and the building of the wall is itself essentially involved with these problems. In Peking, naturally, at the imperial court, there is some clarity to be found on this subject, though even that is more illusive than real. Also the teachers of political law and history in the schools of higher learning claim to be exactly informed on these matters, and to be capable of passing on their knowledge to their students. Except for the nature gods, and their ritual which fills the whole year in such beautiful and rich alternation, we think only about the Emperor. But not about the present one; or rather we would think about the present one if we knew who he was or knew anything definite about him. True and it is the sole curiosity that fills us we are always trying to get information on this subject, but, strange as it may sound, it is almost impossible to discover anything, either from pilgrims, though they have wandered through much of our land, or from near or distant villages, or from sailors, though they have navigated not only our little stream, but also the sacred rivers. So vast is our land that no fable could do justice to its vastness, the heavens can scarcely span it and Peking is only a dot in it, and the imperial palace less than a dot. Page 274 the Emperor as such, on the other hand, is mighty throughout all the hierarchies of the world: admitted. But the existent Emperor, a man like us, lies much like us on a couch which is of generous proportions, perhaps, and yet very possibly may be quite narrow and short. Like us he sometimes stretches himself and when he is very tired yawns with his delicately cut mouth. But how should we know anything about that thousands of miles away in the south almost on the borders of the Tibetan Highlands And besides, any tidings, even if they did reach us, would arrive far too late, would have become obsolete long before they reached us. The Emperor is always surrounded by a brilliant and yet ambiguous throng of nobles and courtiers malice and enmity in the guise of servants and friends who form a counterweight to the imperial power and perpetually labor to unseat the ruler from his place with poisoned arrows. The Empire is immortal, but the Emperor himself totters and falls from his throne, yes, whole dynasties sink in the end and breathe their last in one death rattle. Of these struggles and sufferings the people will never know; like tardy arrivals, like strangers in a city, they stand at the end of some densely thronged side street peacefully munching the food they have brought with them, while far away in front, in the Market Square at the heart of the city, the execution of their ruler is proceeding. There is a parable that describes this situation very well: the Emperor, so it runs, has sent a message to you, the humble subject, the insignificant shadow cowering in the remotest distance before the imperial sun; the Emperor from his deathbed has sent a message to you alone. He has commanded the messenger to kneel down by the bed, and has whispered the message to him; so much store did he lay on it that he ordered the messenger to whisper it back into his ear again. The messenger immediately sets out on his journey; a powerful, an indefatigable man; now pushing with his right arm, now with his left, he cleaves a way for himself through the throng; if he encounters resistance he Page 275 points to his breast, where the symbol of the sun glitters; the way is made easier for him than it would be for any other man. If he could reach the open fields how fast he would fly, and soon doubtless you would hear the welcome hammering of his fists on your door. But instead how vainly does he wear out his strength; still he is only making his way through the chambers of the innermost palace; never will he get to the end of them; and if he succeeded in that nothing would be gained; he must next fight his way down the stair; and if he succeeded in that nothing would be gained; the courts would still have to be crossed; and after the courts the second outer palace; and once more stairs and courts; and once more another palace; and so on for thousands of years; and if at last he should burst through the outermost gate but never, never can that happen the imperial capital would lie before him, the center of the world, crammed to bursting with its own sediment. They do not know what Emperor is reigning, and there exist doubts regarding even the name of the dynasty. In school a great deal is taught about the dynasties with the dates of succession, but the universal uncertainty in this matter is so great that even the best scholars are drawn into it. Long-dead emperors are set on the throne in our villages, and one that only lives on in song recently had a proclamation of his read out by the priest before the altar. The wives of the emperors, pampered and overweening, seduced from noble custom by wily courtiers, swelling with ambition, vehement in their greed, uncontrollable in their lust, practice their abominations ever anew. Page 276 Thus, then, do our people deal with departed emperors, but the living ruler they confuse among the dead. But we shall obey in earnest no one but our present ruler, for not to do so would be a crime. And behind the departing sedan chair of the official there rises in might as ruler of the village some figure fortuitously exalted from an urn already crumbled to dust. Similarly our people are but little affected by revolutions in the state or contemporary wars. What caused it I can no longer remember, nor is it of any importance now; occasions for revolt can be found there any day, the people are an excitable people. It happened to be a feast day, our rooms were filled with guests, the priest sat in the center and studied the sheet. Suddenly everybody started to laugh, in the confusion the sheet was torn, the beggar, who however had already received abundant alms, was driven out of the room with blows, the guests dispersed to enjoy the beautiful day. The dialect of this neighboring province differs in some essential respects from ours, and this difference occurs also in certain turns of the written word, which for us have an archaic character. If from such appearances anyone should draw the conclusion that in reality we have no Emperor, he would not be far from the truth. Over and over again it must be repeated: There is perhaps no people more faithful to the Emperor than ours in the south, but the Emperor derives no advantage from our fidelity. Syndromes
Collect refuse produced by personnel in: a 32 gallon galvanized can with cover women's health center canfield ohio buy cheap estrace 1 mg online, a 55 gallon drum with improvised cover breast cancer facts 2014 buy estrace overnight delivery, or in plastic bags (rubbish only) womens health institute of texas buy generic estrace 2mg line. Incinerate combustible refuse when the tactical situation and local policy permits menopause leg cramps generic 1mg estrace visa. Burial methods depend on the amount of refuse to be buried small amounts (1 2 barrels) can be buried using a pit, but large amounts will need to be placed in a sanitary landfill on the local economy. These sources are prioritized in the order in which they should be chosen for use: a. Easy access to large quantities of water will usually make surface water the best emergency source. When selecting a water source for a Special Operations unit, consider certain factors: a. Quantity of Water: Is there enough water in the source to sustain the troops for the desired time Quality of the Water: A detailed site survey is critical in selecting a quality water source. Check the site for possible sources of pollution: dead fish, frogs, or other animals; excessive algae growth; oil slicks or sludge deposits; and the conditions of vegetation around the site. If possible, reconnoiter for a distance of two miles upstream of the source to locate any possible sources of contamination. During deployments personnel will utilize the following prioritization and standards for water treatment of the four types of water sources: (1) Fixed Facility Chlorinate to a minimum of 2 ppm prior to consumption. If individual containers (2 quarts or less) are to be used for transport/storage of water, treat with iodine tabs (2 tabs/quart) or chlorinate to 2 ppm prior to consumption. If bulk containers (> 5 gallons) are to be used for storage/transportation of water, chlorinate to 2 ppm. If the containers are broken down and the water is placed in other containers (not the originals), treat the water with iodine (2 tabs/quart) or chlorine (2 ppm). Prepare a solution by pouring the contents of one (1) ampule of calcium hypochlorite into 1/2 canteen cup of water. Loosen cap to allow water to seep around the threads of the neck and cap of the canteen. In areas where Giardia, Entamoeba histolytica or viral hepatitis are known to be present, boil 5-119 5-120 water for thirty (30) minutes to ensure destruction of the microorganisms. Boiling provides no residual protection against recontamination and should only be used as a last resort. Identify the type(s) of malaria, information regarding malaria drug resistance, the geographic areas at risk and the seasons of the year for risk. Design a prevention and control program to include the use of prophylactic drugs; personal protective measures like skin and clothing repellents, and Permethrin bed nets; and area mosquito control measures and education programs. Administer prophylatic drugs when indicated to those who are not allergic, comply with pre-deployment dosing requirements and advise patients of side effects such as photosensitivity with doxycycline. Provide alternative, effective drug prophylaxis for those unable to take the first line regimen. Ensure that all infected patients are protected from biting mosquitoes to prevent transmitting malaria to others. Depending on the nature and extent of the operation, determine the need to conduct area mosquito control operations, to include control or elimination of breeding sites, use of larvicides and use of sprays. Identify and eliminate breeding sites for mosquitoes and other insects by improving drainage, disposing of refuse properly and applying appropriate chemicals. Ensure that the chemical pesticides you are using are effective against the vectors you want to control. Mix chemical pesticides in proper concentrations and dispense in sufficient density to control the desired pest. Trap rodents when feasible, since it is a safer alternative to chemical pesticides. Wear eye protection, rubber gloves and facemask respirator when handling pesticides. Ensure that chemical pesticides used inside living areas are labeled safe for such use. Properly dispose of all empty pesticide containers and materials contaminated with pesticides according to product labels. They harbor fleas, ticks and other insects and can attract mosquitoes and other pests. Assess the rabies threat in the deployment area and initiate a control program if needed. Maintain and review current guidelines for pre and post-exposure rabies management. Identify rabies testing laboratory (if available) and domestic and wild animal control resources in the deployment area. Work with animal control personnel to reduce the wild animal reservoir if necessary and feasible. Inform at-risk personnel about the transmission, prevention and clinical aspects of rabies. Stress the importance of reporting animal bites or other suspicious animal contact. Suggestions for a host nation landfill operation: Identify a large area of land that will not be used for many years after the landfill is closed. Find an area close to the site to store excavated dirt while the landfill is constructed. The pit will need to be lined will a nonporous membrane (such as clay) to prevent pollutants from leaching into the water table and contaminating the water. The pit must be accessible to vehicles (dump trucks) and allow them to enter the pit. The bucket loader must cover the refuse throughout the day and at the end of the day. Accept only those animals that are healthy, free of harmful diseases and chemicals and capable of being converted into wholesome products for consumption. A postmortem exam should be conducted prior to consuming any tissue or organ system (see section on Postmortem Exam). What You Need: Gloves and a stethoscope What To Do: Observe the animal at rest and in motion. You may see lameness, pain, neuromuscular deficits and/or systemic disease states in a moving animal that are not apparent in an animal at rest. Look for abnormal conditions such as continuous scratching/rubbing, emaciation or depression. Examination Specics: Lameness: Reject if limbs are deformed or have gross swelling around joints. Emaciation: Reject animal if in poor state of nutrition, as evidenced by extreme thinness. Organ Systems Analysis: Respiratory: Reject if animal has difficulty breathing, severe coughing or excessive muco-purulent discharges. Urinary: Reject if posture is abnormal when urinating, if animal strains to urinate or if urine has an unnatural color (hematuria). Reproductive: Reject animals with foul discharges from vulva, mammaries or prepuce; or with retained placentas/fetal membranes. Skin and Hair coat: Reject if skin is yellow-colored or has diffuse discolorations (red or black) or lesions. Consider rejecting animals that have obvious hair loss indicative of systemic disease. If lesions are localized they may be trimmed and the carcass retained for consumption. Do not consume an animal from an unknown source unless the carcass passes the antemortem and postmortem examinations and is cleared for consumption. The following guide is one of many ways to humanely slaughter and dress animals in a field environment. Perform an antemortem exam prior to slaughtering the animal, and a post mortem exam after.
Founder 1 gives rise women's health clinic lake haven cheap estrace 1 mg online, via a branching ar biological classifcation of leukaemias pregnancy diabetes discount 1 mg estrace with mastercard, But the stark fact remains that the chitecture menstruation and breastfeeding discount estrace 1 mg visa, to variants A menstruation during menopause order generic estrace online, B, C, and D. His research Billions of dollars are riding on the has greatly contributed to the premise that personalized medicine and targeted therapy will come to dramatic reduction in mortality from the rescue. But do we really have childhood leukaemia in the past 30 an adequate grasp of the underly years. Do we have a coherent include confrming the role that framework for accommodating and common childhood infections play in rationalizing all the multilayered complexity that exists Here, I ad the development of leukaemia and vance the argument that cancer is identifying the major causal factors of a complex adaptive system and that the disease. Professor Greaves is also its causation, stepwise emergence, a successful popular science writer and therapeutic resistance all fol low an evolutionary biology logic. Evolutionary determinants of vulnerability to cancer Principle Liability Impact in cancer Principle 1. Stem cells have inherent malignant potential: extensive, replicative, potential migratory phenotype, and quiescence option. Benefcial adaptive responses: infammation, wound healing, and angiogenesis facilitate cancer promotion. Delayed frst pregnancy, minimal breast feeding, estrogen-fuelling diets versus non-seasonal estrus: breast cancer, ovarian cancer. Diminished infection in infancy versus programmed anticipation of infection in the immune system: childhood acute lymphoblastic leukaemia. There is little or no evolutionary Our adaptive phenotypes are optimized for reproductive life Natural selection can only operate resilience for deleterious versus extensive (decades) post-reproductive longevity: on phenotypes that have impacts phenotypes in the post time for accidents to happen (via liabilities 1 and 2 above) on survival and reproduction. Adaptive features that are benefcial for reproductive life can later impose a trade-off or penalty (= antagonistic pleiotropy). Progressive selection of more robust or resilient clonal Natural selection will always variants, metastasis, and drug resistance. Winners who ic relationships of species and sig gene-centric view of cancer can survive and reproduce have the natures of prior, positive selection. Our apparent best adaptive phenotypes or ftness How odd, then, that medical prac vulnerability to cancer and our lim in relation to the prevailing selective tice, which deals with dysfunctional ited success in treating advanced forces. This is very different from biology, should have, until very re disease can be seen in a different intelligent design in that evolution cently, remained impervious to this light. And, critically, an evolutionary can only select from random varia principle [1]. How can we under biology paradigm can contribute tion in prior forms, or from the best stand emergent infectious diseas novel ideas to the challenge of how we might best control cancer. These consid Evolutionary determinants of Perspective, I summarize the ar vulnerability to cancer erations can help rationalize the gument that evolutionary biology Evolution operates by stochastic, counterintuitive or paradoxical role provides a coherent framework that or random, genetic variation that of endogenous processes in can recognizes and rationalizes the in provides the substrate for selec cer, the ubiquity of mutant clones herent, multilayered complexity of tion in the context of environmental and premalignant lesions, and the 338 Fig. All cells have been metastasis and drug resistance in interrogated for the eight mutations listed on the left. Cellular adaptability de by exome sequencing and single-nucleotide polymorphism arrays on whole leukaemic sample B1 (7. The idea that cancer involves sequential genetic changes in cells was evident from chromosome stud ies for many years [19,20] but was frst clearly posited as the clonal high frequency of cancer in ageing metabolism and signalling and re evolution paradigm by Peter Nowell humans in modern societies. Recent genome have been subject to positive, adap concept and revealed the extensive wide association studies have pro and dynamic intraclonal genetic di tive selection during human evolution vided an audit of inherited gene versity that exists in cancer [7]. But why Genetic diversity Drug (or immunological) targets or components of cellular response mutate [61]. A signifcant fraction of the variants that affect breast and pros Epigenetic Cells bypass redundant signalling pathways blocked by drugs [45]. An evolutionary foundation for cancer control 339 clonal architecture, as long recog Fig. The different colours represent nized in ecological speciation (Figs genetically distinct subclones. Endogenous selective pressures include inflammation, anoxia, and metabolic stress [57]. Genetically distinct sub clones of cancer frequently exist in distinctive, topographically different regions of tissues [25,26]. This is anticipated from evolutionary prin ciples (consider Galapagos Islands fnches) and poses considerable problems for traditional approaches to biopsy-based sampling and prog nostics, as well as for biopsy-based genomics [27]. Although mutations are sto response to selective pressures, of shifts in clonal architecture, with chastic in origin, sequencing reveals which environmental and therapeu minor subclones emerging after se mutational signatures that are indic tic exposures are clear examples. Chance is gain-of-function mutants (activat of evolution is often characterized all-pervasive in evolutionary biolo ing oncogenes) and loss-of-function by long periods of stasis or slow gy and cancer because mutations mutants (deleted tumour suppressor change, with occasional abrupt or are stochastic with respect to the genes), similar to bacteria adapting catastrophic changes [8,32], par functions encoded by genes [3]. Oncogenic the emergence of subclones with plex mutation profles of individual mutations are extremely common in all of us; premalignant lesions are Table P4. Evolutionary parameters are predictive of cancer progression and probably ubiquitous, but only a frac clinical outcome tion of them evolve to fully fedged malignancy [34]. The implication of Evolutionary parameter Clinical outcome [source] this modest evolutionary penetration Measures of intraclonal Progression of Barrett oesophagus [64] and chronic is that restraints are largely effective genetic diversity (substrate for lymphocytic leukaemia [65]. The challenge for epidemi Burden of stem cells (units of Progression and outcome in multiple cancers ([67] and ologists is taking this protracted and selection) references therein; [68]). C, cell; D+, differentiating cells; Q, quiescent (out have epigenetic plasticity and di of-cycle) cells. Pathways are spatiotemporally expressed involved are indicated around the outside of the cell. These data derive from genetic (mutational) analysis of gene interactions in yeast cells. The figure underestimates complexity by showing tates evasion of a therapeutic chal interaction networks under single, steady-state conditions. Each cell has an extensive, complex signalling net work that is highly dynamic, robust, and adaptable (Fig. In cancer, all functionally relevant mu tations [44] effectively corrupt these networks, resulting in dysregulation or resetting to a new steady state. The critical nodes in the signalling net works of normal cells, as well as cancer cells, have built-in redun dancy, which provides yet another adaptive route to clonal escape in cancer, for example from targeted therapy (Table P4. The in trinsic adaptability or epigenetic plasticity of cells is itself an ancient evolutionary legacy refecting built in safeguards to combat adverse circumstances, particularly for stem cells in more complex long-lived or ganisms.
Depletion of the 237 high molecular weight chains results in more predictable pharmacokinetics women's health center elmhurst hospital cheap 1 mg estrace amex, allowing dosing by body weight without routine coagulation monitoring the women's health big book of exercises free download buy estrace 1 mg fast delivery. Fondaparinux acts primarily to accelerate antithrombin inhibition of factor Xa menstrual headache relief estrace 1mg sale, with no significant activity versus thrombin the women's health big book of exercises epub estrace 1 mg with amex. Fondaparinux does not appear to be associated with heparin-induced thrombocytopenia. Fondaparinux is not neutralized by protamine sulfate; there is no specific antidote for it. In practice, protamine is not often used as overdose may independently result in a coagulopathy. However, the recent introduction of direct thrombin and factor Xa inhibitors (see below) has begun to impact chronic oral anticoagulant treatment. The gla residues form tight Ca binding sites that are necessary to order the overall structure of the amino-terminus domain, and facilitate the binding of these coagulation factors to the membrane surface. Warfarin interferes with reduction of vitamin K and thereby depletes the body of this vitamin. In the absence of vitamin K, under carboxylated clotting factors with markedly reduced or absent coagulant activity are produced. However, the therapeutic effect of this drug does not occur until clotting factor levels decline to about 20 30% of normal. Approximately 5% of patients treated with warfarin develop significant bleeding, thus the relative risk of thrombosis versus hemorrhage must be weighed. Its anticoagulant effect is affected by genetic factors, by changes in diet (particularly foods containing vitamin K), and by changes in drug metabolism and serum protein binding induced by other drugs. Physicians also prescribe warfarin to reduce the risk of stroke and other arterial emboli from the heart in patients with chronic atrial fibrillation, prosthetic heart valves and other cardiac disorders. An overdose of warfarin can be counteracted by administering Vitamin K1 (phytonadione). In cases of severe overdose or major bleeding, rapid correction of warfarin-induced clotting factor deficiency can be accomplished by giving the patient plasma or prothrombin complex concentrate, a plasma-derived preparation enriched in vitamin K-dependent clotting factors. Warfarin readily crosses the placenta, and can cause fetal hemorrhage, fetal malformations (first trimester), or even intrauterine death. Oral anticoagulants are not secreted in breast milk and so can be given to mothers who are breast-feeding. Warfarin-induced skin necrosis, characterized by thrombosis of the microvasculature causing lesions that can become necrotic. This rare complication is thought to be due to suppression of protein C production by warfarin. Warfarin is particularly susceptible to drug-drug interactions, a feature that constitutes an important disadvantage to its use and that must always be kept in mind when prescribing new medications to warfarin-treated patients. Direct Thrombin Inhibitors small peptides or peptide-mimetics (chemicals that have peptide-like structure) that directly bind to and inhibit the active site of thrombin. These molecules can bind to and inhibit both clot-bound thrombin and circulating thrombin, which may potentially increase their efficacy compared to the antithrombin-heparin complex. Advantages and disadvantages of new oral anticoagulants vs warfarin: Initial cost of the new agents is ~10-fold greater than warfarin. A portion of this cost differential is recouped because these drugs have predictable pharmacokinetics, fewer drug interactions, and do not require routine monitoring. Strategies for inhibition of platelet function Arterial thrombi form under high-flow conditions and are platelet dependent. Antiplatelet drugs are often used together with heparin-based therapies in the acute setting, particularly in coronary disease. In platelets, this enzyme converts arachidonic acid to thromboxane A2, a powerful platelet activator. The inhibition of cyclooxygenase is irreversible, resulting in a suppression of platelet aggregation for the life of the platelet 7-10 days. Note that higher doses of aspirin also inhibit cyclooxygenase in the vascular endothelium, resulting in decreased prostacyclin production. Because endothelial cells, unlike platelets, can make more cyclooxygenase, the antiplatelet effect of aspirin predominates. This procedure physically disrupts the occluding atherosclerotic plaque or thrombus with a catheter inserted into the artery. There is significant risk of reocclusion since the procedure damages the endothelial lining of the vessel wall, providing a site for thrombus formation. Trials with the combination of dipyridamole and aspirin suggest a reduction in the incidence of reocclusion by decreasing thrombus formation. This is a syndrome of the cerebral circulation that may be initiated by atherosclerotic lesions. Low doses (50-150 mg/day) inhibit the platelet cyclooxygenase more than the vascular enzyme, resulting in net platelet inhibition. If used with other anticoagulants, aspirin often potentiates antiplatelet effects. The use of these drugs has been associated with increased risk of cardiovascular events, leading to the recent withdrawal of rofecoxib (Vioxx) from the market. Eptifibatide is a cyclic peptide containing six amino acids, derived from a rattlesnake venom peptide. Oral versions were tried, but had partial agonist function, and resulted in immune response against drug. Thrombolytic Therapy Thrombolytic therapy is sometimes used to treat patients with established thrombosis, in order to dissolve the clot and limit or reverse tissue and organ injury caused by vessel occlusion. Thrombolytic drugs convert the inactive zymogen plasminogen to the active enzyme plasmin. Clots become more resistant to lysis as they age, and tissue injury caused by vessel occlusion tends to become irreversible over time, so thrombolytic therapy has the greatest benefit when it is initiated early after clot formation. Clot lysis may expose clot-bound thrombin, and thus enhance platelet activation and aggregability. Therefore thrombolytic drugs are often given in conjunction with antiplatelet or antithrombotic drugs, such as aspirin and heparin. Mechanism of action these agents convert plasminogen to plasmin, which then digests the fibrin thrombus. Because these drugs activate clot-bound and not circulating plasminogen, most of the fibrinolytic activity is confined to the clot. When given within 2-3 hours of symptom onset thrombolytic drugs can limit or reverse ischemic damage, improve cardiac function, and decrease mortality. When given within 3 hours of symptom onset), thrombolytic therapy improves neurologic outcome and decreases mortality in acute ischemic stroke. Its use in venous thromboembolic disease has not conclusively been shown to improve long term clinical outcomes. This plasminogen activator is a naturally occurring serine protease present in most normal and neoplastic cells. Factors Determining the Success of Thrombolytic Therapy Time of administration of thrombolytic agent the earlier, the better. To prevent reocclusion, prolonged periods of thrombolytic treatment or combination therapy with heparin or aspirin has been used. Side effects: o Increases water resorption from the kidneys (also prescribed for bedwetting) o Hyponatremia o Headaches, nausea, seizures are possible 2. Aminocaproic Acid (also known as Amicar, -aminocaproic acid, or 6-aminohexanoic acid) Aminocaproic acid is an anti-fibrinolytic. Indications: Treatment of excessive post-operative bleeding Reduce blood loss during coronary bypass Treatment of bleeding associated with administration of thrombolytic drugs Prevention of bleeding in patients with severe, chronic thrombocytopenia A recent clinical trial showed that administration of tranexamic acid to trauma patients within 3 hours of injury decreased the likelihood of death from bleeding 2. Vitamin K Several of the coagulation factors are vitamin K-dependent for their production. Order line estrace. Jeevanarekha Women's Health | 23rd September 2019 | Full Episode | ETV Life. |
