Basic Pathology Note And Stening Tissue Procedure And S Pdf
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Digital subtraction angiography DSA is a fluoroscopic technique used extensively in interventional radiology for visualizing blood vessels. Radiopaque structures such as bones are eliminated "subtracted" digitally from the image, thus allowing for an accurate depiction of the blood vessels.
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AA indicates acetylsalicylic acid; Cox, cyclooxygenase. Aspirin irreversibly blocks cyclooxygenase and inhibits thromboxane A 2 production throughout the 7 to 10 days lifetime of the anucleated platelet. Prostacyclin is synthesized in endothelial cells, which recover their cyclooxygenase function quickly, making aspirin effect on endothelial cells marginal compared with its antiplatelet effect. NSAID indicates nonsteroidal anti-inflammatory drug.
Low-dose aspirin reaches appreciable plasma levels by 20 minutes and exerts antiplatelet effects within 60 minutes. Arch Intern Med. Platelet adhesion, activation, and aggregation are central to thrombus formation, which follows atherosclerotic plaque disruption and causes acute coronary syndromes. Aspirin and clopidogrel exert their antiplatelet effects by inhibiting thromboxane A 2 production and adenosine diphosphate—induced platelet aggregation pathways, respectively.
Aspirin has proven benefits in primary and secondary prevention of coronary artery disease. Clopidogrel, an alternative antiplatelet agent used in patients with aspirin intolerance, is especially useful in combination with aspirin after coronary stent procedures. The CURE Clopidogrel in Unstable Angina to Prevent Recurrent Events study demonstrates for the first time the benefit of adding clopidogrel to aspirin rather than using aspirin alone in patients having acute coronary syndromes without ST-segment elevation myocardial infarction.
Aspirin resistance can be assessed through platelet aggregometry testing, measurement of urinary thromboxane metabolites, and, possibly, genomic testing in the future. The major finding of the study is that clopidogrel given in conjunction with aspirin improves the outcome of patients with ACS compared with aspirin treatment alone. Clopidogrel appears to add incremental value to conventional therapy.
The purpose of this review is to critically analyze the findings of several antiplatelet trials with a focus on the CURE study, and to provide guidance in the use of aspirin and clopidogrel for patients with ACS.
Acute coronary syndrome is a spectrum of ischemic coronary events that share thesame pathophysiology and includes unstable angina, non—ST-segment elevation myocardial infarction MI , ST-segment elevation MI, and sudden death. Acute thrombus formation on a disrupted atherosclerotic plaque seems to be the major mechanism responsible for the onset of ACS.
The magnitude and stability of the thrombus formed is regulated by the nature of the exposed substrate ie, the biochemical composition of the lesion and the degree of injury ; the local rheological conditions; and the presence of certain systemic factors affecting blood thrombogenicity eg, hyperlipidemia and diabetes.
Plaque disruption depends on both passive and active phenomena. Macrophages produce proteolytic enzymes, especially matrix metalloproteinases, that actively dissolve the matrix of the fibrous cap, leading to plaque rupture and exposure of the underlying lipid core.
These released substances, especially thromboxane A 2 and adenosine diphosphate ADP , induce the binding of platelets to each other, causing platelet aggregation and formation of white thrombus.
While platelets secure the primary hemostasis at the site of ruptured plaque, tissue factor induces thrombin formation by activating the extrinsic coagulation cascade. Thrombin then converts fibrinogen to fibrin and stabilizes the final clot or red thrombus secondary hemostasis 8 that leads in some cases to ACS. A meta-analysis of several postmortem studies involving patients who had died from cardiovascular causes showed the presence of thrombus on disrupted lesions in approximately two thirds of cases.
Eroded lesions usually induce more severe stenosis and occur more commonly at a younger age, in women, and in diabetic and hyperlipidemic patients. The key role of platelet activation and thrombosis in ACS is emphasized by the significant clinical benefits associated with the use of antiplatelet agents, such as aspirin which blocks thromboxane A 2 formation and clopidogrel which inhibits ADP-induced platelet aggregation Figure 1.
However, platelet aggregation is a complex pathophysiologic process; multiple therapeutic agents may be required simultaneously to block its redundant pathways.
Aspirin is known today to be an inexpensive, safe, and effective antiplatelet drug but its beginnings were less than easy. Piria isolated salicylic acid from the willow bark in , but it was not until that Hoffman, a chemist at Bayer's laboratories, became interested in salicylic acid. At that time, Hoffman's rheumatic father had grown intolerant to the sodium salicylate available.
Though aspirin was first recognized in the s to reduce the incidence of MI, 13 mechanisms of its action remained unclear until when Weiss and Aledort 14 published the first article to acknowledge the inhibitory effects of aspirin on platelets. Sir John R. Vane, 15 , 16 who received the Nobel Prize for his work, found a dose-dependent inhibition of prostaglandin formation with aspirin, salicylate, and indomethacin, and provided further support for the therapeutic benefits of aspirin.
His work and the work of others led also to the discovery of thromboxane A 2 and prostacyclin PGI 2 in and , respectively. Aspirin irreversibly inhibits cyclooxygenase, an enzyme responsible for the formation of eicosanoids, which include PGI 2 and thromboxane A 2 15 , 20 , 21 Figure 2. Because thromboxane A 2 promotes platelet aggregation, the acetylation of cyclooxygenase by aspirin decreases thromboxane generation in platelets, and therefore platelet aggregability, throughout the platelet's lifetime, which averages 7 to 10 days.
PGI 2 is an eicosanoid that inhibits platelet aggregation and antagonizes the "blood-thinning" effects of aspirin; but endothelial cells, unlike the platelets, recover their cyclooxygenase function quickly, and this effect of aspirin appears to be short-lived and marginal compared with its antiplatelet effects.
The benefits of aspirin emanate not only from its antiplatelet effects, but potentially also from its anti-inflammatory properties. Atherosclerosis is known to be a chronic inflammatory disease of the vessel wall, 26 and it is not surprising that in a prospective study involving apparently healthy men participating in the Physicians' Health Study, baseline C-reactive protein levels predicted future MI and stroke events.
The relative quantitative antiplatelet and anti-inflammatory benefits of aspirin in the treatment of coronary disease are not entirely clear. Recent evidence also points to potential antioxidative properties of aspirin. In one study, 28 long-term administration of aspirin to both normotensive and hypertensive rats resulted in a decrease in nicotinamide adenine dinucleotide phosphate oxidase activity and, therefore, its generation of superoxide anion.
However, the antioxidative properties of aspirin still need to be demonstrated in humans. The earliest comprehensive evidence for the efficacy of antiplatelet therapy in preventing cardiovascular events comes from the Antiplatelet Trialists' Collaboration study.
No evidence of increase in nonvascular death rates was noted with antiplatelet therapy. Not unexpectedly, the beneficial effect of antiplatelet therapy was demonstrated across all patient subsets of the study, but the benefits were greater in the high-risk group.
The Antithrombotic Trialists' Collaboration group recently published an updated meta-analysis of all randomized antiplatelet trials in high-risk patients.
It also included patients at risk of embolism and other conditions that placed them at high risk diabetes, hemodialysis, carotid disease. The main outcome measured was serious vascular event defined as nonfatal MI, nonfatal stroke, or vascular death. Most importantly, indirect comparisons of various aspirin regimens in the meta-analysis showed that a daily dose of aspirin in the range of 75 to mg appears adequate.
However, in clinical situations demanding immediate antithrombotic effect, such as ACS, a loading dose of to mg of aspirin is still considered the standard choice. Several landmark trials established the efficacy of aspirin, particularly in primary and secondary prevention of CAD Table 1.
Lewis and colleagues 31 conducted one of the earliest placebo-controlled randomized trials of aspirin in patients with ACS. Although the survival curves converged slightly over time, a significant survival benefit was still maintained after 15 months of median follow-up. There was an accompanying small absolute excess in minor bleeding events 0. Aspirin therapy has now become conventional for all patients suspected of having an ACS. Aspirin's benefits in primary prevention of CAD are supported by many trials as well.
The US Physicians' Health Study 33 was the first and largest primary prevention study of aspirin in cardiovascular disease. This beneficial effect was seen primarily in patients older than 50 years. However, there was no beneficial effect of aspirin on cardiovascular mortality the primary end point. Treated patients also showed a nonsignificant trend toward higher rates of strokes, mostly hemorrhagic, compared with patients taking placebo.
The benefits of aspirin in primary prevention of cardiovascular disease in high-risk patients were later corroborated by other primary prevention studies. The beneficial effect of the daily mg dose of aspirin used in this study consisted almost entirely in the incidence reduction of nonfatal events. They concluded that aspirin in primary prevention is safe and useful in patients with a 1-year coronary event risk greater than or equal to 1. The benefits of aspirin in primary prevention of CAD apply to women as well.
Adenosine diphosphate is a substance released by activated platelets that amplifies platelet aggregability. Clopidogrel has a quicker onset of action, and appears to be safer than ticlopidine, an earlier thienopyridine. Inhibition of ADP-induced platelet aggregation occurs 2 hours after a mg loading dose of clopidogrel.
Clopidogrel was approved in for use in secondary prevention of cardiovascular disease, and has been in widespread use since then Table 2. It is most commonly used for the unlabeled indication of antiplatelet activity following percutaneous coronary intervention, where its efficacy is proven. Clopidogrel, the newer thienopyridine, has not been compared with placebo. Older trials, however, compared the therapeutic effects of ticlopidine and placebo and found a statistically significant superiority of ticlopidine.
Clopidogrel vs Aspirin in Patients at Risk of Ischemic Events CAPRIE 47 was a randomized head-to-head trial comparing the efficacy and safety of a daily mg dose of clopidogrel with a daily mg dose of aspirin in patients with cardiovascular disease.
After an average of 1. Severe intracranial hemorrhage and gastrointestinal bleeding events occurred in 0. The rate of ever-reported gastrointestinal bleeding complication was significantly lower in the clopidogrel group than in the aspirin group 1. Despite clopidogrel's apparent success, the difference between the 2 antiplatelet therapies was modest equivalent to 5 events per patients. Lower event rates might have occurred because of the "healthy patient" selection bias inherent in studies such as CAPRIE, and this may translate into a lower number of patients needing treatment and better cost-effectiveness for clopidogrel in clinical practice.
In a post hoc analysis from the CAPRIE study, Bhatt et al 50 demonstrated the benefit of clopidogrel over aspirin in patients who had prior surgical revascularization. Clopidogrel has an efficacy similar to that of ticlopidine in preventing stent thrombosis. Neutropenia is associated with ticlopidine but not with clopidogrel; and although rare cases of thrombotic thrombocytopenic purpura have been described with clopidogrel cases per million , causality has not been established.
Clopidogrel is usually given for 1 month after stent implantation, but many physicians argue for a longer duration of therapy. How long one should use clopidogrel after percutaneous coronary intervention has recently been the subject of a clinical trial. Clopidogrel for the Reduction of Events During Observation CREDO was a multicenter, double-blind study of patients with stable and unstable angina who were undergoing percutaneous coronary intervention.
The trial emonstrated the safety and efficacy of clopidogrel treatment before the procedure, and the beneficial effects of prolonged 1-year vs short-term 1-month dual antiplatelet therapy. Recently, Bhatt and colleagues 57 performed a meta-analysis of the major randomized trials and registries comparing clopidogrel and ticlopidine use after coronary stent deployment.
They demonstrated lower rates of major adverse cardiac events and in addition to the known adverse effects with clopidogrel and concluded that clopidogrel plus aspirin should be the standard antiplatelet regimen after stent deployment. Experimental studies have shown synergy between the thienopyridines and aspirin. Their combination inhibits ADP-induced platelet activation and thromboxane A 2 production, 2 different pathways that affect platelet aggregability. Study Design. It investigated whether prolonged combined treatment with aspirin and clopidogrel would have incremental benefit over aspirin alone in vascular outcomes in patients having ACS without ST-segment elevation MI.
The clopidogrel group received an immediate loading dose of mg of clopidogrel followed by 75 mg of clopidogrel daily, while aspirin was given to both groups at doses ranging from 75 mg to mg daily at the treating physician's discretion. Treatment continued from 3 to 12 months mean, 9 months , during which the patients had serial follow-up evaluations. The mean age of patients was 64 years. Main Results.
Using clopidogrel plus aspirin significantly reduced the risk of the first primary composite end point of nonfatal MI, stroke, and cardiovascular death 9. It must be stressed, however, that the composite end points were driven mainly by the statistically significant decrease in the MI risk reduction rate 5. The superiority of the combination of aspirin and clopidogrel appeared early in the course of treatment, with significant benefit occurring during the first 24 hours.
This superiority was maintained through the month study.
Surgery Cases Pdf
Intestinal obstruction is significant mechanical impairment or complete arrest of the passage of contents through the intestine due to pathology that causes blockage of the bowel. Symptoms include cramping pain, vomiting, obstipation, and lack of flatus. Diagnosis is clinical and confirmed by abdominal x-rays. Treatment is fluid resuscitation, nasogastric suction, and, in most cases of complete obstruction, surgery. See also Acute Abdominal Pain.
RadInfo 4 Kids: My chest x-ray exam. A ballooning out of a segment of artery caused by disease or weakness in the vessel wall called an aneurysm that occurs in the portion of the aorta that runs through the abdomen. For more information, see the Abdominal aortic aneurysm page. In radiation or medical physics, the number of disintegrations per second of a radionuclide. See also definitive treatment. Allopurinol A drug that lowers an elevated level of uric acid in the blood caused by some cancer treatments. Alpha-1 antitrypsin A1AT A protein that protects the lung.
What to know about cerebrovascular disease
AA indicates acetylsalicylic acid; Cox, cyclooxygenase. Aspirin irreversibly blocks cyclooxygenase and inhibits thromboxane A 2 production throughout the 7 to 10 days lifetime of the anucleated platelet. Prostacyclin is synthesized in endothelial cells, which recover their cyclooxygenase function quickly, making aspirin effect on endothelial cells marginal compared with its antiplatelet effect.
A stroke is a medical condition in which poor blood flow to the brain causes cell death. The main risk factor for stroke is high blood pressure. Prevention includes decreasing risk factors, surgery to open up the arteries to the brain in those with problematic carotid narrowing , and warfarin in people with atrial fibrillation.
Metrics details. Chronic pancreatitis is a progressive and persistent inflammatory disease resulting in pancreatic insufficiency leading to diabetes and steatorrhea.
Glossary of terms
Когда Мидж заговорила, ее голос был мрачным: - Стратмор мог обойти фильтры. Джабба снова вздохнул. - Это была шутка, Мидж. - Но он знал, что сказанного не вернешь. ГЛАВА 62 Коммандер и Сьюзан стояли у закрытого люка и обсуждали, что делать. - Итак, внизу у нас погибший Чатрукьян, - констатировал Стратмор. - Если мы вызовем помощь, шифровалка превратится в цирк.