The blood and bone marrow constitute the hematologic organ system. Unlike other organ systems, hematologic organs are distributed in space and provide for a variety of seemingly unrelated functions. The hematologic system has both cellular and fluid-phase elements. Cellular elements include erythrocytes, leukocytes, and platelets; fluid phase elements include coagulation factors, natural antithrombotics, and proteins of the fibrinolytic system. The most common abnormalities of the hematologic system in patients with sepsis are anemia, leukocytosis, thrombocytopenia, and activation of the hemostatic system. Dysfunction of the hematologic organ system is an early manifestation of severe sepsis and is seen in virtually all patients with this disease. In concert with alterations in the endothelium, hematologic changes reflect both the body's reaction to an infectious insult as well as attempts to restore homeostasis. Dysfunction of the hematologic organ system can contribute to multiple organ dysfunctions and death. Recognizing these sepsis-associated changes and understanding the underlying pathophysiology are key to improving outcomes in patients with this deadly disease.
No abstract
Cachexia, usually defined as the loss of >5% of an individual's baseline bodyweight over 2-6 months, occurs with a number of diseases that includes not only AIDS and advanced cancer but also chronic heart failure, rheumatoid arthritis, chronic obstructive pulmonary disease, Crohn disease, and renal failure. Anorexia is considered a key component of the anorexia-cachexia syndrome. Progestogens, particularly megestrol acetate, are commonly used to treat anorexia-cachexia. The mechanism of action of megestrol is believed to involve stimulation of appetite by both direct and indirect pathways and antagonism of the metabolic effects of the principal catabolic cytokines. Because the bioavailability of megestrol acetate directly affects its efficacy and safety, the formulation was refined to enhance its pharmacokinetics. Such efforts yielded megestrol acetate in a tablet form, followed by a concentrated oral suspension form, and an oral suspension form developed using nanocrystal technology. Nanocrystal technology was designed specifically to optimize drug delivery and enhance the bioavailability of drugs that have poor solubility in water. Megestrol acetate nanocrystal oral suspension is currently under review by the US FDA for the treatment of cachexia in patients with AIDS. Preclinical pharmacokinetic data suggest that the new megestrol acetate formulation has the potential to significantly shorten the time to clinical response and thus may improve outcomes in patients with anorexia-cachexia.
Severe sepsis is a major public health concern and a burden on the healthcare system. Despite improvements in efforts to control the source of infection and increased recognition by healthcare providers of patients with the disease, the mortality rate remains unacceptably high, from 30% to 50%. The systemic inflammatory response syndrome criteria are used as diagnostic indicators of sepsis when they occur in patients with known or suspected infection. The outcome of a patient with severe sepsis is often related to the occurrence of sepsis-induced multiple organ dysfunction syndrome. Multiple organ dysfunction syndrome appears to result from a cascade of organism-related factors, inflammatory mediators, endothelial injury, disturbed hemostasis, and microcirculatory abnormalities. In patients with severe sepsis, derangements of inflammation and coagulation are tightly linked. Although numerous clinical trials focused on interventions in one or the other of the inflammatory and coagulation systems failed to show reduced mortality due to sepsis, a member of a new class of drugs called “cogins” was effective. In its active form, protein C has anti-inflammatory, antithrombotic, and profibrinolytic properties that can reduce organ injury associated with severe sepsis. A recombinant form of activated protein C, drotrecogin alfa (activated), significantly reduces 28-day mortality due to all causes in patients with severe sepsis and has an acceptable safety profile. This review provides an overview of severe sepsis, highlighting recent advances in treatment of the disease and the role of critical care nurses.
The authors observed rosette formation and partially fibrillar, blue-grey, extracellular material in Wright-Giemsa-stained bone marrow aspirate smears in five preparations from three cases of neuroblastoma metastatic to bone marrow. These features are little publicized in the literature and textbooks. These findings in neuroblastoma metastatic to bone marrow should prove helpful in differentiating that entity from acute leukemia and from other metastatic small-cell neoplasms in bone marrow.
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