Disseminated Necrosis

Biopsy findings show disseminated muscle fiber atrophy which is confined to type 2 fibers, in many instances with type 2B (glycolytic) fibers most affected (Figure 23). Muscle necrosis is not seen, though at ultrastructural level focal myofibrillar disruption and myofilament loss may be evident. The muscle atrophy seems to be due to decreased protein synthesis, and at high doses, to increased catabolism. The reason for the selective effect on phasic, glycolytic fibers is not clear since, although steroids interfere with carbohydrate metabolism and oxidative capacity, there seems to be no overall effect on ATP levels. Nevertheless it has been... 

Pancreatic necrosis is a diffuse inflammation of the pancreas with infectious etiology. Pancreatic necrosis occurs within the first 2 weeks of acute pancreatitis and develops in 10% to 30% of patients with acute pancreatitis. The necrotic pancreas can become secondarily infected with enteric gramnegative bacteria (such as E. coli), and disseminated infection may result from pancreatic necrosis.7,8... 

IV colchicine should be avoided because it is associated with serious adverse effects (e.g., bone marrow suppression, tissue necrosis from local extravasation, disseminated intravascular coagulation, hepatocellular toxicity, and renal failure). If considered necessary, the recommended initial IV dose is 2 mg (if renal function is normal) diluted in 10 to 20 mL of normal saline administered slowly over 10 to 20 minutes in a secure, free-flowing IV line to avoid extravasation. This may be followed by two additional doses of 1 mg each at 6-hour intervals, with the total dose not exceeding 4 mg. After a full IV course, patients should not receive colchicine by any route for at least 7 days. 

Colchicine often causes diarrhea and may occasionally cause nausea, vomiting, and abdominal pain. Hepatic necrosis, acute renal failure, disseminated intravascular coagulation, and seizures have also been observed. Colchicine may rarely cause hair loss and bone marrow depression as well as peripheral neuritis, myopathy, and in some cases death. The more severe adverse events have been associated with the intravenous administration of colchicine. 

Acute exposure of rats to 1,2-dichloroethane caused disseminated haemorrhagic lesions, mainly in the liver chronic exposure caused degeneration of the liver and tubular damage and necrosis of the kidneys (lARC, 1979). The limited organ toxicity of... 

Cytokines, eg, interferons, interleukins, tumor necrosis factor (TNF), and certain growth factors, could have antitumor activity direcdy, or may modulate cellular mechanisms of antitumor activity (2). Cytokines may be used to influence the proliferation and differentiation of T-cells, B-cells, macrophage—monocyte, myeloid, or other hematopoietic cells. Alternatively, the induction of interferon release may represent an important approach for synthetic—medicinal chemistry, to search for effective antiinflammatory and antifibrotic agents. Inducers of interferon release may also be useful for lepromatous leprosy and chronic granulomatous disease. The potential cytokine and cytokine-related therapeutic approaches to treatment of disease are summarized in Table 4. A combination of cytokines is a feasible modality for treatment of immunologically related diseases however, there are dangers inherent in such an approach, as shown by the induction of lethal disseminated intravascular coagulation in mice administered TNF-a and IFN-y. 

F3. Fitz, R. H., Acute pancreatitis A consideration of pancreatic hemorrhage, hemorrhagic suppurative and gangrenous pancreatitis and of disseminated fat necrosis. Boston Med. Surg. 120, 181-187 (1889). 

Single-cell necrosis Necrotic hepatocytes are found both as groups and in isolation. Initially, they either form small patches or are disseminated throughout the liver. The reticular fibres at first remain, but are later removed. 

Ascorbic acid has been thought to precipitate widespread tumor hemorrhage and necrosis with disastrous consequences in patients with very rapidly proliferating and widely disseminating tumors. These observations suggest that ascorbic acid should be prescribed with extreme caution for persons with advanced cancer (40). 

DiCato M-A, Ellman L. Letter Coumadin-induced necrosis of breast, disseminated intravascular coagulation, and hemolytic anemia. Ann Intern Med 1975 83(2) 233-4. 

A 53-year-old man had a side-to-side Ueo-descending colostomy for disseminated carcinoma. FlnoronracU was given in doses of 15 mg/kg for 4 days, then 7.5 mg/kg intravenously on days 6 and 8. He developed severe diarrhea and severe ulceration of the bypassed portion of the colon, resulting in necrosis, and death occurred as the result of bronchopneumonia. Autopsy showed ulcers from the ileocecal valve to the ileo-colostomy site. The mucosa of the stomach, small intestine, and colon distal to the colostomy were not involved. 

A 54-year-old man with rheumatoid arthritis for 12 years was given infliximab, with remission. He then developed a painful, confluent, erythematous, pustular rash over his trunk and limbs. Skin biopsy showed an acute pustular dermatitis. Five hours later he collapsed with a tachycardia (140/minute) and a blood pressure of 120/70 mmHg. He was apyrexial. His left leg was very tense, painful, and swollen, and he had a disseminated intravascular coagulopathy. There was marked necrosis of his adductor compartment and fascia of his left thigh and necrotic muscles were debrided. Blood cultures and skin swabs grew group A hemolytic streptococci. He then became unstable and died, despite efforts at resuscitation. 

Helbling D, Breitbach TH, Krause M. Disseminated cytomegalovirus infection in Crohn s disease following antitumour necrosis factor therapy. Eur J Gastroenterol Hepatol 2002 14(12) 1393-5. 

The hematological effects of tumor necrosis factor alfa mostly consist of dose-related thrombocytopenia and granulocytopenia, and decreased monocyte or lymphocyte counts (SED-13, 1111) (11,12). Septic episodes are sometimes associated with leukopenia. Coagulopathy with laboratory evidence of disseminated intravascular coagulopathy was found in 30% of patients and was sometimes associated with thromboembolic events (13). Other coagulation disorders include transient alterations in prothrombin time, and a rise in the plasma concentrations of von Willebrand factor was found in healthy volunteers (14). 

The effects of amphetamines on the kidney are mainly acute tubular necrosis on the basis of rhabdomyolysis (with myoglobinuria) and a disseminated intravascular coagulopathy. But, malignant hypertension and the resultant effects on the kidneys, must always be a consideration in the differential diagnosis of renal failure [45-50]. These effects are likely to be chronic and irreversible. Bingham et al reported a case of necrotising vasculopathy after the ingestion of... 

Hypoglycemia can be seen. Rhabdomyolysis, acute renal failure, disseminated intravascular coagulation, liver necrosis, and traumatic injury are reported complications. The anesthetic dose of phencyclidine is 0.25 mg kg intravenously. Doses of 1-5 mg are purported to cause euphoria and numbness, 5-10 mg cause excitation and hallucinations, and 20 mg or more cause coma and serious toxicity or death. Plasma concentrations of phencyclidine vary widely after overdose. Phencyclidine crosses the placenta resulting in hyperirritability, tremors and hypertonia, depressed reflexes, and nystagmus in neonates. 

Disorders of fibrinogen also occur in the liver. For example, dysfibrinogenemia may be seen in both acute and chronic liver disease and leads to prolongation of the partial thromboplastin time, Disseminated intravascular coagulation occurs with acute hepatic necrosis, presumably as a result of the release of tissue thromboplastin and defective clearance of inhibitors such as antithrombin and protein C. Thrombocytopenia may contribute to ineffective intravascular coagulation. Although commonly attributed to splenic sequestration (hypersplenism), there is evidence of antibody-mediated platelet destruction, as occurs in... 

Disseminates from entry point via bloodstream to organs, esp kidneys (interstitial nephritis), liver (centrilobular necrosis), and muscle (focal necrosis)... 

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