Abstract-Acute-phase proteins, which respond to systemic proinflammatory cytokines such as interleuken-6, are elevated in cardiovascular disease and are predictive markers of future ischemic events, even over decades. This suggests a role for proinflammatory cytokines and/or acute phase proteins in early lesion development. To explore this issue, we fed C57Bl/6 and nonobese diabetic male mice high-fat (20% total fat, 1.5% cholesterol) diets and ApoE-deficient male mice both high-fat and normal chow diets for 6 to 21 weeks, injecting them weekly with either 5000 U recombinant interleukin-6 (rIL-6) or saline buffer. Blood was collected when animals were euthanized and assayed for cytokines, acute-phase proteins, and cholesterol. Across all mice, IL-6 injection resulted in significant increases in proinflammatory cytokines (IL-6, 4.6-fold; IL-1, 1.6-fold; and tissue necrosis factor-␣, 1.7-fold) and fibrinogen (1.2-fold) and with decreased concentrations of albumin (0.9-fold) in plasma. Total cholesterol levels were unchanged between rIL-6 -treated and nontreated groups. Serial sections through the aortic sinus were stained with oil red O to detect fatty streaks, and area of the lesions was determined by image analysis. Although no fatty streaks were detected in the nonobese diabetic mice with or without rIL-6 treatment, rIL-6 treatment increased lesion size in C57Bl/6 and ApoE-deficient mice 1.9-to 5.1-fold over lesions in saline-treated animals. These results suggest that under the appropriate circumstances changes in circulating proinflammatory cytokines and acute-phase proteins may be more than just markers of atherosclerosis but actual participants in early lesion development.
The nasogastric tube can produce sudden, life-threatening bilateral vocal cord paralysis and is often an unrecognized cause of this clinical entity. The pathophysiologic mechanism is thought to be paresis of the posterior cricoarytenoid muscles secondary to ulceration and infection over the posterior lamina of the cricoid. Since our initial report of this entity in 1981, several cases have been photo-documented. Study of whole organ sections of an involved larynx have demonstrated the histopathology. Diabetic renal transplant patients appear to be particularly susceptible to the condition, due to prolonged gastroparesis and requirement for nasogastric tube drainage. Esophagoscopy should be performed promptly in these patients when pharyngodynia, hoarseness, or evolving stridor present in the postoperative period.
Experimental evidence suggests that tumor growth beyond the earliest stages is dependent on angiogenesis, or neovascularization, and that angiogenesis may also promote metastasis. Recent clinical studies demonstrate that angiogenesis is a prognostic marker in breast, lung, and prostate cancer. To investigate whether tumor angiogenesis also correlates with metastasis and survival in early head and neck carcinoma, we quantified the microvascularity of 106 primary carcinomas prior to treatment and correlated the counts with eventual outcome after 3 to 15 years of follow-up. Microvessels were stained immunocytochemically for von Willebrand factor and then counted by light microscopy. Microvessels were counted per 200x and 400x fields, and their density was graded from 1 to 4, in the area of most intense neovascularization. We found that neither microvessel counts nor density grades correlated with metastatic disease, local recurrence, or survival in early head and neck carcinoma. These results are in contradistinction to those recently reported for other tumor sites.
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