Antonio Leone

OBJECTIVE: Studies in animals have indicated that increased production of nitric oxide from an inducible isoform of nitric oxide synthase contributes to the pathophysiology of endotoxic and cytokine induced shock. The aim of this study was to determine the role of nitric oxide in septic shock in humans. METHODS: The study was a randomised, double blind, placebo controlled investigation of the effects of the nitric oxide synthase inhibitor NG monomethyl-L-arginine (L-NMMA) in 12 patients with severe sepsis associated with hypotension. Measurements of haemodynamic, haematological, and biochemical variables were made. RESULTS: L-NMMA (0.3 and 1 mg.kg-1) produced a dose dependent increase in mean arterial pressure, systemic vascular resistance, pulmonary vascular resistance, central venous pressure, and pulmonary artery occlusion pressure, and a decrease in cardiac output and heart rate. In response to the highest dose of L-NMMA systemic vascular resistance increased from 547(SEM 92) to 889(143) dyne.s.cm-5, mean arterial blood pressure increased from 80.9(2.9) to 100.5(6.1) mm Hg, and cardiac output decreased from 11.2(2.1) to 8.9(1.9) litres.min-1. Continuous infusion of L-NMMA (1 mg.kg-1 x h-1) produced sustained haemodynamic changes. Platelet numbers decreased during the course of the study in both the L-NMMA and the placebo group and did not differ significantly between the groups. CONCLUSIONS: Low doses of L-NMMA cause a widespread increase in vascular tone and raise blood pressure in patients with septic shock. Overproduction of nitric oxide appears to be an important mechanism in septic shock in patients, and inhibition of nitric oxide synthesis might provide a novel therapeutic approach to this condition. However, L-NMMA produced a fall in cardiac output and it is possible that this would worsen tissue perfusion. Larger studies examining the effects of L-NMMA on mortality and morbidity are now required.

Intervertebral instability of the lumbar spine is thought to be a possible pathomechanical mechanism underlying low back pain and sciatica and is often an important factor in determining surgical indication for spinal fusion and decompression. Instability of the lumbar spine, however, remains a controversial and poorly understood topic. At present, much controversy exists regarding the proper definition of the condition, the best diagnostic methods, and the most efficacious treatment approaches. Clinical presentation is not specific, and the relationship between radiologic evidence of instability and its symptoms is controversial. Because of its simplicity, low expense, and pervasive availability, functional flexion-extension radiography is the most thoroughly studied and the most widely used method in the imaging diagnosis of lumbar intervertebral instability. In this article, we provide an overview of the current concepts of vertebral instability, focusing on degenerative lumbar intervertebral instability, and review the different imaging modalities most indicated in diagnosing vertebral instability.