Antibodies against oxidized low-density lipoproteins in systemic sclerosis.

OBJECTIVE: To investigate whether circulating concentrations of antibodies against oxidized low-density lipoproteins (LDL) are increased in patients with systemic sclerosis (SSc). METHODS: Oxidation of LDL and anti-oxidized LDL antibodies were measured in 26 patients with limited cutaneous SSc (LCSSc), in eight patients with diffuse cutaneous SSc (DCSSc) and in 24 healthy control subjects. Results were adjusted for age, sex and smoking. RESULTS: Binding to oxidized LDL was increased in patients with both limited and diffuse cutaneous disease (geometric mean 0.35 and 0.39 optical density units respectively) compared with controls (0.28) (P=0.03 and P=0.01 respectively). Circulating concentrations of anti-oxidized LDL were increased only in patients with diffuse SSc (geometric mean 0.22 optical density units) compared with controls (geometric mean 0.16, P=0.02). CONCLUSION: These preliminary findings lend further weight to the concept that oxidation of LDL contributes to the vascular pathology of SSc, particularly in patients with diffuse cutaneous disease. Prospective longitudinal studies are required to investigate whether anti-oxidized LDL antibodies may be a marker of vascular damage in SSC.

Herniated intervertebral disc-associated periradicular fibrosis and vascular abnormalities occur without inflammatory cell infiltration.

STUDY DESIGN: Prospective histologic comparison of perineural tissues from patients requiring decompression surgery for herniated intervertebral disc with those from cadaveric controls. OBJECTIVES: To examine the significance of herniated intervertebral-disc-associated perineural vascular and fibrotic abnormalities with respect to back pain symptom generation. SUMMARY OF BACKGROUND DATA: Previous cadaveric studies have demonstrated perineural vascular congestion, dilatation, and thrombosis and perineural and intraneural fibrosis occurring in association with herniated intervertebral disc. It was suggested that these neural abnormalities were the result of ischemia, due to venous outflow obstruction, and also represented a possible cause of ongoing back pain symptoms. Criticisms of such a conclusion arose, however, because the possibility could not be excluded that these abnormalities were the result of postmortem artifact. METHODS: Histologic and immunohistochemical comparison of discal and peridiscal tissues removed from 11 patients with radiographically proven herniated intervertebral disc requiring decompressive surgery and from 6 fresh cadavers without history of back pain in life. RESULTS: Histology and immunohistochemistry of perineural and extraneural tissues from patients revealed vascular congestion, neovascularization, and endothelial abnormalities including luminal platelet adhesion, in association with reductions in von Willebrand factor levels, together with perivascular and perineural fibrosis. Elevated fibrogenic cytokine concentrations were also detected in patients' tissues. These changes occurred without evidence of inflammation and were absent in cadaveric control tissues. CONCLUSIONS: The vascular abnormalities detected in patients may represent an important etiopathologic factor predisposing to intraneural and perineural fibrosis, and hence to chronic pain symptoms, after disc herniation. It seems important to preserve the perineural microcirculation following disc herniation.

A double blind placebo controlled trial of recombinant tissue plasminogen activator in the treatment of digital ischemia in systemic sclerosis.

The treatment of digital ischemia in systemic sclerosis remains inadequate. We report a double blind, placebo controlled trial of recombinant tissue plasminogen activator (rtPA), a potent thrombolytic agent. Ten patients received rtPA. A potent, acute fibrinolytic effect was observed. During the infusion of rtPA, improvements in skin blood flow were seen. These improvements were shortlived.

The role of epidural fibrosis and defective fibrinolysis in the persistence of postlaminectomy back pain.

Clinical features, contrast-enhanced lumbar tomographic findings, and biochemical plasma fibrinolytic parameters were critically assessed in 70 patients suffering severe, chronic postsurgical low-back and radicular pain to determine the cause of their persisting symptoms. Patients exhibited gross functional disability and significant impairment of plasma fibrinolytic activity, compared with 84 normal control subjects. This fibrinolytic defect appeared attributable to disproportionate increases in circulating plasminogen activator inhibitor-1 levels. Clinical features were slightly worse in patients with radiologic epidural fibrosis, whereas the frequency of radiologic abnormalities, including epidural fibrosis, was higher in patients with fibrinolytic abnormalities. The results, however, demonstrated no significant associations between patients' symptoms and signs and their biochemical and radiologic abnormalities.

Fibrinolytic enhancement with stanozolol fails to improve symptoms and signs in patients with post-surgical back pain.

An open trial with the fibrinolytic enchancing agent stanozolol was completed by eighteen patients (14 male) with severe back and radicular pain, despite previous lumbar surgery for prolapsed intervertebral disc. Assessments of their pain, disability and plasma fibrinolytic activity were undertaken before and after 12 or 24 months of therapy. Prior to treatment patients exhibited significant fibrinolytic abnormalities when compared with 84 normal controls; euglobulin clot lysis time (ELT) 442 vs 157 mins and fibrin plate lysis area (FPLA) 61 vs 113 mm2 respectively (p less than 0.01 for both). Stanozolol therapy normalised patients' fibrinolytic activity within three months. Disappointingly there were no concomitant clinical improvements in spinal pain or mobility despite 12 or 24 months of treatment. These results may indicate that perineural fibrosis, once formed, is not amenable to such therapy.