Emma Gonzales

Circulating levels of IL-2R, ICAM-1, and IL-6 in spinal cord injuries☆☆☆

OBJECTIVE To measure circulating levels of well-studied, easily quantifiable surrogate markers or mediators of inflammation and tissue remodeling in patients with spinal cord injury (SCI) suffering from pressure ulcers. Cytokines or their receptors, eg, interleukins IL-6 and IL-2, IL-2R (the soluble interleukin-2 receptor), and the intercellular adhesion molecule ICAM-1, are mediators of immune response, inflammatory processes, and tissue remodeling involving the skin and other organs. Activation of these immune effectors and their accumulation in tissue can be associated with pathological changes or healing, and elevated plasma concentrations can indirectly reflect the magnitude of immune activation. DESIGN Participants were consecutively enrolled in a controlled, gender-specific study of the relationship between circulating IL-1 beta, IL-2, IL-2R, and ICAM-1 and pressure ulcers in patients with chronic SCI. SETTING The department of medicine of a university-affiliated medical center and the spinal cord injury service at a Department of Veterans Affairs medical center. PATIENTS OR OTHER PARTICIPANTS Seventy men with longstanding SCI (19 with pressure ulcers). The mean age was 49 +/- 14 (range 25 to 74 years). Duration of SCI ranged between 1 and 46 years, and the level of injury varied from C2 to L5. The control group consisted of 20 healthy, able-bodied volunteers (10 men and 10 women aged 25 to 50 years). MAIN OUTCOME MEASURES Circulating plasma levels of IL-6, IL-2, IL-2R, and ICAM-1 and their relation to the rate of wound healing in subjects with SCI. RESULTS Plasma concentrations of bioactive molecules IL-6, IL-2R, and ICAM-1 were numerically or significantly elevated in all patients with SCI as compared to able-bodied individuals. The greatest increase in concentration was seen in those patients with pressure ulcers who demonstrated slow healing of their wounds. CONCLUSIONS SCI and trauma to insensitive tissue result in immunoactivation. In patients with SCI and pressure ulcers, elevated levels of circulating ICAM-1 and IL-2R may have diagnostic, prognostic, and therapeutic value in predicting or differentiating subgroups of patients who will vary in the severity or the rate of healing of their wounds.

Coagulation, fibrinolytic, and inhibitory proteins in acute myocardial infarction and angina pectoris

Abstract background and method: The role of thrombus formation in the pathogenesis of acute myocardial infarction (AMI) and unstable angina pectoris has been well established. However, comprehensive and systematic studies of the blood coagulation, fibrinolytic, and inhibitory proteins are not available in patients with these conditions. Fourteen patients with AMI, 10 patients with angina pectoris, and 32 normal volunteers were studied. Plasma antigen concentrations and/or activities of high-molecular-weight kininogen (HMWK), fibrinogen, fibronectin, plasminogen, D-dimer, tissue plasminogen activator (t-PA), α 2 -antiplasmin, α 2 -macroglobulin, α 1 -antitrypsin, protein C, total and free protein S, antithrombin III (AT-III), von Willebrand factor (vWF), factors (F) XII, XI, IX, VIII, VII, X, V, II, and XIII, and plasma antiplasmin activity were measured using appropriate functional or immunologic assays. results: The AMI group showed a significant reduction in F XII activity, F XII activity-to-concentration ratio, and HMWK concentration. In addition, the AMI patients exhibited a significant elevation of plasma F XI activity, F IX concentration, and F IX activity, and vWF, fibrinogen, D-dimer, and t-PA concentrations. This was associated with significant reductions in F V, F II, and AT-III activity-to-concentration ratio. Many of the changes observed in AMI patients were also present in patients with angina pectoris. Furthermore, the latter group exhibited an elevation of F VIII activity, α 2 -macroglobulin activity, and α 1 -antitrypsin concentration and a significant reduction of antiplasmin activity despite a normal α 2 -antiplasmin concentration. conclusions: The observed reduction of the plasma F XII activity-to-antigen concentration ratio combined with a reduced HMWK concentration suggests intrinsic pathway activation, while the elevation of the D-dimer concentration indicates thrombin generation and fibrin formation and degradation in the AMI group. The latter changes were also present in patients with angina pectoris. Both AMI and angina groups showed several other abnormalities of the coagulation, fibrinolytic, and inhibitory systems. The results suggest the presence of a prothrombotic state associated with the activation of coagulation and fibrinolytic systems in patients with acute myocardial ischemia or infarction.

Plasma concentration and urinary excretion of erythropoietin in adult nephrotic syndrome

Abstract purpose: Nephrotic syndrome (NS) is associated with a significant alteration of protein metabolism. While lowering the plasma concentrations of certain proteins, the disease often raises the level of certain other proteins. The current study was undertaken to determine the effect of NS on erythropoietin (EPO) metabolism. patients and methods: We measured the EPO concentration in plasma and urine of 26 patients with NS by an immunologic assay using a rabbit antiserum against recombinant human EPO. The results were compared with those obtained in a group of 12 normal control subjects. results: Despite a significant reduction in the hemoglobin concentration in the NS group compared with the control group (125 ± 25 g/L versus 148 ± 11 g/L, p conclusion: We conclude that plasma EPO is inappropriately low in patients with NS. This is due, at least in part, to the urinary/renal losses of this protein and can potentially contribute to anemia in NS patients or compound the problem in those with concurrent renal insufficiency and diminished EPO production.

Coagulation cascade, fibrinolytic system, antithrombin III, protein C and protein S in patients maintained on continuous ambulatory peritoneal dialysis.

We studied the coagulation cascade, fibrinolytic system and naturally occurring anticoagulants in a group of 14 patients with end-stage renal disease maintained on continuous ambulatory peritoneal dialysis (CAPD). The results were compared with those obtained in a group of ten normal volunteers. Plasma procoagulant activities of factors XII, XI, IX, VIII, VII, X and II were significantly greater in the CAPD group as compared to the normal control group. Likewise plasma concentrations of total and free protein S were increased in the CAPD group. Although the mean value for plasma factor V activity in the CAPD group was higher than that found in the control group the difference did not attain statistical significance. In addition plasma fibrinogen concentration and factor VIII-related antigen level were significantly increased in CAPD patients. No significant difference was found between the CAPD patients and the control group with respect to plasma levels of protein C, antithrombin III, plasminogen or alpha 2-antiplasmin. In summary, the results demonstrate a tendency for increased levels of various coagulation factors and protein S in CAPD patients with no significant alterations in the levels of various fibrinolytic and endogenous anticoagulant agents, i.e. antithrombin III and protein C. The clinical significance and the mechanism responsible for the observed changes require further investigation.

Increased Levels of Protein C Activity, Protein C Concentration, Total and Free Protein S in Nephrotic Syndrome

Plasma protein C (PC) antigen concentration has been shown to be normal or increased in patients with proteinuria. However, the available data concerning PC anticoagulant activity in nephrotic syndrome (NS) are limited. We measured plasma PC antigen concentration. PC anticoagulant activity, total and free protein (PS) concentrations, and antithrombin III (AT-III) antigen concentration in 21 adult patients with NS. The results were compared with those obtained in a control group of normal volunteers. PC antigen concentration and its anticoagulant activity were significantly increased in the NS group when compared with the normal control group. Likewise, plasma total and free PS values were significantly higher in the NS patients than the corresponding values found in the control group. In contrast, plasma AT-III antigen concentration was significantly reduced in patients with NS. A negative correlation was found between plasma PC and AT-III levels. These observations suggest that increased plasma PC concentration and anticoagulant activity in NS may afford some protection against the thrombotic diathesis associated with antithrombin deficiency and other coagulation abnormalities in this otherwise hypercoagulable state.

Blood coagulation, fibrinolytic and inhibitory profiles in renal transplant recipients: comparison of cyclosporine and azathioprine.

Renal transplant recipients treated with cyclosporine (CS) have been reported to be at increased risk of thrombotic complications. The present study was intended to examine the blood coagulation, fibrinolytic, and inhibitory systems in such patients. Eight transplant recipients on maintenance immunosuppression with CS and prednisone were studied. Five transplant recipients maintained on azathioprine (AZA) and prednisone and 32 normal volunteers served as controls. Plasma antigen concentrations and/or activities of various proteins in the above pathways were measured. Both the CS and AZA groups exhibited significant elevations of factor IX activity, von Willebrand factor (vWF), D-dimer, protein C and tissue type plasminogen activator (t-PA) levels when compared with the normal controls. In addition, CS group showed a significant elevation of α2-macroglobulin activity and AZA group showed a significant reduction in factor XII activity when compared with the normal controls. Comparison of data from CS and AZA groups revealed higher factor XII activity and vWF concentration in the former group. In conclusion, transplant recipients treated with long-term cyclosporine and prednisone exhibited significant elevation of plasma vWF, D-dimer and protein C concentrations. In addition, both CS and AZA-treated transplant recipients showed increased plasma concentrations of D-dimer and t-PA. The latter observations suggest in vivo thrombin generation, fibrin formation and degradation.

The relationship of arterial compliance with endothelial-derived proteins of the hemostatic system

Cardiovascular risk factors associated with hypertension include alterations in arterial compliance and an increased tendency to thrombosis. In this study we examined the relationship between arterial compliance and endothelial derived components of the hemostatic system: von Willebrand factor (vWF) and tissue plasminogen activator (t-PA). Ten males (4 normal and 6 untreated hypertensives, 41 +/- 12 years) were studied. Compliance of proximal (large vessel) and distal (small vessel) arteries was measured by intraarterial pulse wave analysis; left ventricular wall thickness by echocardiography; and vWF and t-PA by immunoassay of plasma obtained before and immediately after maximum treadmill exercise. Baseline t-PA and vWF correlated inversely with distal compliance (r = -0.74, p = 0.01; r = -0.56, p = 0.09). Exercise strengthened the relationship between vWF and both distal compliance (r = -0.56 to r = -0.86) and proximal compliance (r = -0.44 to r = -0.70). Moreover, post-exercise levels of vWF and t-PA were each significantly related to left ventricular posterior wall and septal thickness. Of note, these protein concentrations correlated more strongly with arterial compliance and left ventricular wall thickness than with blood pressure. Thus, arterial compliance and left ventricular wall thickness appear to be more powerful than blood pressure as predictors of the endothelial release of vWF and t-PA in response to exercise. These findings indicate that some of the key cardiac and arterial characteristics of hypertension might be linked to increased endothelial reactivity to hemodynamic stress.

Erythropoietin in preeclampsia

To investigate the possible effect of preeclampsia on erythropoietin metabolism, we measured plasma and urine erythropoietin concentrations and complete blood count in 19 women with preeclampsia and nine healthy gravidas. Hemoglobin concentration and hematocrit values in the preeclamptic patients did not differ significantly from those of the normal pregnant controls. However, the plasma erythropoietin concentration tended to be higher in the preeclamptic group than in the normal pregnant controls (26.9 ± 31.2 versus 11.2 ± 9.9 mU/mL), though the difference was not statistically significant. Plasma erythropoietin concentration correlated negatively with both hemoglobin concentration and hematocrit (r=–0.85, P < .01). The pattern and magnitude of the erythropoietin response to anemia paralleled that previously reported in individuals with iron deficiency anemia. No significant correlation was found between urinary erythropoietin excretion and blood pressure, qualitative albumin excretion, hematocrit, hemoglobin concentration, or plasma erythropoietin concentration. Based on our results, the erythropoietin response to anemia appears to be intact in preeclampsia, at least in the absence of renal failure.

Fibronectin and factor XIII in spinal cord injured patients with end-stage renal disease

Fibronectin and factor XIII play a major role in blood coagulation cascade and contribute to wound healing and phagocytic function of macrophages. Spinal cord injured (SCI) patients with end-stage renal disease (ESRD) have been shown to exhibit a variety of coagulation abnormalities, a high incidence of infection and poor healing pressure ulcers. Earlier studies in SCI patients with no discernible renal disease revealed a marked rise in plasma fibronectin in patients with fast healing pressure ulcers. However, no significant rise is found in those with poor healing ulcers. We compared plasma concentrations of fibronectin and factor XIII in a group of 13 SCI-ESRD patients with those of a normal control group. Despite the presence of pressure ulcers, the SCI-ESRD patients as a group failed to show a significant rise in plasma fibronectin concentration. In addition, the mean plasma factor XIII value in the SCI-ESRD group was not significantly different from that of the normal control group. Accordingly, the combination of SCI, ESRD and associated conditions seems to impair the patients ability to mount a rise in plasma fibronectin concentration in response to the presence of pressure ulcers. Failure of SCI-ESRD patients to produce a rise in plasma fibronectin concentration may, in part, account for the poor healing property of pressure ulcers in this population.

Fibrinolytic and Protease Inhibitory Systems in Spinal Cord Injured Patients with End-Stage Renal Disease

Earlier studies have revealed a variety of coagulation abnormalities in patients with long-standing spinal cord injury (SCI) and end-stage renal disease (ESRD). The present study was undertaken to examine the fibrinolytic and protease inhibitory systems in this population. Twelve spinal cord injured men with ESRD were studied. All patients had chronic active urinary tract infections, pressure ulcers and were practically bed-bound. The results were compared with those obtained in a group of 32 normal volunteers. Plasma plasminogen and unstimulated tissue-type plasminogen activator (t-PA) concentrations in the SCI-ESRD group were comparable with those found in the control group. No significant difference was found in plasma plasminogen activator inhibitor (PAI) activity in the two groups. In contrast, plasma alpha 2-antiplasmin antigen concentration and antiplasmin activity were significantly reduced in the study population. In addition, plasma alpha 1-antitrypsin activity and antigen concentration were significantly increased while the alpha 2-macroglobulin activity-to-antigen concentration ratio was significantly reduced in the SCI-ESRD group. Although the mechanism of the observed reduction in alpha 2-antiplasmin and total antiplasmin activity is uncertain, its presence could enhance fibrinolysis in this otherwise thrombosis-prone population. Likewise, elevated alpha 1-antitrypsin could attenuate tissue damage by leukocyte-derived proteases in the face of persistent suppurative infections. The reduced alpha 2-macroglobulin activity-to-antigen concentration ratio was thought to reflect the presence of alpha 2-macroglobulin complexes with various proteases generated by the activation of leukocytes, coagulation, fibrinolytic and other proteolytic systems.