C-Reactive Protein and Erythrocyte Sedimentation Rate in Patients With Heterotopic Ossification After Spinal Cord Injury

Abstract

Background/Objective: Formation of heterotopic ossification (HO) in soft tissue afterspinal cord injury (SCI) is associated with various degrees of inflammation. Recent studies have shown that inhibition of inflammatory reaction with nonsteroidal anti-inflammatory drugs is an effective prevention of HO after SCI. The goal of this study was to monitor the activity of the most widely used indicators of acute inflammation-namely, erythrocyte Sedimentation rate (ESR) and C-reactive protein (CRP)-in patients with HO.

Methods: In a retrospective study, the results of 37 patie nts with HO were evaluated. There were 25 patients with tetraplegia and 12 with paraplegia. The age (mean ± SD) of the patients was 2 8 ± 8 years (range = 19-46 years). The patients were admitted to the rehabilitation center 2 to 5 weeks after SCI. HO was confirmed by bone scintigraphy. Blood samples were obtained from the patients at the time of diagnosis of HO and du ring the therapy. ESR was measured with the Westergren method, and serum CRP was determined by enzyme-linked immunosorbent assay.

Results: In the acute stage of HO, both tests were e levated in all patients. ln the later stages when clinical signs and symptoms of inflammat ion were resolving, both tests showed a gradual decline. When clinical sig ns and symptoms of inflammation (fever, acute soft tissue swelling, and erythema) were not present, the concentration of CRP was normal in 91 .2% of patients, whereas only 1 7 .6% of patients had normal ESR. Mean serum concentrations of CRP were 8.9 ±5.6 mg/L in the inflammatory phase and 0.9 ± 0.6 mg/L in the noninflammatory phase.

Conclusion: The data indicate that serum CRP is a useful and more specific test than is ESR for monitaring the inflammatory activity of HO after SCI. The normalization of CRP was seen during the first 3 to 4 weeks of etidronate therapy, indicating a resolution of acute-phase inflammatory reaction.     

Serum C-reactive protein levels correlate with clinical response in patients treated with antibiotics for wound infections after spinal surgery.

BACKGROUND CONTEXT: C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) have been used to diagnose postoperative infections after spinal surgery. However, it has not been demonstrated if resolution of the signs and symptoms of postoperative spinal wound infections in patients who are being treated with intravenous antibiotics correlates with these markers. PURPOSE: The objective of this study was to determine if improvement of the signs and symptoms of postoperative wound infection after spinal surgery correlates with a decrease in serum CRP and ESR while intravenous antibiotics are administered. STUDY DESIGN: Retrospective review. PATIENT SAMPLE: The study consisted of 21 patients (mean age 63.8 years; 13 female, 8 male) with postoperative wound infections after spinal surgery. They were studied for a minimum of 20 weeks. OUTCOME MEASURES: CRP and ESR were measured at the time of diagnosis and at serial time-points. METHODS: All patients received intravenous antibiotic therapy for 6-8 weeks. Patients were monitored for clinical signs and symptoms of infection such as fever, drainage, erythema, or a need for continued wound packing at 4, 7, and 20 weeks after being diagnosed with a wound infection. RESULTS: The average CRP for all 21 patients at time of diagnosis was 11.7+/-9.0 mg/dL (range 1.2 to 37.8 mg/dL). At the 4-week time-point, 16 patients ("early responders") showed clinical improvement with no fevers, no wound drainage, no erythema, and no need for wound packing. The average CRP of this group at the 4-week time-point decreased to 0.3+/-0.5 mg/dL. In contrast, at the 4-week time-point five patients ("late responders") still had signs and symptoms of infection (2 with continuing drainage requiring wound packing; 1 with vertebral osteomyelitis requiring irrigation and debridement; 2 with erythema without fevers). The average CRP for this group was still elevated at the 4-week time-point at 7.3+/-3.5 mg/dL. The CRP value difference was statistically significant between the two groups (p<.05). As treatment continued, at the 20-week time-point the average CRP of the late responders gradually decreased to 0.8+/-0.8 mg/dL, which was not statistically different from that of the early responders (average CRP=0.6+/-1.1 mg/dL). All 21 patients had resolution of infection at the 20-week time-point. The ESR did not correlate well with clinical improvement. At time of diagnosis, the ESR of both early responders (average=57.6+/-27.6 mm/hr) and late responders (average=64.0+/-21.9 mm/hr) was elevated. It remained elevated for both groups from the beginning of the study to the end at all time-points. The final ESR at the 20-week time-point was not different between the early responders and late responders (average=27.6+/-22.3 mm/hr vs. 31.0+/-2.6 mm/hr, respectively; p>.05). CONCLUSIONS: Our data suggest that CRP may be of value in following the treatment response to antibiotics in wound infections after spinal surgery. The ESR can remain elevated in the presence of a normal CRP despite a resolution of clinical signs and symptoms of postoperative wound infection.     

C reactive protein in patients with chronic renal diseases

Base-line serum levels of plasma C-reactive protein (CRP) are predictive of future myocardial infarction and sudden cardiac death in apparently healthy subjects, suggesting the hypothesis that chronic inflammation might be important in the pathogenesis of atherothrombosis. CRP production is mediated by several inflammatory mediators: interleukin 6 (IL-6) is currently felt to be the major cytokine influencing the acute phase response. CRP and other acute phase proteins are elevated in dialysis patients and cardiovascular diseases represent the single largest cause of mortality in chronic renal failure patients. Little information is available, however regarding CRP and IL-6 plasma levels in pre-dialysis renal failure. Plasma CRP was determined by a modification of the laser nephelometry technique; IL-6 by immunoassay (RD System); and fibrinogen, serum albumin, cholesterol, triglycerides, hematocrit, white blood cell count, erythrocytic sedimentation rate (ESR) and urinary protein levels by standard laboratory techniques. Results were obtained in 102 chronic pre-dialysis patients whose mean age was 53+/-5.8 years with a mean creatinine clearance (C(Cr)) of 52+/-37 mL/min). CRP was greater than 5 mg/L in 25% of the global population. CRP and IL-6 were 4.0+/-4.6 mg/L and 5.8+/-5.6 pg/mL, respectively and were not significantly correlated (r=0.11, p=n.s.). CRP and IL-6 were however related with renal function (CRP versus C(Cr) r=-0.40 p <0.001; IL- 6 versus C(Cr) r=-0.45; p <0.001). When patients were divided in two groups according to renal function, CRP resulted 7.4+/-6.3 mg/L in the group of patients with a C(Cr) lower than 20 mL/min (n=32) and 2.76+/-4.35 in the group of patients with a C(Cr) higher than 20 mL/min (n = 70) (p <0.0001). CRP and IL-6 were positively related with ESR (r=0.32 and 0.46 respectively). Serum albumin levels were not significantly different in the two groups of patients (3.2+/-0.4 versus 3.0+/-0.5 g/dL). CRP and serum albumin were not significantly related (r=0.17). CRP and IL-6 correlated positively with ESR (r=0.32 and 0.46 respectively). In pre-dialysis patients we have demonstrated an increase in both CRP and IL-6 that occurs as renal function decreases. These data provided evidence of the activation - even in the predialysis phase of renal failure - of mechanisms known to contribute to the enhanced cardiovascular morbidity and mortality of the uremic syndrome.     

Deep vein thrombosis and heterotopic ossification in spinal cord injury: a 3 year experience at the Swiss Paraplegic Centre Nottwil

STUDY DESIGN: Retrospective review of patient data. OBJECTIVES: (i) To determine the incidence and time of deep vein thrombosis (DVT) under low molecular weight heparin (LMWH) prophylaxis in spinal cord injury (SCI), (ii) to determine the incidence and time of heterotopic ossification (HO) and (iii) to assess a possible aetiologic relationship in the pathogenesis of DVT and HO. SETTING: Swiss Paraplegic Centre, Nottwil. METHODS: We analyzed the incidence of DVT and HO in 1209 SCI patients (275 first rehabilitations) at the Swiss Paraplegic Centre Nottwil from 1998 to 2000. Clinical files and laboratory data were scrutinised for particularities preceding DVT and HO. RESULTS: The incidence of DVT was 6.55% for first rehabilitation compared to only 1.59% in all patients hospitalised. DVT was complicated by pulmonary embolism (PE) in 1.45% and 0.47% respectively. Incidence of HO was 8% for first rehabilitation and 1.82% for all patients hospitalised. In first rehabilitation patients the peak for DVT occurred around day 30 contrary to HO with a peak around day 120. In single patients HO was identified by MRI as a rapidly progressing process. Laboratory profiles were inflammatory in both HO and DVT. Increased physical activity preceding HO was observed in four patients. In two patients acute HO was complicated by ipsilateral DVT. CONCLUSION: Prophylaxis with LMWH and elastic stockings significantly reduces the frequency of DVT during first rehabilitation in SCI. DVT and HO are both associated with laboratory parameters of non-infectious inflammation. The later onset of HO coinciding with ongoing mobilisation, argues for a different pathogenetic mechanism. Acute HO of the hip region appears to favour ipsilateral DVT by well known thrombogenic mechanisms.     

Pretransplant systemic inflammation and acute rejection after renal transplantation

BACKGROUND: There are presently no established pre-transplant tests that consistently identify patients who may be at increased risk for acute rejection episodes after renal transplantation. We studied whether pretransplant serum levels of C-reactive protein (CRP), a marker for the presence of systemic inflammation, would predict the occurrence of acute rejection episodes after renal transplantation. METHODS: Pretransplant serum was tested for CRP level in 97 consecutive renal transplant recipients. Time to acute rejection after transplantation was stratified by CRP level and compared using the Kaplan-Meier method. In addition, Cox regression multivariate analysis was performed to assess whether any pretransplant covariates could independently predict the subsequent occurrence of acute rejection episodes. RESULTS: Pretransplant mean CRP levels were higher in patients who subsequently had a rejection episode versus those who had no rejection (22.2+/-2.9 vs. 11.7+/-1.8 microg/ml, respectively, P=0.003). Patients less than the median CRP value had a significantly longer time to rejection compared to those with higher CRP levels (P=0.002). Similarly, patients within the lowest CRP quartile had longer times to rejection when compared with the highest quartile (P=0.006). Cox proportional hazards regression multivariate analysis identified CRP level as the only independent pretransplant risk factor for rejection identified (P=0.044). CONCLUSIONS: Pretransplant systemic inflammation as manifested by elevated serum CRP level independently predicts the risk of acute rejection after renal transplantation and may be useful in stratifying patients at the time of transplantation according to immunological risk. Thus, assessment of pretransplant systemic inflammatory status may be helpful in prospective individualization of immunosuppression therapy after renal transplantation.     

Prevention of heterotopic ossification after spinal cord injury with indomethacin

STUDY DESIGN: A randomized, prospective, double-blind, placebo-controlled clinical trial. OBJECTIVES: To determine the effect of indomethacin on the prevention of heterotopic ossification (HO) following spinal cord injury (SCI). SETTING: County Hospital, Miami, Florida, USA. METHODS: Sixteen patients were treated with slow-release indomethacin 75 mg daily and 17 patients received placebo for a period of 3 weeks. Prevention was started 21+/-14 days after SCI. In both groups of patients there was similar age of the patients as well as the level of SCI and ASIA impairment scale. Two methods were used to diagnose HO, bone scintigraphy and radiographic examination. Bone scintigraphy with technetium labeled methylene-diphosphonate was used for diagnosis of early stage, while radiography was used for diagnosis of late stage of HO development. RESULTS: A significantly lower incidence of early HO was found in the indomethacin group (25%) than in the placebo group (65%; P<0.001). Similarly there was a significant reduction of late HO in the indomethacin group (12.5%) as compared to the placebo group (41%; P<0.001). CONCLUSION: Our data suggest that indomethacin used during the first 2 months after SCI is effective in prevention of HO in a significant number of patients.     

Effect of the hemodialysis membrane on the inflammatory reaction in vivo

BACKGROUND: Increased levels of C-reactive protein (CRP), a marker of systemic inflammation, are associated with myocardial infarction, stroke and the development of peripheral arterial disease. Hemodialysis patients show signs of an inflammatory reaction indicated by elevated plasma levels of CRP and by increased plasma levels of interleukins. PATIENTS AND METHODS: To investigate the effect of the dialysis membrane on the inflammatory reaction, we conducted a randomized study in 18 hemodialysis patients. Patients were subsequently treated with dialyzers containing polyamide, polycarbonate or cuprophan for 8 weeks on each dialyzer in a crossover design. During each treatment period, CRP plasma levels were measured 6 times at weekly intervals. The total content and the spontaneous and lipopolysaccharide- (LPS) stimulated production of interleukin-1beta (IL-1beta), IL-6 and IL-1 receptor antagonist (IL-1Ra) were determined in whole blood samples. RESULTS: CRP plasma levels were significantly higher in hemodialysis patients (all patients, 1.63 +/- 0.23 mg/dl) compared to normals (0.14 +/- 0.02 mg/dl, p < 0.0001). CRP levels were lower when patients were dialyzed with polyamide (1.19 +/- 0.18 mg/dl) compared to the levels when the same patients were dialyzed with cuprophan (1.77 +/- 0.37 mg/dl, p = 0.02) or with polycarbonate (1.34 +/- 0.2 mg/dl, n.s). The whole blood content of IL-1Ra in non-incubated samples was significantly lower in normal subjects (512 +/- 60 pg/ml) compared to hemodialysis patients (980 +/- 80 pg/ml, p < 0.01). The whole blood content of IL-1Ra was higher when patients were dialyzed with cuprophan (1,062 +/- 119 pg/ml) compared to the same patients on polyamide (906 +/- 78 pg/ml, p < 0.05) or on polycarbonate (973 +/- 80 pg/ml, n.s.). Spontaneous and LPS-induced production of IL-1beta and IL-6 was similar for all dialyzers. CONCLUSION: We conclude that the inflammatory reaction in hemodialysis patients is affected by the choice of the dialyzer.     

Inflammatory sacroiliitis in a man with spinal cord injury

BACKGROUND: Inflammatory sacroiliitis associated with spinal cord injury (SCI) as an unusual cause of elevated erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) level has not been reported previously to our knowledge. OBJECTIVE: To represent a case of SCI associated with bilateral sacroiliitis causing ESR and CRP level elevation. METHODS: Case report of a man with T9 paraplegia. FINDINGS: ESR and CRP levels were high. Pelvic radiography was nearly normal, except for mildly blurred sacroiliac joints with normal margins. A 3-phase bone scan revealed bilateral sacroiliitis and heterotopic ossification at medial side of the left knee. Past history was significant for a recent urinary tract infection. Indomethacin and etidronate were prescribed. Significant decreases in ESR and CRP level were seen 1 month later. CONCLUSIONS: Sacroiliitis might be an unusual cause of elevated ESR and CRP levels in patients with SCI. Sensory and motor deficits may obscure the typical clinical presentation; therefore, imaging studies are essential for the diagnosis.     

Prevention of heterotopic ossification after spinal cord injury with COX-2 selective inhibitor (rofecoxib)

STUDY DESIGN: A randomized, prospective, double-blind, placebo-controlled clinical trial. OBJECTIVES: To determine the effect of COX-2-selective inhibitor on the prevention of heterotopic ossification (HO) after spinal cord injury (SCI). SETTING: County and University Teaching Hospital, Miami, FL, USA. METHODS: A total of 76 patients were enrolled in the study. Among them, 39 patients received placebo, and 37 received COX-2-selective inhibitor rofecoxib 25 mg daily for a period of 4 weeks. Prevention was started 3 weeks after spinal cord injury (SCI). In both groups of patients there was similar age as well as the level of SCI and ASIA impairment scale. Two methods were used to diagnose early HO, clinical symptoms and bone scintigraphy. Radiography was used for diagnosis of late stages of HO development. RESULTS: A significantly lower incidence of HO was found in the rofecoxib group (13.4%) than in the placebo group (33.3%: P<0.05). In patients receiving rofecoxib, there was a 2.5 times lower relative risk of developing HO than in the placebo group (95% CI, 2.3-6). There were no patients who discontinued the study due to adverse effects of medication. CONCLUSION: Our data suggest that COX-2-selective inhibitor rofecoxib is an effective medication in prevention of HO after SCI.     

Correlation between erythrocyte sedimentation rate and C-reactive protein level in patients with rheumatic diseases

Objectives

Erythrocyte sedimentation rate (ESR) and serum level of C-reactive protein (CRP) are the acute phase reactants most commonly determined in patients with rheumatic diseases. The indices are affected by different factors, but both of them are applied for evaluation of the disease activity in patients with inflammatory disorders of the musculoskeletal system.

Material and methods

The authors compared the results of ESR and CRP, which were carried out during routine diagnosis in 200 patients admitted to the Department of Rheumatology.

Results

A significant correlation between ESR and CRP was found (ESR after 1 h/CRP: correlation coefficient 0.6944, ESR after 2 h/CRP: correlation coefficient 0.6126). There was no difference in ESR or CRP between male and female patients, and patients older than 40 years had higher ESR and CRP.

Conclusions

The obtained results support the usefulness of both indices in the clinical practice of rheumatologists.     

Markers of inflammation before and after renal transplantation

BACKGROUND: This study aims to compare serum C-reactive protein (CRP), interleukin (IL-6), and tumor necrosis factor (TNF)-alpha in end-stage renal disease (ESRD) patients before versus after receiving renal transplantation (RT) and versus donors. METHODS: Serum samples from 37 ESRD patients (24 male, age 34+/-13 years) were collected before and after RT; in addition, samples from 31 donors were obtained at transplantation. CRP concentrations were measured using nephelometry, and TNF-alpha and IL-6 were measured by enzyme-linked immunoadsorbent assay. RESULTS: Ninety-two percent of recipients had a living donor, 73% received cyclosporine A, 27% tacrolimus, and 70% induction with daclizumab. Thirteen percent had acute rejection and 16% chronic allograft nephropathy. All inflammation markers decreased 6 months after RT, but only CRP was below baseline values (baseline: 5.0+/-3.5; 6 months: 3.0+/-0; 12 months: 3.2+/-0.7; 18 months: 3.2+/-0.6; donors: 3.6+/-1.5 mg/L; P<0.05), whereas median TNF-alpha (baseline: 0.1 [0.03-0.2]; 6 months: 0 [0-0.1]; 12 months: 0.3 [0.1-2.6]; 18 months: 0.6 [0.1-1.9]; donors: 0 [0-0.1] pg/mL; P<0.05) and IL-6 (baseline: 1.9 [1.2-7.1]; 6 months: 1.2 [0.6-28.3]; 12 months: 2.6 [1.3-3.4]; 18 months: 2.7 [1.7-4.2]; donors: 1.1 [0.6-1.9] pg/mL; P<0.05) significantly increased up to the end of follow-up. Before RT, CRP correlated with age (r 0.45, P=0.006) and albumin (r -0.36, P=0.04). TNF-alpha and IL-6 were correlated before (r 0.34, P=0.04) and after (r 0.55, P=0.02) RT. Inflammation markers were not different in patients who had acute rejection episodes or chronic nephropathy. CONCLUSIONS: Compared with controls, patients displayed an inflammatory phenomenon before receiving RT. Serum CRP decreased significantly after RT, whereas TNFalpha and IL-6 increased.     

C-Reactive protein and inflammatory response associated to neurocognitive decline following cardiac surgery

BACKGROUND: It has been recognized that neurocognitive decline (NCD) often occurs as a complication in cardiac surgery. The early inflammatory response and C-reactive protein (CRP) was examined in relation to NCD and to a marker of axonal central nervous system (CNS) injury after cardiopulmonary bypass. METHODS: A cohort of patients undergoing coronary artery bypass grafting and/or valve procedures using cardiopulmonary bypass were administered a neurocognitive battery preoperatively and postoperatively at 6 hours and day 4. CRP, interleukin 1 beta, and interleukin 10 were quantified from serum. Increase of serum tau protein after surgery was used as a marker of axonal CNS damage. RESULTS: The rate of NCD was found to be 40.5% in this group. Surprisingly, known predictors of NCD did not differ significantly between patients with/without NCD. Patients with NCD had an early increase of CRP of a significantly higher magnitude than those without NCD (38.01 +/- 11.4 vs 16.49 +/- 3.5 mg/L, P = .042), interleukin 1ss (2.35 +/- 0.3 vs 1.20 +/- 0.2 pg/mL, P = .002), and interleukin 10 (29.77 +/- 4.7 vs 12.94 +/- 2.2 pg/mL, P < .001). Increase in serum Tau protein was significantly correlated to NCD (r = 0.50, P = .02). CONCLUSION: Perioperative increases in CRP and inflammatory cytokines are associated with NCD in patients after cardiopulmonary bypass. Thus, it appears that inflammation plays a key role in NCD pathophysiology, likely via axonal CNS injury, and could become a target for prevention.     

The hematocrit-corrected erythrocyte sedimentation rate can be useful in diagnosing inflammation in hemodialysis patients.

BACKGROUND/AIMS: We aimed to determine predictors of erythrocyte sedimentation rate (ESR), and the ESR level pointing to the presence of inflammation in 60 chronic hemodialysis (HD) patients. METHODS/RESULTS: On bivariate analysis, increased Westergren ESR of 62 (4-160) mm/h correlated inversely with hematocrit (Hct) and serum albumin, and positively with age, plasma fibrinogen, serum C-reactive protein (CRP), immunoglobulins A and G, alpha(1)-acid-glycoprotein and alpha(1)-antitrypsin. On multivariable analysis, independent predictors of the ESR were raised CRP (p < 0.0001), low Hct (p < 0.0001), increased fibrinogen (p < 0.0001) and immunoglobulin A (p = 0.009), and older age (p = 0.015). The Hct-corrected ESR level [ESR x (Hct/45)] of 38 (4-91) mm/h was independently predicted by CRP (p < 0.0001), fibrinogen (p < 0.0001), and age (p = 0.001). In the patients with normal CRP and albumin, the Hct-corrected ESR value was normal (23 mm/h) and lower than that of 59 mm/h in the subjects with elevated CRP and hypoalbuminemia. Using these cut-off points, the positive and negative predictive values of the Hct-corrected ESR on the presence of inflammation were 1.0, and its sensitivity and specificity were 100%. CONCLUSION: Increased Westergren ESR in HD patients is associated with activated acute-phase response, anemia, and aging. The Hct-corrected ESR values of 23 and 59 mm/h precisely select the HD patients with severe inflammation from those without.     

Asymmetric dimethyl-arginine (ADMA) response to inflammation in acute infections.

BACKGROUND AND METHODS: The endogenous inhibitor of nitric oxide synthase (NOs) asymmetrical dimethyl-arginine (ADMA) has been implicated as a possible modulator of inducible NOs during acute inflammation. We examined the evolution in the plasma concentration of ADMA measured at the clinical outset of acute inflammation and after its resolution in a series of 17 patients with acute bacterial infections. RESULTS: During the acute phase of inflammation/infection, patients displayed very high levels of C-reactive protein (CRP), interleukin-6 (IL-6), procalcitonin and nitrotyrosine. Simultaneous plasma ADMA concentration was similar to that in healthy subjects while symmetric dimethyl-arginine (SDMA) levels were substantially increased and directly related with creatinine. When infection resolved, ADMA rose from 0.62 +/- 0.23 to 0.80 +/- 0.18 micromol/l (+29%, P = 0.01) while SDMA remained unmodified. ADMA changes were independent on concomitant risk factor changes and inversely related with baseline systolic and diastolic pressure. Changes in the ADMA/SDMA ratio were compatible with the hypothesis that inflammatory cytokines activate ADMA degradation. CONCLUSIONS: Resolution of acute inflammation is characterized by an increase in the plasma concentration of ADMA. The results imply that ADMA suppression may actually serve to stimulate NO synthesis or that in this situation plasma ADMA levels may not reflect the inhibitory potential of this methylarginine at the cellular level.     

Inflammatory Sacroiliitis in a Man With Spinal Cord Injury

Abstract

Background: Inflammatory sacroiliitis associated with spinal cord injury (SCI) as an unusual cause of elevated erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) level has not been reported previously to our knowledge.

Objective: To represent a case of SCI associated with bilateral sacroiliitis causing ESR and CRP level elevation.

Methods: Case report of a man with T9 paraplegia.

Findings: ESR and CRP levels were high. Pelvic radiography was nearly normal, except for mildly blurred sacroiliac joints with normal margins. A 3-phase bone scan revealed bilateral sacroiliitis and heterotopic ossification at medial side of the left knee. Past history was significant for a recent urinary tract infection. Indomethacin and etidronate were prescribed. Significant decreases in ESR and CRP level were seen 1 month later.

Conclusions: Sacroiliitis might be an unusual cause of elevated ESR and CRP levels in patients with SCI. Sensory and motor deficits may obscure the typical clinical presentation; therefore, imaging studies are essential for the diagnosis.     

False-negative triple-phase bone scans in spinal cord injury to detect clinically suspect heterotopic ossification: a case series

BACKGROUND/OBJECTIVE: Heterotopic ossification (HO) is a complication seen in patients after spinal cord injury (SCI). Triple-phase nuclear bone scanning is the most sensitive test for the detection of HO. This retrospective study assesses whether patients with clinically suspected HO but negative triple-phase nuclear bone scans develop delayed positive nuclear bone scans. METHODS: Case series: A cohort of patients with SCI and clinically suspected HO who underwent triple phase nuclear bone scans over a period of 2 years was identified from retrospective chart review of an acute inpatient SCI rehabilitation service. A subgroup of 7 patients with initially negative but subsequently positive triple-phase nuclear bone scans was identified, and the following data were collected: date, mechanism, admission level, and admission completeness of injury as well as date, number, and results of bone scans. Laboratory studies were also collected during the time of imaging. RESULTS: Over a 2-year period, 343 patients were admitted to the SCI rehabilitation service; 60 patients were suspected of having HO and underwent a total of 85 triple-phase nuclear bone scans. Seven patients were identified with initially negative but subsequently positive bone scans. CONCLUSIONS: In patients with clinically suspicious HO but negative bone scans, follow-up scans are indicated to identify initial false-negative studies.     

Serum alpha1-antitrypsin but not complement C3 and C4 predicts chronic inflammation in hemodialysis patients

BACKGROUND: We studied whether predialysis serum levels of positive acute phase markers such as alpha1-antitrypsin (AT), and complement components C3 and C4 could identify the presence of chronic inflammation in maintenance hemodialysis (HD) patients. METHODS/RESULTS: In 103 stable HD patients, AT directly correlated with C-reactive protein (CRP) (P < 0.005), alpha1 acid-glycoprotein (P < 0.005), fibrinogen ( P < 0.05), lipoprotein (a) (P < 0.01) and von Willebrand factor antigen (P < 0.05), while C3 and C4 were not related to any of these inflammatory markers. In the patients with elevated CRP and hypoalbuminemia, the mean AT value of 1.74 +/- 0.50 g/L was higher (P = 0.008) than that of 1.38 +/- 0.27g/L in the subjects with normal CRP and albumin. Using the above cut-off levels, the positive and negative predictive values of AT on the presence of severe inflammation were 0.86 and 0.62, respectively, and the sensitivity and specificity were 86% and 73%, respectively. CONCLUSION: Serum AT levels above 1.74 g/L and below 1.38 g/L may select the HD patients with severe inflammation from those without. Measurements of C3 and C4 are not helpful in this situation.     

C-reactive-protein and cytokine plasma levels in hemodialysis patients

BACKGROUND: Markers of an acute phase reaction, such as C-reactive protein (CRP) or interleukin-6 (IL-6), are predictive for cardiovascular morbidity and mortality in normal subjects and in hemodialysis (HD) patients. Le-vels of acute phase proteins (APP) may vary with time even in the absence of an acute illness and this may weaken the relationship between APP and clinical outcome. We investigated the intra- and inter-individual patterns of several inflammatory markers in HD patients. METHODS: Plasma levels of CRP, IL-10, RANTES, TNF-RI, leptin, ferritin and albumin were measured weekly for 12 weeks after the long inter-dialytic interval by ELISA in ten stable HD patients with no clinical signs of infection. RESULTS: Considerable variability was observed. Intra-individual differences were largest for RANTES (coefficient of variation - CV - 80%, followed by CRP (51%), and low for albumin (11%) and ferritin (12%). Inter-individual variability was highest for IL-10 (135%) followed by CRP (88%). CONCLUSIONS: The present data suggest that single point measurements of APP, particularly CRP, may not be sufficient to assess the cardiovascular risk in HD patients. Even in patients with no apparent signs of infection, there is considerable variability in plasma levels of APP and repeated measurements are recommended to identify patients at high cardiovascular risk.     

Elevated high-sensitivity C-reactive protein levels are associated with local inflammatory findings in patients with osteoarthritis

OBJECTIVE: C-reactive protein (CRP) has been associated with disease progression in patients with osteoarthritis (OA), but the reasons for this remain unclear. We hypothesized that higher CRP would be related to local inflammatory findings in the joints of patients with OA. METHODS: Plasma and synovial membrane specimens from 54 OA patients undergoing total hip or knee arthroplasty or arthroscopy were obtained. Synovial fluid was obtained from 25 of these patients. Hematoxylin and eosin stained synovial membrane sections were scored for degree of inflammatory cell infiltration. Plasma high-sensitivity CRP (hsCRP) levels, and serum and synovial fluid interleukin (IL)-6 and IL-1beta levels were measured by enzyme-linked immunosorbent assay. RESULTS: Fifty-seven percent of patients with idiopathic OA had inflammatory infiltrates within the synovial membrane. The mean hsCRP level in patients with inflammatory infiltrates was significantly higher than those without inflammation (4.7 +/- 5.0 mg/L vs 1.7 +/- 3.6 mg/L, P = 0.003). There were significant correlations between hsCRP levels and synovial fluid IL-6 (r = 0.64, P = 0.0006), degree of synovial inflammatory infiltration (r = 0.43, P = 0.002), and body mass index (r = 0.31, P = 0.02). Multivariate analysis indicated that only degree of inflammatory infiltrate was significantly associated with hsCRP level (P = 0.026). CONCLUSION: These results suggest that systemic hsCRP levels reflect synovial inflammation in OA patients, perhaps by means of synovial IL-6 production. Future studies are needed to clarify how these infiltrates and their products may contribute to disease pathogenesis.     

Leptin is a negative acute phase protein in chronic hemodialysis patients

BACKGROUND: Hypoalbuminemia strongly predicts death in hemodialysis patients and results from both inflammation and malnutrition. One potential link between malnutrition and inflammation is appetite suppression triggered by inflammation. Leptin is secreted by adipose tissue and suppresses appetite, and it is also a positive acute phase protein in the rat. Factored for body weight, leptin is known to be increased in hemodialysis patients, but its relationship to inflammation is unknown. METHODS: We examined the relationship between spontaneously occurring activation of the acute phase response and leptin levels in 29 chronic hemodialysis patients. Serum samples were obtained three times weekly for six weeks and then monthly from 29 chronic hemodialysis patients, and the levels of the positive acute phase proteins [C-reactive protein (CRP), alpha1-acid glycoprotein (alpha1 AG), serum amyloid A, ceruloplasmin] and the negative acute phase proteins (albumin and transferrin) as well as leptin and interleukin-6 (IL-6) were measured. RESULTS: Positive and negative acute phase proteins were evaluated at the maximum CRP (mean, 9.42 +/- 1.14 mg/dL) and minimum values (mean, 0.41 +/- 0.09 mg/dL). When CRP was elevated, leptin levels were significantly reduced, as were the negative acute phase proteins albumin and transferrin. Serum amyloid A, ceruloplasmin, alpha1 acid glycoprotein, and IL-6 were all significantly increased at the maximum CRP level, compatible with general activation of the acute phase response. The change in leptin correlated negatively with the change in CRP (R = 0.437, P = 0.018), as did changes in albumin (R = 0.620, P < 0.001). CONCLUSIONS: Leptin is not increased as a consequence of inflammation in hemodialysis patients, but behaves as a negative rather than as a positive acute phase protein. Inflammation is unlikely to reduce appetite in dialysis patients through a leptin-mediated mechanism.