A comparison of acute phase proteins and traditional risk factors as markers of combined plaque and intima-media thickness and plaque density in carotid and femoral arteries.

OBJECTIVES: To test the hypothesis that some acute phase proteins may be better independent predictors of objective measures of arterial wall impairment than traditional risk factors. DESIGN: Cross-sectional study. MATERIALS AND METHODS: C-reactive protein (CRP), fibrinogen, C3 complement and traditional risk factors were measured in 288 men aged 55-64 years, randomly chosen from the local registry lists. By ultrasound assessment of the bifurcations of carotid and femoral arteries, maximum combined plaque/intima-media thickness (CPIMTmax) and mean plaque density (MPD, in a grey scale from 0 to 255) were also measured. RESULTS: In multivariate analysis only traditional risk factors remained associated with the overall CPIMTmax: smoking (r = 0.35, p < 0.0001), cholesterol (r = 0.23, p = 0.0001), age (r = 0.22, p = 0.0002), glucose (r = 0.18, p = 0.002) and systolic blood pressure (r = 0.13, p = 0.02). However, with regard to carotid disease only, fibrinogen was the strongest covariate of CPIMT (r = 0.18, p = 0.002). The overall MPD was independently associated with CRP (r = 0.25, p = 0.0008), physical activity (r = 0.19, p = 0.009), triglycerides (r = -0.18, p = 0.02) and body mass index (r = 0.15, p = 0.04). CRP was mainly associated with femoral MPD, while triglycerides were the major (inverse) covariate of carotid MPD. CONCLUSIONS: Traditional risk factors are the main determinants of CPIMTmax, although fibrinogen seems to play a role in carotids. CRP was associated with high density femoral plaques. Finally, no acute phase protein was independently associated with low density, potentially vulnerable, plaques.

Different associations of C-reactive protein, fibrinogen and C3 with traditional risk factors in middle-aged men.

BACKGROUND: Some acute phase proteins are associated with both ischemic events and traditional risk factors. Since they are strongly interrelated, each of them partly reflects the characteristics of other proteins. This study was carried out to ascertain the specific preferential associations of some acute phase proteins with traditional risk factors for atherosclerotic disease. METHODS: High-sensitivity C-reactive protein, fibrinogen and C3-complement were assessed in 288 unselected men aged 55-64 years. Three multiple linear regression analyses were performed, in which each of the three acute phase proteins was considered the dependent variable of both traditional risk factors and the other two proteins. RESULTS: The three acute phase proteins strongly correlated with each other. Moreover, C-reactive protein was independently associated with triglycerides (P<0.0001), age (P=0.0130), body mass index (P=0.0179), and acute (P=0.0280) and chronic (P=0.0582) inflammations (R2=0.17). Fibrinogen was associated with alcohol consumption (inversely, P=0.0001) and smoking (P=0.0598) (R2=0.06). Finally, C3 was associated with insulin (P<0.0001), cholesterol (P=0.0001), sedentarity (P=0.0028), glucose (P=0.0077), and systolic blood pressure (P=0.0124) (R2=0.28). CONCLUSIONS: When simultaneously studied in multivariate analysis, acute phase proteins have different preferential associations with traditional risk factors, a probable consequence of their involvement in different cellular activations and metabolic processes.

Conditional risk factors in men with previous myocardial infarction: relevance of C3 and homocysteine.

OBJECTIVE: To establish which traditional and conditional risk factors were effectively treated, and which remained active, in patients with previous myocardial infarction (PMI). METHODS AND RESULTS: In 47 PMI patients recently submitted to cardiological assessment and in 42 controls (50-70 years old men), traditional risk factors (total cholesterol, high-density lipoprotein cholesterol, blood glucose, blood pressure, cigarette smoking and body mass index) and the following variables were measured: fibrinogen, plasminogen activator inhibitor-1 (PAI-1), lipoprotein(a) [Lp(a)], total homocysteine, plasma folates, vitamin B12, high sensitivity C-reactive protein and C3 complement. Most patients were taking beta-blockers, ACE inhibitors and statins. Accordingly, patients had lower blood pressure and cholesterol values than controls. Moreover, they consumed less alcohol and coffee and did not differ from controls in cigarette smoking and body mass index. Conversely, patients had higher levels of homocysteine, fibrinogen, C3 complement and Lp(a), although of these factors only C3 and homocysteine remained significantly associated with PMI in multivariate analysis. C-reactive protein, PAI-1 and especially C3 often correlated with traditional risk factors in controls, but these correlations tended to disappear or reverse in PMI patients. Fibrinogen inversely correlated with alcohol consumption. Homocysteine correlated (inversely) with plasma folates only. Lp(a) did not correlate with any variable. CONCLUSIONS: Forty-seven patients with previous myocardial infarction displayed an excellent control of traditional risk factors, but they had higher mean C3 and homocysteine levels than the control group.

Simultaneous serum assays of lipase and interleukin-6 for early diagnosis and prognosis of acute pancreatitis.

BACKGROUND: There are no systems for the rapid diagnosis and prognosis of acute pancreatitis in the Emergency Department. Our aim was to evaluate whether the combined use of serum lipase and interleukin-6 or serum lipase and C-reactive protein is able to simultaneously establish both the diagnosis and the prognosis of acute pancreatitis. METHODS: Eighty patients with acute abdomen were studied on admission to the Emergency Room. Forty patients had nonpancreatic acute abdomen, and 40 had acute pancreatitis (25 had mild acute pancreatitis and 15 had severe pancreatitis). Forty healthy subjects comparable for sex and age were also studied as controls. Lipase, interleukin-6, and C-reactive protein were determined on serum in all subjects. RESULTS: Using lipase to discriminate between patients with nonpancreatic acute abdomen and patients with acute pancreatitis (cutoff values ranging from 419 to 520 U/L), one patient with acute pancreatitis was not identified correctly. To discriminate between patients with severe acute pancreatitis and those with mild pancreatitis in the remaining 39 patients, interleukin-6 (cutoff value, <3.7 microgram/L) had a sensitivity of 100% (15 of 15) and a specificity of 83% (20 of 24); 75 of 80 (94%) patients were classified correctly. C-reactive protein (cutoff values ranging from 6 to 7 mg/L) showed a lower prognostic efficiency than interleukin-6: sensitivity of 87% (13 of 15) and specificity of 46% (11 of 24). Sixty-four of 80 patients (80%) were classified correctly. The area under the ROC curve for interleukin-6 (0.911 +/- 0.049) was significantly (P = 0.013) greater than that for C-reactive protein (0.685 +/- 0.090). CONCLUSION: The combined use of serum lipase and interleukin-6 is useful in simultaneously establishing both the diagnosis and the prognosis of acute pancreatitis.

Behavior of serum interleukin 12 in human acute pancreatitis.

We evaluated the behavior of sera interleukin p70 (IL-12p70) and IL-12p40 in patients with acute pancreatitis. Twenty-three acute pancreatitis patients were studied (12 had severe pancreatitis and 11 had mild pancreatitis). Twenty healthy subjects were studied as controls. Serum concentrations of total IL-12, IL-12p70, IL-12p40, and IL-6 were determined in all subjects on admission to the hospital; in patients with acute pancreatitis, the serum levels of these molecules also were determined for the 5 days after admission. Acute pancreatitis patients had serum concentrations of total IL-12, IL-12p40, and IL-6 significantly higher (p < 0.05) than those of the healthy subjects from the first to the sixth day of the study; serum concentrations of IL-12p70 were significantly higher in acute pancreatitis patients (p < 0.02) than in the healthy subjects on the first of the disease and significantly lower (p < 0.05) on the second, third, and fourth days of illness. Reduction of IL-12p70 in acute pancreatitis patients was not due to a failure of the monocytes because the production of IL-6 was increased. Increased amounts of IL-12p40 in acute pancreatitis patients may be responsible for their increased susceptibility to infection.

Rhabdomyolysis and acute pancreatitis.

AIMS: To establish the incidence of rhabdomyolysis in patients with acute pancreatitis and to determine the effectiveness of myoglobin in assessing the severity of the disease. METHODS: Sixty-one patients having acute pancreatitis (33 males, 28 females, mean age 66 years, range 16-97 years) were studied; diagnosis of acute pancreatitis was based on the typical abdominal pain associated with elevated concentrations of serum lipase and further confirmed by imaging techniques. Rhabdomyolysis was defined as a level of serum myoglobin which is two or more times greater than the upper normal test limit. All patients had normal renal function at the time of the study, none had clinical and/or electrocardiographic signs of acute myocardial infarction and none were drug addicts. Forty-five patients had mild acute pancreatitis and 16 had the severe form of the disease. Serum myoglobin was determined using a nephelometric technique. RESULTS: Patients with mild pancreatitis had serum concentrations of myoglobin (median and range; 35.7, 24-713 microg/L) similar to those with severe pancreatitis (26.8, 24-710 microg/L). Twelve of the 61 patients with acute pancreatitis (20%) had serum myoglobin concentrations above the upper normal limit: eight of the 45 patients with mild pancreatitis (17.7%) and four of the 16 patients with severe pancreatitis (25.0%). Four of the 61 patients with acute pancreatitis (7%) had serum myoglobin levels more than twice the upper normal limit: two with mild disease and two with the severe form of pancreatitis. CONCLUSIONS: Rhabdomyolysis may occur asymptomatically in patients with acute pancreatitis, especially in those with the severe form of the disease. Serum myoglobin determination is not useful in establishing the severity of acute pancreatitis.

Serum interleukin 6 in the prognosis of acute biliary pancreatitis.

BACKGROUND: Data concerning the interleukin 6 pattern in acute biliary pancreatitis are lacking. AIM: To define the best cut-off point of this molecule in differentiating the severe form of acute biliary pancreatitis from the mild form and to evaluate its sensitivity, specificity and diagnostic accuracy in the prognosis of acute biliary pancreatitis in comparison with those of serum C-reactive protein. PATIENTS: Forty-four patients with acute biliary pancreatitis: 27 patients with mild pancreatitis and 17 with the severe form of the disease. METHODS: Serum interleukin-6 and C-reactive protein concentrations were assessed in all patients on admission and for the following 5 days. RESULTS: Serum interleukin-6 levels were significantly higher (p < 0.02) in patients with severe acute biliary pancreatitis than in those with the mild form of the disease. No significant difference in serum C-reactive protein levels was found in the first 2 days in patients with mild biliary pancreatitis when compared to those with the severe form of the disease. Using a cut-off point of 2.7 pg/ml for serum interleukin-6 and 11 mg/dl for serum C-reactive protein, the sensitivity of the two molecules in assessing the severity of acute pancreatitis on the first day of the study was 87.5% for interleukin-6 and 6.3% for C-reactive protein, the specificity, 83.3% for interleukin-6 and 91.7% for C-reactive protein, and the accuracy 85.0% for interleukin-6 and 57.5% for C-reactive protein. CONCLUSIONS: Serum determination of interleukin-6 in the first 24 hours of the disease is a better marker of the severity of acute biliary pancreatitis than C-reactive protein.

Is the association of serum lipase with beta2-microglobulin or C-reactive protein useful for establishing the diagnosis and prognosis of patients with acute pancreatitis?

In the Emergency Department it is mandatory to establish the diagnosis and the prognosis of acute pancreatitis as soon as possible. To evaluate whether the association of serum lipase either with serum beta2-microglobulin or with C-reactive protein allows simultaneously to establish the diagnosis and the prognosis of acute pancreatitis, 96 patients with acute abdomen were studied. Fifty-eight patients had non-pancreatic acute abdomen and the remaining 38 had acute pancreatitis: 23 mild acute pancreatitis, and 15 severe acute pancreatitis. Forty healthy subjects were studied as controls. Lipase, beta2-microglobulin and C-reactive protein were determined in the serum of all subjects, using commercial kits. One patient with acute pancreatitis was not correctly classified when lipase was used to discriminate between patients with non-pancreatic acute abdomen and those with acute pancreatitis. For the discrimination of patients with severe acute pancreatitis from those with the mild form of the disease in the remaining 37 acute pancreatitis patients, beta2-microglobulin had a sensitivity of 53.3 %, specificity of 81.8%, and prognostic accuracy of 70.3 % (27 of the 37 patients correctly classified); 87.5 % of the 96 cases were correctly classified. C-reactive protein showed a lower prognostic accuracy than beta2-microglobulin: sensitivity 86.7%, specificity 45.5%, accuracy 62.2 %; 84.4 % of the cases were correctly classified. Using the polychotomous logistic regression analysis we found the same accuracy in discriminating between patients with acute pancreatitis and those with non-pancreatic acute abdomen (99.0%) but a lower accuracy (54.1%) between patients with severe acute pancreatitis and those with the mild form of the disease. Our study shows that the association of serum lipase with beta2-microglobulin or with C-reactive protein is not useful in simultaneously establishing the diagnosis and prognosis of acute pancreatitis.

Serum C-reactive protein in acute biliary pancreatitis. Is it a reliable marker for the early assessment of severity of the disease?

BACKGROUND: The cut-off point of serum C-reactive protein to differentiate the mild from the severe form of acute pancreatitis is still debated; data concerning the C-reactive protein pattern in assessing the severity of acute biliary pancreatitis are lacking. AIM: To define the best cut-off point in differentiating the severe from the mild form of acute biliary pancreatitis. PATIENTS: Fifty patients with acute biliary pancreatitis: 34 patients with mild pancreatitis and 16 with the severe form of the disease were studied. METHODS: Serum C-reactive protein concentrations were assessed in all patients upon admission and for the following 5 days. RESULTS: No significant difference in serum C-reactive protein levels was found in the first 2 days in patients with mild pancreatitis compared to those with the severe form of the disease. Using a cut-off point of 11 mg/dl, the sensitivity of serum C-reactive protein in assessing the severity of acute pancreatitis during the first two days of the study was 9% and 57%, the specificity, 93% and 81%, and the accuracy 71% and 74%, respectively. CONCLUSIONS: Serum determination of C-reactive protein in the first 48 hours of the disease is not a reliable marker of the severity of acute biliary pancreatitis.

Serum interleukin-6, interleukin-8, and beta 2-microglobulin in early assessment of severity of acute pancreatitis. Comparison with serum C-reactive protein.

The aim of this study was to compare the sensitivity, specificity, and diagnostic accuracy of serum interleukin-6, interleukin-8, beta 2-microglobulin, and C-reactive protein in the assessment of the severity of acute pancreatitis using commercial kits for their respective assays. Thirty-eight patients with acute pancreatitis (25 men, 13 women, mean age 59 years, range 16-97) were studied; the diagnosis was based on prolonged upper abdominal pain associated with a twofold increase of serum lipase, and it was confirmed by imaging techniques. According to the Atlanta criteria, 15 patients had severe illness and 23 had mild disease. The four serum markers were determined in all patients on admission, as well as daily for the following five days. On the first day of the disease, the sensitivity (calculated on patients with severe pancreatitis), specificity (calculated on patients with mild pancreatitis), and the diagnostic accuracy of these serum markers for establishing the severity of acute pancreatitis were 100%, 86%, and 91% for interleukin-6 (cutoff level 2.7 pg/ml); 100%, 81% and 88% for interleukin-8 (cutoff level 30 pg/ml); 58%, 81%, and 73% for beta 2-microglobulin (cutoff level 2.1 mg/liter); and 8%, 95%, and 64% for C-reactive protein (cutoff level 11 mg/dl). The results of our study indicate that, when assayed during the first 24 hr of disease onset, interleukin-6 and interleukin-8 are better markers than beta 2-microglobulin or C-reactive protein for evaluating the severity of acute pancreatitis.

Serum beta 2-microglobulin in chronic diseases of the pancreas.

Elevated serum concentrations of beta 2-Microglobulin (beta 2-MG) has been reported in a variety of chronic diseases and solid tumors. We determined serum beta 2-MG concentrations in 140 subjects divided into five groups: group 1, 34 patients with proven chronic pancreatitis, 8 of whom were studied during a painful relapse; group 2, 40 patients with pancreatic cancer staged according to the Cubilla-Fitzgerald classification; group 3, 40 healthy subjects; group 4, 10 patients with digestive nonpancreatic carcinomas; group 5, 16 patients with benign digestive nonpancreatic diseases. Serum soluble interleukin-2 receptor (sIL-2R) was also determined in all patients with pancreatic diseases as an index of immune system activation. In addition, serum CA 19-9 was assayed in patients of groups 2 and 4, and C-reactive protein (CRP) of groups 1 and 5. Renal function, evaluated by serum creatinine determination, was normal in all subjects studied. Patients with pancreatic cancer and those with chronic pancreatitis had serum concentrations of beta 2-MG significantly higher than those of healthy subjects (p < 0.001 and p < 0.005, respectively). Patients with stage I and stage III pancreatic cancer had similar serum levels of beta 2-MG, and these concentrations were significantly lower than those of patients with stage II tumors (p < 0.002 and p < 0.05, respectively). In chronic pancreatitis patients, those studied during painful relapse of the disease had serum concentrations of beta 2-MG similar to those studied during clinical remission.(ABSTRACT TRUNCATED AT 250 WORDS)

[Clinical and immunologic test of the activity of a polymicrobial vaccine in patients with chronic bronchitis during a flare-up]. / Verifica clinica ed immunologica dell'attività di un vaccino polimicrobico in pazienti affetti da bronchite cronica in fase di riacutizzazione.

The authors evaluated the effect of an orally administered polymicrobial vaccine in a group of chronic bronchitis patients in order to assess its efficacy in preventing recurrent infections and as adjuvants during minor acute episodes. Compared to the control group, vaccinated patients had 1) a reduced number of flare-ups, and these were less severe and symptoms were improved; II) lymphocyte phenotype was not altered in any of the patients but nevertheless the response to skin tests for delayed sensitivity was improved in the vaccinated patients only; III) more rapid symptomatic improvement of flare-ups. The authors stress the improvement of cell-mediated lymphocyte function as a result of vaccination, probably due to macrophage activation and with resulting improvement of the clinical course of the bronchial disorder.