C-reactive protein in clinical practice with special regard to infectious diseases
Abstract: A new simple affinity purification methodfor human CRP using Arginine-Sepharose4B was developed with a recovery of >90 %and containing < 5-10 % contaminatingproleins .In a multicenter study including 607consecutive patients in general practice,erythrocyte sedimen-tation rate (ESR) andserum CRP were compared. Comparableresults were obtained in 71 % of the patients.In 20 % of the patients CRP was increasedmore than ESR. In patients with increase inserum CRP above 50 mg/l but with "normal"or only marginally increased ESR, theincreased CRP concentration was often due tothe presence of inflammatory diseases,mostly infections. Patients with an increasedESR but a normal or marginally increasedCRP concentration were all more than 50years of age and the high ESR was usually aconsequence of an earlier infectious disease.The serum CRP, ESR, white blood cell count(WBC), and polymorphonuclear granulocytes(PMN) were significantly more increased inpatients with either septicae-mia/endocarditis(N=176) or complicated influenza (N=22)than in patients with uncomplicatedinfluenza (N=59). Serum CRP was moreefficient than WBC, PMN, and ESR todifterentiate between bacterial infection andpure viral infection. Five of 56 patients withuncomplicated influenza had serum CRPvalues >100 mg/l. However, 32 % of thepatients with bacterial infections had WBC<9.0 x 109/1 and 30 % had PMN < 75 %.CRP in cerebrospinal fluid (CSF) was evalu-ated in 710 patients with suspected centralnervous system (CNS) infection for the dif-ferential diagnosis of meningitis. In a subsetof these patients (N=235) the ability of se-rum CRP to differentiate between acute bac-terial and viral meningitis was evaluated. Anoverlap existed for both CSF and serum CRPbetween the different etiological groups.Even though CSF-CRP was the second bestCSF test for the diagnosis of bacterial men-ingitis compared to CSF lactate CSF-CRPoffered little or no additional information.For patients 26 years of age a serum CRPlevel of 50 mg/l was empirically choosen as adecision limit between patients with bacterialand non-bacterial CNS-diseases. For children<6 years of age a decision limit for serumCRP as low as 20 mg/l could be used with asensitivity of 97 % and a specificity of 86 %.Seven of the patients with bacterial meningi-tis had serum CRP values below 50 mg/l. fourof them were children below the age of sixyears. Five of the seven patients had a dura-tion of symp-toms at admission of less than12 hours. Patients with high serum CRP level(>100 mg/l) and viral meningitis ohen hadsigns of extensive tissue involvement.The median duration of illness prior to ad-mission for 97 patients (mean age 69.6years) with community-acquired pneumonia(CAP) was four days (range: <1-25 days). Onadmission 64 % of the patients were hy-poalbuminemic (<37g/1). The serum level ofalbumin at admission did not correlate withthe nutritional measurements, however. a sig-nificant negative correlation was found forserum albumin with the acute phase proteins:CRP, haptoglobin, a-l-antitrypsin and oro-somucoid. These results strongly indicate thatinflammatory reaction is the main causes ofthe low serum albumin level in patients withCAP. The serum level of CRP was high-est atadmission (geometric mean: 154 mg/l) andbegan to decrease from day 3 indicating avery earlier response to the recovery of thepatients. The median normalisation rate ofCRP was 3.3 days. Albumin, transferrin. a-1anti-trypsin, haptoglobin, and orosomucoidwere not useful for evaluation of response totherapy during the hospitalisation phase inpatients with CAP.CRP was evaluated together with other plasmaproteins as prognostic markers in patientswith malignant melanoma (N=643). Theserum levels of the different serum proteinshad independent prognostic value in relationto the clinical stage in multivariate analyses.For each clinical stage the serum valuesbelow respectively above the different cut-offlevels for albumin and transthyretin on onehand and the acute phase proteins CRP,haptoglobin, and orosomucoid on the otherhand significantly influenced the survivalrate and the relative hazard with respect todeath .Key words: CRP, general practice, septi-caemia, endocarditis, influenza, bacterialmeningitis, viral meningitis, community-acquired pneumonia, malignant melanoma,albumin, transferrin, a-1 anti-trypsin, hapto-globin, orosomucoid, transthyretin, iron.
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