Rat resistance to schistosomiasis: platelet-mediated cytotoxicity induced by C-reactive protein.

In rats infected with the parasite Schistosoma mansoni, the concentration of C-reactive protein in the serum increases after the lung stage of infection and is at its highest at the time of terminal worm rejection. The peak of platelet-mediated cytotoxicity induced by infected serum that has been heated (and is free of immunoglobulin E) as well as the time course for the development of platelet cytotoxic activity in infected rats was found to be correlated with the concentration of C-reactive protein. Rat and human platelets treated with homologous serum obtained during an acute phase of inflammation or with purified C-reactive protein were able to kill the immature forms of the worm in vitro. Platelets treated with C-reactive protein were furthermore capable of conferring significant protection against schistosomiasis in transfer experiments. Collectively these data indicate that a system that includes C-reactive protein and platelets participates in the natural resistance of the rat to schistosomal infection.

Severity, duration, and mechanisms of insulin resistance during acute infections.

Acute infections provoke insulin resistance. These experiments were designed to study the severity, duration, and mechanisms of insulin resistance caused by acute infections. First, we studied eight patients [mean age, 29 +/- 11 (+/- SD) yr; body mass index, 23 +/- 2 kg/m2] with acute viral or bacterial infections during the acute stage of their infection and 1-3 months after recovery. The rate of glucose infusion required to maintain normoglycemia during hyperinsulinemia (approximately 500 pmol/L) was used as a measure of insulin action. During infection, the glucose requirements in the patients [21 +/- 2 (+/- SE) mumol/kg.min] were 52% less than those in weight- and age-matched normal subjects (44 +/- 2 mumol/kg.min; P less than 0.001). Compared to data from a large group of normal subjects, the resistance to insulin during infection corresponded to that predicted for a weight-matched 84-yr-old normal person or an age-matched obese person with a body mass index of 37 kg/m2. One to 3 months after recovery, the patients' glucose requirements were still significantly lower (37 +/- 3 mumol/kg.min; P less than 0.02) than those in matched normal subjects. To assess the mechanism of insulin resistance, seven additional patients were studied during the acute stage of infection using a low dose insulin infusion (plasma insulin, 215 pmol/L) combined with a [3-3H]glucose infusion and indirect calorimetry. Again, the glucose requirements were 59% lower in the patients (14 +/- 2 mumol/kg.min) than in matched normal subjects (34 +/- 2 mumol/kg.min; P less than 0.001). This decrease was due to a defect in glucose utilization (18 +/- 2 vs. 37 +/- 1 mumol/kg.min; P less than 0.001, patients vs. normal subjects) rather than impaired suppression of glucose production (4 +/- 1 vs. 3 +/- 1 mumol/kg.min, respectively). Total carbohydrate oxidation rates were similar in both groups (16 +/- 2 vs. 14 +/- 1 mumol/kg.min, respectively), whereas the apparent glucose storage was neglible in the patients (2 +/- 1 mumol/kg.min) compared to that in normal subjects (22 +/- 2 mumol/kg.min; P less than 0.001). We conclude that acute infections induce severe and long-lasting insulin resistance, which is localized to glucose-utilizing pathways. The rate of carbohydrate oxidation is normal during infections, whereas the rate of nonoxidative glucose disposal, as determined by indirect calorimetry, is nearly zero. The apparent blockade in glucose storage could result from diminished glycogen synthesis, accelerated glycogenolysis, or both.

Serum C-reactive protein as detector of pretreated childhood bacterial meningitis.

Serum C-reactive protein (CRP) levels were measured at presentation to the hospital in 15 children with proven bacterial meningitis (BM) pretreated with antibiotics. CRP exceeded the upper normal limit of 19 mg/l in all cases; the mean value was 195 mg/l (range, 55 to 375 mg/l). On the other hand, CRP levels were normal in 12 patients with viral meningitis or meningoencephalitis. Rapid determination of serum CRP should be performed whenever BM is suspected.

Reduction of postoperative pain and swelling by ultrasound treatment: a placebo effect.

Ultrasound (US) therapy is used to reduce pain and inflammation and to accelerate healing after soft tissue injury. However, there is little objective evidence of its effectiveness and the mechanisms which may cause these effects are unknown. In a placebo-controlled double-blind clinical trial we examined the contribution of placebo and massage effects in ultrasound therapy following bilateral surgical extraction of lower third molars. Four to 6 h after surgery the patients (25 per group) received either no therapy, US (0.1 W/cm2), 'mock' US with massage, 'mock' US without massage, or 'self-massage' with a dummy applicator. Facial swelling, trismus, serum C-reactive protein, serum cortisol, pain and anxiety were measured 24 h postoperatively. The results showed that the beneficial analgesic and anti-inflammatory effects of US therapy were placebo-mediated, with maximum effect in the placebo ('mock' US) group without circular massaging with the applicator). Self-massage by the patient produced no significant effect. This placebo action was independent of changes in serum cortisol or patient anxiety state. US therapy can significantly reduce postoperative morbidity, but by placebo-mediated mechanisms which are unrelated to the US itself.

Serum C-reactive protein concentrations in cyclosporine-treated renal allograft recipients.

Acute or persistent elevations in serum C-reactive protein (CRP) concentration have been shown to be of value in diagnosing acute rejection episodes in azathioprine (AZA)-treated renal transplant recipients. To assess whether changes in serum CRP level might assist in differentiating nephrotoxicity from acute rejection in cyclosporine (CsA)-treated renal transplant recipients, we measured changes occurring in serum CRP concentrations in 74 CsA patients in response to transplant operation, acute rejection, cyclosporine nephrotoxicity, and serious infection, and compared these values with changes in AZA patients. Serum CRP concentration rose in response to operation in virtually all patients, regardless of immunosuppressive regimen, from mean baselines of 5.9 +/- 2.7 mcg/ml (AZA) and 6.8 +/- 6.5 mcg/ml (CsA) to mean peak levels of 43.8 +/- 33.4 mcg/ml and 65.1 +/- 39.5 mcg/ml, respectively. CRP rose during 76% of acute rejection episodes in AZA patients by a mean of 29.7 +/- 37.4 mcg/ml. In contrast, in 80% of acute rejection episodes of CsA patients, CRP remained undetectable or failed to rise above a stable, minimally elevated baseline. Similarly, there was no elevation in CRP in 9 of 10 episodes of nephrotoxicity. In 14 CSA patients with serious infections (8 pulmonary, 3 intraabdominal, 3 genitourinary), CRP rose by a mean of 67.7 +/- 50.7 mcg/ml. Thus, although CRP rises significantly with operation or serious infection in CsA patients, CRP fails to rise with nephrotoxicity or acute rejection.

Hematologic and iron-related measurements in rheumatoid arthritis.

The hematologic status of 265 patients with rheumatoid arthritis was assessed. In the group as a whole, a mild depression in the hemoglobin concentration and mean cell volume (MCV) was associated with an increase in the red blood cell distribution width (RDW), erythrocyte sedimentation rate (ESR), and platelet count. Bone marrow trephine biopsies and further measurements of iron status and disease activity were done in [a further] 38 more anemic patients, and the findings in those with absent marrow iron (iron deficiency) were compared with those having stainable stores (anemia of chronic disorders). The RDW was raised in both, and there was no significant difference between the two groups. The concentrations of nonheme iron in the marrow and of serum ferritin were significantly lower in the iron-deficient group, but the geometric mean serum ferritin of 34 micrograms/L was still a good deal higher than that associated with uncomplicated iron deficiency. This was presumably because of the fact that the serum ferritin, which was significantly correlated with the ESR (r 0.55; P less than 0.0004) and C-reactive protein (CRP) r 0.41; P less than 0.01), was also functioning as an acute phase protein. While there was a weak correlation (r 0.37; P less than 0.04) between the marrow nonheme iron and the serum ferritin concentrations, it disappeared when nonactive patients with normal CRP concentrations were excluded. The absence of a correlation is unlike the findings that have previously been noted in other chronic inflammatory conditions and in neoplasia. This raises the possibility that serum ferritin concentrations in rheumatoid arthritis may reflect, in part at least, another store of iron located in affected joints.

Purification and characterization of human serum C-reactive protein.

A simple and rapid purification method for human serum C-reactive protein (CRP) was developed. CRP was strongly adsorbed on a DEAE-cellulose column and was easily separated from other serum proteins. CRP was purified approximately 1,000-fold with a high yield (50%). The final preparation showed a single band as judged by SDS-polyacrylamide gel electrophoresis, polyacrylamide gel disc electrophoresis, and polyacrylamide gel isoelectric focusing. The fluorescence of the complex of CRP and 8-anilino-1-naphthalene sulfonate (ANS) changed with change of the pH, suggesting that CRP may show pH-dependent conformational change. This finding could account for the peculiar behavior of the protein in isoelectric focusing; it shows an isoelectric point of 7.4 when the starting pH is 7.0, whereas it shows two isoelectric points, 5.3 and 7.4, when the starting pH is 5.5. Ca2+-dependent change of the fluorescence of the complex of CRP and ANS was also detected. These results suggest a pH- and Ca2+-dependent conformational change of CRP.

Aggregation of white cells and C-reactive protein: relation between these two indices in acute phase reaction.

The association between aggregates of leucocytes in blood drawn from patients with various inflammatory conditions and the serum concentration of C-reactive protein (CRP) was examined: serum concentration of CRP might contribute to the development of cellular aggregations. A total of 213 patients with various inflammatory or necrotic conditions were examined (including 31 women with normal pregnancy and 59 controls). A significant correlation between the degree of leucocyte aggregation and CRP concentration was noted in patients with bacterial infections and in a group of patients with various inflammatory conditions. In contrast, there was no correlation between the extent of leucocyte aggregation and CRP concentrations in patients with viral infections, malignancies, or pregnancy. The presence or absence of aggregated leucocytes can help in differentiating between the respective bacterial or viral infections. The serum concentrations of CRP were increased in both types of infection, although when a quantitative CRP assay was used, considerably higher concentrations were detected in bacterial diseases.

Early plasma protein and mineral changes after surgery: a two stage process.

Sequential changes in albumin, transferrin, alpha 1-acid glycoprotein, C reactive protein, fibrinogen, copper, iron, and zinc in plasma up to 24 h after hysterectomy were measured. No increases in the concentrations of the acute phase proteins alpha 1-acid glycoprotein, C reactive protein, and fibrinogen were observed until 6 h after the skin incision. These increases were preceded by significant falls at 2-4 h, and this was shown also by albumin, transferrin, iron, zinc, and copper. The ratios of iron and zinc to their binding proteins, transferrin and albumin, did not decrease until 4-6 h and their concentrations remained low for at least 24 h. These patterns suggest that at least two mechanisms operate after trauma. The early fall in the concentrations of the proteins in plasma is consistent with a prompt increase in microvascular permeability. The later decrease in binding of the metals iron and zinc to their transport proteins and the increase in concentrations of the acute phase proteins could be initiated by a common mediator.

Haemorrheological effects of prostaglandin E1 infusion in Raynaud's syndrome.

Eighteen patients with severe Raynaud's syndrome had impaired deformability of erythrocytes, as measured by filtration through 5 micron diameter pores, compared with 19 healthy controls. The patients were given prostaglandin E1 (PGE1) or placebo by intravenous infusion for 72 h to assess the haemorrheological action of PGE1. Contrary to a previous report, PGE1 did not improve erythrocyte filterability. Infusion of PGE1 did, however, evoke an acute phase response with hyperproteinaemia and a leucocytosis and is a potentially important mediator of this stress response in patients with vascular disease.

Hematologic, iron-related, and acute-phase protein responses to sustained strenuous exercise.

This study was undertaken to gain insight into the mechanisms responsible for the hypoferremia occurring after severe exercise. To this end, 18 athletes who were competing in a 160-km triathlon involving canoeing, cycling, and running were evaluated before the race, immediately after the finish, and thereafter at 30 min, 24 h, and 48 h. The evaluation included plasma iron, total iron-binding capacity, lactoferrin, ferritin, haptoglobin, cortisol, various enzymes, and white cell count. The cortisol, white cell count, and lactoferrin were significantly increased immediately after the race, while the plasma iron and transferrin saturation were significantly decreased. There was a 40% but nonsignificant rise in the plasma ferritin at the completion of the race, while the C-reactive protein was raised by nearly 300% at 24 h. In contrast, haptoglobin declined significantly by 24 h but was normal again 24 h later. Quantitative considerations suggested that the lactoferrin was not responsible for removing transferrin iron from circulation and hence causing the hypoferremia. Instead, it seemed more likely that the iron-related changes were occurring as part of an acute phase response initiated by muscle injury.

Measurement of C-reactive protein to compare ceftizoxime versus cefoxitin/doxycycline therapy for septic pelvis: a preliminary report.

C-reactive protein (CRP), a biological marker of inflammation, may be a useful indicator of therapeutic response in patients with septic pelvis. In a study comparing ceftizoxime and cefoxitin/doxycycline in patients with septic pelvis, quantitative CRP levels were closely correlated with the responses and failures of therapy. The results of this study showed the two antibiotic regimens to be equally effective, with 23 of 25 patients in each treatment group achieving a satisfactory response. The fact that ceftizoxime was effective in four of five patients with Chlamydia trachomatis in cervical isolates suggests that intravenous therapy for the acute infection can be accomplished without the addition of an antichlamydial agent. Upon discharge from the hospital, patients can continue therapy with an oral drug that is specifically active against Chlamydia.

[C-reactive protein in inflammatory articular diseases: comparison of concentrations in blood and synovial fluid]. / La proteine C-reactive dans les affections inflammatoires articulaires: comparison des dosages sanguin et synovial.

We evaluated the diagnostic value of measuring C-Reactive Protein (CRP) in blood and in synovial fluid for the detection of inflammatory articular diseases in 154 patients. High concentrations of CRP in blood were found in microcrystalin arthritis, polymyalgia rheumatica and Horton's disease. Our results show a good correlation between CRP and erythrocyte sedimentation rate for ankylosing spondylitis (p less than 0.01), systemic lupus erythematosus (p less than 0.01), rheumatoid arthritis (p less than 0.05), polymyalgia rheumatica and Horton's disease (p less than 0.05). The CRP measurement in blood did not separate seropositive versus seronegative rheumatoid arthritis, systemic lupus erythematosus versus rheumatoid arthritis and treated versus non-treated rheumatoid arthritis. There was a good correlation between CRP concentration in blood and in synovial fluid but the concentration was lower in synovial fluid than in blood (p less than 0.01). Then, the CRP measurement in synovial fluid does not have a higher diagnostic value than in blood.

Serum concentrations of a granulocyte-derived calcium-binding protein in cystic fibrosis patients and heterozygotes.

Serum samples from cystic fibrosis homozygotes and heterozygotes contain elevated levels of a protein, known as cystic fibrosis antigen, which is synthesized primarily in granulocytes. We have produced monoclonal antibodies against cystic fibrosis antigen and developed a sensitive two-site immunoassay. Antigen levels were evaluated in serum samples from 50 cystic fibrosis homozygotes, 34 heterozygotes, 60 healthy controls and 25 disease controls. Simultaneous measurement was made of another granulocyte-derived serum protein, lactoferrin, and also of the acute-phase reactant, C-Reactive Protein. Attempts to use the concentrations of cystic fibrosis antigen in serum to distinguish cystic fibrosis patients from heterozygotes were unsuccessful, even when these concentrations were expressed as a ratio with lactoferrin or with C-Reactive Protein. However, examination of the ratio of cystic fibrosis antigen to lactoferrin in serum samples from cystic fibrosis heterozygotes suggests that there is some specific association between this antigen and the cystic fibrosis gene.

The latency of serum acute phase proteins in meningococcal septicemia, with special emphasis on lactoferrin.

Serum lactoferrin concentrations were elevated in almost all children with meningococcal septicemia, in whom the disease had been clinically apparent for less than 18 hours, while the concentrations were normal or only moderately elevated in patients who had had the disease longer before being admitted. Concentrations of C-reactive protein (CRP) were markedly elevated, even with a time lapse of less than six hours, making this the most suitable parameter for the early diagnosis of severe meningococcal infection. Following an operative injury on children the lactoferrin concentrations changed very little. More than six hours after an operation, however, a marked increase in CRP-values was observed, possibly indicating differentiation of this response from that of bacterial infection. The concomitant study of serum alpha 1-antitrypsin, alpha 1-antichymotrypsin, orosomucoid and haptoglobin did not uncover results of great significance with regard to early changes.

Serum amyloid A protein and C-reactive protein in systemic amyloidosis.

In 106 patients with systemic amyloidosis (56 primary, 27 secondary, and 23 familial), serum amyloid A protein (SAA) was measured by solid-phase radioimmunoassay and C-reactive protein (CRP) was measured by rate nephelometry. SAA and CRP concentrations were highly correlated (r = 0.75, P less than 0.001) throughout the normal and abnormal concentration ranges. In systemic amyloidosis, SAA was more sensitive than CRP as an indicator of the acute-phase response, particularly in secondary amyloidosis. Acute-phase proteins are only occasionally increased during the course of familial amyloidosis. The overlap of acute-phase protein levels does not permit reliable separation of primary amyloidosis from secondary amyloidosis solely on the basis of such studies despite the significantly higher SAA and CRP levels in the latter.

The value of C-reactive protein in the diagnosis of intestinal perforation in typhoid fever.

Serum C-reactive protein concentrations were measured in 28 Nigerian patients with typhoid fever on presentation at hospital and at intervals thereafter. Five of the 28 (18%) were subsequently diagnosed as suffering from ileal perforation. These patients had concentrations of C-reactive protein during the first 24 h of admission which were significantly higher (mean = 229 mg/L) than those without perforation (mean = 91 mg/L). C-reactive protein may have a role in the prediction of early diagnosis of perforation in patients with typhoid fever.

Changes in serum ferritin and other 'acute phase' proteins following major surgery.

We have measured ferritin concentrations in healthy women, and ferritin, C-reactive protein, iron and total iron-binding capacity in patients undergoing hysterectomy or major gastrointestinal surgery. Pre-operative serum ferritin concentrations in patients awaiting hysterectomy were significantly lower than those for patients awaiting gastrointestinal surgery and also lower than those for healthy women of similar age. Healthy women aged between 51 and 60 years had significantly higher ferritin levels than women aged 35-50 years. All patients studied showed large increases in serum ferritin and C-reactive protein concentrations after surgery and approximately similar decreases in iron and in total iron-binding capacity.

Clinical and laboratory findings in patients with acute tonsillitis.

In 82 patients with acute tonsillitis studied, beta-hemolytic group A streptococci were isolated from 30 (37%), and group C or G streptococci from 12 (15%). In the 40 patients with non-streptococcal tonsillitis there was a significantly higher isolation rate of pneumococci, H. influenzae and/or B. catarrhalis, as compared with those with beta-hemolytic streptococci. Patients were classified regarding clinical status according to standardized criteria as severe, moderate, or mild. The patients with group A streptococcal tonsillitis were significantly more often classified clinically as 'severe' and had significantly shorter duration of symptoms before seeking medical care, as compared with those with non-streptococcal tonsillitis. Significant increases in white blood cell count and in anti-DNase B were found in the patients with group A streptococcal tonsillitis, whereas their antistreptolysin O levels did not increase significantly. C-reactive protein concentrations were consistently higher in the patients with group A streptococcal tonsillitis. No evidence of polyclonal beta-lymphocyte stimulation was found when measuring antibodies against pneumococci and group B streptococci. The findings show clinical and simple laboratory tests to be useful aids in distinguishing group A streptococcal tonsillitis from non-streptococcal tonsillitis, and that other bacteria may be involved in non-streptococcal tonsillitis.

Clinical value of serum amyloid A and C-reactive protein measurements in secondary amyloidosis.

Serum amyloid A protein (SAA) and C-reactive protein (CRP) are acute-phase reactants synthesized by the liver. A close relationship was found between SAA and CRP concentrations in various rheumatic diseases (rs = 0.74 to 0.83). The serum concentration of these proteins reflected the activity of the rheumatic inflammation in a sensitive way. In secondary amyloidosis, persistently high SAA and CRP levels correlated closely with the progression of the renal amyloid manifestations. The findings show that measurements of SAA and CRP concentrations are valuable in assessing disease activity and the effect of therapy in rheumatic diseases, as well as in the assessment of the prognosis in secondary amyloidosis. Therapeutic measures that decrease SAA levels may reduce amyloid formation.