[C-reactive protein and transthyretin in early diagnosis of infection after open fractures of the lower limbs (a preliminary study)]. / La protéine C-réactive et la transthyrétine dans le diagnostic précoce de l'infection après fracture ouverte des membres inférieurs (étude préliminaire).

PURPOSE OF THE STUDY: The authors investigated the value of C-reactive protein (CRP) and transthyretin (TTR) in the early diagnosis of infection after open fractures of the lower limb in an open, prospective study. MATERIAL AND METHODS: Eighty patients were treated with acute debridement and bone fixation. Follow-up included clinical, radiological, bacteriological and biological assessment: white cell blood count (WBC), erythrocyte sedimentation rate (ESR), CRP and TTR. Diagnosis of infection was based on macroscopic presence of pus. RESULTS: Post-operative reference biological profiles were defined in 74 cases without infection. Reference profiles of WBC and ESR showed unreliable interindividual variations and could not be considered for the diagnosis of infection. Reference profiles of CRP and TTR showed a respective increase (for CRP) and decrease (for TTR) in the early post-operative course, with return to normal values after 12 days. In 6 infected patients, CRP concentrations were suddenly increased and TTR concentrations decreased at the time (3 cases) or even before (3 cases) clinical diagnosis of infection. These variations were mostly simultaneous. No unusual profile was found. The ratio of CRP/TTR concentrations experienced also a sudden increase in infected cases. DISCUSSION: Because of not specifical and unreliable variations in the post-operative outcome of non infected patients, WBC and ESR cannot be considered for the early diagnosis of infection. CRP and TTR concentrations with a respective cut-off value of 100 mg/L and 120 mg/L were found efficient for the early diagnosis of infection, and preceded clinical diagnosis in three of them. A CRP/TTR ratio over 60 p. 100, 8 days or more after initial surgery was found to be very specific (93 p. 100) and sensitive (100 p. 100) for the diagnosis of infection. CONCLUSION: Serial quantifications of CRP and TTR should be performed every four days during the follow-up of open fractures in order to early diagnose a post-operative infection. Comparison of both CRP and TTR could allow a higher accuracy, because of the possible lack of variation of one the two markers.

Incomplete or absent acute phase response in some postoperative patients.

In a prospective study, 74 patients were admitted for an open fracture of the lower limb and treated by osteosynthesis. None of them presented infectious complication during the postoperative period. Among them, 67 exhibited a classical acute phase response. In 5 patients, the response was apparently incomplete since no serum C-reactive protein (CRP) rise was observed after the injury; i.e. CRP concentrations remained inferior to the detection limit of the assay used; in contrast, serum alpha-1 acid glycoprotein (AAG) concentrations were temporarily increased, a variation associated with a concomitant decrease of transthyretin (TTR) concentration. In 2 other patients, CRP and AAG levels were not significantly modified. The 7 patients did not suffer hepatic insufficiency or protein malnutrition. In our series, incomplete or absent acute phase response was not rare (prevalence 9%) and was not related to an increased risk of postoperative infection. In contrast to CRP, the TTR response, i.e. a transitory decrease, was observed in all the 7 patients.

Diagnostic value of C-reactive protein and transthyretin in bone infections of the lower limb.

In a prospective study, white and red blood cell counts, hematocrit, erythrocyte sedimentation rate (ESR), albumin, alpha-1 acid glycoprotein, C-reactive protein (CRP), and transthyretin (TTR) values were determined by serial measurements during 23 days in 80 patients with an open fracture of the lower limb. Postoperative reference profiles were defined in 74 patients without septic complications. In the six remaining patients, serum CRP and TTR concentrations were found efficient for the early diagnosis of postoperative infections: a CRP/TTR mass concentration ratio higher than 0.6 from the 8th day after surgery was sensitive (100%) and specific (93%). Variations of CRP and TTR concentrations often preceded the clinical diagnosis in patients with early infection. ESR was found unreliable with regard to postoperative infection because of its high dependence with respect to red blood cell count.

Immunocytological analysis of the Tn associated antigen 83D4 in serous effusions from patients with cancer: comparison with Tn soluble glycoprotein.

AIMS: To determine whether the monoclonal antibody (MoAb) 83D4, previously shown to be highly specific for carcinoma cells, can be used as an immunocytological marker to discriminate between benign and malignant cells in serous effusions; and to test for a correlation between expression of the antigen reacting with MoAb 83D4 on effusion cells and the amount of soluble 83D4 antigen in effusion fluids. METHODS: Thirty three pleural and 23 peritoneal effusions from 56 cancer patients with metastatic disease were tested for the presence of Tn associated 83D4 antigen by immunocytochemical staining, and for the presence of soluble antigen in supernatants. The patients had undergone various chemotherapy and radiation therapy protocols. RESULTS: As a result of the various types of treatment, the cytological characteristics of the cells were often modified and the antigenic epitopes may have been altered. Positive staining for 83D4 MoAb was obtained in 36 (97%) of the 37 malignant effusions, eight (73%) of 11 suspect effusions, and three (38%) of the eight apparently benign effusions (free of malignant cells). In these latter cases, cytological reassessment showed a few suspect cells in two cases. 83D4 soluble antigen was detected in 30 of 37 malignant effusions (81%), five of 11 suspected infusions (46%), and five of eight apparently benign effusions (63%). CONCLUSIONS: Immunocytochemical staining with anti-83D4 antibody is useful for differentiating reactive or atypical mesothelial cells from epithelial cells, especially in breast cancer effusions.

Human pharmacokinetics of a new Vinca alkaloid S 12363 with use of a monoclonal antibody-based radio- or enzyme immunoassay.

S 12363 is a new Vinca alkaloid derivative, characterized by the grafting of an alpha-aminophosphonate, onto the Vinca nucleus, facilitating drug penetration and increasing intracellular drug retention. As a high cytotoxic activity had been demonstrated in in vitro and in vivo models recommended by the National Cancer Institute, a phase I trial was initiated in cancer patients. In order to quantify S 12363 systemic levels in humans, two monoclonal antibody-based immunoassays, RIA (radio-) and EIA (enzyme immunoassay) were developed. The gamma-emitting probe used in the RIA, 125I-(deacetyl-O4-vinblastine)-tyramine, bound very tightly to the monoclonal antibody (dissociation constant, Kd = 2.5 x 10(-11) M), demonstrating a high affinity mainly directed toward the catharantine nucleus (vindesine, vincristine, vinblastine, 100% cross-reactivity; vinorelbine, 0.3% cross-reactivity). In the EIA, a deacetyl O4-vinblastine/ovalbumine conjugate was used as the competing antigen. Its binding to the monoclonal antibody was revealed by an anti-mouse immunoglobulin G conjugated to biotin which interacts with streptavidin labeled with alkaline phosphatase. This method permitted obtaining nearly the same sensitivity and reproducibility with EIA as with RIA, their respective minimum quantitation limits being 0.100 and 0.040 ng/ml (106 and 42 pM) of S 12363 in plasma. These assays allowed the study of S 12363 systemic pharmacokinetics in cancer patients during a phase I trial up to 72 h after dosing. As determined by RIA, the S 12363 plasma profile was triphasic with a terminal half-life; t1/2 gamma = 49 +/- 16 h, a plasma clearance, CL = 0.14 +/- 0.04 liter/h/kg, and a volume of distribution at steady state, Vdss = 5.0 +/- 2.8 liter/kg. The pharmacokinetics of S 12363 is linearly related to dose when increased from 0.08 up to 0.84 mg/m2 in humans. Its plasma profile and pharmacokinetic parameters are close to those of other Vinca alkaloids with clearance and terminal half-life being intermediate between those of vinblastine and vincristine. Therapeutic doses are 4 to 10 times lower and should be a direct consequence of the higher uptake and retention by the cells of this new aminophosphonate Vinca alkaloid derivative.

Soybean oil, blackcurrant seed oil, medium-chain triglycerides, and plasma phospholipid fatty acids of stressed patients.

Thirty-six adult severe head injury and cerebral stroke patients in four intensive-care units were randomized to receive one of three enteral diets for 21 days. These diets, which supplied 45% of calories from fat, differed only in lipid composition. Diet A was comprised of 100% soybean oil, diet B contained a 50:50 (wt/wt) mixture of soybean oil and medium-chain triglycerides (MCTs), and diet C contained 42.5% MCT, 50% soybean oil, and 7.5% blackcurrant seed oils. Plasma phosphatidylcholine and fatty acid composition of plasma total phospholipids were determined before initiating treatment (day 0) and weekly throughout the study. Results indicated that at the start of the study, all patients had low linoleic acid (18:2 omega 6) levels compared with healthy subjects. Emulsion A disturbed the balance between several fatty acids of the omega 6 series, as exemplified by the significant increase in 18:2 omega 6 proportions. In contrast, both emulsions B and C introduced a less-pronounced rise in 18:2 omega 6 associated for emulsion C with a significant increase in dihomo-gamma-linolenic acid (20:3 omega 6) and docosapentaenoic acid (22:5 omega 3) in plasma phospholipids. Furthermore, 18:3 omega 6 change was significantly different between groups A and C and that of 20:3 omega 6 between group A and both groups B and C. Throughout the study, arachidonic acid (20:4 omega 6) exhibited remarkable steady-state levels regardless of the diet. This study shows that providing the injured body with high amounts of 18:2 omega 6 does not lead to high levels of its upper derivatives in plasma phospholipids.(ABSTRACT TRUNCATED AT 250 WORDS)

Detection of a soluble antigen defined by monoclonal antibody 83D4 in serous effusions associated with breast carcinoma.

Monoclonal antibody (MoAb) 83D4 was generated by immunization with cell suspensions obtained from sections of formol-fixed paraffin embedded human breast cancer. It recognized an antigen expressed in breast carcinomas but not in normal breast tissue. Pleural and ascitic fluids from 66 patients were studied by an 83D4 heterologous sandwich radioimmunoassay (SRIA) using solid-phase immobilized wheat germ agglutinin to detect the 83D4 soluble antigen. Using a cutoff level of 5 units/ml of 83D4 antigen, higher values were found in 22 of 27 breast cancer-associated effusions (mean = 10.72 +/- 6.80 units/ml). The 20 nonmalignant effusion fluids tested showed lower values (mean = 1.16 +/- 1.49 units/ml, P less than 0.001). The antigen was undetectable or present in low levels in effusions from patients with hematologic malignancies. When SRIA results were compared with conventional cytologic diagnosis in breast-cancer effusions, elevated levels of 83D4 soluble antigen were found in all patients (8 of 8) in whom malignant cells had been detected, in 4 of 8 patients with the diagnosis of "suspected malignancy," and in 10 of 11 patients with negative cytologic findings. Using an immunoglucosidase method on cell smears of various origins, MoAb 83D4 stained metastatic cells of breast and ovary carcinomas but did not reactive with mesothelial cells and other normal or malignant cell types. These results suggest that quantitation of the 83D4 soluble antigen may be used to improve the diagnosis of cancer in serous effusions.

Competitive prognostic value of clinicopathologic and bioimmunologic factors in primary breast cancer.

Fourteen clinical, pathologic, and pretreatment bioimmunologic variables were evaluated for their significance in predicting the survival or the length of disease-free interval of 55 patients with primary breast cancer. The variables studied were: patient age; clinical stage of disease according to the International Union Against Cancer TNM classification; number of involved nodes; sedimentation rate; peripheral lymphocyte, leucocyte, and monocyte counts; serum levels of immunoglobulins IgG, IgA, and IgM; percentages of E-, "active" E-, and EAC-rosettes; and finally, the lymphoblastic transformation test value (PHA-LTT). A multivariate analysis using the Cox proportional hazards regression model was carried out, in a stepwise manner, to identify those variables most highly related to survival or to the length of disease-free interval. The Cox analysis showed that clinical stage, number of involved nodes, percentage of EAC-rosettes, sedimentation rate, and T-lymphocyte reactivity, (i.e., the T-lymphocyte sensitivity to PHA, expressed as the ratio between the PHA-LTT in counts per minute and the percentage of E-rosettes) were the significant prognostic factors for survival, whereas the number of involved nodes and the sedimentation rate were independent of importance in predicting the length of disease-free interval. The results obtained from this analysis proved the importance of some immunologic parameters in the estimation of prognosis. In addition, a prognostic score for summarizing multiple factors with potential use in stratification was derived from the multivariate analysis.

[An unusual way of manifesting acute granulocytic leukemia: granulocytic sarcoma of the breast. Apropos of a case with trisomy 22]. / Un mode inhabituel de révélation des leucémies aiguës granuleuses: le sarcome granulocytaire du sein. A propos d'un cas porteur d'une trisomie 22.

A case of granulocytic breast sarcoma in a 19 year-old-girl is reported. Surgical excision of the tumor was followed by radiotherapy of the breast and lymph nodes. Then 3 months later acute M2 myelocytic leukemia was diagnosed, complete remission being attained using rubidazone-cytarabine and maintained by monthly reinduction courses. Trisomy of chromosome 22 was present in leukemic cells and disappeared during remission. Its pathogenic significance is briefly discussed.

[Acute lymphoblastic leukemia secondary to Ewing's sarcoma treated by a combination of surgery-radiotherapy-chemotherapy]. / Leucémie aiguë lymphoblastique secondaire à un sarcome d'Ewing traité par association chirurgie-radiothérapie-chimiothérapie.

An acute lymphocytic leukaemia develops in a fourteen years old boy, treated five and a half years earlier for an Ewing's sarcoma of the right fibula, by an association of surgery, radiotherapy and chemotherapy. The Ewing's sarcoma is still in remission. Chemotherapy induces easily a complete remission. The authors discuss the links between the two malignancies and their treatment.

[Plasma variations in severe head injuries: prognosis and post-traumatic surveillance. I. Enzymes]. / Variations plasmatiques chez les traumatisés crâniens sévères: intérêt pronostique et surveillance post-traumatique I.--Les enzymes.

Variations of four enzymatic activities (aldolase, aspartate aminotransferase, creatine kinase and lactate dehydrogenase) were followed in human plasma for four days after head injury. Univariate analysis showed that each plasma enzyme activity significantly differed as early as 72 h after head injury according to the clinical evolution (survival or death). Multivariate analysis performed with these four tests allowed us to correctly divide, in terms of survival or death, 75 to 91% of unselected patients (n = 280). Combining these four tests increased discriminant power in severe head injury. Most of the patients who were misclassified according to their biochemical data received phenobarbital for treatment. Valuable prognostic information may thus be obtained by daily determinations of four enzymatic activities.

Prognostic value of combined data on enzymes and inflammation markers in plasma in cases of severe head injury.

We measured certain enzyme activities (aldolase, aspartate aminotransferase, creatine kinase, and lactate dehydrogenase) and inflammation markers (alpha 1-antitrypsin, C-reactive protein, fibrinogen, and leukocytes) each day for four days in plasma of patients with severe head injury. The univariate prognostic efficiency of each biochemical parameter was assessed 24, 48, 72, and 96 h after trauma. By stepwise multivariate analysis applied every day, we found that (a) four variables, two enzymes (lactate dehydrogenase and aspartate aminotransferase) and two inflammation markers (C-reactive protein and leukocytes), sufficed to reliably predict the patient's outcome and (b) data recorded at 72 h best discriminated between survivors and nonsurvivors. A risk index based on the four selected variables and validated on a large control sample allowed the correct allocation of, respectively, 90% of survivors and 88% of nonsurvivors at 72 h. We discuss why results obtained at 72 h are more predictive than those obtained at any other of the times considered.

Modifications of plasma enzyme activities after severe head injury; evaluation of prognosis using multivariate methods.

The aim of this study was to analyse the plasma variations of four enzymatic activities (lactate dehydrogenase, aldolase, creatine kinase, aspartate aminotransferase) in 134 patients suffering from severe head injury. Enzymatic activities were assayed daily for 3 days after the trauma. Means of the four enzymatic activities were significantly different according to their evolution (death or survival), except for creatine kinase, 48 h after the trauma. Multivariate analysis indicated that lactate dehydrogenase and aldolase levels were useful in order to discriminate between potential survivors and non-survivors. The value of multivariate analysis in head traumatology is discussed.