Perioperative management and neuraxial analgesia in women with factor XI deficiency (<60 IU/dL): a French multicenter observational study of 314 pregnancies.

Background: Factor (F)XI deficiency is a rare bleeding disorder with a poor correlation between bleeding tendency and FXI level. Management of pregnant women with FXI deficiency is not clearly established, especially regarding neuraxial analgesia (NA). Objectives: A retrospective multicenter observational study was conducted in French hemostasis centers on pregnant women with FXI of <60 IU/dL. Methods: Data to report were (i) FXI levels before pregnancy and at time of delivery, (ii) type of NA and delivery management modalities, and (iii) possible complications related to NA and bleeding complications. Results: Three hundred fourteen pregnancies in patients with FXI deficiency of <60 IU/dL were reported (from 20 centers); among them, 199 NA procedures have been completed (137 epidurals and 61 spinals, 1 had both). The period of childbirth was mostly from 2014 to 2020 (281/314; 89.5%). Congenital FXI deficiency was established with certainty by investigators in 32.8% patients (n = 103). Previous bleedings were described in 20.4% of the patients (64/314; 45.3% cutaneous, 31.3% gynecologic, and 15.6% postsurgical). Thirteen deliveries had an NA procedure with FXI of <30 IU/dL, 42 with FXI of 30-40 IU/dL, and 118 with FXI of 40-60 IU/dL. Median FXI levels at delivery in the epidural and spinal groups were not significantly different but were significantly lower in the group without NA by medical staff contraindications. There were no complications related to NA. A 17.5% postpartum hemorrhage or excessive postpartum bleeding incidence was reported, which is consistent with previous data. Conclusion: Our data support the use of a 30 IU/dL FXI threshold for NA, as suggested by the French proposals published in August 2023.

Impact of choice of treatment for bleeding episodes on inhibitor outcome in patients with mild/moderate hemophilia a and inhibitors.

Patients with mild/moderate hemophilia A (MHA) may develop inhibitors to factor VIII (FVIII). In this condition, FVIII clotting activity (FVIII:C) baseline levels may remain stable for some patients, but may be reduced to less than 0.01 U/mL for others. Several risk factors for the development of inhibitors in MHA have been proposed. Genetic factors, such as mutations in the FVIII gene, may play a central role; however, other influences, such as intensive treatment with FVIII products, may also be important. Optimal treatment regimens have yet to be determined, not only for the eradication of inhibitors, but also for the management or surgical prophylaxis of hemorrhages associated with this condition. Several treatment options for the control of bleeding in patients with MHA and inhibitors (MHAI) are currently available, and the choice of therapeutic strategy should be given careful consideration; some treatments may produce an anamnestic response, thus delaying the return to FVIII:C baseline levels and adversely affecting the duration of the severe bleeding phenotype. To increase our knowledge of MHAI, a retrospective collection of data is currently being performed among hemophilia centers in France and Belgium. Based on five examples of patients with MHAI collated from preliminary study data, we illustrate the impact on inhibitor outcome of the therapeutic choices used to treat bleeding episodes in these patients.

Recurrences following primary osteosarcoma in adolescents and adults previously treated with chemotherapy.

In this retrospective analysis, we report on the detailed management of 33 recurrent osteosarcoma patients from a population of 81 adolescents and adults previously treated (between November 1979 and November 1998) at the La Timone Adults Hospital, for an extremity-localised osteosarcoma. The site of the first recurrence was limited to the lung in 24 patients (73%), was local in 4 patients (12%), at multiple sites in 4 patients (12%), and limited to the bone for 1 patient (3%). The median interval between the diagnosis of the primary osteosarcoma and the first recurrence was 16 months (range 4-108 months). For all patients, the treatment combined aggressive chemotherapy and surgical resection of the recurrences whenever possible. 19 patients (58%) achieved a second complete remission. The median follow-up time from the first recurrence was 18 months (range 4-150 months). For all patients, the median overall survival from first recurrence was 17 months (95% confidence interval (CI), 11-22 months) and the projected 3- and 5-year survival rates were 31.6 and 23.7%, respectively. Patients with a second complete remission had a better 5-year survival than patients without (44.6% versus 0%, P=0.001). The achievement of a second complete remission has an independent significant prognostic value for an improved survival. Aggressive surgery with the removal of recurrence sites combined with multi-agent chemotherapy can either cure patients with recurrent osteosarcoma or significantly prolong their survival.

Video-assisted parathyroidectomy via the lateral approach vs conventional surgery in the treatment of sporadic primary hyperparathyroidism: results of a case-control study.

BACKGROUND: We previously demonstrated that minimally invasive video-assisted parathyroidectomy (VAP) can be performed via a lateral approach on the line of the sternocleidomastoid muscle. The aim of this study was to compare the results of this technique with those of conventional parathyroidectomy (CP) in a case-control study. METHODS: Over a 2-year period, 80 VAP were attempted. The selection criteria were as follows: sporadic primary hyperparathyroidism, no history of previous neck surgery, no thyroid disease, suggestion of a single adenoma on preoperative imaging. A rapid intraoperative parathyroid hormone (PTH) assay was performed. The procedure was completed successfully in 68 patients. A case-control study of 68 patients who underwent CP for a single adenoma was performed. The controls were matched for age and sex. RESULTS: All of the patients were normocalcemic at follow-up. No statistically significant differences between the VAP and the control groups were found for age, sex, pre- and postoperative calcemia and PTH, adenoma weight, operating time, complication rate, or postoperative stay. One VAP patient developed recurrent laryngeal nerve palsy. Patients who underwent VAP required less analgesics (p < 0.0001) and were more satisfied with the cosmetic results (p < 0.0001). CONCLUSIONS: This study suggests that VAP by the lateral approach has some advantages over CP in terms of postoperative pain and cosmetic results.

Lidocaine inhibits potassium efflux and hemolysis in erythrocytes during oxidative stress in vitro.

Lidocaine is a widely used local anesthetic agent. The aim of this work was to study the action of lidocaine on human red blood cells exposed to an oxidative stress in vitro. Blood was obtained from healthy volunteers. After separation from plasma, the erythrocytes were suspended in phosphate buffer. Oxidative stress was induced by incubation with a free radical generator, the 2,2' azobis (2-amidinopropane) hydrochloride (AAPH). Erythrocytes were incubated with or without lidocaine at two concentrations (36.93 and 73.85 microM) and with or without AAPH (20 mM). Electron paramagnetic resonance (EPR) spectroscopy was performed to identify the free radical species generated by AAPH using the spin trap 5-5'-dimethyl-L-pyroline-N-oxide (DMPO). Different sets of experiments were run. Potassium efflux was measured by flame photometry in each group at time 0 min and every 30 min of the experiment for 2 h. Hemolysis was studied by the Drabkin method at increasing concentrations of AAPH (20, 50, and 100 mM) and with or without lidocaine (36.93 microM). The oxygen radical absorbance capacity (ORAC) was measured by using allophycocyanin (APC) as a fluorescent indicator protein, and the antioxidant capacity of lidocaine (36.93 microM) was studied by the analysis of fluorescence of the APC. AAPH was shown to produce alkoxyl free radicals. Oxidative stress induced a marked increase in the potassium efflux and the hemolysis that was AAPH dose-dependent. Lidocaine inhibited the potassium efflux and delayed the occurrence of hemolysis. Lidocaine did not show any antioxidant properties for the free radical species generated by AAPH. In this model, lidocaine protects erythrocytes against oxidative stress. This effect is not explained by a free radical scavenging property. The results may be of great interest in clinical practice such as intravenous regional anesthesia or the prevention of ischemia-reperfusion injury.

[IGM hyperimmunoglobulinemia anti-phosphatidylethanolamine antibodies of the IgM isotype: clinical and biological study of 72 patients with immune disorders]. / Hyper-immunoglobulinémie M et anticorps antiphosphatidyléthanolamine d'isotype IgM: étude clinicobiologique de 72 patients porteurs d'immunopathie.

PURPOSE: Antiphosphatidylethanolamine antibodies (aPE) are zwitterionic antiphospholipid antibodies that have been recently described in antiphospholipid syndrome. IgM is the most frequently observed isotype. We assessed the potential relationship between serum IgM levels and their presence. METHODS: Seventy-two patients (66 females, 6 males) positive for aPE of the IgM isotype were followed up for 2 years. They suffered from either an autoimmune disease or had clinical signs suggesting the existence of antiphospholipid syndrome or other immune disorders. Seventy-two control patients (58 females, 14 males) of similar age, with other immune disorders were also included in the study. For each of them, the IgM level was obtained and hyper-immunoglobulinemia M (hyper-IgM) was defined as a value upper than 2.5 g/L. Search for aPE of the IgM isotype was made using an in-house Elisa test. RESULTS: Half of the aPE-positive patients had serum hyper-IgM, whereas none of the aPE-negative patients had hyper-IgM. All IgMs were polyclonal. There was a positive correlation (r = 0.57, P = 0.001) between the level of IgM and the optical densities obtained by Elisa. The presence of a hyper-IgM did not modify the clinical manifestations (arterial and venous thromboses, recurrent fetal losses), nor the positivity of lupus anticoagulant, anticardiolipin and anti-beta-2-glycoprotein 1 antibodies. CONCLUSION: The positive correlation between the IgM level and aPE level is of value, as it suggests a possible relationship between lymphocytic activation and auto-antibodies production, which does not concern only aPE. Further studies regarding the antigenic specificity of IgM will probably provide further insights on IgM and phospholipid interactions.

Osteosarcomas of flat bones in adolescents and adults.

BACKGROUND: Osteosarcomas typically are long bone tumors and rarely affect the flat bones of the axial or appendicular skeleton. METHODS: The authors examined cases of high grade osteosarcoma of flat bones diagnosed at La Timone Adults University Hospital during a 16-year period. RESULTS: Sixteen patients with flat bone osteosarcomas were treated between 1980-1997. The median age of the patients was 25 years, with a male-to-female ratio of 14:2. Common presenting symptoms were swelling, pain, or both. Primary therapy included resection (n = 11 patients: alone in 8 patients and with radiation therapy in 3 patients), radiation therapy (n = 2 patients), or no local treatment (n = 3 patients). All patients received polychemotherapy, 7 preoperatively and postoperatively and 9 in the adjuvant setting. The overall 5-year survival rate was 47.7%; the overall median survival was 39 months (range, 4-211 months). The adequate local control rate was 68.7%. The local recurrence rate in patients who benefited from local treatment was 54%. Significant adverse prognostic factors on survival included the presence of synchronous metastases (three patients), metastases at any time during the course of the disease (eight patients), and inadequate local control (five patients). The overriding predictor of survival appeared to be the presence of metastases. Local recurrence appeared to have no influence on survival. No patient with metastases was alive at 3 years, whereas patients without recurrence or with local recurrence alone had a 5-year survival rate of 100%. Because the majority of patients with flat bone osteosarcomas ultimately die of metastatic disease, intensive systematic polychemotherapy should be an important component of treating these tumors. CONCLUSIONS: Based on the very encouraging results observed in the treatment of long bone osteosarcomas, the therapy for flat bone osteosarcomas should combine radical surgery with preoperative and postoperative adjuvant chemotherapy.

Effects of bupivacaine on human erythrocytes submitted to stress and evidence for an interaction between bupivacaine and flumazenil.

AIMS: To examine the effects of bupivacaine on erythrocytes submitted to an oxidative stress (AAPH) and to provide evidence for an in vitro interaction between bupivacaine and flumazenil. METHODS: Human erythrocytes were studied with or without AAPH in the presence of different concentrations of bupivacaine (0.15, 0.3, 0.9 and 1.8 mmol l-1 ), or flumazenil (0.16 mmol l-1 ) and with the association of flumazenil and two doses of bupivacaine (0.15 and 0.3 mmol l-1 ). Potassium efflux was measured by flame photometry at T0, and every 30 min for 2 h. RESULTS: In the absence of AAPH, extracellular potassium remained unchanged. Oxidative stress induced a significant increase in extracellular potassium, which was not modified by incubation with flumazenil. Bupivacaine significantly lowered the increase in extracellular potassium in a dose-related fashion. The association with flumazenil blunted the effects of bupivacaine. Discussion In this model, bupivacaine proved effective in protecting erythrocytes against oxidative stress. Flumazenil interacted with bupivacaine and blunted its protective effects.

Mutation patterns of the reverse transcriptase and protease genes in human immunodeficiency virus type 1-infected patients undergoing combination therapy: survey of 787 sequences.

The aim of the present study was to evaluate the resistance-associated mutations in 302 human immunodeficiency virus type 1 (HIV-1)-infected patients receiving combination therapy and monitored in Marseille, France, hospitals from January 1997 to June 1998. In the reverse transcriptase (RT) gene, the most frequent mutations were found at codons 215 (53%), 41 (34%), and 67, 70, 184, and 210 (>20%). One deletion and two insertions in the beta3-beta4 hairpin loop of the finger subdomain (codon 69) were detected. Interesting associations and/or exclusions of specific mutations were observed. In 96% of RT genes, a mutation at codon 70 (most frequently, K70R) was associated with a wild-type genotype at position 210 (P < 10(-5)). Similarly, a mutation at codon 210 (most frequently, L210W) was generally associated with mutations at codons 41 (92%) and 215 (96%) but not at codon 219 (16%) or codon 70 (4%) (P < 10(-5)). In the protease gene, the most prevalent mutations were at codons 63 (84%), followed by codons 10, 36, 71, 77, and 93 (ca. 20%). As for RT, pairwise associations of mutations were observed. Analysis of the mutation patterns for patients with undetectable HIV-1 loads revealed a high proportion (65%) of wild-type RT genotypes but only 18% wild-type protease genotypes. For patients with high viral loads (>100,000 copies/ml), more than 50% of the RT and protease genes displayed three or more mutations. The significant correlation between the level of viremia in plasma and the number of resistance mutations in the protease (P = 0.007) and RT (P = 0.00078) genes strengthens the importance of defining the genotype of the predominant HIV-1 quasispecies before initiating antiretroviral therapy.

Value and limitations of the Duke criteria for the diagnosis of infective endocarditis.

OBJECTIVES: The purpose of this study was to assess the value and limitations of Duke criteria for the diagnosis of infective endocarditis (IE). BACKGROUND: Duke criteria have been shown to be more sensitive in diagnosing IE than the von Reyn criteria, but the diagnosis of IE remains difficult in some patients. METHODS: Both classifications were applied in 93 consecutive patients with pathologically proven IE. Blood cultures, and transthoracic and transesophageal echocardiography were performed in all patients. RESULTS: Sensitivities for the diagnosis of IE were 56% and 76% for von Reyn and Duke criteria, respectively. Fifty-two patients were correctly classified as "probable IE" by von Reyn and "definite IE" by Duke criteria (group 1). However, discrepancies were observed in 41 patients. Eleven patients (group 2) were misclassified as "rejected" by von Reyn, but were "definite IE" by Duke criteria; this difference could be explained by negative blood cultures and positive echocardiogram in all patients. In eight patients (group 3), the diagnosis of IE was "possible" by von Reyn but "definite" by Duke criteria. This difference was essentially explained by the failure of the von Reyn classification to consider echocardiographic abnormalities as major criteria. Twenty-two patients (group 4) were misclassified as possible IE using Duke criteria, being false negative of this classification. Echocardiographic major criteria were present in 19 patients, but blood cultures were negative in 21 patients. The cause of negative blood cultures was prior antibiotic therapy in 11 patients and Q-fever endocarditis diagnosed by positive serology in three cases. CONCLUSIONS: Twenty-four percent of patients with proved IE remain misclassified as "possible IE" despite the use of Duke criteria, especially in cases of culture-negative and Q-fever IE. Increasing the diagnostic value of echographic criteria in patients with prior antibiotic therapy and typical echocardiographic findings and considering the serologic diagnosis of Q fever as a major criterion would further improve the clinical diagnosis of IE.

Micronucleated lymphocyte rates from head-and-neck cancer patients.

We investigated whether head-and-neck cancers are associated with an increased micronucleated cell rates (MN cell rates) and whether risk factors for these cancers are associated with alterations in micronucleated lymphocytes. MN cell rates were assessed in cytokinesis-blocked lymphocytes of 57 head-and-neck cancer patients (CP) before any anticancer treatment and of 198 male and female healthy subjects (HS). In the HS group, only smoking status significantly affect MN cell rates. In CP group age, sex, tobacco status, alcohol status, tumor stage, family history of cancer had no significant effect. For the non-smokers, the comparison between MN cell rates in HS and CP adjusted for age and sex showed a significant difference. The increase of MN cell rates in non-smokers patients may be attributable to cancer status. For the smokers, the comparison of MN cell rates in HS and CP matched for age and sex showed no significant difference. Pathological status could mask the smoking effect on peripheral blood lymphocytes in patients. Moreover, it probably could partly explain why MN cell rates in matched-CP smokers and HS smokers were similar. The authors do not recommend the CBMN assay in this present form to study smoking DNA-damage effects in peripheral blood lymphocytes of cancer patients, especially for patients with upper aero-digestive tract cancers or lung cancers for which tobacco is the major risk factor.

ARIANE: integration of information databases within a hospital intranet.

Large information systems handle massive volume of data stored in heterogeneous sources. Each server has its own model of representation of concepts with regard to its aims. One of the main problems end-users encounter when accessing different servers is to match their own viewpoint on biomedical concepts with the various representations that are made in the databases servers. The aim of the project ARIANE is to provide end-users with easy-to-use and natural means to access and query heterogeneous information databases. The objectives of this research work consist in building a conceptual interface by means of the Internet technology inside an enterprise Intranet and to propose a method to realize it. This method is based on the knowledge sources provided by the Unified Medical Language System (UMLS) project of the US National Library of Medicine. Experiments concern queries to three different information servers: PubMed, a Medline server of the NLM; Thériaque, a French database on drugs implemented in the Hospital Intranet; and a Web site dedicated to Internet resources in gastroenterology and nutrition, located at the Faculty of Medicine of Nice (France). Accessing to each of these servers is different according to the kind of information delivered and according to the technology used to query it. Dealing with health care professional workstation, the authors introduced in the ARIANE project quality criteria in order to attempt a homogeneous and efficient way to build a query system able to be integrated in existing information systems and to integrate existing and new information sources.

Review of biomedical knowledge and data representation with conceptual graphs.

The basis of conceptual graphs theory is an ontology of types of concepts. Concepts issued from the ontology are interlinked by semantic relationships and constitute canonical conceptual graphs. Canonical graphs may be combined to derive new conceptual graphs by means of formation rules. This formalism allows to separate knowledge representation into a conceptual level and a domain-dependent level, and enables to share and reuse a representation. This paper presents conceptual graph applications to biomedical data and concept representation, classification systems, information retrieval, and natural language understanding and processing. A discussion on the unifying role conceptual graphs theory plays in the implementation of knowledge-based systems is also presented.

Coagulation abnormalities in lacunar and cortical ischemic stroke are quite different.

In order to clarify the coagulation profile accompanying ischemic stroke, which may have implications on therapeutic strategies, we performed a prospective study to evaluate the hemostatic parameters in the first 24 h after the onset of cortical atherothrombotic infarct and lacunar infarction. Twenty-seven patients with cortical atherothrombotic infarction and 27 patients with lacunar infarction, diagnosed on clinical and CT-scan criteria, had blood samples taken within the first 24 h after onset of the stroke, and before anticoagulant treatment had been started. Levels of fibrinogen, von Willebrand factor, D-dimers, prothrombin factors 1 + 2, anti-thrombin III, and C-protein and S-proteins, were measured. Laboratory tests detected the following abnormalities: a protein C deficiency was observed in 1 case of cortical infarction and in 1 case of lacunar infarction; a decrease in S-protein was observed in 1 case of cortical infarction, and the presence of lupus anticoagulant in 4 cases (2 in cortical and 2 in lacunar infarction). Various degrees of coagulation activation were observed. Statistically significant activation of the coagulation was observed in the patients with cortical infarction, compared to normal patients adjusted for age: the levels of DDI were significantly raised (2298 +/- 2221 ng ml-1 vs. 750 +/- 400 ng ml-1) (p < 0.03) as were F1 + 2 levels (3.9 +/- 2.8 nmol l-1 vs. 1.5 +/- 0.9 nmol l-1). (p < 0.01). In the lacunar infarction group, there was a significant rise in F1 + 2 compared with normal patients adjusted for age (2.2 +/- 1.7 nmol l-1 vs. 1.5 +/- 0.9 nmol l-1) (p < 0.01), while the DDI level was in the normal range, when age was taken into account. In the cortical infarction group, we observed a significantly raised fibrinogen level (4.8 +/- 1.7 g l-1 vs. 3.7 +/- 1.0 g l-1) (p < 0.05) and von Willebrand factor level (271 +/- 104% vs. 178 +/- 103%) (p < 0.01) compared to the lacunar infarction group. In addition, we observed a significantly low level of S-protein in the cortical infarction group (105 +/- 29%) compared to the lacunar infarction group (127 +/- 28%) (p < 0.01). Confirmation of the role of enhanced thrombin activity in the pathogenesis of acute stroke may be an important determinant in its therapeutic management.

UMLS-based conceptual queries to biomedical information databases: an overview of the project ARIANE. Unified Medical Language System.

OBJECTIVE: The aim of the project ARIANE is to model and implement seamless, natural, and easy-to-use interfaces with various kinds of heterogeneous biomedical information databases. DESIGN: A conceptual model of some of the Unified Medical Language System (UMLS) knowledge sources has been developed to help end users to query information databases. A query is represented by a conceptual graph that translates the deep structure of an end-user's interest in a topic. A computational model exploits this conceptual model to build a query interactively represented as query graph. A query graph is then matched to the data graph built with data issued from each record of a database by means of a pattern-matching (projection) rule that applies to conceptual graphs. RESULTS: Prototypes have been implemented to test the feasibility of the model with different kinds of information databases. Three cases are studied: 1) information in records is structured according to the UMLS knowledge sources; 2) information is able to be structured without error in the frame of the UMLS knowledge; 3) information cannot be structured. In each case the pattern-matching is processed by the projection rule according to the structure of information that has been implemented in the databases. CONCLUSION: The conceptual graphs theory provides with a homogeneous and powerful formalism able to represent both concepts, instances of concepts in medical contexts, and associations by means of relationships, and to represent data at different levels of details. The conceptual-graphs formalism allows powerful capabilities to operate a semantic integration of information databases using the UMLS knowledge sources.

Towards interoperability of information sources within a hospital Intranet.

Information is usually available in heterogeneous data format and various legacy sources. Interoperability appears to be a major approach for applications to access information. The project ARIANE is devoted to provide end-users with an easy to use and natural access to information databases. In this frame we defined actors able to operate the mediation between end-users and information servers: a "broker" which selects appropriate resources and "mediators" which access data suppliers. We have implemented a web-oriented stand-alone prototype accessing three types of information sources: a bibliographical server, a SQL database server and a hypertext server. Both broker and mediators exploit the Unified Medical Language System knowledge sources, especially the Information Sources Map which allows a way to identify information servers.

Different patterns of IL-1beta secretion, adhesion molecule expression and apoptosis induction in human endothelial cells treated with 7alpha-, 7beta-hydroxycholesterol, or 7-ketocholesterol.

Among oxysterols oxidized at C7 (7alpha-, 7beta-hydroxycholesterol, and 7-ketocholesterol), 7beta-hydroxycholesterol and 7-ketocholesterol involved in the cytotoxicity of oxidized low density lipoproteins (LDL) are potent inducers of apoptosis. Here, we asked whether all oxysterols oxidized at C7 were able to trigger apoptosis, to stimulate interleukin (IL)-Ibeta and/or tumor necrosis factor (TNF)-alpha secretion, and to enhance adhesion molecule expression (intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and E-selectin) on human umbilical venous endothelial cells (HUVECs). Only 7beta-hydroxycholesterol and 7-ketocholesterol were potent inducers of apoptosis and of IL-1beta secretion. TNF-alpha secretion was never detected. Depending on the oxysterol considered, various levels of ICAM-1, VCAM-1 and E-selectin expression were observed. So, oxysterols oxidized at C7 differently injure and activate HUVECs, and the alpha- or beta-hydroxyl radical position plays a key role in apoptosis and IL-1beta secretion.

Conceptual integration of information databases into an Intranet.

Large information systems handle massive volume of data stored in heterogeneous sources of information. Each server has its own model of concepts representation with regard to its aims. One of the main problems encountered by end-users when accessing different servers is to match their own viewpoint on biomedical concepts with their various representations that are made in the database servers. The aim of the project ARIANE is to provide end-users with easy-to-use and natural means to access and query heterogeneous information databases. The objectives of this research work consist in building a conceptual interface by means of the Internet technology inside an enterprise Intranet, and to propose a method to realize it. Moreover, this method provides designers of web sites with a powerful tool to manage them on the basis of an ontology of the biomedical domain. This method is based on the knowledge sources provided by the Unified Medical Language System project of the U.S. National Library of Medicine and exploits intensively the conceptual graphs theory.

Comparison between micronucleated lymphocyte rates observed in healthy subjects and cancer patients.

Micronucleated cell rates were assessed in cytokinesis-blocked lymphocytes of 198 male and female healthy subjects (HS) not occupationally exposed to genotoxic risks and of 70 male and female cancer patients (CP) prior to any anticancer treatment. In the HS group, spontaneous micronucleated cell rates (MN cell rates) were 9.7 +/- 2.8 per 1000 binucleated lymphocytes and 9.8 +/- 3.1 for males and females respectively. In the CP group, spontaneous MN cell rates were 21.1 +/- 15.3 per 1000 binucleated lymphocytes and 19.1 +/- 11.2 for males and females respectively. Moreover, they were shown to have a large inter-individual variability in the two groups. The study of inter-individual variation factors showed that only tobacco could affect MN cell rate in HS whereas age and sex apparently had no significant effect. In the CP group, only age significantly affected MN cell rate, whereas sex, tobacco, alcohol, imaging techniques and tumour stage had no significant effect. There was no significant difference in the distribution of gender between HS and CP, whereas there was a significant difference in the distribution of age and tobacco between the two groups. The comparison of MN cell rates in 54 HS and 54 CP matched for age and sex showed a statistically significant difference. Spontaneous MN cell rates of these two populations reflect environmental exposure. Moreover, for CP it most probably refers to various cellular lesions and genetic damage.

A UMLS-based method for integrating information databases into an Intranet.

The Internet and the World Wide Web provide today end-users with capabilities to access universally to information in various and heterogeneous databases. The biomedical domain benefits from this new technology, specially for information retrieval by searching and browsing various sites. Nevertheless, end-users may be disoriented by specific ways to access information on different servers. In the framework of an Intranet design and development, we present a method for integrating information databases based on knowledge sources of the UMLS. The method provides designers of a Web site with facilities to implement an easy and homogeneous access to information. The pages are built dynamically and displayed according to a style sheet and their content stored in a database during the design phase. The database also describes the links between pages. Moreover, this organization provides administrators with powerful capabilities to manage Web sites.