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Circulating proteinic biomarkers are secreted by tumor cells or by their environmental cells and they have a variable specificity. In case of breast cancer, carcino-embryonic antigen (CEA) was for a long time the only circulating biomarker used. Nowadays, the most useful biomarkers measure circulating levels of fragments of MUC1-polymorphic epithelial mucin (MUC1-PEM): cancer antigen (CA) 15.3, mucin-like carcinoma-associated antigen (MCA), CA 27-29, CA 549... They are useful for general disease follow-up. Other circulating markers belonging to keratins (tissue polypeptide antigen, TPA, TPS or Cyfra 21.1) are correlated with proliferative activity of breast tumors. More recently, the measure of the c-erb B2 circulating part (extra cellular domain, ECD) was proposed as a prognostic biomarker for breast tumors with c-erb B2 overexpression. Moreover, the determination of urinary level of trefoil factor1 (PS2-TFF1) might be useful for the follow-up of hormonodependent breast cancers. The present review describes the clinical interest of these different circulating biomarkers in case of breast cancer, emphasizing their biological characteristics.

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OBJECTIVE: To improve the planning of hepatic surgery, we have developed a fully automatic anatomical, pathological, and functional segmentation of the liver derived from a spiral CT scan. MATERIALS AND METHODS: From a 2 mm-thick enhanced spiral CT scan, the first stage automatically delineates skin, bones, lungs, kidneys, and spleen by combining the use of thresholding, mathematical morphology, and distance maps. Next, a reference 3D model is immersed in the image and automatically deformed to the liver contours. Then an automatic Gaussian fitting on the imaging histogram estimates the intensities of parenchyma, vessels, and lesions. This first result is next improved through an original topological and geometrical analysis, providing an automatic delineation of lesions and veins. Finally, a topological and geometrical analysis based on medical knowledge provides hepatic functional information that is invisible in medical imaging: portal vein labeling and hepatic anatomical segmentation according to the Couinaud classification. RESULTS: Clinical validation performed on more than 30 patients shows that delineation of anatomical structures by this method is often more sensitive and more specific than manual delineation by a radiologist. CONCLUSION: This study describes the methodology used to create the automatic segmentation of the liver with delineation of important anatomical, pathological, and functional structures from a routine CT scan. Using the methods proposed in this study, we have confirmed the accuracy and utility of the creation of a 3D liver model compared with the conventional reading of the CT scan by a radiologist. This work may allow improved preoperative planning of hepatic surgery by more precisely delineating liver pathology and its relationship to normal hepatic structures. In the future, this data may be integrated with computer-assisted surgery and thus represents a first step towards the development of an augmented-reality surgical system.

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The aim of this study was to evaluate the effect of insulin on the release of vWf in vivo during an oral glucose tolerance test (OGTT) performed in normal, glucose-intolerant and diabetic subjects and in vitro on human endothelial cells. Twenty-eight subjects exhibiting risk factors for diabetes underwent an OGTT: 11 subjects proved to be normal, 7 were glucose-intolerant and 10 diabetic. In each group, the vWf and PAI-1 plasmatic levels were measured at t = 0, 30 min and 180 min after the beginning of the test. Human endothelial cells from non-diabetic and diabetic subjects were incubated in the presence of human insulin at various concentrations (0.25, 2.5, 25 and 250 mUI/ml). After 1, 4, and 24 hours of incubation, the release of vWf and endothelin 1 was measured in the cell supernatant and the intracellular amount of vWf in the cell lysate. During the OGTT, the vWf levels in plasma were not affected despite a 4.5-, 6-, and 2.5-fold increase in insulin levels in normal, glucose-intolerant and diabetic subjects, respectively. Although raised in all three groups, PAI-1 plasmatic levels remained constant during the test. After 24 hours of exposure to insulin (0.25 mU/ml), the release of vWf by endothelial cells reached 35.94 +/- 23.08 % of the basal value for non-diabetic subjects, and 27.57 +/- 10.05 % for diabetic patients. Similar results were observed in non-stimulated cells. Insulin had no influence on intracellular vWf content, which remained comparable to control values. Regardless of its concentration, insulin failed to stimulate the release of vWf by endothelial cells of non-diabetic and diabetic subjects, while its ability to stimulate the release of endothelin 1 was preserved. In conclusion, hyperinsulinemia had no adverse effect on circulating vWf in normal or diabetic subjects. Neither release nor intracellular vWf content in non-diabetic or diabetic endothelial cells was influenced by insulin in vitro.

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AIM: Serum cystatin C (SCyst) has been proposed as a novel indicator of GFR. PATIENTS AND METHODS: We compared SCyst, serum creatinine (SCreat) and Cockcroft and Gault's estimated clearance (CCG) using inulin clearance (Cin) as gold standard. 140 subjects (161 samples; aged 39 +/- 14; male/female: 79/82) underwent simultaneous measurements. RESULTS: A highly significant correlation r = 0.70, 0.74, 0.77 (p < 0.0001) was found between 1/SCyst, 1/SCreat, C(CG), respectively, and Cin. Receiver-operating characteristic (ROC) analysis was performed on SCyst, SCreat and C(CG) using a Cin cut-off of 90 ml/min/1.73 m2. Best fit for SCyst was 0.90 mg/l with a sensitivity of 75% and a specificity of 92%. The area under the ROC curve was not significantly greater for SCreat or C(CG) than for SCyst (p = 0.91,0.13, respectively). When relationship between Cin and SCyst was plotted, experimental data deviated from the theoretical model, suggesting that cystatin C may not be solely filtered. Additional patients were selected in our database on the basis of discordant SCreat/GFR values: false negative (n = 46 samples, 31 patients) and false positive (n = 16 samples, 9 patients). In this highly selected subgroup, 38% of the SCreat false positive had normal SCyst values and 48% of the false negative SCreat had abnormally elevated SCyst. CONCLUSION: This study suggests that SCyst is not more sensitive than SCreat or C(CG) for detecting renal failure, however, SCyst could be proposed as a confirmatory test for patients with elevated SCreat.

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UNLABELLED: PROBLEM/BACKGROUND: In order to improve patient care by minimal invasive surgery (MIS), we perfected a Virtual TeleSurgical University that allows for teleeducation, teleconcertation, surgical planning and telemanipulation, through new Virtual Reality and multimedia systems. TOOLS AND METHODS: The organization of this innovative school was federated around three major research programs. First, the TESUS program focused on the teletransmission of medical information, allowing for videoconferencing around the world and telementoring. Next, the WeBS-Surg program is a multimedia continuous surgical education system on internet, that allows for teleeducation and teleconcertation between world experts in MIS. Then, the MASTER program (Minimal Access Surgery by Telecommunications and Robotics) allowed the development of the third millenium Operating room. It included Virtual Reality systems that delineate automatically anatomical and pathological structures of a patients from him CT-scan, and that allow for an interactive surgical planning and force-feed-back simulation. It also included a telesurgical robot named Zeus controlled by surgeons through telemanipulation system. RESULTS: Tests and validation shows that all these systems improved all steps of the surgical procedure: preoperatively due to a better continuous education and a computer assisted surgical planning, and peroperatively due to teleconcertation, telementoring and telemanipulation systems. CONCLUSION: Revolutionary tools for minimal invasive surgery learning, planning and performing are all ready available. These tools represents the first prototype of the computer assisted tele-robotical surgery that will be the future of surgery.

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UNLABELLED: PROBLEM/BACKGROUND: In order to help hepatic surgical planning we perfected automatic 3D reconstruction of patients from conventional CT-scan, and interactive visualization and virtual resection tools. TOOLS AND METHODS: From a conventional abdominal CT-scan, we have developed several methods allowing the automatic 3D reconstruction of skin, bones, kidneys, lung, liver, hepatic lesions, and vessels. These methods are based on deformable modeling or thresholding algorithms followed by the application of mathematical morphological operators. From these anatomical and pathological models, we have developed a new framework for translating anatomical knowledge into geometrical and topological constraints. More precisely, our approach allows to automatically delineate the hepatic and portal veins but also to label the portal vein and finally to build an anatomical segmentation of the liver based on Couinaud definition which is currently used by surgeons all over the world. Finally, we have developed a user friendly interface for the 3D visualization of anatomical and pathological structures, the accurate evaluation of volumes and distances and for the virtual hepatic resection along a user-defined cutting plane. RESULTS: A validation study on a 30 patients database gives 2 mm of precision for liver delineation and less than 1 mm for all other anatomical and pathological structures delineation. An in vivo validation performed during surgery also showed that anatomical segmentation is more precise than the delineation performed by a surgeon based on external landmarks. This surgery planning system has been routinely used by our medical partner, and this has resulted in an improvement of the planning and performance of hepatic surgery procedures. CONCLUSION: We have developed new tools for hepatic surgical planning allowing a better surgery through an automatic delineation and visualization of anatomical and pathological structures. These tools represent a first step towards the development of an augmented reality system combined with computer assisted tele-robotical surgery.

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BACKGROUND AND AIMS: As reactive oxygen has been demonstrated to participate in immune genes transcription, the aim of this study was to examine the relationship between systemic concentrations of several antioxidants and markers of inflammatory and immune activation in patients with Crohn's disease (CD). METHODS: In 26 CD patients and 15 controls we compared plasma selenium and zinc concentrations, erythrocyte glutathione peroxidase (GSHPx) and superoxide dismutase activities, as well as erythrocyte sedimentation rate (ESR), C-reactive protein, tumor necrosis factor-alpha, interleukin-6, blood neopterin and soluble receptors of interleukin-2 (sIL-2R), and examined the link between these parameters. RESULTS: Selenium concentration and GSHPx activity were decreased in CD patients (54.5 +/- 3.2 vs 79 ± 2.2 microg/l, P<< 0.05; 28 +/- 1.6 vs 38 +/- 2.6 IU/g Hb, P<< 0.05) and positively correlated to each other's (r= 0.59, P<< 0.01). TNF-alpha was significantly increased in patients (18 +/- 2.6 vs 5 +/- 0.6 pg/ml;P<< 0.001), negatively correlated to GSHPx activity (r= -0.56, P<< 0.05) and selenium concentration (r= -0.72, P<< 0.001), and positively to neopterin and sIL-2R concentrations. Selenium showed negative correlation with sIL-2R (r= -0.83, P<< 0.0001) and ESR. CONCLUSIONS: In CD patients low selenium concentration may participate in reduced GSHPx activity facilitating inflammatory and immune activation. In these patients, selenium monitoring and, if needed, supplementation may be of therapeutical interest.

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OBJECTIVE: Increased nitric oxide (NO) has been demonstrated in inflammatory bowel diseases (IBD). Plasma and urinary nitrite and nitrate are usually considered to reflect global NO generation. Recently it has been suggested that plasma nitrate may be a discriminant indicator between infectious enterocolitis (IC) and IBD. To investigate this hypothesis we compared plasma and 24 h urinary nitrite and nitrate in 13 healthy controls, 44 patients with IBD [Crohn's disease (CD) n = 30; ulcerative colitis (UC) n = 14], 16 patients presenting with IC and seven chronic radiation enterocolitis (RE) patients. RESULTS: Despite a trend towards higher plasma nitrate in IC (54.6+/-11.4 micromol/l) than in the other groups (CD: 38.4+/-4.8, UC: 34.8+/-8.4, RE: 34.7+/-7.5, controls: 31.1+/-5.2), this difference was not statistically significant. Urinary nitrate was higher in IBD, IC and RE than in controls, with no difference between these groups. Nitrite concentrations were not different. Nitrate levels were positively correlated with blood and 24 h urinary neopterin (e.g. plasma nitrate and blood neopterin: r = 0.54, P<0.0001), and in some cases, to C-reactive protein. CONCLUSIONS: High nitrate (in our case only urinary nitrate) appears to be secondary to the magnitude of the inflammation rather than the aetiology of the diarrhoea. It should therefore more likely be considered as a marker of the severity of the inflammatory response rather than used as a discriminant indicator between IC and IBD patients.

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BACKGROUND: Haemodialysis patients exhibit an excessive burden of atherothrombotic disease, which is not explained adequately by traditional risk factors. Hyperhomocyst(e)inaemia, a consistent finding in uraemic patients, is now widely recognized as an independent risk factor for vascular disease. The aim of this study was to examine the hypothesis that hyperhomocyst(e)inaemia is associated with cardiovascular complications in dialysed patients. METHODS: In a cohort of 63 stable chronic haemodialysis patients, we examined the causal relationship between hyperhomocyst(e)inaemia and vascular endothelial and haemostatic function. All their markers were determined before and after an 8-week course of a 10 mg per day oral folate supplementation, a manoeuvre known to decrease hyperhomocyst(e)inaemia in uraemic patients. RESULTS: History of at least one cardiovascular atherothrombotic event was present in 47.6% of the haemodialysed patients, and radiographic evidence of vascular calcifications in 70%. Hyperhomocyst(e)inaemia was found in all patients, averaging 3.5-fold the upper limit of normal values (P<0.001), despite the lack of clinical and biological evidence of malnutrition. Fibrinogen, von Willebrand factor and plasminogen activator inhibitor type 1, but not endothelin 1, were significantly higher in haemodialysis patients than in controls. After adjustment for all variables, past history of cardiovascular events was independently associated with higher levels of homocyst(e)inaemia only (odds ratio (OR) 1.06; 95% confidence interval (CI) 1.01-1.12; P<0.026). The presence of aortic calcifications was independently and significantly associated with age (OR 1.37; 95% CI 1.07-1.75; P<0.025), homocyst(e)inaemia (OR 1.14; 95% CI 1.02-1.27; P<0.05) and fibrinogen concentration only (OR 9.74; 95% CI 1.25-75.2; P<0.05). None of the endothelial haemostatic factors was, however, related to homocyst(e)ine levels. Mid-term folate supplementation decreased plasma homocyst(e)ine levels significantly without achieving normal values. No significant change of endothelial-haemostatic markers was observed, however, despite the drop in plasma homocyst(e)ine. CONCLUSIONS: Hyperhomocyst(e)inaemia is associated with increased cardiovascular risk in haemodialysis patients. Folate supplementation was partially effective in lowering hyperhomocyst(e)inaemia, but its usefulness in terms of reduction in cardiovascular morbidity and mortality remains to be determined in prospective trials.

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The French national neonatal screening program for congenital hypothyroidism (CH) was initiated in 1978. The purpose of this study was to ascertain the incidence of congenital extrathyroid anomalies (ETAs) among the infants with congenital hypothyroidism (CH) and to compare it with the Northeastern France Birth Defect Monitoring System data from 1979 to 1996. Among 129 CH infants on whom adequate data were available, 20 infants (15.5%) had associated congenital anomalies. Eight out of 76 infants with persistent CH had ETAs (10.5%) whereas 12 out of 53 children with transient hypothyroidism had ETAs (22.6%, p < 0.05). Some additional anomalies were considerably more common than in the general population. Nine infants had congenital cardiac anomalies (6.9%). This rises the question if teratogenic effects active during organogenesis may affect simultaneously many organs, including the developing thyroid, causing a relatively high percentage of CH infants with congenital ETAs.

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The demonstrated teratogenicity of maternal zinc deficiency in rats has led to burgeoning interest in zinc and other trace elements as important factors in embryonic development. Levels of zinc, copper, manganese, magnesium, folic acid, vitamin B12 and vitamin A were evaluated at the beginning of pregnancy in the plasma of pregnant women who later delivered a malformed newborn. Fetal chromosomal anomalies and recognizable nonchromosomal syndromes were excluded. The results were compared to control women who delivered normal babies. One hundred seventy mothers had malformed children. The more frequent congenital malformations were congenital heart diseases (72 cases including 24 VSD), musculoskeletal malformations (21 cases), urogenital malformations (23 cases), spina bifida (6 cases), hydrocephaly (6 cases), and labial cleft (14 cases). Maternal plasma concentrations of zinc, copper, magnesium, manganese, folate, vitamin B12, and vitamin A of malformed children did not differ from controls. Thus vitamin profiles do not form a suitable means for identifying women at risk for having a child with congenital malformations.

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OBJECTIVE: This article describes a preliminary work on virtual reality applied to liver surgery and discusses the repercussions of assisted surgical strategy and surgical simulation on tomorrow's surgery. SUMMARY BACKGROUND DATA: Liver surgery is considered difficult because of the complexity and variability of the organ. Common generic tools for presurgical medical image visualization do not fulfill the requirements for the liver, restricting comprehension of a patient's specific liver anatomy. METHODS: Using data from the National Library of Medicine, a realistic three-dimensional image was created, including the envelope and the four internal arborescences. A computer interface was developed to manipulate the organ and to define surgical resection planes according to internal anatomy. The first step of surgical simulation was implemented, providing the organ with real-time deformation computation. RESULTS: The three-dimensional anatomy of the liver could be clearly visualized. The virtual organ could be manipulated and a resection defined depending on the anatomic relations between the arborescences, the tumor, and the external envelope. The resulting parts could also be visualized and manipulated. The simulation allowed the deformation of a liver model in real time by means of a realistic laparoscopic tool. CONCLUSIONS: Three-dimensional visualization of the organ in relation to the pathology is of great help to appreciate the complex anatomy of the liver. Using virtual reality concepts (navigation, interaction, and immersion), surgical planning, training, and teaching for this complex surgical procedure may be possible. The ability to practice a given gesture repeatedly will revolutionize surgical training, and the combination of surgical planning and simulation will improve the efficiency of intervention, leading to optimal care delivery.

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We analyse the most important clinical, CT, surgical, histopathological, biological, biochemical, mycological and bacteriological features of caseous sinusitis, i.e. chronic, poorly symptomatic sinusitis which are resistant to usual treatment. CT shows an opacity of the maxillary sinus with often a hyperdense foreign body (dental overfilling) but no valid predictive criteria for fungal etiology. The endoscopic or surgical procedures point out a caseous mass often called fungal mass or aspergilloma. The biochemical composition of this mass (water, proteins, lipids) is similar to that of tissues surrounding the sinus. The calcium value is variable and shows no correlation with CT imaging. The qualitative and quantitative analysis of the metals (zinc, lead, silver, copper, iron) is of relevance for exogenic origin (dental overfilling). The fungal etiology is inconstant (20 cases) after the mycological investigations. We discuss the nosologic and diagnostic features of caseous sinusitis, fungal or not, and which are often or too often called aspergillosis sinusitis.

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Various enzymatic urinary activities have been proposed to assess renal proximal tubule damage in children, including neonates. Nevertheless comprehensive knowledge on the developmental aspects of physiological enzymuria is limited, particularly with regard to lysosomal and brush border enzymuria. Urinary activities of two lysosomal enzymes, N-acetyl-beta-D-glucosaminidase (NAG) and beta-galactosidase (GAL), and of two brush border enzymes, alanine aminopeptidase (AAG) and gamma-glutamyltransferase (GGT) were comparatively investigated in normal prematures (n = 28), term neonates (n = 52), infants aged less than 2 years (n = 19) and children (n = 33), and compared to urinary excretion of beta 2-microglobulin (B2M). Enzymatic activities were assayed using either spectrophotometrical (NAG, AAP, GGT) fluorimetrical (GAL) or radioimmunological (B2M) methods, and were related to urinary creatinine excretion. Developmental profiles of both the studied lysosomal enzymes and of B2M were similarly characterized with significantly decreasing values from prematures (NAG 9.29 +/- 1.44, GAL 2.26 +/- 0.26 IU/mmol creatinine, indicated as mean +/- SEM) to term neonates (6,94 +/- 0.58 and 1.76 +/- 0.15 IU/mmol creatinine, respectively) and older infants and children. Lysosomal enzymatic urinary activities correlated linearly with a coefficient of r = 0.75, (p < 0.05), while correlations between each lysosomal enzymatic activity and B2M urinary excretion were weaker.(ABSTRACT TRUNCATED AT 250 WORDS)

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It has been found that opiate abusers once detoxified are afflicted with personality disorders. An attempt was made to test the origin of drug abuse by comparing a group of drug abusers with personality disorders diagnosed as borderline or schizotypal with a group of people suffering from similar personality disorders but who did not use drugs. The results of the test are discussed.

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Serum levels of zinc, copper, manganese, magnesium, folates and vitamin B12 and A, were titrated in the early stage of pregnancy in women who delivered children presenting malformations. These levels were compared with those of control patients who delivered normal children. There were 65 malformations. The most frequent were cardiac, musculo-skeletal, urogenital and chromosomal malformations. Only 2 cases of spina bifida were studied. The oligo-elements and vitamin levels are not different in both groups of women: those who carry malformed fetuses and those carrying normal fetuses. These results are compared with those from the literature.

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To determine the degree of mononuclear blood cell activation in Crohn's disease (CD), 65 patients were prospectively investigated (22 with mild, 26 with moderate and 17 with severe disease). Serum levels of soluble receptors for interleukin-2 (SR-IL-2) were measured by ELISA. In CD patients SR-IL-2 levels were significantly higher (m = 707 +/- 326 U/ml) than in three other groups: 70 controls (m = 258 +/- 87 U/ml, p less than 0.0001); 8 patients with acute infectious colitis (m = 405 +/- 216 U/ml, p less than 0.0001); 101 HIV seropositive subjects (m = 564 +/- 216 U/ml, p less than 0.002). There was a positive correlation between SR-IL-2 level and the Van Hees activity index (r = 0.595, p less than 0.0001). On the other hand, the numbers of activated T cells (CD 3+, HLA DR+), CD 4+, CD 8+ and NK cells did not differ according to the CD activity groups. Furthermore, CD patients treated with steroids (n = 39) did not differ from those without any medication. As a marker of monocyte activation, serum neopterin level was determined by RIA. All CD patients considered as a group, serum neopterin level was 2.89 +/- 1.44 ng/l (n less than 2.5 ng/l). Neopterin level increased with disease activity (1.97 +/- 0.92 vs 3.10 +/- 1.46 vs 3.74 +/- 1.36, p less than 0.01), and was positively correlated with SR-IL-2 (r = 0.609, p less than 0.0001). These results suggest a monocyte-macrophage activation in CD, which parallels disease activity.(ABSTRACT TRUNCATED AT 250 WORDS)

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