Reliability of hemostasis biomarkers is affected by time-dependent intra-patient variability.

Essentials Nucleosomes and free DNA are two newly described biomarkers in venous thromboembolism (VTE). Reliability of nucleosomes, plasma free DNA and conventional hemostasis markers were studied. Hemostasis biological parameters vary over a short time-frame in VTE patients. Hemostasis biological parameters also vary over a short time-frame in healthy controls. SUMMARY: Background Previous studies have associated neutrophil-derived circulating nucleosomes and plasma free DNA with venous thromboembolism (VTE). However, there are few data concerning these two biomarkers and no studies have compared the reliability of nucleosomes and plasma free DNA against that of conventional hemostasis markers. Objectives We performed a 3-year prospective study of nucleosomes and plasma free DNA levels in comparison with conventional hemostatic biomarkers and blood cells. Patients/Methods Fifteen healthy controls and 22 randomly selected patients with a history of VTE were followed monthly for 6 months. The reliability of these markers was evaluated by the intraclass correlation coefficient (ICCs). Results and Conclusions In healthy controls and patients, we found a low reliability for nucleosomes and plasma free DNA, with ICCs at 0.538 (95% confidence interval [CI], 0.334-0.764) and 0.091 (95% CI, -0.026-0.328), respectively, in the healthy controls, and at 0.213 (95% CI, 0.042-0.463) and 0.161 (CI 95%, 0.008-0.398) in the patient group. For the conventional hemostasis biomarkers and for blood cells, reliability ranged from poor to good in the healthy volunteers and from poor to acceptable in the patient group. Our study shows for the first time that hemostasis biological parameters spontaneously vary over a short time-frame in VTE patients and, more surprisingly, in normal individuals. The clinical value of such intra-individual variations is currently unknown. This variability might mean reinterpreting diagnostic or prognostic models based on static evaluation of individuals. Studying the intrinsic value of individual patterns of markers' variability is warranted.

Reflection on the measurement and use of the topography of the indentation imprint.

The goal of this paper is to study the main uses of the residual imprint of the indentation test. It also discusses the different technologies and methods employed in this context. The difficulties encountered when trying to exploit the full potentials of the imprint are thoroughly examined. A survey of the literature on the quantification of the pile-up clearly shows that there is a lack of consensus on the measurement of the residual imprint as well as on treatment methods. Therefore, in order to widen the application fields of the indentation residual imprint, relevant and standardized indicators should be established.

[A new automated haematology analyser: the Excell 2280]. / Un nouvel automate de cytologie hématologique: l'Excell 2280.

Excell 2280 analyser is a new automated haematology analyser manufactured by Drew Scientific Inc, Texas, USA, and distributed in France by MAXMAT S.A., Montpellier. It can achieve 80 complete blood cell counts per hour, with leukocyte differential counts. Three sampling possibilities are included: a direct one (open tubes, 180 microL), a blood saver one (80 microL) and an automatic, through-the-cap one (180 microL). The analytic principles are: electrical impedance for cell counting (WBC, RBC, platelets, MCV) and RBC/platelet sizing; and a new multidimensional optical system using a laser light scattering flow cytometer for WBC counting and classification. We evaluated the Excell 2280 in our laboratory: we quantified intra-run and within-run variations, correlations between the automatic and the direct sampling method, stability of the results over time, linearity of the detections and finally correlation between results obtained with this analyzer and the Gen'S one from Beckman-Coulter Inc. The obtained results were within the theoretical ranges given by the manufacturer. The presence of any abnormal result, or of any flag, must systematically lead to check the blood smear. This new automated haematology analyser appears to be convenient for emergency room-related laboratories, and for routine small-to-medium laboratories.

[Evaluation of an automated method for measuring low-density lipoprotein cholesterol]. / Evaluation du dosage direct du cholestérol des lipoprotéines LDL.

We evaluated an automated method for measuring low-density lipoprotein cholesterol (LDL-cholesterol) with Integra 800 (Roche Diagnostics). This method uses detergents which show selectivity for the different lipoproteins. Our evaluation has shown a within run imprecision of 2% and a between-assay imprecision of 1.2%. This method was not perturbed by haemoglobin, bilirubin or lipids. However, the reagents remain expensive: we will use it when calculation or interpretation of lipid results are not possible.

Role of laparoscopy in blunt perforations of the small bowel.

BACKGROUND: The purpose of this study was to determine whether laparoscopy could improve our ability to diagnose and treat perforations of the small bowel. METHODS: From 1985 to 2001, among 250 patients admitted for a blunt abdominal trauma, 195 surgical explorations were performed, comprising 42 laparoscopies. On admission, 108 patients underwent an abdominal ultrasonography (US) and 104 a computed tomography (CT). Thirty-nine patients had a blunt small bowel trauma (BSBT) that was explored and/or treated by laparoscopy (n = 15) or celiotomy (n = 24). We compared the patients who underwent emergency surgery (23) and those who were operated on after a mean delay of 51 h. RESULTS: On admission, for detecting free intraperitoneal fluid with a BSBT, the sensitivity of CT was 93.3% and specificity was 13.6%. Regarding the 23 patients who underwent emergency surgery, 8/20 had positive US and 10/15 had positive CT, whereas the 15 celiotomies and 8 laparoscopies indicated BSBT. Regarding the 16 patients who underwent delayed surgery, 9 patients underwent a celiotomy and 7 a laparoscopy; all BSBTs were diagnosed. In searching for BSBT, the sensitivity and specificity of laparoscopy were both 100%, whereas the sensitivity of CT was 83.3% and specificity was 22.2%. Twenty of 23 patients undergoing emergency surgery had bowel suture repair compared to 3/16 after delayed surgery. In contrast, a resection was necessary in 10/12 patients treated after a delay compared to 2/17 operated in emergency. Five BSBTs were sutured by laparoscopy, whereas 10 required conversion. Laparoscopy avoided celiotomy in 15 cases. There were no deaths and no enterostomy. CONCLUSION: In hemodynamically stable patients with blunt abdominal trauma, laparoscopy safely and effectively identifies small bowel injuries. Early recognition of these injuries and timely surgical treatment offer the best prognosis.

Polypeptide composition of an adenovirus type 5 used in cancer gene therapy.

For cancer gene therapy, a recombinant adenovirus serotype 5 named RPR/INGN201 has been constructed by susbtitution of the E1 region with human tumor suppressor gene p53. The protein components of RPR/INGN201 virions were separated by reversed-phase HPLC and were individually identified by electrospray time-of-flight mass spectrometry and N-terminal sequencing, both on intact proteins and on their proteolytic fragments after trypsin digestion. Twenty-five peptide components of the proteome (including fiber) with greater than 0.25-0.5% contribution to the protein content of the virus were identified and characterized. Fiber was confirmed to be partially glycosylated (both the non-glycosylated and the monoglycosylated states were identified), and two proteins were isolated and identified as phosphorylation derivatives, namely protein V (non-phosphorylated and monophosphorylated) and protein IIIa (mono- and diphosphorylated). This new analytical tool proved to be very useful not only for refining our current knowledge of the polypeptide repertoire of purified infectious virions but also for monitoring and very rapidly identifying structural modifications resulting from changes in the manufacturing process. It was also used successfully for the characterization of various adenoviral constructs.

Elliptic flow in Au+Au collisions at square root(S)NN = 130 GeV.

Elliptic flow from nuclear collisions is a hadronic observable sensitive to the early stages of system evolution. We report first results on elliptic flow of charged particles at midrapidity in Au+Au collisions at square root(S)NN = 130 GeV using the STAR Time Projection Chamber at the Relativistic Heavy Ion Collider. The elliptic flow signal, v2, averaged over transverse momentum, reaches values of about 6% for relatively peripheral collisions and decreases for the more central collisions. This can be interpreted as the observation of a higher degree of thermalization than at lower collision energies. Pseudorapidity and transverse momentum dependence of elliptic flow are also presented.

[Prosthetic treatment of bilateral inguinal hernias via laparoscopic approach or Stoppa procedure]. / Traitement prothétique des hernies inguinales bilatérales par voie laparoscopique ou par opération de Stoppa.

AIM OF THE STUDY: The aim of this prospective non-randomized study was to compare Stoppa's technique to laparoscopic approach in totally extraperitoneal repair of bilateral inguinal hernia. PATIENTS AND METHOD: From December 1996 to December 1998, 117 consecutive patients with 234 hernias underwent either Stoppa's technique (74 patients) or a totally extraperitoneal laparoscopic approach (43 patients). Patients were randomized in two groups according to the surgeon to whom they were referred. All patients were reviewed in December 1999. RESULTS: There was no mortality. Complications occurred in 3% of patients after Stoppa's technique (group S) and in 4% of patients in the laparoscopic group (group L). The conversion rate was 7% (3 cases). Postoperative analgesia use, hospital stay, and duration of disability were significantly shorter in group L, the cost was lower, but the operating time was significantly longer than in group S. Recurrence rates were similar in the two groups: 2% in group S, 1.1% in group L. CONCLUSION: The laparoscopic approach appears to be preferable to Stoppa's technique in the treatment of bilateral inguinal hernia.

[Excision of the duodenojejunal angle for tumor. From simple excision to locoregional excision]. / Résection de l'angle duodéno-jéjunal pour tumeur. De l'exérèse simple à l'exérèse loco-régionale.

Locoregional extensions are often observed in tumors of the duodenojejunal angle, either because of their anatomic situation or in cases diagnosed late. Endoscopic and radiographic explorations (basically abdominal CT scan) are indicated to search determine the degree of extensions to neighboring organs and vessels. Colic and mesocolic involvement are at the limit of preoperative explorations. Based on 4 observations of increasing complexity, we describe our operative strategy allowing tumor exeresis in a single block. Extension to the superior mesenteric artery is the main contraindication for exeresis.

[Cystic and papillary tumor of the pancreas: diagnostic and developmental uncertainties. Apropos of a case]. / Tumeur papillaire et kystique du pancréas: incertitudes diagnostiques et évolutives. A propos d'un cas.

We reported a case of papillary and cystic tumor (Frantz's Tumor) associated with familial adenomatous polyposis in a young man, 29 years old. This case emphasized the interest of fine needle biopsy and the difficulties for determination of the final pathology. Close long term follow up is essential as local recurrencies and metastasis in the long term had been recorded, undergoing resection with curative intent. Papillary and cystic tumors should be resected.

Alteration of T4 lysozyme structure by second-site reversion of deleterious mutations.

Mutations that suppress the defects introduced into T4 lysozyme by single amino acid substitutions were isolated and characterized. Among 53 primary sites surveyed, 8 yielded second-site revertants; a total of 18 different mutants were obtained. Most of the restorative mutations exerted global effects, generally increasing lysozyme function in a number of primary mutant contexts. Six of them were more specific, suppressing only certain specific deleterious primary substitutions, or diminishing the function of lysozymes bearing otherwise nondeleterious primary substitutions. Some variants of proteins bearing primary substitutions at the positions of Asp 20 and Ala 98 are inferred to have significantly altered structures.

[Cystic lymphangiomas of the colon. Apropos of 2 cases]. / Les lymphangiomes kystiques du côlon. A propos de 2 observations.

The authors report about two observations of cystic lymphangioma of the right colon. The patients complained of intermittent abdominal pain. Preoperative diagnosis is based on endoscopic findings (2 cases) and computed tomography films (1 case). A colonic carcinoma is associated in one case. Endoscopic polypectomy will be curative for pedunculated or small lymphangiomas. In other cases segmental resection seems to be the treatment of choice.

[Cystic dystrophy of the duodenal wall on aberrant pancreas. Apropos of 2 cases]. / Dystrophie kystique de la paroi duodénale sur pancréas aberrant (DKPA). A propos de deux observations.

Cystic dystrophy in heterotopic pancreas is characterized by the presence in the duodenal thickened muscularis of cysts corresponding to dilated ducts lined with exocrine epithelium. The pancreas proper is normal. Cystic dystrophy in heterotopic pancreas occurs mostly in men, in the periampullary region. Two cases, revealed by duodenal stenosis, are reported here. Symptoms and morphologic investigations favoured a diagnosis of malignancy: in one case, partial portal thrombosis was observed; this complication has not been previously described in association with cystic dystrophy in heterotopic pancreas. Endosonography was non-contributory in these 2 cases because of duodenal stenosis. A pancreaticoduodenectomy was performed associated in one case with portal thrombectomy. Pathologic findings allowed diagnosis of cystic dystrophy in heterotopic pancreas.

Second-site reversion of a structural defect in bacteriophage T4 lysozyme.

A plasmid-borne gene encoding bacteriophage T4 lysozyme with a structural mutation, Tyr161-Ala, was mutagenized by by the use of polymerase chain reaction. The mutagenized gene was inserted into a specialized bacteriophage lambda cloning vector that must acquire a functional lysozyme gene in order to form plaques. Functional variants of the mutant lysozyme were selected. Three compensatory second-site revertants were obtained: Thr152-Met, Lys43-Ile, and Thr151-Ala. The effects of these mutations are interpreted in light of previous structural and genetic studies of T4 lysozyme.

Autopsies of sudden infant death syndrome--classification and epidemiology.

An enquiry into sudden infant death syndrome (SIDS) in 1987 furnished us with detailed epidemiological data for 281 cases that underwent a thorough post-mortem examination. This analysis uses these data to evaluate the role the autopsy plays in explaining sudden death. The cases were classified into three diagnostic groups: explained causes of death (group 1), unexplained deaths with anomalies (group 2), and no anomaly (group 3). These 281 cases show the three essential features that characterize SIDS: over-representation of males, increased deaths during the second and third months of life, and increased deaths during winter. The autopsy examination revealed that many of these deaths had a medical explanation. Almost half were assigned to group 1. At the time of autopsy, no precise pathology could be diagnosed for 147 deaths; of these, 140 showed histological anomalies. There were only seven sudden deaths for which no abnormal sign was evident at the autopsy. These results are compared with those of similar studies and discussed in connection with three factors: the initial selection of cases, the nature and degree of the investigations, and the possible interpretations of the symptoms uncovered.

[Well-differentiated papillary mesothelioma of the peritoneum: an attenuated malignant tumor. Review of the literature apropos of a case]. / Le mésothéliome péritonéal papillaire bien différencié: une tumeur à malignité atténuée. Revue de la littérature à propos d'un cas.

The authors present a new case of a well-differentiated papillary mesothelioma of the peritoneum. This is an uncommon tumor which have a slow evolution like a low malignant potential tumor. But, because of its tendency to recurrence, the designation of Well-Differentiated Tumor is better. The diagnosis with others peritoneal tumors is sometimes difficult, especially with the Peritoneal Serous Tumors. Tumor recurrence must be treated by curative surgery. Adjuvant therapy is discussed for the diffuse form.

[Gastric adenocarcinomas (excluding linites). Prognostic factors apropos of a series of 101 cases]. / Adénocarcinomes gastriques (linites exclues). Facteurs pronostiques à propos d'une série de 101 cas.

The incidence of some factors on prognosis of adenocarcinoma of the stomach was evaluated in 101 cases. Linites as well as cancers of the cardia were excluded from the analysis. There were 47 total gastrectomies with more or less extensive node dissection and 54 partial gastrectomies. Overall actuarial survival was 34.5% despite the large number of advanced stage cancers (70% positive lymph nodes, 35 with invasion of neighbouring organs, 13 cases of carcinosis and 13 with liver metastasis). Univariate analysis showed that the following factors were associated with poor prognosis: invasion of the serous layer, nodal involvement, emboli, degree of differentiation. Peritumoural reactional lymphoid infiltration, the presence of a chronic gastritis and intestinal metaplasia were found to be favourable factors. Gastric resection appeared to have less impact than the quality of the nodal dissection. These findings emphasize the importance of extensive dissection of the lymph nodes (survival ranging from 31 to 78% depending on the node score). Extensive dissection, allowing better locoregional control of the disease, improved prognosis whatever the size of the tumour (14.8% survival in case extending to neighbouring organs). The only exceptions were palliative exereses and N4+ cases.

[Cancer of the penis: the value of systematic biopsy of the superficial inguinal lymph nodes in clinical N0 stage patients]. / Cancer du pénis: valeur de la biopsie systématique des ganglions inguinaux superficiels chez les patients N0 clinique.

From 1985 to 1991, bilateral surgical biopsy of the superomedial group of superficial inguinal lymph nodes, considered to be the first draining nodes, was performed in 24 patients with clinical stage T1-3 N0 M0 squamous cell carcinoma of the penis at the same time as surgical treatment of the primary. This procedure was technically successful in every case, but no lymph node metastases were detected. As bilateral biopsy was negative in these 24 patients, clinical surveillance was implemented: review every 2 months for 2 years and self-palpation by the patient. Seven patients (29.1%) developed one or more suspicious ilio-inguinal lymph nodes after a mean interval of 11.85 +/- 8.02 months: 1) In 6 patients, bilateral ilio-inguinal lymph node dissection was then performed, confirming the neoplastic nature of the inguinal node metastases without iliac metastases in 3 of these patients. 2) As the remaining patient presented with unilateral iliac node metastases, proven histologically by surgical biopsy, systemic chemotherapy was introduced prior to ipsilateral inguinal lymph node dissection. This finding questions the theory according to which the sentinel superomedial inguinal node constitutes the first draining node and demonstrates the existence of several pathways of lymphatic drainage towards superficial and deep inguinal nodes. This biopsy, which was always negative in our series, is insufficient to guide our therapeutic approach in clinical N0 patients. The decreased complication rate following inguinal lymph node dissection should certainly encourage us to prefer surgery, particularly superficial inguinal lymph node dissection with preservation of the great saphenous vein.

[Results of 81 supra-articular femoro-popliteal bypasses using PTFE]. / Résultats de 81 pontages prothétiques fémoro-poplités sus-articulaires en P.T.F.E.

The indications for supra-articular prosthetic bypass is still a controversial subject in cases where the internal saphenous vein can be used, or in stage II cases. These bypasses cannot be performed unless they are as permeable as venous bypasses and do not greatly increase the risk of exaggerating the symptomatology in case of thrombosis. In order to evaluate the outcome of these bypasses, we evaluated retrospectively our series of 81 surpa-articular femoro-popliteal prosthetic bypasses performed between 1987 and 1989. The man age of the patients was 64 years and 38% of them had coronary artery disease. Forty-six bypasses (57%) were performed in advanced stage II patients, 20 in stage III patients (25%) and 15 in stage IV (18%). Mean follow-up is 42 months. At 36 months, primary overall permeability was 65%. This level of permeability is in agreement with the data in the literature and is independent of the initial clinical stage, the downstream arterial network and the size of the prosthesis. The outcomes observed in our series would favour use of P.T.F.E. in the first intention operation to save the vein for possible subsequent use at stages III and IV. Inversely, for stage II, prospective randomized studies should be conducted in order to compare endovascular techniques and medical treatments.