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Hypothesis: The more rapid and less complicated recovery after palliative stent insertion compared with surgery may theoretically facilitate the early administration of chemotherapy., Design: A retrospective study., Setting: University tertiary care referral center., Patients: From January 1, 1996, to September 15, 2005, 58 patients with obstructing colon cancer and nonresectable synchronous metastases were treated with self-expanding colonic metallic stent (SEMS) (n = 31) or surgery (n = 27)., Main Outcome Measures: Comparison of the use of SEMS and emergency surgery as palliative measures to treat obstructing colon cancer with special reference to time to chemotherapy administration and survival., Results: Mortality and morbidity were comparable between the 2 groups. Median hospital stay was shorter after SEMS insertion than after surgery (median, 8.0 vs 13.5 days, respectively; P < .01). Incidence of stoma creation was lower in patients treated with SEMS than in patients treated with surgery (6% vs 37%, respectively; P = .02). The median time to chemotherapy administration was shorter after SEMS insertion than after surgery (14.0 vs 28.5 days, respectively; P = .002). Three patients with SEMS and 0 patients in the surgical group underwent a curative colonic and hepatic resection after downstaging by chemotherapy (P = .27). Two patients (6%) with SEMS and undergoing chemotherapy had a tumor perforation requiring emergency surgery. There was no difference in survival between the 2 groups (median survival, 13.7 months for SEMS vs 11.4 months for surgery; P = .19)., Conclusions: Insertion of SEMS should be the first step to treat obstructing colon cancer with nonresectable synchronous metastases because it allows chemotherapy to be administered earlier, may increase the resectability rate of metastases, and favorably impacts survival. The risk of tumor perforation while receiving chemotherapy requires attention.

Diaphragmatic invasion is not uncommon in patients undergoing hepatectomy for liver tumors. Where there are limited attachments of the diaphragm to the tumor, the authors describe a stapled technique for en bloc resection of the diaphragm without opening the chest cavity, thus performing an oncologic resection, while avoiding the need for pleural drainage.

Von Willebrand disease is the most common inherited bleeding disorder, with autosomal genetic transmission, dominant in most cases. It is due to quantitative and/or qualitative deficiency of Von Willebrand factor, a multimeric complex glycoprotein that plays 2 central roles in hemostasis, since it is implicated in adhesion and aggregation of platelets under conditions of high shear forces and acts as a carrier for coagulation factor VIII in plasma. Clinically, this disease is mostly characterized by mucocutaneous bleeding and marked clinical heterogeneity, even in the same family, going from severe to uncouth forms or even asymptomatic. Laboratory diagnosis is based on 3 levels of hemostasis testing. Screening tests making suspicion of the disease, must be completed by specific assays to estabilish the diagnosis. Discriminating tests allow accurate characterization of the numerous types and subtypes of the disease, a crucial step to adapt therapeutics. The classification based on the accumulating knowledge of the different phenotypes, differentiate between quantitative (types 1 and 3) and qualitative deficiencies (types 2). Von Willebrand disease's diagnosis is not, often easy. In fact, several technical or genetic factors and different physiopathological circumstances interfere in the interpretation of explorations results and cause diagnostic difficulties that will be discussed.

Intravascular papillary endothelial hyperplasia is considered to be an unusual form of thrombus organization that is marked by an excessive papillary endothelial proliferation. This lesion has the propensity to occur in the skin and the subcutis. Occurrence in the gastrointestinal tract is very rare. The authors report an exceptional case of a 20-year-old young woman with intravascular papillary endothelial hyperplasia in the jejunum. The patient was referred to the hospital with a 1-week history of melena. The lesion did not recur after surgery. Histopathological examination revealed a papillary endothelial hyperplasia with an underlying arteriovenous malformation.

Gene alterations which have been implicated in colorectal carcinogenesis are characterized by three major mechanisms: chromosomal instability, microsatellite instability, and epigenetic mechanisms (i.e., CpG island hypermethylation). Progress in understanding of these genetic and epigenetic instabilities has led to advances in the individualization and characterization of more homogeneous sub-groups of colorectal tumors with regard to progression, prognosis and response to therapy.

Tumors arising sporadically represent 70-80% of colorectal cancer (CRC). The two best defined forms of inherited CRC-familial multiple polyposis (FMP) and Hereditary Non-Polyposis Colon Cancer (HNPCC) account respectively for<1% and 2-3% of CRC. These rare genetic syndromes (FMP, HNPCC, Peutz-Jeghers Syndrome) are caused by major predisposing gene mutations (APC gene, MMR gene, BMPR1A. SMAD4,...) and local environmental factors play only a minor role. In the sporadic forms of CRC, 25% have significant genetic predisposition probably related to alleles with weak penetration (APC*I1307K, TGFbR1*6Ala...) and are more strongly affected by environmental factors.

Background: Since 1997, the authors have performed laparoscopic left lateral sectionectomy of lesions of the liver in preference to open surgery. The aim of this study was to assess the outcome., Methods: Between October 1997 and March 2005, 36 laparoscopic left lateral sectionectomies were performed using five trocars and a small incision for specimen retrieval. Liver resection was performed mainly using a harmonic scalpel and staplers. The Pringle manoeuvre was used in 24 patients., Results: The mean patient age was 55.2 (range 31-80) years. Twelve patients had underlying cirrhosis. Surgery was performed for 20 malignant lesions and 16 benign lesions with a mean size of 42.7 (range 5-110) mm. Conversion to laparotomy occurred in one patient. The mean operating time was 171.5 (range 90-240) min. Operatiing time and use of the Pringle manoeuvre were significantly decreased in the second half of the series. Mean blood loss was 208 (range 50-600) ml. No transfusion was required. There were no deaths. Two patients had postoperative complications (one incisional hernia and one pneumonia). The median postoperative stay was 5.2 days., Conclusion: The laparoscopic approach to left lateral sectionectomy was safe and feasible in this series and could be considered as a routine approach in selected patients., (Copyright 2006 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd.)

The shortage of organ donors and the increased demand for liver transplantation has led to new strategies to increase the availability of liver grafts for transplantation. Occasionally, previous liver transplant recipients may experience brain death and become organ donors. Although this is a very rare situation, we and others have showed that reuse of liver grafts could be performed successfully within one week after transplantation. Late reuse has, however, not been reported to date. We report the first case in which a liver graft was successfully reused 13 years after the first transplantation.

Background: Prolonged systemic preoperative chemotherapy induces pathologic changes in liver parenchyma. The consequences of vascular occlusion on liver submitted to prolonged preoperative systemic chemotherapy are not known. The aim of this case-matched study was to assess which method of vascular occlusion is most appropriate for major liver resection in patients who have undergone prolonged preoperative systemic chemotherapy., Methods: Among 305 patients who had liver resection for colorectal metastases from 1998 to 2003, 28 underwent major liver resections under portal triad clamping after more than 6 cycles of preoperative chemotherapy (TC group). These 28 patients were compared with 32 patients matched for age, sex, ASA status, number of liver metastases, type of liver resection, and type of preoperative chemotherapy, but who had major liver resection under hepatic vascular exclusion after more than 6 cycles of preoperative chemotherapy (VE group)., Results: There was no postoperative mortality. The morbidity rate was 18% after TC and 43% after VE (P = 0.044). Pulmonary complication rate was greater after VE (31% vs 3%, P = 0.017). The transfusion rate was 50% in the TC group and 40% in the VE group (P = 0.482). Postoperative changes of liver function tests were comparable in the two groups except for the prothrombin time, which was more prolonged from day 1 (P = 0.003) to day 5 (P = 0.04) after VE., Conclusion: Vascular occlusion can be used with no mortality and acceptable morbidity for major liver resection after prolonged preoperative chemotherapy. TC should be preferred to VE, permitted by the location of the neoplasm.

Introduction: Causes of leg ulcers vary widely, although venous insufficiency and peripheral arteriopathy are most common. Ulcers are much rarer in patients treated by hydroxyurea., Case: A 66-year-old woman who had been treated with hydroxyurea for polycythemia vera for four years came to our consultation a month after ulceration of the left lateral malleolus had begun. Symmetric peripheral pulses were present and there was no patent venous insufficiency. After two months of local symptomatic treatment, the size of the ulcer had increased. The possible involvement of hydroxyurea in the genesis and maintenance of this leg ulcer was then considered. Hydroxyurea was stopped, and the ulcer progressively grew smaller, finally healing completely two months later., Discussion: We conclude that hydroxyurea was the primary cause of the malleolar ulcer, for it healed rapidly when this treatment stopped. Hydroxyurea causes cutaneous atrophy; when followed by microtrauma, associated with deterioration in DNA repair mechanisms, it may lead to the formation of persistent cutaneous ulcers. Hydroxyurea can also affect the microcirculation and induce tissular anoxia, which may also explain both the occurrence of cutaneous ulcers after microtrauma and their often painful character.

Objectives: Restorative proctocolectomy with ileoanal anastomosis (IPAA) is the surgical standard for patients with ulcerative colitis (UC). Significant reduction in female fertility and fecundity after IPAA has been shown in recent studies. In selected cases, colectomy with ileorectal anastomosis (IRA) is another surgical option. The aim of this study was to evaluate fertility in women with UC who underwent IRA., Patients and Methods: This study included all women with UC who underwent IRA between 1962 and 1999 and who were 40 years old or younger at the time of surgery, and older than 18 years of age at the time of the interview. Data were collected using a structured telephone interview concerning reproductive behavior and waiting times to pregnancy., Results: Among 40 eligible patients, 37 whose mean age at IRA was 28 years (range 11-39) answered the questionnaire. Twenty-two were unmarried, not wishful of pregnancy and/or already had children. Among 15 females wishing children after IRA, 10 (66%) became pregnant: one had therapeutic abortion, two had a miscarriage, four had 1 child, two had 2 children and one had 4 children. Five patients were sterile after IRA., Conclusion: These preliminary results suggest that IRA for UC preserves female fertility. If confirmed in other series this information should be provided to young women with UC before deciding surgical option.

Objective: Report the midterm results of laparoscopic resection for hepatocellular in chronic liver disease (CLD)., Summary Background Data: Surgical resection for hepatocellular carcinoma (HCC) in chronic liver disease (CLD) remains controversial because of high morbidity and recurrence rates. Laparoscopic resection of liver tumors has recently been developed and could reduce morbidity., Methods: From 1998 to 2003, patients with HCC and CLD were considered for laparoscopic liver resection. Inclusion criteria were chronic hepatitis or Child's A cirrhosis, solitary tumor < or =5 cm in size, and location in peripheral segments of the liver. Mortality, morbidity, recurrence rates, and survival were analyzed., Results: A total of 27 patients were included. Liver resections included anatomic resection in 17 cases and non anatomic resection in 10. Seven conversions to laparotomy (26%) occurred for moderate hemorrhage in 5 cases and technical difficulties in 2 cases. Mortality and morbidity rates were 0% and 33%, respectively. Postoperative ascites and encephalopathy occurred in 2 patients (7%) who both had undergone conversion to laparotomy. Mean surgical margin was 11 mm (range, 1-47 mm). After a mean follow-up of 2 years (range, 1.1-4.7), 8 patients (30%) developed intrahepatic tumor recurrence of which one died. Treatment of recurrence was possible in 4 patients (50%), including orthotopic liver transplantation, right hepatectomy, radiofrequency ablation, and chemoembolization in 1 case each. There were no adhesions in the 2 reoperated patients. Overall and disease-free 3-year survival rates were 93% and 64%, respectively., Conclusion: Our study shows that laparoscopic liver resection for HCC in selected patients is a safe procedure with very good midterm results. This approach could have an impact on the therapeutic strategy of HCC complicating CLD as a treatment with curative intent or as a bridge to liver transplantation.

Objective: : To assess the effects of preoperative systemic chemotherapy on remnant liver parenchyma, liver function, and morbidity after major liver resection for colorectal liver metastases., Background: : Many patients operated upon for colorectal cancer liver metastases receive previous chemotherapy. Whether systemic chemotherapy alters liver parenchyma in such way that it increases the risks of liver resection remains unclear., Patients and Methods: : Among 214 patients who received a liver resection for colorectal liver metastases between 1998 and 2002 in a single institution, 67 who underwent a major liver resection under total hepatic vascular exclusion form the basis of this report. Forty-five patients operated upon after systemic chemotherapy were compared with 22 who did not receive any chemotherapy in the 6 months prior to resection. Postoperative mortality, morbidity, liver function tests, and pathology of the resected liver in the two groups were compared., Results: : There was no postoperative mortality. Values of liver function tests on days 1, 3, 5, and 10 were similar in both groups. Morbidity rate was higher in the chemotherapy group (38% versus 13.5%, P = 0.03). Postoperative morbidity was correlated with the number of cycles of chemotherapy administered before surgery but not to the type of chemotherapy. Preoperative chemotherapy was significantly associated with sinusoidal dilatation, atrophy of hepatocytes, and/or hepatocytic necrosis (49% versus 25%, P = 0.005)., Conclusion: : Prolonged neoadjuvant systemic chemotherapy alters liver parenchyma and increases morbidity after major resection under total hepatic vascular exclusion, but it does not increase operative mortality. This should be taken into consideration before deciding a major liver resection in patients who have received preoperative chemotherapy.

Bacterial chromosomes are organized in replichores of opposite sequence polarity. This conserved feature suggests a role in chromosome dynamics. Indeed, sequence polarity controls resolution of chromosome dimers in Escherichia coli. Chromosome dimers form by homologous recombination between sister chromosomes. They are resolved by the combined action of two tyrosine recombinases, XerC and XerD, acting at a specific chromosomal site, dif, and a DNA translocase, FtsK, which is anchored at the division septum and sorts chromosomal DNA to daughter cells. Evidences suggest that DNA motifs oriented from the replication origin towards dif provide FtsK with the necessary information to faithfully distribute chromosomal DNA to either side of the septum, thereby bringing the dif sites together at the end of this process. However, the nature of the DNA motifs acting as FtsK orienting polar sequences (KOPS) was unknown. Using genetics, bioinformatics and biochemistry, we have identified a family of DNA motifs in the E. coli chromosome with KOPS activity.

Pachydermoperiostosis or primary hypertrophic osteoarthropathy is a benign genetically determined disease, manifested by finger clubbing, hypertrophic skin changes and periosteal bone formation. It is rarely reported and was for a long time misdiagnosed and confused with secondary hypertrophic osteoarthropathy. We present the imaging features in two cases and review the literature.

Objective: To report a case of streptomycin-induced toxic epidermal necrolysis (TEN)., Case Summary: A 55-year-old woman was admitted for treatment of active pulmonary tuberculosis (TB). She was given standard oral anti-TB chemotherapy including isoniazid, rifampin, pyrazinamide, and streptomycin. On the fourth day of therapy, she experienced high fever at 39 degrees C, chills, vomiting, pruritus, and diffuse erythema, followed by extensive bullae formation and skin denudation. Diagnosis of TEN was considered, and all anti-TB drugs were discontinued. Skin biopsy disclosed complete epidermal necrosis with dermal-epidermal cleavage and absence of inflammatory infiltrate, highly suggestive of TEN. The patient was transferred to the intensive care unit. Her general condition and skin lesions improved. A staged-fashion exposure test to the 4 anti-TB drugs allowed the incrimination of streptomycin as the offending agent., Discussion: Anti-TB drugs, mainly rifampin, ethambutol, and isoniazid, have been incriminated in TEN. Streptomycin-induced TEN remains an extremely rare event. However, minor allergic skin reactions (rash, urticaria) have been described with this drug. Our patient presents a rare case of streptomycin-related TEN. Even though dangerous, a step-wise exposure test was necessary to allow safe treatment of active pulmonary TB. It also provided a strong argument of a cause-effect relationship between TEN and streptomycin. An objective causality assessment using the Naranjo rating scale revealed that the adverse drug event was highly probable., Conclusions: Streptomycin should be added to the list of drugs that induce TEN.

Purpose: Restorative proctocolectomy is the elective surgical procedure of choice for ulcerative colitis and familial adenomatous polyposis. Most patients have a satisfactory outcome, but at ten years 15 percent or more will have failed, needing indefinite defunctioning or excision of the pouch. There is little information on the morbidity of pouch excision. The study was designed to present the early results of surgical removal of the pouch after failed restorative proctocolectomy with reference to the indications and intermediate complications, particularly of the perineal wound., Methods: Between 1977 and 2002, 996 patients underwent a restorative proctocolectomy at our hospital and 245 patients were referred for potential salvage. The pouch was excised in 58 and 10 patients respectively. There were 40 females and 28 males (median age, 34 (14-65) years) including 47 with ulcerative colitis, 10 with Crohn's disease, and 11 with familial adenomatous polyposis. The median follow-up was 79 (range, 3-312) months from excision., Results: There was one (1.4 percent) postoperative death. The overall morbidity rate was 62.3 percent (immediate 30 days (25 percent), late (53.7 percent)). Thirty-six patients (53.7 percent) were readmitted on 67 occasions for a late complication. The risk of readmission from the time of pouch excision was 38 and 58 percent at one and five years, respectively. Surgical treatment was required during 48 of these readmissions. A persistent perineal sinus was the most common late complication. The perineal wound was not healed at 6 months in 27 patients (40 percent) and at 12 months in 7 patients (10 percent). No factor, including age at the time of pouch excision, gender, indication for excision, or final histologic diagnosis, was associated with an unhealed perineal wound. Two males (7 percent) had impotence. One female suffered from short-bowel syndrome with the need of permanent parenteral nutrition. The median overall hospital stay for all admissions was 20 (range, 8-220) days., Conclusions: Pouch excision is associated with high morbidity. Perineal wound-delayed healing is the commonest late complication and often requires further surgery.

The Indirect Fluorescent Antibody Test (IFAT) remains so far the most commonly used test for sero-epidemiological investigations on tropical theileriosis (infection of cattle with Theileria annulata). The present studies evaluated the ability of both IFAT with schizont antigen (schizont IFAT) and blood smears to detect infected animals just after the theileriosis season. This evaluation was performed on a group of 89 calves of known infection status for T. annulata at first disease season, from farms with endemic stability for tropical theileriosis. An additional retrospective group of 84 cattle free of infection was also used for the estimation of the specificity of the schizont IFAT. The sensitivity and the specificity of schizont IFAT were 88.9% (64/72) and 97% (98/101), respectively. Blood smears showed a lower sensitivity of 63.9% (46/72). The agreement between the two detection techniques and the infection status of the animals, evaluated by the Kappa coefficient, was 0.85 and 0.64 for IFAT and blood smears, respectively.

Background & Aims: The peroxisome proliferator-activated receptor gamma (PPAR gamma) has been proposed as a key inhibitor of colitis through attenuation of nuclear factor kappa B (NF-kappa B) activity. In inflammatory bowel disease, activators of NF-kappa B, including the bacterial receptor toll-like receptor (TLR)4, are elevated. We aimed to determine the role of bacteria and their signaling effects on PPAR gamma regulation during inflammatory bowel disease (IBD)., Methods: TLR4-transfected Caco-2 cells, germ-free mice, and mice devoid of functional TLR4 (Lps(d)/Lps(d) mice) were assessed for their expression of PPAR gamma in colonic tissues in the presence or absence of bacteria. This nuclear receptor expression and the polymorphisms of gene also were assessed in patients with Crohn's disease (CD) and ulcerative colitis (UC), 2 inflammatory bowel diseases resulting from an abnormal immune response to bacterial antigens., Results: TLR4-transfected Caco-2 cells showed that the TLR4 signaling pathway elevated PPAR gamma expression and a PPAR gamma-dependent reporter in an I kappa kappa beta dependent fashion. Murine and human intestinal flora induced PPAR gamma expression in colonic epithelial cells of control mice. PPAR gamma expression was significantly higher in the colon of control compared with Lps(d)/Lps(d) mice. Although PPAR gamma levels appeared normal in patients with CD and controls, UC patients displayed a reduced expression of PPAR gamma confined to colonic epithelial cells, without any mutation in the PPAR gamma gene., Conclusions: These data showed that the commensal intestinal flora affects the expression of PPAR gamma and that PPAR gamma expression is considerably impaired in patients with UC.

The purpose of this study was to evaluate the results of percutaneous transhepatic management (PTM) of anastomotic biliary strictures (BS). Among 168 liver transplant adult recipients, BS was identified in 30 patients. In 6 patients, narrowing of the anastomosis was found early, and in all cases disappeared spontaneously with prolonged draining of the bile tube. Within a mean time of 14 months after transplantation, 24 patients had symptomatic BSs, revealed by cholestasis (n = 17) or cholangitis (n = 7). Twenty-two patients underwent PTM as first treatment of BS (balloon dilatation or stent placement). We evaluated the primary and secondary patency rate of PTM. In 1 patient, PTM failed because the stricture could not be passed with the guide wire, necessitating conversion to a Roux-en-Y choledochojejunostomy (CDJ). Fourteen patients were treated by percutaneous balloon dilatation from which 8 patients (57.2%) were recurrence-free with a mean follow-up of 61 months. One patient with a patent biliary anastomosis underwent retransplantation for acute rejection. Twelve patients received metallic expandable stent placement as their primary treatment (n = 7) or after failure of balloon dilatation (n = 5). Recurrent stricture was found in 7 cases (58%) and was treated by PTM (n = 6) or surgery (n = 1). The primary patency rate for PTM was 58.8% at 12 months and the secondary patency rate 88.4%, with a mean follow-up of 47 months (median: 44 months). The mortality rate was 3.5% (one death). PTM with balloon dilatation, stent placement, or both, represent a safe method to treat anastomotic BSs after orthotopic liver transplantation (OLT) resulting in a secondary patency rate of 88% at 5 years.

Parvovirus B19 infection is often associated with acute and chronic joint diseases thus suggesting an etiologic role for the virus in these pathologies. In this work, we looked for a possible correlation between Parvovirus B19 infection and certain types of chronic inflammatory rheumatisms. We therefore, screened a population of 100 patients with different chronic inflammatory rheumatismal affections for serological markers of Parvovirus B19 infection. All patients were Tunisians of both sexes, who presented at the service of Rheumatology of the Charles Nicolle Hospital, Tunis. One hundred blood donors were taken as controls. Specific Immunoenzyme Assays of the ELISA type (Biotrin International, France) were used to detect anti-Parvovirus IgG and IgM. On the other hand, viral DNA was sought by nested PCR in synovial fluid from 14 patients. The data obtained indicate that specific anti-Parvovirus B19 IgG was detectable in the sera of 80.7% of patients and 43% of controls. In contrast, none of the sera was found positive for specific IgM antibodies. Synovial fluid samples could be collected from 14 anti-Parvovirus B19 seropositive patients and were tested for the presence of viral DNA. None of the samples was found positive. The results of our serological study reinforce the hypothesis that Parvovirus B19 infection is associated with rheumatismal joint affections. However, the lack of detectable viral DNA in synovial fluid of the tested seropositive patients points to an indirect role of the virus in these joint disorders.

Germline specific point mutations in the gene encoding fibroblast growth factor receptor 3 (FGFR3) are associated with autosomal dominant human skeletal dysplasia and craniosynostosis syndromes. Mutations identical to the germinal activating mutations found in severe skeletal dysplasias have been identified in certain types of cancer: at low frequency in multiple myeloma and cervix carcinoma and at high frequency in bladder carcinoma. We analysed, by SSCP and sequencing, the prevalence of FGFR3 mutations in 116 primary tumours of various types (upper aerodigestive tract, oesophagus, stomach, lung and skin). The regions analysed encompassed all FGFR3 point mutations previously described in severe skeletal dysplasia and cancers. No mutations were detected in the tumour types examined, suggesting that FGFR3 mutations are restricted to a few tumour types, the evidence to date suggesting that they are very specific to bladder carcinomas.

In bacteria, double-strand DNA break (DSB) repair involves an exonuclease/helicase (exo/hel) and a short regulatory DNA sequence (Chi) that attenuates exonuclease activity and stimulates DNA repair. Despite their key role in cell survival, these DSB repair components show surprisingly little conservation. The best-studied exo/hel, RecBCD of Escherichia coli, is composed of three subunits. In contrast, RexAB of Lactococcus lactis and exo/hel enzymes of other low-guanine-plus-cytosine branch gram-positive bacteria contain two subunits. We report that RexAB functions via a novel mechanism compared to that of the RecBCD model. Two potential nuclease motifs are present in RexAB compared with a single nuclease in RecBCD. Site-specific mutagenesis of the RexA nuclease motif abolished all nuclease activity. In contrast, the RexB nuclease motif mutants displayed strongly reduced nuclease activity but maintained Chi recognition and had a Chi-stimulated hyperrecombination phenotype. The distinct phenotypes resulting from RexA or RexB nuclease inactivation lead us to suggest that each of the identified active nuclease sites in RexAB is involved in the degradation of one DNA strand. In RecBCD, the single RecB nuclease degrades both DNA strands and is presumably positioned by RecD. The presence of two nucleases would suggest that this RecD function is dispensable in RexAB.

Homologous recombination is needed to assure faithful inheritance of DNA material, especially under stress conditions. The same enzymes that repair broken chromosomes via recombination also generate biodiversity. Their activities may result in intrachromosomal rearrangements, assimilation of foreign DNA, or a combination of these events. It is generally supposed that homologous recombination systems are conserved, and function the same way everywhere as they do in Escherichia coli, the accepted paradigm. Studies in an 'older' microorganism, the gram-positive bacterium of the low GC branch Lactococcus lactis, confirm that many enzymes are conserved across species lines. However, the main components of the double strand break (DSB) repair system, an exonuclease/helicase (Exo/hel) and a short DNA modulator sequence Chi, differ markedly between bacteria, especially when compared to the gram-negative analogues. Based on our studies, a model is proposed for the functioning of the two-subunit Exo/hel of L. lactis and other gram-positive bacteria, which differs from that of the three-subunit E. coli enzyme. The differences between bacterial DSB repair systems may underlie a selection for diversity when dealing with DSB. These and other features of homologous recombination in L. lactis are discussed.

Background: In Escherichia coli, the Chi sequence modulates the activity of RecBCD, a powerful double-stranded (ds) DNA exonuclease/helicase. Chi attenuates RecBCD exonuclease activity and stimulates homologous recombination in an orientation-dependent manner. ChiEc is frequent and over-represented on its genome, which is thought to be related to its role in dsDNA break repair. We previously identified a Chi-like sequence (referred to as ChiLl) and an exonuclease/helicase in the Gram-positive bacterium Lactococcus lactis. ChiLl and RexAB are functional analogues of ChiEc and RecBCD., Results: We report that ChiLl attenuates RexAB exonuclease activity and stimulates homologous recombination in an orientation-dependent manner. Analysis of ChiLl distribution on the L. lactis chromosome reveals that ChiLl is frequent, highly over-represented, and oriented with respect to the direction of replication., Conclusion: Our results show that a single orientation of ChiLl interacts with RexAB. The active orientation is preferentially found on the replication leading strand of the L. lactis genome, consistent with a primary role of ChiLl in repair of dsDNA breaks at the replication fork. We propose that orientation-dependence of Chi activity and over-representation of Chi sequences on bacterial genomes may be conserved properties of exonuclease/helicase-Chi couples. Other properties of the Chi sequence distribution on the genomes might reflect more specific characteristics of each couple and of the host.

Castleman's disease (or angiofollicular lymph node hyperplasia) is a rare pathologic process of unknown etiology. Commonly, it is an unique tumor localized in the mediastinum (unicentric disease). Extrathoracic localizations are however reported with an increasing frequency. We describe two cases of mesenteric Castleman's disease. Diagnosis can be suggested by preoperative morphologic explorations (ultrasonography with Doppler, computed tomography scan, magnetic resonance imaging and angiography) and confrontation with clinical and biological data (young age, biological signs of inflammation). In the classical unique tumor of hyalin-vascular type, surgical removal allows definitive cure. Prognosis is poor in the plasma cell type, mostly in multicentric disease due to a high incidence of malignancy.

Objective: Five-year survival after simple resection of liver metastases from colorectal carcinoma ranges from 20 to 40%. The aim was to study the reliability and long term results of adjuvant intra-arterial chemotherapy after resection of colorectal liver metastases., Patients and Method: From 1991 to 1997, 30 patients after a complete resection of liver metastases from colorectal cancer were included (16 men, 14 women, mean age: 62 years). There were 2 stage I, 19 stages II, 2 stages III, 5 stages IV and 2 stages V according to Gayowski staging system. During laparotomy, a catheter was placed in the gastroduodenal artery in order to perfuse the proper hepatic artery. Chemotherapy included 5 Fluorouracil (12 mg/m2) and Leucovorin (200 mg/m2) and was administered once a week during six months. Mean follow-up was 52 months., Results: Adjuvant intra-arterial chemotherapy had to be interrupted before six months in 9 patients because leukopenia (n = 2), infection or obstruction of the catheter (n = 5), duodenal migration of the catheter (n = 1) and occurrence of multiple extrahepatic metastases (n = 1). No death was in relation with the method. Five-year survival rate was 41.8% for the global series. Five-year disease free survival rate was 21.4%. Causes of death were: hepatic recurrence only (n = 3), extrahepatic + hepatic recurrence (n = 4), extrahepatic recurrence (n = 2). Two patients died of another carcinoma (esophagus, ovary), without evidence of recurrence of the colorectal carcinoma. At the present, there is a recurrence in 4 living patients., Conclusion: Although the benefit on survival is not significant, these results suggest a longest time of remission in patients with adjuvant intra-arterial chemotherapy. Trials comparing and/or combining this method to intravenous chemotherapy should be proposed in patients after resection of colorectal liver metastases.

The availability of full genome sequences provides the bases for analyzing global properties of the genetic text. For example, oligonucleotide sequences that are over- or underrepresented can be identified by taking into account the overall genome composition and organization. One of the most overrepresented oligonucleotides in Escherichia coli is the Chi site, an octanucleotide that stimulates DNA repair by homologous recombination. Here we analyze the genomic distribution of Chi in E. coli and in the three other bacteria where a Chi sequence has been identified; note that Chi is a different sequence in each organism. For each bacterial genome, Chi sequences are frequent, regularly distributed, and overrepresented. This suggests that selection for Chi may have occurred during evolution to favor efficient repair of a damaged chromosome. Other characteristics of Chi distribution are not conserved and might reflect specific features of DNA repair in each host. The different sequence and characteristics of Chi in each microorganism suggest that selection for Chi occurred independently in different bacteria.

The Escherichia coli Chi site 5'-GCTGGTGG-3' modulates the activity of the powerful dsDNA exonuclease and helicase RecBCD. Genome sequence analyses revealed that Chi is frequent on the chromosome and oriented with respect to replication on the E. coli genome. Chi is also present much more frequently than predicted statistically for a random 8-mer sequence. Although it is assumed that Chi is ubiquitous, there is virtually no proof that its features are conserved in other microorganisms. We therefore identified and analysed the Chi sequence of an organism for which the full genome sequence was available, Haemophilus influenzae. The biological test we used is based on our finding that rolling circle plasmids provide a specific substrate for RecBCD analogues in different microorganisms. Unexpectedly, several related sequences, corresponding to 5'-GNTGGTGG-3' and 5'-G(G/C)TGGAGG-3', showed Chi activity. As in E. coli, the H. influenzae Chi sites are frequent on the genome, which is in keeping with the need for frequent Chi sites for dsDNA break repair of chromosomal DNA. Although statistically over-represented, this feature is less marked than that of the E. coli Chi site. In contrast to E. coli, the H. influenzae Chi motifs are only slightly oriented with respect to the replication strand. Thus, although Chi appears to have a highly conserved biological role in attenuating exonuclease activity, its sequence characteristics and statistical representation on the genome may differ according to the particular features of the host.

Studies of RecBCD-Chi interactions in Escherichia coli have served as a model to understand recombination events in bacteria. However, the existence of similar interactions has not been demonstrated in bacteria unrelated to E. coli. We developed an in vivo model to examine components of dsDNA break repair in various microorganisms. Here, we identify the major exonuclease in Lactococcus lactis, a Gram-positive organism evolutionarily distant from E. coli, and provide evidence for exonuclease-Chi interactions. Insertional mutants of L. lactis, screened as exonuclease-deficient, affected a single locus and resulted in UV sensitivity and recombination deficiency. The cloned lactococcal genes (called rexAB) restored UV resistance, recombination proficiency, and the capacity to degrade linear DNA, to an E. coli recBCD mutant. In this context, DNA degradation is specifically blocked by the putative lactococcal Chi site (5'-GCGCGTG-3'), but not by the E. coli Chi (5'-GCTGGTGG-3') site. RexAB-mediated recombination was shown to be stimulated approximately 27-fold by lactococcal Chi. Our results reveal that RexAB fulfills the biological roles of RecBCD and indicate that its activity is modulated by a short DNA sequence. We speculate that exonuclease/recombinase enzymes whose activities are modulated by short DNA sequences are widespread among bacteria.

In E. coli, lesions introduced by agents such as UV radiation, chemical agents, thymine starvation, lead to the induction of a series of bacterial fonctions called the "SOS response" (DNA reparation, mutagenesis, filamentation, prophages induction etc...). Genetics and biochemical study set up the evidences of a regulated mechanism. The central effector of this mechanism is the Rec A protéin. When a cell's DNA is damaged or its DNA replication is inhibited, an inducing signal is generated. The inducing signal reversebly activates a specific protease activity of Rec A which allows it to cleave the Lex A repressor. Thus inducing operons repressed by Lex A. These operons are implicated in DNA reparations and also in cellular division. A coordination between reparation and cellular division is thus established.