Search

In less than ten years, two very serious viral hepatic diseases have spread through Leporidae populations (rabbits and hares) in numerous countries. In May 1989, the Office International des Epizooties designated this new disease of rabbits "viral haemorrhagic disease" and entered it as a List B disease in the International Animal Health Code. Clinically, the disease is very similar to the European brown hare syndrome. However, numerous uncertainties prevail today on the true nature of the viruses of the two species. Although they are related, the viruses appear to be different and cross infection between species has given contradictory results. Hepatitis of Leporidae have probably existed in Europe for several years, although their viral aetiology has been demonstrated only recently. The acute form has occurred in hares in Northern Europe since approximately 1980, while the inapparent (or ignored) form has been present in rabbits in Czechoslovakia since 1975. These diseases of Leporidae are true viral hepatitis which, in their fulminating forms, bear a remarkable resemblance to human viral hepatitis (B and non-A non-B) with regard to clinical symptoms, pathological lesions and mode of transmission. The dominant faecal-oral transmission observed for types A and E hepatitis would explain the particular susceptibility of family-kept rabbits, as they are fed potentially contaminated fodder. As the clinically similar fulminating hepatitis in human beings is caused by a diversity of viruses (both RNA and DNA), the disease in Leporidae might also be caused by different viruses.(ABSTRACT TRUNCATED AT 250 WORDS)

Forty-three patients with nonmetastatic inflammatory breast carcinoma have been treated by initial doxorubicin, 5-fluorouracil, and cyclophosphamide (FAC) combination chemotherapy. After three chemotherapy cycles, responding patients underwent surgery. Chemotherapy was then completed for nine cycles of FAC followed by locoregional radiation therapy. All patients received tamoxifen 40 mg/day for 1 year from the time of diagnosis. Thirty-eight patients (88%) had a clinical response to chemotherapy and underwent surgery. On histologic examination 17 patients had a residual tumor mass less than 1 cm diameter or a complete tumor disappearance; lymph nodes dissection was negative in 15 patients. With a median follow-up of 48 months, the predicted 5-year disease-free survival (DFS) is 48% (median DFS, 46 months). Analysis of prognosis factors shows that age, menopausal status, and histologic grade have no predictive value. The DFS and overall survival were significantly improved by the presence of hormonal receptors and a low number of positive lymph nodes (less than 4) at surgery. The most significant prognosis factor was the residual tumor mass after initial chemotherapy with an 80% predicted 5-year DFS for the responding patients versus 30% for the no responding patients (P less than 0.001).

Effets des conditions d’ambiance et de l’apport d’additif de type prébiotiques sur les performances de croissance et l’état sanitaire de dindons mâles. 7. Journées de la Recherche Avicole

International audience; The identification of genes as markers for chromosome aberrations in specific tumors might facilitate oncogenesis mechanism comprehension, cancer detection, prediction of clinical outcomes, and response to therapy. Previous physiologic and oncologic data identified the TWIST gene as a marker for mesodermal derivative and bone tissue differentiation, but its contribution to bone malignancies has not been investigated. In the present study, search for genomic alterations in high-grade pediatric osteosarcomas was focused on the 7p21 region, and more specifically on the TWIST gene. In a cohort of 74 patients, we observed by allelotyping that 31 of 68 informative tumors were rearranged at the TWIST locus. Among them, analysis by quantitative PCR (QPCR) revealed that, surprisingly, mostly deletions (22/68), but also amplifications (9/68), of the TWIST gene were detected. Furthermore, deletions at TWIST were statistically correlated to other molecular abnormalities, like alterations at the APC or c-kit loci, as well as to clinical features such as a poor outcome. This work shows that the TWIST gene seemed to be involved in high-grade pediatric osteosarcomas and is a new marker with a possible initial predictive value.

National audience

The two main complications of severe chronic neutropenia are fatal sepsis and myelodysplasia/acute leukemia (MDS/AL). Granulocyte colony-stimulating factor (G-CSF) therapy has significantly reduced the frequency and severity of infections, but its possible influence on the risk of malignancy is not known.The French Severe Chronic Neutropenia (SCN) Registry has prospectively collected data since 1994 on 231 patients with various forms of SCN, namely severe congenital neutropenia (n=101), cyclic neutropenia (n=60), glycogen storage disease type Ib (GSDIb) (n=15) and Shwachman-Diamond syndrome (SDS)(n=55). The median overall follow-up is 11.1 years. Parameters of exposure to G-CSF therapy, such as the time averaged dose, follow up after first use of G-CSF, and the cumulative dose, have been recorded.Eight septic deaths occurred, of which 6 among patients with severe congenital neutropenia and 2 in patients with cyclic neutropenia; none of these 8 patients was receiving G-CSF therapy. No septic deaths occurred during G-CSF therapy. Thirteen cases of MDS/AL were recorded. The cumulative incidence of MDS/AL was 2.7% (SD 1.3%) at 10 years and 8.1% (SD 2.7%) at 20 years.Risk factors for MDS/AL were the diagnostic category, the severity of neutropenia, younger age at diagnosis, and strong exposure to G-CSF. MDS/AL only occurred in patients with severe congenital neutropenia and SDS. Owing to their particular susceptibility to infections, patients with severe congenital neutropenia had the strongest exposure to G-CSF; the risk of leukemia increased with the degree of G-CSF exposure in this subgroup.

Purpose: To evaluate a strategy aimed at avoiding radiotherapy during first-line treatment of children with progressive optic pathway tumors (OPT), by exclusively administering multiagent chemotherapy during 16 months. Patients and Methods: Between 1990 and 1998, 85 children with progressive OPT were enrolled onto this multicenter nationwide trial. Chemotherapy alternating procarbazine plus carboplatin, etoposide plus cisplatin, and vincristine plus cyclophosphamide was given every 3 weeks. At the time of relapse or progression, second-line chemotherapy was authorized before recourse to radiotherapy. Results: Objective response rate (partial response [PR] + complete response [CR]) to chemotherapy was 42%. Five-year progression-free survival (PFS) and overall survival rates were 34% and 89%, respectively. The 5-year radiotherapy-free survival rate was 61%. In the multivariate analysis of the 85 patients that entered onto the study, factors associated with the risk of disease progression were age younger than 1 year at diagnosis (P = .047) and absence of neurofibromatosis type 1 (P = .035). In the multivariate analysis of the 74 patients that remained on study after the first cycle of chemotherapy, factors associated with the risk of disease progression were age younger than 1 year at diagnosis (P = .0053) and no objective response to chemotherapy (P = .0029). Three-year PFS was 44% in infants ≤ 1 year versus 66% in children older than 1 year. Three-year PFS was 53% in the absence of an objective response to chemotherapy versus 68% after a PR or CR. Conclusion: A significant proportion of children with OPT can avoid radiotherapy after prolonged chemotherapy. Deferring irradiation with chemotherapy protocols did not compromise overall survival of the entire population or visual function.

BACKGROUND Neuroblastoma (NB) occurs rarely during adolescence, and information is scarce on its characteristics and clinical course in this age group. METHODS Patients with NB who were included in the Italian Neuroblastoma Registry were considered for the current study. The clinical characteristics and survival of adolescents (age at diagnosis between 10 yrs and 18 yrs) were compared with those of children (ages 1–9 yrs). Infants (age < 1 yr) were excluded because of their well known favorable clinical course. RESULTS Between 1116 children and 53 adolescents who were evaluated, no differences were documented with regard to the primary tumor site and the prevalence of advanced stage at diagnosis. If only patients with Stage IV NB were considered, then adolescents were less likely to be diagnosed with bone/bone marrow metastases (77%) compared with children (94%; P = 0.038), but adolescents were more likely to have metastases at unusual sites, such as the lung parenchyma or the central nervous system (23% vs. 7%, respectively; P = 0.005). With regard to biologic characteristics, adolescents did not differ significantly from children, although they always had a lower prevalence of unfavorable markers. In particular, MYCN amplification was documented in 21% of children and in 11% of adolescents (P = 0.173). At age 10 years, adolescents had a 20% overall survival rate and a 22% event-free survival rate. Adolescents who had resectable disease had a 73% overall survival rate, which was worse compared with the rate among children with the same disease stage (89%), although the difference did not reach statistical significance (P = 0.159). No differences in survival were observed among patients with Stage IV NB, and adolescents had a probability of survival almost identical to that among children (6% vs. 16%, respectively; P = 0.481). However, when the analysis was restricted to events that occurred after patients developed a recurrence, even if the final outcome was poor for both groups, the difference was statistically significant (P = 0.022) mostly because of the more indolent disease course observed among the adolescents. This effect was even more evident for patients with Stage IV NB. When the 6-year cut-off point was used to separate children from adolescents, a significantly worse overall survival rate (P = 0.036) was documented for adolescents who had resectable disease (81% vs. 93% in children). CONCLUSIONS NB in adolescents had clinical and biologic characteristics similar to those observed among children. The clinical course of NB probably is correlated significantly with age at diagnosis, but information is scarce on the role of the biologic risk factors in this age group. The authors were able to identify a group of patients with a cut-off age between 6 years and 10 years that had a more indolent course but a worse prognosis. Cancer 2006. © 2006 American Cancer Society.

The EORTC Children Leukemia Group (CLG) is part of the offspring of the EORTC Hemopathies Working Party which in 1978 split into a paediatric and to an 'adult' branch. At that time, the Berlin-Frankfurt-Munster (BFM) designed by H. Riehm for acute lymphoblastic leukaemia (ALL) appeared much more efficacious than all others and the CLG decided to adapt that treatment strategy for its own clinical trials. The main results of these may be summarised as follows:for standard risk patients, the deletion of cyclophosphamide from consolidation and reconsolidation courses does not jeopardise the patient's outcomefor medium- and high-risk patients receiving high-dose methotrexate (MTX), cranial radiotherapy is superfluouswith the dose scheduling of the BFM regimen, E-Coli L-Asparaginase is more efficacious than Erwinia L-Asparaginasethe addition of monthly intravenous (i.v.) 6-mercaptopurine to conventional maintenance chemotherapy is detrimentalthe assessment by quantitative polymerase chain reaction (PCR) of minimal residual disease at completion of induction is feasible in a cooperative setting and can be used as a powerful and independent prognostic factor. The CLG also conducted clinical studies of acute myeloblastic leukaemia. Since 1989, lymphoblastic non-Hodgkin's lymphomas have been treated within the ALL trials. The CLG collaborates with other Groups within the I-BFM Study Group and participants in the meta-analytic studies conducted by the Oxford team by the Oxford Children ALL Collaborative Group.

A prospective cohort study was conducted in the Brittany region to identify the risk factors related to foot-pad dermatitis (considered an indicator of animal well-being) in chicken and turkey broilers reared under commercial conditions. Factors related to the shed, equipment, litter management and stocking density were recorded; the dependent variable was the prevalence of lesions observed on the slaughterhouse chain. Lesions were scored from 0 (no lesion) to 3 (severe lesion). Our survey lasted from May 1999 to October 2000. Fifty flocks of chicken broilers (15 farms), 27 flocks of female turkey broilers (21 farms) and 41 flocks of male turkey broilers (27 farms) were surveyed. In chicken broilers, 10% of flocks were of high quality (80% of birds with score 0) and this was related to the use of concrete floors with a thin layer of wood shavings. In turkey broilers, 48% of female and 46% of male flocks were of bad quality (>10% of birds with score 3). A poor fan ventilation system ( 3 /h/kg) was a significant risk factor. Turkey flocks of high quality were not observed. Stocking density had no influence on the prevalence of foot-pad dermatitis. We concluded that it is possible under high commercial stocking densities to have flocks with a low prevalence of foot-pad dermatitis in chicken broilers, whereas it is not in turkey broilers. Hence in chicken broilers, implementing a monitoring system based on the observation of foot-pad dermatitis prevalence at slaughter appears to be more appropriate than to legislate stocking density. In turkey broilers, it would probably be necessary either to reduce the stocking density drastically or to investigate new systems of floor drainage.

International audience

Two myxoma virus-rabbit hemorrhagic disease virus (RHDV) recombinant viruses were constructed with the SG33 strain of myxoma virus to protect rabbits against myxomatosis and rabbit viral hemorrhagic disease. These recombinant viruses expressed the RHDV capsid protein (VP60). The recombinant protein, which is 60 kDa in size, was antigenic, as revealed by its reaction in immunoprecipitation with antibodies raised against RHDV. Both recombinant viruses induced high levels of RHDV- and myxoma virus-specific antibodies in rabbits after immunization. Inoculations by the intradermal route protected animals against virulent RHDV and myxoma virus challenges.

In order to protect domestic and wild rabbits against RVHD, we constructed a recombinant vaccinia-RHDV virus, using the Copenhagen strain of the vaccinia virus. This recombinant virus expressed the RHDV capsid protein (VP60). Analysis of the expressed product showed that the recombinant protein, which is 60 kDa in size, was antigenic as revealed by its reactions in immunoprecipitation and indirect immunofluorescence with the antibodies raised against RHDV. The recombinant virus induced high level of RHDV specific antibodies in rabbits following immunization. Inoculations by both the intradermal and oral routes allow protection of animals against a challenge with virulent RHDV.

Over 11 years we treated 30 osteosarcomas: 20 of them were high grade non metastatic osteosarcomas of the lower limb, which were treated by neoadjuvant chemotherapy (Rosen T10, or OS 87 protocol of the French Society for Pediatric Oncology).There were 12 males and 8 females; the mean age was 19 years (range 12-51). The site of the tumor was the femoral neck (1 case), femoral diaphysis (2 cases), distal femur (12 cases), proximal tibia (4 cases), distal tibia (1 case), 3 were IIA and 17 IIB according to Enneking system. Conservative treatment was performed in 17 cases: there were 12 knee prostheses, 4 allografts and 1 knee arthrodesis with allograft.a) Surgical complications: Mechanical complications occurred in 10 patients. The function was preserved 8 times. In 2 patients the knee became stiff. An infection occurred in 3 patients: a conservative treatment was possible in 2 of them with a fair result. In the third case, an above-the-knee amputation had to be done. b) Functional results were studied according to Enneking rating. 14 arthroplasties (12 done as first surgical treatment and 2 after mechanical complication) had a 68, 19 score. c) Oncologic results: 8 patients were good respondents and 12 patients were bad respondents to chemotherapy according to Huvos grading. One local relapse was observed which could be treated by mean of a second chemotherapy and a prosthetic reconstruction. The patient is still alive and disease-free at 7 years (9 years after the diagnosis of the osteosarcoma). 5 patients had distant metastasis (lung, bones, and brain). One out of 5 was good respondent and 4 out of 5 are presently dead. Using Kaplan Meier statistical analysis, the overall survival wzs 76.8 per cent and the event-free survival was 67.4 per cent at 80 months.We preferred a simple prosthetic reconstruction without osseous sleeve or an intercalary allograft if possible: these procedures allow the patient very rapid autonomy to have despite a prolonged chemotherapy.

We report a case of local recurrence after a limb salvage procedure for high grade osteosarcoma. We carried out a second salvage operation because the lesion was small, there were no distant metastases, the patient had initially responded to chemotherapy and was able to receive more drugs. She is still alive, well and free of disease more than 6 years after the second operation, and 9 years after the diagnosis was made. Amputation is not always needed for every case of recurrence.

The present study evaluated the clinical efficacity and tolerability of the subcutaneous (SC) administration of lenograstim, a glycosylated form of rHuG-CSF identical to human G-CSF, in the treatment of congenital agranulocytosis. Assessment criteria included neutrophil response and response stability, incidence and severity of infection and gingivostomatitis and quality of life. Lenograstim, at induction dosages of 5 (n = 9), 10 (n = 2) or 20 (n = 1) microgram/kg/day SC, produced neutrophil recovery in all of 12 children with congenital agranulocytosis. There was a median delay of 7 days to recovery after establishment of the effective induction dose. Whereas this dosage maintained a stable neutrophil response in 7 patients, the remaining 5 required dosage increases and dose reduction during maintenance therapy was not possible in these 5 cases. Among 4 patients stabilised at a dosage of 5 micrograms/kg/day, in 2 cases a lower minimum effective dose of 2 micrograms/kg/day was attained over the maintenance phase. Administration of twice the daily dose of lenograstim on alternate days was feasible in 3 of 8 patients. Lenograstim therapy reduced the incidence of infection and hospitalisation for infection relative to the prestudy period, while in 6 of 9 cases there was complete recovery from gingivostomatitis. Only one patient discontinued treatment on account of adverse events. Finally, perceived health and disease related symptoms showed a significant (p0.001) amelioration in the course of the study. Thus, lenogastrim produced sustained neurotrophil recovery in patients with congenital agranulocytosis, decreased the incidence and severity of infection and improved the quality of life.

Bone marrow transplantation (BMT) is the last chance of recovery for some children suffering from malignant hemopathy or congenital blood disease. BMT with related donor radically alters previous family relationships: each member of the nuclear family becomes actively involved. Parents and siblings all undergo HLA typing. Only 30% of those who would benefit from bone marrow transplantation are lucky enough to have an HLA matched related donor, brother or sister. Our retrospective study concerned related donors and their parents. This paper reports the parents study. It was carried out at Strasbourg University Hospital. Parents were invited to speak about the child's illness, the graft reasons and their own position to regarding the choice of donor. Semi-structured interviews were used and their content analysed. The results highlight the expression by the parents of the need to maintain some control over the action which will save their child and establish an other gift system to keep their parental status.

Forty-three children with malignant diseases who received 48 totally implanted venous accesses (TIVA) were retrospectively analyzed. More than half the patients had acute leukemia. Mean age was 6 years 10 months. Mean duration of use of the TIVA was 473 +/- 50 days (range 28 to 1,285 da; median 424 days). Removal of the TIVA was required because of an adverse event in 33% of cases. Main reasons for removal included infection (22.9%), thrombosis (6.25%), and catheter dysfunction (4.16%). Catheter-related infections were most often due to staphylococci (90%), especially S. epidermidis (63%). Infection rate was 0.48 per 1,000 patient-days. Flushing with a vancomycin-heparin solution can be expected to decrease this rate. Selection of the implantation site is discussed. In children under 6 years of age, the cephalic vein and external jugular vein are often frail or absent and are therefore less appropriate than the internal jugular vein or subclavian vein.

The authors report a case of rhabdomyosarcoma in a 17 year old boy which recurred after combination chemotherapy and radical prostatectomy, followed by death of the patient due to haematological complications of second-line chemotherapy. The diagnosis of these rhabdomyosarcomas is facilitated by the various immunohistochemical stains now available. Chemotherapy is undeniably effective and, combined with surgery and radiotherapy, ensures a 5-year survival of 47% to 93% depending on the stage. The first-line chemotherapy avoids the need for radiotherapy in the early stages and allows less mutilating surgical procedures, while maintaining the survival rate.

The causative agent of rabbit viral haemorrhagic disease (VHD) was purified by CsCl density gradient centrifugation from liver homogenates of rabbits infected with a strain of VHD virus isolated in France. Electron microscopy observations revealed that the virions were icosahedral with a diameter of 33-35 nm, and with an average buoyant density of 1.33. Structural proteins were investigated by SDS-polyacrylamide gel electrophoresis and western blotting. The results indicated the presence of a major structural protein of 64 kDa and other minor proteins of molecular weight of 43, 36 and 32 kDa, the last presumably resulting from the proteolytic degradation of VP 64. These results correspond with the description made by the different authors who identify the VHD virus as a member of the Caliciviridae family.

In less than ten years, two very serious viral hepatic diseases have spread through Leporidae populations (rabbits and hares) in numerous countries. In May 1989, the Office International des Epizooties designated this new disease of rabbits "viral haemorrhagic disease" and entered it as a List B disease in the International Animal Health Code. Clinically, the disease is very similar to the European brown hare syndrome. However, numerous uncertainties prevail today on the true nature of the viruses of the two species. Although they are related, the viruses appear to be different and cross infection between species has given contradictory results. Hepatitis of Leporidae have probably existed in Europe for several years, although their viral aetiology has been demonstrated only recently. The acute form has occurred in hares in Northern Europe since approximately 1980, while the inapparent (or ignored) form has been present in rabbits in Czechoslovakia since 1975. These diseases of Leporidae are true viral hepatitis which, in their fulminating forms, bear a remarkable resemblance to human viral hepatitis (B and non-A non-B) with regard to clinical symptoms, pathological lesions and mode of transmission. The dominant faecal-oral transmission observed for types A and E hepatitis would explain the particular susceptibility of family-kept rabbits, as they are fed potentially contaminated fodder. As the clinically similar fulminating hepatitis in human beings is caused by a diversity of viruses (both RNA and DNA), the disease in Leporidae might also be caused by different viruses.(ABSTRACT TRUNCATED AT 250 WORDS)

The value of MRI in evaluating tumors of the musculoskeletal system has been previously noted by many authors; T.J. Brady et al. (1983), W.D. Zimmer et al. (1985), A.M. Aisen (1986), B. Roger (1986) and D. Vanel et al. (1987). Our purpose is to present an original observation with MRI follow-up in osteogenic sarcoma and to discuss the findings.

Forty-three patients with nonmetastatic inflammatory breast carcinoma have been treated by initial doxorubicin, 5-fluorouracil, and cyclophosphamide (FAC) combination chemotherapy. After three chemotherapy cycles, responding patients underwent surgery. Chemotherapy was then completed for nine cycles of FAC followed by locoregional radiation therapy. All patients received tamoxifen 40 mg/day for 1 year from the time of diagnosis. Thirty-eight patients (88%) had a clinical response to chemotherapy and underwent surgery. On histologic examination 17 patients had a residual tumor mass less than 1 cm diameter or a complete tumor disappearance; lymph nodes dissection was negative in 15 patients. With a median follow-up of 48 months, the predicted 5-year disease-free survival (DFS) is 48% (median DFS, 46 months). Analysis of prognosis factors shows that age, menopausal status, and histologic grade have no predictive value. The DFS and overall survival were significantly improved by the presence of hormonal receptors and a low number of positive lymph nodes (less than 4) at surgery. The most significant prognosis factor was the residual tumor mass after initial chemotherapy with an 80% predicted 5-year DFS for the responding patients versus 30% for the no responding patients (P less than 0.001).

The authors reported one documented observation of a deep-frozen, non irradiated, intercalary allograft; it was perforated by drilling and then fixed by a blade plate. This allograft was removed 27 months after its implantation. Histological examination of the removed bone graft showed newly formed mature bone which developed near preexisting devitalized bone. The external cortex was also revitalized and reossified close to the periosteum, as it was previously reported. But osteogenesis filled all the paths of the perforations and extended to the haversian canals located in the vicinity of the perforations. The authors conclude that cortical perforations induce both cortical and medullary osteogenesis of the graft. If osteogenesis is observed in the whole medullary canal, it is more focal and located in the vicinity of the holes in the cortex.