Chemoradiotherapy versus radiotherapy in patients with advanced nasopharyngeal cancer: phase III randomized Intergroup study 0099.

PURPOSE: The Southwest Oncology Group (SWOG) coordinated an Intergroup study with the participation of Radiation Therapy Oncology Group (RTOG), and Eastern Cooperative Oncology Group (ECOG). This randomized phase III trial compared chemoradiotherapy versus radiotherapy alone in patients with nasopharyngeal cancers. MATERIALS AND METHODS: Radiotherapy was administered in both arms: 1.8- to 2.0-Gy/d fractions Monday to Friday for 35 to 39 fractions for a total dose of 70 Gy. The investigational arm received chemotherapy with cisplatin 100 mg/m2 on days 1, 22, and 43 during radiotherapy; postradiotherapy, chemotherapy with cisplatin 80 mg/m2 on day 1 and fluorouracil 1,000 mg/m2/d on days 1 to 4 was administered every 4 weeks for three courses. Patients were stratified by tumor stage, nodal stage, performance status, and histology. RESULTS: Of 193 patients registered, 147 (69 radiotherapy and 78 chemoradiotherapy) were eligible for primary analysis for survival and toxicity. The median progression-free survival (PFS) time was 15 months for eligible patients on the radiotherapy arm and was not reached for the chemo-radiotherapy group. The 3-year PFS rate was 24% versus 69%, respectively (P < .001). The median survival time was 34 months for the radiotherapy group and not reached for the chemo-radiotherapy group, and the 3-year survival rate was 47% versus 78%, respectively (P = .005). One hundred eighty-five patients were included in a secondary analysis for survival. The 3-year survival rate for patients randomized to radiotherapy was 46%, and for the chemoradiotherapy group was 76% (P < .001). CONCLUSION: We conclude that chemoradiotherapy is superior to radiotherapy alone for patients with advanced nasopharyngeal cancers with respect to PFS and overall survival.

[Radiotherapy of breast cancer]. / Radiothérapie du cancer du sein.

In breast cancer, radiotherapy is an essential component of the treatment. After conservative surgery for an infiltrating carcinoma, radiotherapy must be systematically performed, regardless of the characteristics of the disease, because it decreases the rate of local recurrence and by this way, specific mortality. Partial breast irradiation could not be proposed routinely but only in very selected and informed patients. For ductal carcinoma in situ, adjuvant radiotherapy must be also systematically performed after lumpectomy. After mastectomy, chest wall irradiation is required for pT3-T4 tumours and if there is an axillary nodal involvement, whatever the number of involved lymph nodes. After neo-adjuvant chemotherapy and mastectomy, in case of pN0 disease, chest wall irradiation is recommended if there is a clinically or radiologically T3-T4 or node positive disease before chemotherapy. Axillary irradiation is recommended only if there is no axillary surgical dissection and a positive sentinel lymph node. Supra and infra-clavicular irradiation is advised in case of positive axillary nodes. Internal mammary irradiation must be discussed case by case, according to the benefit/risk ratio (cardiac toxicity). Dose to the chest wall or the breast must be between 45-50Gy with a conventional fractionation. A boost dose over the tumour bed is required if the patient is younger than 60 years old. Hypofractionation (42.5 Gy in 16 fractions, or 41.6 Gy en 13 or 40 Gy en 15) is possible after tumorectomy and if a nodal irradiation is not mandatory. Delineation of the breast, the chest wall and the nodal areas are based on clinical and radiological evaluations. 3D-conformal irradiation is the recommended technique, intensity-modulated radiotherapy must be proposed only in case of specific clinical situations. Respiratory gating could be useful to decrease the cardiac dose. Concomitant administration of chemotherapy in unadvised, but hormonal treatment could be start with radiotherapy.

[Early-stage endometrial cancer: Sentinel node or lymphadenectomy?]. / Cancer de l'endomètre au stade pécoce : ganglion sentinelle ou curage pelvien ?

The endometrial cancers are mainly discovered at an early stage justifying a less aggressive treatment. The therapeutic choices are today based on preoperative classifications themselves based on histo-prognostic factors of the tumor and its extension measured in MRI: consequently, lymph node dissection in case of low and intermediate risk cancer is not systematically achieved. But a number of patients have lymph node involvement finally, probably justifying an adapted surgical and adjuvant treatment. The technique of sentinel node would compensate the weaknesses of preoperative prognostic evaluation. This new operative technique needs to be precised and evaluated: the topics subject to discussion are the technical implementation, the definition of its quality standards and the management of its histological results especially in cases of low volume lymph node metastasis.

[How were used recommendations for endometrial carcinoma? Britain retrospective study]. / Application des recommandations dans la prise en charge du cancer de l'endomètre en pratique clinique. Étude rétrospective bretonne.

OBJECTIVE: To assess the use of French Cancer Institute recommendations for the diagnosis and treatment of endometrial cancer. METHODS: Retrospective observational study involving 137 patients with endometrial cancer between 2011 and 2013. RESULTS: Both MRI and pathological assessment with correct report as recommended were used for 66.4% of patients with endometrial cancer. For patients with correct preoperative assessment, 44.9% of patients were uncorrectly classified and upgraded on final pathological analysis of hysterectomy concerning lymph node involvement risk. These patients did not have confident surgical assessment, according this risk. CONCLUSION: To improve relevance of preoperative assessment in endometrial cancer, radiological and pathological expertise is required. However, even performed optimally, preoperative assessment does not allow correct risk stratification of lymph node involvement in endometrial cancer. This ineffective stratification leads to propose sentinel lymph node biopsy with hysterectomy in case of preoperative low risk endometrial cancer assessment.

Kinematic TKA using navigation: Surgical technique and initial results.

BACKGROUND: Kinematic alignment for total knee arthroplasty (TKA) may be one way of improving outcomes. Previous studies have either used patient-specific instrumentation, which adds cost, or standard instrumentation, which provides no intraoperative feedback on resection alignment. HYPOTHESIS: To determine if computer navigation could reproduce native patient anatomy and simplify ligament balance during TKA whilst giving satisfactory improvements in functional scores at early follow-up. MATERIALS AND METHODS: Computer navigation was used for kinematic distal femoral and proximal tibial cuts in 100 consecutive and unselected TKAs. Resections were modified only if measured angles fell outside a pre-defined safe range of combined coronal orientation within±3 degrees of neutral and/or independent femoral or tibial cuts within±5 degrees. Pre- and postoperative measurements of the hip-knee-ankle (HKA) angle, the lateral distal femoral angle (LDFA) and the medial proximal tibial angle (MPTA) were taken using long-leg standing radiographs. Clinical evaluation was with the WOMAC and KOOS scales. RESULTS: Mean follow-up was 2.4 years (range 1.0-3.7, SD 0.8). The mean pre-op LDFA was 2.1 degrees valgus (9.2 valgus to 3.7 varus, SD 2.5) and 1.8 degrees valgus post-op (5.7 valgus to 4.2 varus, SD 2.0) (P=0.41). The mean pre-op MPTA was 3.0 degrees varus (10.6 valgus to 10.2 varus, SD 3.2) and 2.4 degrees varus post-op (4.0 valgus to 6.8 varus, SD 2.2) (P=0.03). The mean WOMAC score improved from 49.4 (29-85, SD 12.8) to 24.7 (0-73, SD 16.5) (P<0.001) and the mean KOOS score from 37.1 (7.2-77.2, SD 13.0) to 65.1 (26.8-100, SD 16) (P<0.001). Five knees (5%) required additional ligament release, four with valgus OA and one with varus OA. Two knees (2%) required lateral retinacular release for patellar tracking. DISCUSSION: Computer navigation for kinematic TKA provides the operating surgeon with full control and feedback at each step, whilst also allowing partial correction of more extreme anatomy that might be unsuitable for recreation during TKA. This technique helps to preserve ligament isometry and produces satisfactory improvements in functional scores. LEVEL OF EVIDENCE: IV (retrospective case series review).

A phase II multicenter trial of hyperCVAD MTX/Ara-C and rituximab in patients with previously untreated mantle cell lymphoma; SWOG 0213.

BACKGROUND: Rituximab-hyper-CVAD alternating with rituximab-high-dose methotrexate and cytarabine is a commonly utilized regimen in the United States for mantle cell lymphoma (MCL) based on phase II single institutional data. To confirm the clinical efficacy of this regimen and determine its feasibility in a multicenter study that includes both academic and community-based practices, a phase II study of this regimen was conducted by SWOG. PATIENTS AND METHODS: Forty-nine patients with advanced stage, previously untreated MCL were eligible. The median age was 57.4 years (35-69.8 years). RESULTS: Nineteen patients (39%) did not complete the full scheduled course of treatment due to toxicity. There was one treatment-related death and two cases of secondary myelodysplastic syndrome (MDS). There were 10 episodes of grade 3 febrile neutropenia, 19 episodes of grade 3 and 1 episode of grade 4 infection. With a median follow-up of 4.8 years, the median progression-free survival was 4.8 years (5.5 years for those ≤ 65 years) and the median overall survival (OS) was 6.8 years. CONCLUSIONS: Although this regimen is toxic, it is active for patients ≤ 65 years of age and can be given both at academic centers and in experienced community centers.

Relationship between infection, inflammation and premature parturition in mares with experimentally induced placentitis.

REASONS FOR PERFORMING THE STUDY: Ascending placentitis results in premature birth and high foal mortality. By understanding how placentitis induces premature delivery, it may be possible to develop diagnostic markers and to delay premature delivery pharmacologically, thereby decreasing perinatal foal mortality. OBJECTIVE: To identify relationships between bacterial infection, inflammation and premature parturition in mares with experimentally induced placentitis. MATERIALS AND METHODS: Experiment 1: Concentrations of allantoic fluid prostaglandins (PGs) F2alpha and E2 were measured in 8 mares after intracervical inoculation with Streptococcus equi ssp. zooepidemicus (at Days 285-291 of gestation) until parturition and compared with controls (n = 4). Experiment 2: mRNA expression of interleukin (IL)-1beta, IL-6, tumour necrosis factor (TNF)-alpha and IL-8 in the chorioallantois from inoculated mares in Experiment 1 were compared with 7 mares that foaled normally. RESULTS: Bacterial inoculation resulted in 7 aborted fetuses and birth of one premature, viable foal. Infection was associated with inflammation of the chorioallantois in the region of the cervical star, isolation of bacteria and high concentrations of PGE2 and PGF2alpha in allantoic fluid obtained within 48 h of delivery (P = 0.04). Chorioallantois from all mares expressed mRNA for IL-8, TNF-alpha, IL-6 and IL-1beta. Experimentally infected mares expressed more mRNA for IL-6 (P = 0.003) and IL-8 (P = 0.009) in the cervical star region and more mRNA for IL-6 (P = 0.004) in tissues from placental horns than control mares. CONCLUSIONS AND CLINICAL RELEVANCE: Bacterial placentitis may result in liberation of cytokines from the chorioallantois and prostaglandin formation leading to abortion or birth of a precociously mature foal.

[Place of surgery before and after concurrent chemoradiotherapy for locally advanced cervical carcinoma: A retrospective study of 102 cases]. / Place de la chirurgie avant et après radiochimiothérapie des cancers du col localement évolués : à propos de 102 cas.

INTRODUCTION: The treatment of locally advanced cervical carcinoma of uterine cervix is based on concurrent chemoradiotherapy (CCR). The role of laparoscopic lymphadenectomy before CCR and hysterectomy after CCR is not consensual. PATIENTS AND METHODS: Retrospective multicentric study on 102 patients treated for locally advanced carcinoma of uterine cervix between 1999 and 2008. Disease-free survival and overall survival (OS) were studied. RESULTS: Stages were: stage IB 42%, II 47% and stage III and IVA 11%. All patients received CCR. Eighty-one patients had associated brachytherapy. Sixty-two patients underwent laparoscopic lymphadenectomy before CCR and 31 patients had also para-aortic lymphadenectomy. Eighty-two patients had hysterectomy after CCR. Forty-seven percent (29/62) of patients had a histologically proven pelvic lymph node involvement and 58% (18/31) had a histologically proven para-aortic lymph node involvement. There is no predictor of the presence of residual tumor on hysterectomy. The lymph node involvement before treatment and the presence of residual tumor on hysterectomy were poor prognostic factors on relapse-free survival (SSR) and OS. It has not been shown to benefit from surgery pre- or post-CCR on survival. CONCLUSION: Surgery can provide major prognosis factor and especially lymphadenectomy before CCR can improve the therapeutic strategy but does not demonstrate significant survival benefit.

Bevacizumab in combination with FOLFIRI chemotherapy in patients with metastatic colorectal cancer: an assessment of safety and efficacy in the province of Newfoundland and Labrador.

BACKGROUND: In 2005, bevacizumab was approved by Health Canada for patients with metastatic colorectal cancer (mCRC). Newfoundland and Labrador was one of the first Canadian provinces to fund this agent in combination with FOLFIRI (irinotecan, 5-fluorouracil, leucovorin) chemotherapy. In this analysis, the entire provincial bevacizumab sample for the first 2 years was assessed for overall safety and efficacy. METHODS: The medical records of 43 patients with mCRC who had received FOLFIRI with bevacizumab were identified and reviewed. The longitudinal data collection format that was adopted assessed occurrences of adverse events after each cycle of treatment. Toxicity outcomes such as gastrointestinal (GI) perforations, bleeding, diarrhea, myelosuppression, proteinuria, and venous thromboembolic events (VTEs) were collected and graded using the U.S. National Cancer Institute's Common Terminology Criteria for Adverse Events, version 3.0. Time to treatment failure (TTF) and overall survival (OS) were determined using the Kaplan-Meier method. RESULTS: Overall, the 43 study patients received 398 cycles of anticancer therapy (median: 6 cycles; range: 1-24 cycles). No gi perforations were identified. However, 4 bleeding events occurred (9.3%), 3 requiring permanent discontinuation of bevacizumab. Also, 6 grade 3 or 4 VTEs occurred (14.0%), 3 of which required a hospital admission. In addition, grades 3 and 4 diarrhea, febrile neutropenia, and proteinuria showed cumulative incidences of 11.6%, 2.3%, and 2.3% respectively. Median TTF was 6.3 months; median os was 24.4 months. CONCLUSIONS: Bevacizumab in combination with FOLFIRI appears to be well tolerated, and efficacy is consistent with trial reports. However, patients should be closely monitored to avoid potentially serious events such as bleeding and VTEs.

Advances in the diagnosis and treatment of chronic infectious and post-mating-induced endometritis in the mare.

CONTENTS: Rapid physical uterine clearance is paramount for fertility. Mares that are unable to clear the by-products of insemination or foaling quickly may develop post-mating-induced or acute endometritis. If endometritis is not promptly resolved, the infection can become chronic. Endometritis can be difficult to identify because clinical signs, ultrasonographic and laboratory findings can vary between uterine pathogens. Some micro-organisms are associated with an influx of neutrophils and fluid into the uterine lumen while others are associated with only heavy debris on cytological specimens. Identifying the inciting cause may require more than swabbing the endometrium. Culturing endometrial biopsy tissue or uterine fluids are more sensitive methods for identifying Escherichia coli than culture swab while endometrial cytology identifies twice as many mares with acute inflammation than uterine culture swab. While post-mating-induced endometritis is classically treated with uterine irrigation and ecbolics and acute endometritis is treated with either systemic or intra-uterine antibiotics, these therapies are not always effective in resolving chronic uterine inflammation or infections. Mucolytics can be used to break up mucus produced by an irritated endometrium, steroids can modulate the inflammatory response associated with insemination and buffered chelating agents can remove biofilm, a protective mechanism used primarily by gram-negative organisms and yeast to evade the host immune response.

Ascending placentitis in the mare: an update.

CONTENTS: Ascending placentitis is a common cause of premature birth, abortion and delivery of compromised, ill foals. Recent experimental models have investigated diagnostic procedures and treatment strategies in an attempt to improve live foal rate. Diagnostics such as transrectal and transabdominal ultrasonography are used to evaluate foetal well-being and placental separation, while measurement of plasma progestins or oestrogen identifies a stressed or hypoxic foetus. Treatment is directed at stopping spread of infection, maintaining uterine quiescence and blocking production of pro-inflammatory cytokines. It must be instituted early if a pregnancy is to be saved. Treatments include antibiotics, tocolytics and immunomodulators. Prompt, aggressive treatment with antibiotics has improved foal viability in experimental models of placentitis.

Notch signaling is not essential in sonic hedgehog-activated medulloblastoma.

Dysregulated signal transduction through the notch pathway has been noted in human and mouse medulloblastoma studies. Gamma secretase inhibitors (GSIs) impair notch signaling by preventing the cleavage of transmembrane notch proteins into their active intracellular domain fragments. Previous studies have shown that GSI treatment caused apoptosis and impaired medulloblastoma cell engraftment in xenograft systems. In this study, we used in vivo genetic and pharmacologic approaches to quantify the contribution of notch signaling to sonic hedgehog (shh)-activated mouse medulloblastoma models. In contrast to prior in vitro studies, pharmacologic inhibition of notch pathways did not reduce the efficiency of medulloblastoma xenotransplantation nor did systemic therapy impact tumor size, proliferation, or apoptosis in genetically engineered mouse medulloblastoma models. The incidence and pathology of medulloblastomas driven by the SmoA1 transgene was unchanged by the bi-allelic absence of Notch1, Notch2, or Hes5 genes. These data show that notch signaling is not essential for the initiation, engraftment, or maintenance of sonic hedgehog pathway-driven medulloblastomas.

Prognostic value of regulatory T cells, lymphoma-associated macrophages, and MUM-1 expression in follicular lymphoma treated before and after the introduction of monoclonal antibody therapy: a Southwest Oncology Group Study.

BACKGROUND: The purpose was to examine the prognostic impact of features of tumor cells and immune microenvironment in patients with follicular lymphoma treated with and without anti-CD20 monoclonal antibody therapy. PATIENTS AND METHODS: Tissue microarrays were constructed from archived tissue obtained from patients on three sequential Southwest Oncology Group (SWOG) trials for FL. All three trials included anthracycline-based chemotherapy. Anti-CD20 monoclonal antibodies were included for patients in the latter two trials. Immunohistochemistry was used to study the number and distribution of cells staining for forkhead box protein P3 (FOXP3) and lymphoma-associated macrophages (LAMs) and the number of lymphoma cells staining for myeloma-associated antigen-1 (MUM-1). Cox proportional hazards regression was used to evaluate the association between marker expression and overall survival (OS). RESULTS: The number or pattern of infiltrating FOXP3 cells and LAMs did not correlate with OS in sequential SWOG studies for FL. The presence of MUM-1 correlated with lower OS for patients who received monoclonal antibody but not for those treated with chemotherapy alone. CONCLUSIONS: Immune cell composition of lymph nodes did not correlate with OS in this analysis of trials in FL. The mechanism of the observed correlation between MUM-1 expression and adverse prognosis in patients receiving monoclonal antibody therapy requires confirmation.

Clinical and subclinical endometritis in the mare: both threats to fertility.

Endometritis, a major cause of mare infertility arising from failure to remove bacteria, spermatozoa and inflammatory exudate post-breeding, is often undiagnosed. Defects in genital anatomy, myometrial contractions, lymphatic drainage, mucociliary clearance, cervical function, plus vascular degeneration and inflamm-ageing underlie susceptibility to endometritis. Diagnosis is made through detecting uterine fluid, vaginitis, vaginal discharge, short inter-oestrous intervals, inflammatory uterine cytology and positive uterine culture. However, these signs may be absent in subclinical cases. Hypersecretion of an irritating, watery, neutrophilic exudate underlies classic, easy-to-detect streptococcal endometritis. In contrast, biofilm production, tenacious exudate and focal infection may characterize subclinical endometritis, commonly caused by Gram-negative organisms, fungi and staphylococci. Signs of subclinical endometritis include excessive oedema post-mating and a white line between endometrial folds on ultrasound. In addition, cultures of uterine biopsy tissue or of small volume uterine lavage are twice as sensitive as guarded swabs in detecting Gram-negative organisms, while uterine cytology is twice as sensitive as culture in detecting endometritis. Uterine biopsy may detect deep inflammatory and degenerative changes, such as disruption of the elastic fibres of uterine vessels (elastosis), while endoscopy reveals focal lesions invisible on ultrasound. Mares with subclinical endometritis require careful monitoring by ultrasound post-breeding. Treatments that may be added to traditional therapies, such as post-breeding uterine lavage, oxytocin and intrauterine antibiotics, include lavage 1-h before mating, carbetocin, cloprostenol, cervical dilators, systemic antibiotics, intrauterine chelators (EDTA-Tris), mucolytics (DMSO, kerosene, N-acetylcysteine), corticosteroids (prednisolone, dexamethasone) and immunomodulators (cell wall extracts of Mycobacterium phlei and Propionibacterium acnes).

Relationships between uterine culture, cytology and pregnancy rates in a Thoroughbred practice.

Endometrial cytology and culture specimens (n=2123) were collected concurrently with a guarded uterine culture instrument from 970 mares (738 barren, 1230 foaling and 155 maiden mares) during three breeding seasons (2001-2004). Results were compared to the 28-d pregnancy rate for the cycle from which the samples were taken. Cytological smears were evaluated for inflammation at x100 and graded as: not inflammatory (0-2 neutrophils/field), moderate inflammation (2-5 neutrophils/field), severe inflammation (>5 neutrophils/field), or hypocellular (scant epithelial cells and no neutrophils). Uterine culture swabs were plated within 6h, incubated for 72 h and results determined at 24, 48, and 72 h. Approximately, 20% (n=423) cytology samples were positive for inflammation (>2 neutrophils), whereas approximately 11% (n=231) of cultures had microorganisms recovered. A majority (64%) of the positive cultures (147/231) had inflammation on cytology smears. Streptococcus equi subsp. zooepidemicus was associated with more positive cytology results than coliforms (P<0.01). Mares with positive cytology or culture had lower pregnancy rates than mares with normal findings (P<0.01). Lowest pregnancy rates were recorded for mares with severe endometrial inflammation (21%, versus moderate inflammation 48%). Isolation of a microorganism from mares with endometrial inflammation was not associated with a further reduction in pregnancy rates. In barren, foaling and maiden mares, cytology was positive in 28, 17, and 5%, respectively, and culture was positive in 12.2, 11.1, and 3.2%. Foaling and maiden mares had higher pregnancy rates than barren mares (62, 69, and 44%, respectively, P<0.001). In conclusion, a positive cytology was twice as common as a positive culture, and isolation of microorganisms was associated with reduced pregnancy rates, even in the apparent absence of inflammation.

[Antineutrophil cytoplasmic antibodies in cystic fibrosis. Frequency and significance]. / Anticorps anticytoplasme des polynucléaires neutrophiles au cours de la mucoviscidose. Fréquence et signification.

UNLABELLED: Some immune system abnormalities have been reported in cystic fibrosis, particularly the presence of antineutrophil cytoplasmic antibodies (ANCAs). The purpose of this study was to determine the frequency of these antibodies in a population of patients with cystic fibrosis and to assess their relationship with the disease progression. POPULATION AND METHODS: This retrospective study looked for the presence of these antibodies in sera from 64 patients (30 boys and 34 girls) aged one to 29 years. All patients were followed up within the Cystic Fibrosis Center of the University Hospital of Angers. The serum samples were collected in 2001 during the yearly check-up to evaluate disease status. RESULTS: Seven of the 64 patients presented the antibodies. Univariate analysis showed that these patients were significantly older and more often chronically infected with Pseudomonas aeruginosa than the other patients. They also scored significantly more poorly on pulmonary radiography and showed significantly higher IgG and CRP. Multivariate analysis revealed that the two following independent factors were associated with the presence of ANCAs: chronic P. aeruginosa infection and high IgG level. CONCLUSION: This work confirms the abnormally high frequency of antineutrophil cytoplasmic antibodies in patients with cystic fibrosis. These antibodies were observed in the sickest patients with severe infection status. They reflect the impact of inflammatory processes in the pathogenesis of the disease. Detection of these antibodies might be an indication for intensified treatment of bronchial infections.

[Effect of oral biphosphonates in patients with cystic fibrosis and low bone mineral density]. / Efficacité des biphosphonates oraux sur la déminéralisation osseuse des patients atteints de mucoviscidose.

UNLABELLED: Disturbances in bone mineralization are frequent in cystic fibrosis but few studies have focused on the use of biphosphonates in this indication, and none on the use of oral etidronate. We report our experience using this latter treatment. METHODS: The study was retrospective and included five children and three adults with cystic fibrosis (six males and two females) aged seven to 30 years with Z-scores for lumbar bone density lower than -2 SD after one year of calcium (1 g/day) and vitamin D (900 UI/day and 300,000 UI/6 months) supplementation. All were treated during one year with etidronate: four courses of 15 days (one course per trimester) with doses ranging from 4 to 8 mg/kg per day. Calcium and vitamin D supplementation was continued between the etidronate treatment course. Total body and lumbar bone mineral density (BMD) were measured three times: at the beginning and the end of the year of calcium and vitamin D supplementation and at the end of the year of supplementation plus the four courses of etidronate treatment. RESULTS: The increase in BMD in absolute value (g/cm2) and in Z-score was significantly higher (P <0.05) after the year of combined supplementation and etidronate treatment (total body g/cm2: 3+/-1%, Z-score: 2+/-1% and lumbar spine g/cm2: 6+/-5%, Z-score: 3+/-4%) than after supplementation alone (total body g/cm2: -1+/-3%, Z-score: -4+/-3% and lumbar spine g/cm2: -1+/-3%, Z-score: -4+/-4%). Supplementation alone improved the total BMD in only one patient and the lumbar BMD in three, whereas after etidronate treatment the total and lumbar BMD were improved in the eight patients. None of the patients presented with side effects that could be attributed to the treatment. CONCLUSION: Oral etidronate treatment is well-tolerated and capable of improving bone mineralization in patients with cystic fibrosis. Further work will be necessary to determine the optimal dosage and the optimal frequency for the treatment series.

[Prolonged motor blockade after combined epidural and general anaesthesia for oncologic gynaecological surgery]. / Bloc moteur prolongé après anesthésie péridurale combinée à l'anesthésie générale pour chirurgie gynécologique carcinologique.

The case described is a patient submitted to an oncologic gynaecological surgery under combined epidural and general anaesthesia. The anaesthesia involved complications, a prolonged motor blockade for up to 9 h whereas recommended doses had been respected. A few later after a magnetic resonance imaging that did not showed any extradural haematoma, full recovery occurred. The combined epidural and general anaesthesia was approved as an interesting technique for both per and postoperative analgesia, but also for postoperative rehabilitation. Nevertheless, for older patients, inhalational anaesthetics and opioids have to be decreased during the intervention, moreover local anaesthetics doses for epidural anaesthesia have to be reduced too, in order to control motor blockade duration.

Immobilization of arsenite and ferric iron by Acidithiobacillus ferrooxidans and its relevance to acid mine drainage.

Weathering of the As-rich pyrite-rich tailings of the abandoned mining site of Carnoulès (southeastern France) results in the formation of acid waters heavily loaded with arsenic. Dissolved arsenic present in the seepage waters precipitates within a few meters from the bottom of the tailing dam in the presence of microorganisms. An Acidithiobacillus ferrooxidans strain, referred to as CC1, was isolated from the effluents. This strain was able to remove arsenic from a defined synthetic medium only when grown on ferrous iron. This A. ferrooxidans strain did not oxidize arsenite to arsenate directly or indirectly. Strain CC1 precipitated arsenic unexpectedly as arsenite but not arsenate, with ferric iron produced by its energy metabolism. Furthermore, arsenite was almost not found adsorbed on jarosite but associated with a poorly ordered schwertmannite. Arsenate is known to efficiently precipitate with ferric iron and sulfate in the form of more or less ordered schwertmannite, depending on the sulfur-to-arsenic ratio. Our data demonstrate that the coprecipitation of arsenite with schwertmannite also appears as a potential mechanism of arsenite removal in heavily contaminated acid waters. The removal of arsenite by coprecipitation with ferric iron appears to be a common property of the A. ferrooxidans species, as such a feature was observed with one private and three collection strains, one of which was the type strain.

24-hour secretion patterns of plasma oestradiol 17beta in pony mares in late gestation.

The mare exhibits nocturnal uterine contractions in the last 6 days of gestation. It is hypothesized that estradiol 17beta (O17beta) may be associated with the nightly increase in uterine contractions. The 24-h secretion pattern of plasma O17beta was measured in 3 pony mares in late gestation to identify changes in release as the mare neared parturition. Blood was collected weekly at 08:00 hours beginning on day 240 and every third day from day 330 until delivery. Serial blood samples were collected from each mare every 30-min for 24-h beginning on gestation day 310 and every sixth day thereafter until parturition. Concentrations of O17beta were elevated at night with lowest concentrations occurring directly before sunset (p < 0.01). The natural log of the variance was increased at sunset (p < 0.01) and was decreased during the 6-h period immediately after sunrise. This pattern was especially evident in the 6 days that preceded parturition. The contrast between nocturnal and daytime concentrations of O17beta in the last 6 days of gestation may contribute to night-time delivery in the mare.