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Resume Nous rapportons le cas d’un patient de 68 ans presentant une encephalite a anticorps anti-Ma2 responsable d’une narcolepsie secondaire. Le patient presentait une somnolence diurne excessive persistante malgre la ventilation nocturne en pression positive continue dans le cadre de son syndrome d’apnees obstructives du sommeil severe. L’IRM cerebrale etait evocatrice d’encephalite a anticorps anti-Ma2, qui etaient effectivement retrouves dans le sang et le LCS, avec des hypersignaux FLAIR autour du 3e ventricule et de l’aqueduc du mesencephale. Les tests iteratifs de latence d’endormissement (TILE) etaient pathologiques, avec une latence moyenne d’endormissement de 6,2 min (normale > 8 min) mais sans endormissement en sommeil paradoxal. En revanche, le taux d’hypocretine effondre dans le liquide cerebro-spinal permettait de porter le diagnostic de narcolepsie de type 1.

This study enables a better understanding of how nucleation-growth of zeolites affects glass dissolution kinetics in hyperalkaline solutions characteristic of cement waters. A 20-oxide borosilicate glass, an inactive surrogate of a typical intermediate level waste glass, was altered in static mode at 50 °C in a hyperalkaline solution rich in Na+, K+ and Ca2+ and at an initial pH50°C of 12.6. Experiments were performed at four glass-surface-area-to-solution-volume (S/V) ratios to investigate various reaction progresses. Two types of glass alteration kinetics were obtained: (i) at low S/V, a sharp alteration resumption occurred after a rate drop regime, (ii) at high S/V, a high dissolution rate was maintained throughout the test duration with a slight progressive slow-down. In all the experiments, zeolites precipitated but the time taken to form stable zeolite nuclei varied dramatically depending on the S/V. Resulting changes in pH affected zeolite composition, morphology, solubility and growth rate. A change in a critical parameter such as S/V affected all the processes controlling glass dissolution.

International audience; Objective: The aim was to create and validate a community-acquired pneumonia (CAP) diagnostic algorithm to facilitate diagnosis and guide chest computed tomography (CT) scan indication in patients with CAP suspicion in Emergency Departments (ED).Methods: We performed an analysis of CAP suspected patients enrolled in the ESCAPED study who had undergone chest CT scan and detection of respiratory pathogens through nasopharyngeal PCRs. An adjudication committee assigned the final CAP probability (reference standard). Variables associated with confirmed CAP were used to create weighted CAP diagnostic scores. We estimated the score values for which CT scans helped correctly identify CAP, therefore creating a CAP diagnosis algorithm. Algorithms were externally validated in an independent cohort of 200 patients consecutively admitted in a Swiss hospital for CAP suspicion.Results: Among the 319 patients included, 51% (163/319) were classified as confirmed CAP and 49% (156/319) as excluded CAP. Cough (weight = 1), chest pain (1), fever (1), positive PCR (except for rhinovirus) (1), C-reactive protein ≥50 mg/L (2) and chest X-ray parenchymal infiltrate (2) were associated with CAP. Patients with a score below 3 had a low probability of CAP (17%, 14/84), whereas those above 5 had a high probability (88%, 51/58). The algorithm (score calculation + CT scan in patients with score between 3 and 5) showed sensitivity 73% (95% CI 66-80), specificity 89% (95% CI 83-94), positive predictive value (PPV) 88% (95% CI 81-93), negative predictive value (NPV) 76% (95% CI 69-82) and area under the curve (AUC) 0.81 (95% CI 0.77-0.85). The algorithm displayed similar performance in the validation cohort (sensitivity 88% (95% CI 81-92), specificity 72% (95% CI 60-81), PPV 86% (95% CI 79-91), NPV 75% (95% CI 63-84) and AUC 0.80 (95% CI 0.73-0.87).Conclusion: Our CAP diagnostic algorithm may help reduce CAP misdiagnosis and optimize the use of chest CT scan.

Perfluorooctanoic acid (PFOA), a global environmental pollutant detected in both wildlife and human populations, has several pathophysiological effects in experimental animals, including hepatotoxicity, immunotoxicity, and developmental toxicity. However, details concerning the tissue distribution of PFOA, in particular at levels relevant to humans, are lacking, which limits our understanding of how humans, and other mammals, may be affected by this compound. Therefore, we characterized the tissue distribution of 14C-PFOA in mice in the same manner as we earlier examined its analogues perfluorooctanesulfonate (PFOS) and perfluorobutanesulfonate (PFBS) in order to allow direct comparisons. Following dietary exposure of adult male C57/BL6 mice for 1, 3 or 5 days to a low dose (0.06 mg/kg/day) or a higher experimental dose (22 mg/kg/day) of 14C-PFOA, both scintillation counting and whole-body autoradiography revealed the presence of PFOA in most of the 19 different tissues examined, demonstrating its ability to leave the bloodstream and enter tissues. There were no differences in the pattern of tissue distribution with the low and high dose and the tissue-to-blood ratios were similar. At both doses, PFOA levels were highest in the liver, followed by blood, lungs and kidneys. The body compartments estimated to contain the largest amounts of PFOA were the liver, blood, skin and muscle. In comparison with our identical studies on PFOS and PFBS, PFOA reached considerably higher tissue levels than PFBS, but lower than PFOS. Furthermore, the distribution of PFOA differed notably from that of PFOS, with lower tissue-to-blood ratios in the liver, lungs, kidneys and skin.

High-dose exposure of mice to perfluorooctanoate (PFOA) induces both hepatotoxicity and immunotoxicity. Here, we characterized the effects of 10-day dietary treatment with PFOA (0.002-0.02%, w/w) on the liver and complement system of male C57BL/6 mice. At all four doses, this compound caused hepatomegaly and reduced the serum level of triglycerides (an indicator for activation of the peroxisome proliferator-activated receptor-alpha (PPARα)). At the highest dose (0.02%, w/w), this hepatomegaly was associated with the hepatic injury, as reflected in increased activity of alanine aminotranferase (ALAT) in the serum, severe hepatocyte hypertrophy and hepatocellular necrosis. PFOA-induced hepatic injury was associated with in vivo activation of the complement system as indicated by (i) significant attenuation of the serum activities of both the classical and alternative pathways; (ii) a marked reduction in the serum level of the complement factor C3; and (iii) deposition of the complement factor C3 fragment (C3a) in the hepatic parenchyma. PFOA did not activate the alternative pathway of complement in vitro. At doses lower than 0.02%, PFOA induced hepatocyte hypertrophy without causing liver injury or activating complement. These results reveal substantial involvement of activation of complement in the pathogenesis of PFOA-induced hepatotoxicity.

Numerous studies have been conducted on glass and cement durability in contact with water, but very little work to date has focused directly on interactions between the two materials. These interactions are mostly controlled by silicon–calcium reactivity. However, the physical and chemical processes involved remain insufficiently understood to predict the evolution of coupled glass–cement systems used in several industrial applications. Results are reported from borosilicate glass alteration in calcium-rich solutions. Our data show that four distinct behaviors can be expected according to the relative importance of three key parameters: the pH, the reaction progress (short- or long-term alteration) and the calcium concentration. Glass alteration is thus controlled by specific mechanisms depending on the solution chemistry: calcium complexation at the glass surface, precipitation of calcium silicate hydrates (C–S–H) or calcium incorporation in the altered layer. These findings highlight the impact of silicon–calcium interactions on glass durability and open the way for a better understanding of glass–cement mixing in civil engineering applications as well as in nuclear waste storage.

Exposure of mice to perfluorooctanoate (PFOA) evokes pronounced hepatomegaly along with significant alterations in both the histological structure and immune status of the liver. The present study was designed to evaluate the effects of this perfluorochemical on immune-mediated liver damage. In this connection, the influence of both sub-acute (10 days), moderate-dose (0.002% w/w = 3 ± 0.7 mg/kg body weight/day) and short-term (28 days), low-dose (0.00005% w/w = 70 ± 2 μg/kg body weight/day) dietary pretreatment with PFOA on the development of concanavalin A (Con A)-induced liver damage in mice was examined. With sub-acute, moderate, but not short-term, low-dose exposure, PFOA aggravated the acute liver damage caused by Con A, i.e., elevated serum levels of transaminases and led to more pronounced damage of hepatic tissue. This aggravation was associated with significantly enhanced hepatic level of interleukin-6 (IL-6), but unaltered hepatic levels of tumor necrosis factor-alpha (TNF-α), interferon-gamma (IFN-γ) and interleukin-4 (IL-4). Moreover, hepatic DNA fragmentation was not changed by sub-acute exposure to the moderate-dose. Our findings imply that exposure to PFOA may sensitize hepatic parenchymal cells to other toxicants that activate the hepatic immune system and thereby aggravate liver injury during acute inflammation.

It is well established that exposure of mice to perfluorooctanoate (PFOA) or perfluorooctane sulfonate (PFOS) exerts adverse effects on the thymus and spleen. Here, we characterize the effects of a 10-day dietary treatment with these compounds (0.001–0.02%, w/w) on the bone marrow (BM) of mice. At a dose of 0.02%, both compounds reduced food consumption and caused atrophy of the thymus and spleen. At this same dose, histopathological and flow cytometric analysis revealed that (i) the total numbers of BM as well as the numbers of myeloid, pro/pre B, immature B and early mature B cells were all reduced significantly; and (ii) these adverse effects were reversed either partially or completely 10 days after withdrawal of these compounds. At the lower dose of 0.002%, only PFOA reduced the B-lymphoid cell population. Finally, mice fed an amount of diet equivalent to that consumed by the animals exposed to 0.02% PFOA also exhibited atrophy of the thymus and spleen, and a reduction in the number of B-lymphoid population, without affecting myeloid cells. Thus, in mice, immunotoxic doses of PFOA or PFOS induce adverse effects on the myeloid and B-lymphoid cells in the BM, in part as a consequence of reduced food consumption.

The widespread environmental pollutant perfluorooctane sulfonate (PFOS), detected in most animal species including the general human population, exerts several effects on experimental animals, e.g. ...

Exposure of rodents in utero to perfluorooctane sulfonate (PFOS) impairs perinatal development and survival. Following intravenous or gavage exposure of C57Bl/6 mouse dams on gestational day (GD) 16 to (35)S-PFOS (12.5mg/kg), we determined the distribution in dams, fetuses (GD18 and GD20) and pups (postnatal day 1, PND1) employing whole-body autoradiography and liquid scintillation counting. In dams, levels were highest in liver and lungs. After placental transfer, (35)S-PFOS was present on GD18 at 2-3 times higher levels in lungs, liver and kidneys than in maternal blood. In PND1 pups, levels in lungs were significantly higher than in GD18 fetuses. A heterogeneous distribution of (35)S-PFOS was observed in brains of fetuses and pups, with levels higher than in maternal brain. This first demonstration of substantial localization of PFOS to both perinatal and adult lungs is consistent with evidence describing the lung as a target for the toxicity of PFOS at these ages.

Resume Introduction La frequence des cancers bronchiques augmente avec l’âge et constitue un probleme de sante publique. Ces patients sont sous-representes dans les essais cliniques et probablement non traites de facon optimale. Methodes L’enquete nationale a porte sur la prise en charge et le devenir selon la categorie d’âge (70–74 ans, 75–79 ans et 80 ans et plus) de patients atteints d’un cancer bronchique diagnostique entre aout 2002 et septembre 2003. Resultats L’âge median etait de 75 ans (70–96), le ratio hommes/femmes etait de 4,26 avec une diminution de ce dernier avec l’âge de 5,1 a 3. Les comorbidites liees au tabac etaient frequentes et la valeur mediane de l’index de Charlson etait de 2. Le performance status (PS) etait de 0–1 chez 58 % des patients. La proportion de non-fumeurs etait de 11,6 % et augmentait avec l’âge. Le bilan a comporte, chez 83,3 % des patients, au moins un scanner du thorax et du crâne (ou une IRM) et une echographie ou un scanner abdominal. Parmi les patients, 16,1 % n’ont eu qu’un traitement palliatif. Parmi les autres, 22,9 % ont ete operes, 21,8 % ont eu une irradiation thoracique et 71,5 % de la chimiotherapie. La mediane de survie etait de 9,14 mois avec 23,5 % de deces dans les trois premiers mois. La categorie d’âge la plus basse, un bon PS, le fait d’etre non-fumeur et un indice de masse corporelle eleve etaient des facteurs pronostiques favorables independants. Un âge eleve, un mauvais PS et le fait d’etre fumeur etaient pronostiques d’un deces precoce. Conclusions Une grande majorite de patients âges sont pris en charge comme les patients plus jeunes. L’âge reste un facteur independant de survie globale et de deces precoce.

We have previously shown that short-term, high-dose exposure of mice to the environmentally persistent perfluorooctanoate (PFOA) results in thymic and splenic atrophy and the attenuation of specific humoral immune responses. Here we characterize the effects of a 10-day treatment with different dietary doses (1-0.001%, w/w) of perfluorooctanesulfonate (PFOS), a similar fluorochemical, on the immune system of male C57BL/6 mice. At doses greater than 0.02%, PFOS induced clinical signs of toxicity in the animals, whereas at the concentration of 0.02%, this compound caused weight loss, hepatomegaly and atrophy of the thymus, spleen and adipose tissue without toxicity. With this latter dose, histopathological and flow-cytometric analysis revealed that (i) the thymic cortex was virtually depleted of cells; (ii) the total numbers of thymocytes and splenocytes were reduced by 84 and 43%, respectively; (iii) although all populations of thymocytes and splenocytes were smaller, the thymic CD4(+)CD8(+) cells and the splenic B-lymphocytes were most decreased. These alterations resembled those evoked by analogous exposure to PFOA, but were less pronounced. At lower doses (less than 0.02%), PFOS induced hepatomegaly without affecting the thymus or spleen. Finally, comparison of male wild-type 129/Sv mice and the corresponding knock-outs lacking peroxisome proliferator-activated receptor-alpha (PPARalpha) indicated that these effects of PFOS are not strain-dependent. More importantly, hepatomegaly is independent of PPARalpha, the thymic changes are partially dependent on this receptor, and splenic responses are largely eliminated in its absence. Thus, immunomodulation caused by PFOS is a high-dose phenomenon partially dependent on PPARalpha.

This paper focuses on stage I, II and IIIA non-small cell lung cancer treatable with local treatment. It addresses five questions raised by strategies combining local treatments with chemotherapy. Even if chemotherapy increases resectability of stage III disease, the chemotherapy-surgery combination has not been demonstrated to increase survival compared to the standard chemo-radiation treatment. The results of the study by Van Meerbeeck do not support this hypothesis. Does surgery, added to chemo-radiotherapy, improve the outcome in stage IIIAN2 disease? This was the question addressed by the study by K. Albain. There is probably not clear cut answer. However, the trimodality strategy might be interesting in patients undergoing a lobectomy and might have a negative impact when a pneumonectomy has been performed. In patients with a non resectable/inoperable cancer treated with standard chemoradiation, the concomitant strategy has been shown to be superior to sequential treatment. However, due to acute toxicity, it should be delivered to selected patients, who still need to be better defined. The chemotherapy-surgery combination is becoming standard (in stage II disease) and most cooperative groups will probably stand in favour of it in 2006. The best respective timing for chemotherapy and surgery is still debated. There are many advantages in favour of preoperative chemotherapy, including better feasibility and the higher proportion of patients who can benefit. However, there is no statistically reliable demonstration of such superiority.

Resume Etats des connaissances Les instances scientifiques preconisent une attitude minimaliste dans la surveillance des cancers bronchiques operes (examen clinique et radiographie thoracique). D’apres une enquete, 70 % des pneumologues francais ont opte pour l’usage du scanner et souvent de l’endoscopie. Les donnees de la litterature sont disparates, souvent issues d’etudes retrospectives. Methodes Le cancer bronchique est un bon modele pour realiser un essai de surveillance postoperatoire. Les recidives surviennent frequemment dans une aire facile a surveiller, peuvent etre decouvertes alors qu’elles sont encore asymptomatiques, sont parfois accessibles a un traitement curatif, ont un siege identique a celui des 2 e cancers observes. L’Intergroupe Francophone de Cancerologie Thoracique (IFCT) a debute un essai comparant une surveillance legere (examen clinique, radiographie thoracique) a une surveillance lourde (scanner, fibroscopie). La surveillance est realisee tous les 6 mois pendant 2 ans puis annuellement jusqu’a 5 ans. Resultats attendus L’objectif principal est de savoir si une surveillance lourde permet d’augmenter la survie des patients. Toute aussi importante est la question inverse. Si une surveillance couteuse et penible n’interfere pas sur les chances de guerison, il est fondamental d’en tirer les consequences sur les pratiques.

Resume La premiere meta-analyse de Berghmans et coll. faite sur la chimiotherapie preoperatoire dans les cancers bronchiques non a petites cellules reseques et comprenant les six premiers essais connus, demontre son efficacite, malgre le faible nombre de patients inclus. Un rapide expose de ces differents essais est presente. Trois autres essais n’ont pas ete inclus dans cette analyse, celui du SWOG presente a l’ASCO en 2005 et les essais italien et espagnol dont les resultats ne sont pas encore connus. Les arguments en faveur de la chimiotherapie preoperatoire sont discutes. A cote de ces essais, deux autres essais au dessein tres different ont ete concus. Celui d’Albain et coll. cherchait a evaluer l’effet de la chirurgie associee au couple chimiotherapie radiotherapie d’inductiondans les stades IIIaN2. Les resultats semblent interessants chez les patients pouvant beneficier d’une lobectomie. Le 2 e essai cherchait a savoir si l’association chimiotherapie d’induction permettait d’ameliorer la survie des patients en augmentant la resecabilite de tumeurs initialement non resecables. La survie des patients ne semble pas influencee par le choix de la therapeutique, meme si la resecabilite est augmentee par la chimiotherapie premiere.

Introduction We designed this phase II trial to evaluate the efficacy and safety of weekly paclitaxel in combination with monthly carboplatin as first-line treatment in elderly patients with advanced non-small cell lung cancer (NSCLC). Methods Main eligibility criteria were histologically or cytologically proven stage IIIB or IV NSCLC, age ≥70 years, Eastern Cooperative Oncology Group performance status 0-2, and measurable disease. The 4-week–based chemotherapy regimen consisted of carboplatin infusion (area under the concentration-time curve 6 mg/ml -1 /min) on day 1 and paclitaxel 90 mg/m 2 as a 1-hour infusion on days 1, 8, and 15. Tumor response was evaluated using Response Evaluation Criteria in Solid Tumors criteria, and symptoms were evaluated using the Lung Cancer Symptoms Scale. Analyses were performed on an intention-to-treat basis. Results From February 2002 to August 2003, 51 patients (median age, 74 years) participated in the study. One complete and 21 partial responses were reported by the independent review committee, leading to an intention-to-treat objective response rate of 43% (95% confidence interval, 30–57%). The median progression-free and overall survivals were 7.5 (95% confidence interval, 6.2–9.4) and 13.6 (95% confidence interval, 7.5–17) months, respectively. Longitudinal evaluation of the Lung Cancer Symptoms Scale demonstrated lack of quality of life modification during the treatment period. Neurotoxicity was mild to moderate, with 6% of patients suffering from a grade 3 or 4 neuropathy. Myelosuppression was the main toxicity; 39% of patients experienced grade 3 or 4 neutropenia, 18% experienced grade 3 anemia, and 8% experienced grade 3 or 4 thrombocytopenia. There was no treatment-related death. Conclusions The combination of weekly paclitaxel 90 mg/m 2 administered on days 1, 8, and 15 plus monthly carboplatin area under the curve 6 on day 1 of a 4-week cycle was feasible and active as a first-line treatment for elderly patients with NSCLC with a good safety profile. These results deserve further analysis to compare the standard care for these patients (monotherapies) with this doublet.

Resume Les metastases osseuses sont la cause la plus frequente de douleur chez les patients atteints de cancer. Leur prise en charge sur le plan antalgique est un challenge therapeutique. La composante douloureuse ne repond pas toujours aux antalgiques majeurs, a la chimiotherapie et a la radiotherapie. Quand ces traitements sont depasses, la vertebroplastie, la cimentoplastie, la radiofrequence par voie percutanee et la radiotherapie metabolique sont des methodes elegantes et efficaces venant en complement des traitement classiques.

Resume La chimiotherapie preoperatoire des cancers bronchiques non a petites cellules avait le double but de detruire les micrometastases et d’augmenter la resecabilite des tumeurs. Les essais de Rosell et de Roth etaient positifs en faveur de l’association mais avaient de faible effectif. Dans l’essai francais, la survie globale n’etait pas differente pour l’ensemble des patients mais l’etait dans les stades precoces. Les resultats preliminaires de l’essai du SWOG objectivent une difference de 6 % a 2 ans non significative. L’essai EORTC 08941, dans les tumeurs IIIAN2 non resecables, ne montrait pas de difference dans la comparaison de la chirurgie a la radiotherapie apres chimiotherapie d’induction. L’essai INT-0139 etudiait l’apport de la chirurgie apres chimio-radiotherapie d’induction par rapport a l’association exclusive chimio-radiotherapie. Il n’y avait pas de difference entre les 2 strategies mais l’analyse par sous-groupes indique que certains groupes pourraient beneficier de la triple association. Deux essais sont en attente de publications. Le petit nombre de patients finalement inclus par essai conduira a une meta-analyse pour acquerir une opinion definitive. L’association chirurgie et chimiotherapie va devenir un standard, dans les stades II. Seul reste en discussion le meilleur moment, pre ou postoperatoire. Dans l’objectif initial, seule la destruction des micrometastases est actuellement confortee.

Background Pathologic complete response (CR) to preoperative chemotherapy has been shown to be a strong prognostic factor in resected non-small cell lung cancer (NSCLC). This preoperative setting offers the opportunity to evaluate the clinical prediction of CR by investigators and an evaluation committee (EC) using the “gold standard” pathologic examination as the reference. The only published large randomized trial of preoperative chemotherapy (to our knowledge), the French neoadjuvant study, constitutes an interesting database to evaluate CT scan-based CR assessment. Study objectives and design The French trial compared mitomycin-ifosfamide-cisplatin followed by surgery with surgery alone in stage I (except T1N0) to IIIa resectable NSCLC. Response was prospectively assessed in all patients receiving preoperative chemotherapy by the investigator in charge of the patient and by an EC, and was compared with pathologic postoperative data. Results In the preoperative chemotherapy study, 167 patients were operated on. Nineteen patients were found to have a pathologic CR. Only seven patients were classified as having a CR by investigators and five patients by the EC. Evaluation of CR was correct in six of these seven cases and in three of these five cases, respectively. Sensitivity of the CR diagnosis was 31.6% for investigators and 15.8% for the EC. Specificities of the CR diagnosis were 99.4% and 98.8%, respectively. Positive predictive values were 85.7% and 60%, respectively. Negative predictive values were 91.9% and 90.1%, respectively. Accuracies were 91.6% and 89.2%, respectively. Conclusion Investigator assessment of CR was highly predictive of pathologic CR. However, this study showed that clinical CT scan-based assessment, whether performed by investigators or the EC, underestimated the frequency of CR after preoperative chemotherapy in resectable NSCLC.

Background This multicenter, randomized, phase III study compared the efficacy, including progression-free survival (PFS), and safety of gemcitabine–docetaxel (GD) combination versus cisplatin–vinorelbine (CV) in the treatment of advanced non-small-cell lung cancer (NSCLC). Patients and methods Chemonaive patients with stage IIIB or IV NSCLC were treated with GD (gemcitabine 1000 mg/m2 days 1 and 8 plus docetaxel 85 mg/m2 day 8, every 3 weeks for eight cycles) or CV (cisplatin 100 mg/m2 day 1 plus vinorelbine 30 mg/m2, days 1, 8, 15 and 22, every 4 weeks for six cycles). Results A total of 311 patients were enrolled (155 GD and 156 CV). Neither PFS nor overall survival differed significantly between the two arms (median PFS 4.2 and 4 months; median survival 11.1 and 9.6 months; 1-year survival 46% and 42%, for GD and CV, respectively). For the GD arm compared with the CV arm, the hazard ratio for PFS was 1.04 [95% confidence interval (CI) 0.83–1.32], and for overall survival, it was 0.90 (95% CI 0.70–1.16). Objective response rates did not differ significantly (31% for GD, 35.9% for CV). Myelosupression, emesis and frequency of febrile neutropenia were less pronounced on the GD arm, whereas fluid retention and pulmonary events were more pronounced. The CV arm experienced a higher number of serious adverse events and a lower compliance with the protocol. There was no quality of life (QoL) difference between arms. Median time to definite impairment of health-related QoL was 153 and 168 days in GD and CV arms, respectively. Conclusions There was no advantage in PFS with GD compared with CV; however, the CV regimen had higher rate of toxic events, mainly myelosuppression. The herein, non-platinum-containing regimen could be considered as a rational alternative to the cisplatin-based doublet.

Resume La chimiotherapie (CT) associee a la chirurgie des cancers non a petites cellules est a l’etude depuis de nombreuses annees. Elle peut s’administrer en preoperatoire, en perioperatoire ou en postoperatoire (adjuvante). Une longue periode plutot infructueuse s’est close par la meta-analyse du Non-Small Cell Cancer Collaborative Group, publiee dans le British Medical Journal en 1995, laissant esperer un gain de survie de 5 % a 5 ans avec l’addition a la chirurgie d’une chimiotherapie adjuvante. Depuis, les arguments se sont accumules en faveur de cette association. Les etudes de phase II montraient la faisabilite de la CT preoperatoire. Un essai randomise francais objectivait une amelioration de la survie a 5 ans de pres de 10 %, a la limite de la significativite statistique et cet effet benefique etait d’autant plus net qu’il s’agissait de stades precoces. Un exces de morbidite et de mortalite postoperatoire, meme s’il n’etait pas significatif, rendait compte de la necessite du choix d’une CT efficace, mais moins toxique que l’association mitomycine, ifosfamide, cisplatine, choisie initialement. Dans le domaine de la CT adjuvante, les arguments en faveur de l’association s’accumulaient avec les resultats positifs de 3 etudes, l’essai IALT, l’essai BR10 du National Cancer Institute canadien et l’essai 9633 du CALGB, les deux derniers presentes cette annee a l’American Society of Clinical Oncology. Quatre autres essais de CT preoperatoires sont en cours, mais leurs resultats ne sont pas attendus avant quelques annees. Dans le choix du meilleur timing entre les differents modes d’administration de la CT autour de la chirurgie, des arguments plaident en faveur de la CT preoperatoire : la possibilite d’apprecier la chimiosensibilite de la tumeur permettant l’arret precoce de celle-ci en cas d’inefficacite (actuellement 40 % des patients), la meilleure acceptabilite de la CT par les patients, l’augmentation de la resecabilite des tumeurs. A son detriment, il faut noter la plus grande difficulte d’apprecier le TNM et l’augmentation des risques postoperatoires, essentiellement chez les patients N2, qui devrait disparaitre avec l’utilisation des CT de 3e generation.

Brain metastases are a frequent feature of the course of non-small cell lung carcinoma (NSCLC). The potential usefulness of prophylactic cranial irradiation (PCI) has led to the search for target groups likely to derive benefit. This multivariate analysis looked for factors predictive of brain metastases in a group of stages I-III NSCLC patients under care of the thoracic oncology unit of Besancon University Hospital from 1977 to 2001. All the patients had the same follow-up. They were divided into two groups: BM+ when they had a brain metastasis as the first site of progression, whether solitary or not, and BM(-) otherwise. Variables analysed were age, gender, performance status (0-1 versus 2-3), weight-loss stage T-status, N-status, pathological type, type of treatment, administration of chemotherapy, use of cisplatin and response to treatment. Three hundred and five patients were eligible and there were 77 patients (25.25%) in the BM+ group. Median time to onset of brain metastases was 12 months (1-163 months) and median survival from the diagnosis of brain metastases was 6 months (1-65 months). Factors predictive of brain progression were age < or =62 years (RR: 2.5, 95% CI: 1.33-4.76 and P = 0.004), T4 tumour status (RR: 3.75, 95% CI: 1.72-8.21 and P = 0.0009), N2-3 (RR: 2.61, 95% CI: 1.32-5.15 and P = 0.0057), and adenocarcinoma (RR: 3.39, 95% CI: 1.78-6.46 and P = 0.0002). No aspect of treatment plays a role in the frequency of this type of metastasis. These factors predictive of brain progression could serve as a basis for the selection of patients with the aim of sitting of studies on prophylactic cranial irradiation in NSCLC.

Background The survival benefit associated with first-line chemotherapy in advanced lung cancer led to the need for second-line chemotherapy. Docetaxel (Taxotere®) has proven efficacy in both settings. This study evaluated the safety and efficacy of two doses of docetaxel in patients with non-small-cell lung cancer who had failed first-line platinum-based chemotherapy. Patients and methods In total, 182 patients from 24 French centres were randomised and treated with either docetaxel 75 mg/m2 (arm A) or 100 mg/m2 (arm B) every 3 weeks. Baseline characteristics were well balanced, except more patients in arm A had metastatic disease (91.4% versus 78.7%) and therefore the median number of sites involved for arm A was three compared with two for arm B. Results Median time to treatment failure was 1.34 months [95% confidence interval (CI) 1.28–1.64] for arm A and 1.64 months (95% CI 1.34–2.62) for arm B. Median overall survival was 4.7 months (95% CI 3.8–5.9) for arm A versus 6.7 months (95% CI 4.8–7.1) for arm B. According to a blinded expert panel, disease control was achieved in 35 (43.8%) patients in arm A and 39 (49.4%) patients in arm B. More patients in arm B experienced grade 3–4 neutropenia (B: 72.7% versus A: 44.0%), asthenia (B: 20.2% versus A: 10.8%) and infection (B: 6.7% versus A: 2.2%). Three treatment-related deaths were reported in each arm. Conclusions The optimal docetaxel dosage in this second-line setting is 75 mg/m2, as it has a more favourable safety profile and on balance a similar efficacy to the 100 mg/m2 dose.

Introduction Les medecins du travail et leurs services ont un role primordial a jouer sur le plan de la prevention de desinsertion professionnelle (PDP). La PDP devient ainsi une des missions prioritaires des services de sante travail etablie par la loi de 2011 et le volet obligatoire du CPOM de chaque service. Cela a ete reaffirme dans le 5 e objectif de l’axe 2 du Plan sante travail 3. Objectifs Sensibiliser les services de sante travail franciliens a la PDP ; donner annuellement des indicateurs de maintien en emploi des salaries ayant fait l’objet de la declaration d’au moins un probleme de sante aupres de leurs medecins du travail avec des statistiques departementales et regionales ; des indicateurs de maintien en emploi par secteur d’activite. Methodologie Une etude descriptive transversale au 31/12/2013 ou un cliche instantane de la situation des salaries ayant fait l’objet de l’officialisation d’au moins un probleme de sante au travail durant l’annee civile 2013. Population etudiee Tous les salaries ayant eu un probleme de sante et ayant donne lieu a un avis medical autre que « apte » ou « pas d’avis ». La periode d’enquete s’etend de janvier 2014 a fin fevrier 2014. Recueil des donnees Il se fait par l’equipe pluridisciplinaire de chaque service participant (medecin, infirmier, secretaire medical) sur le devenir de ces salaries au 31/12/2013. Les donnees sont rendues anonymes avant la collection et exploitation. Resultats Ils concernent 22 365 salaries sur un effectif suivi de 787 085 franciliens actifs. Les variables etudiees sont classees par la typologie de : – entreprise par code Naf 2008 ; – salarie par annee de naissance et sexe ; – contrat Interim ou non ; – visite de pre-reprise ; – pathologie declencheur (moteur, psychique, maladie invalidante, deficit sensoriel) ; – le devenir du salarie (maintien en emploi dans l’entreprise, hors entreprise, sortie du travail avec solution sociale, precarite, perdu de vue, deces).

We have previously demonstrated that severe adipose tissue atrophy occurs upon dietary treatment of mice with potent peroxisome proliferators (PPs). This atrophy occurs subsequent to peroxisome proliferation in the liver and may represent a novel addition to the pleiotropic effects exerted by PPs. In the present study we have characterized the recovery of mice from such atrophy following cessation of exposure. Following termination of treatment with perfluorooctanoic acid (PFOA) for 7 days, the adipose tissue atrophy was rapidly reversed, beginning on 2-5 days of recovery and being complete within 10 days. In contrast, hepatic peroxisome proliferation recovered much more slowly, indicating that these processes are not strictly coordinated. Analysis of lipoprotein lipase and hormone-sensitive lipase activities in adipose tissue revealed that the decrease and increase in these activities, respectively, caused by PFOA were both reversed within 10 days of recovery. Overall, these data provide further support for our previous conclusion that the adipose tissue atrophy induced by PFOA is caused, at least in part, by changes in the activities of lipoprotein lipase and hormone-sensitive lipase. The serum level of cholesterol, which increased after termination of PFOA treatment, returned to normal with a time-course similar to the recovery of adipose tissue weight, although hepatic peroxisome proliferation was still present. The possible relationship between the reduction in serum cholesterol and/or in its availability to peripheral tissues and the associated atrophy of adipose tissues caused by PPs is discussed.

Dimethyl sulfoxide (DMSO) is widely and routinely used as a vehicle in various investigations, especially within the pharmaceutical industry. It has been used for the evaluation of the effects of hydrophobic xenobiotics on cells, as well as for the cryopreservation of biological material. Isothermal microcalorimetry is a powerful tool for monitoring heat production, which is a function of general cellular metabolic activity. Employing this microcalorimetric technique, a low concentration of DMSO routinely used for the addition of hydrophobic substances to, e.g., cell cultures, was shown to decrease heat production (per unit DNA) by the rat hepatoma cell lines FAO, Morris 7800C1 and H4IIE by 32–38%. However, such low concentrations of DMSO did not influence the cell cycle or the degree of apoptosis in these cell populations. Caution is thus advisable when utilizing DMSO as a vehicle in cell culture experiments.

Peroxisome proliferators (PPs) are a large class of structurally diverse chemicals, which includes drugs designed to improve the metabolic abnormalities linking hypertriglyceridemia to diabetes, hyperglycemia, insulin-resistance and atherosclerosis. We have recently demonstrated that exposure of rodents to potent PPs indirectly causes a number of immunomodulating effects, resulting in severe adaptive immunosuppression. Since the peroxisome proliferator-activated receptor alpha (PPARalpha) plays a central role in mediating the pleiotropic responses exerted by PPs, we have compared here the immunomodulating effects of the PPs perfluorooctanoic acid (PFOA) and Wy-14,643 in wild-type and PPARalpha-null mice. The reductions in spleen weight and in the number of splenocytes caused by PP treatment in wild-type mice was not observed in PPARalpha-null mice. Furthermore, the reductions in thymus weight and in the number of thymocytes were potently attenuated in the latter animals. Similarly, the dramatic decreases in the size of the CD4(+)CD8(+) population of cells in the thymus and in the number of thymocytes in the S and G2/M phases of the cell cycle observed in wild-type mice administered PPs were much less extensive in PPARalpha-null mice. Finally, in contrast to the case of wild-type animals, the response of splenocytes isolated from the spleen of PP-treated PPARalpha-null mice to appropriate T- or B-cell activators in vitro was not reduced. Altogether, these data indicate that PPARalpha plays a major role in the immunomodulation caused by PPs. The possible relevance of these changes to the alterations in plasma lipids also caused by PPs is discussed.

The regulation of the aldo-keto reductase AKR7A1 was examined in the livers of male and female rats during development by using Western blots, and its contribution to carbonyl metabolism was assessed by using enzyme assays. Hepatic levels of AKR7A1 are low in fetal rats and rise to a peak at around 6 weeks of age in animals of both sexes. Higher levels of the enzyme are found in adult male rat liver than in adult female rat liver. The reductase, therefore, appears to be subject to sex-specific regulation. The effect of growth hormone in mediating this difference in expression was examined by using hypophysectomized animals whose serum growth hormone levels had been feminized by continuous administration. Results demonstrate that such treatment leads to a reduction in AKR7A1 expression. AKR7A1 was found to be constitutively expressed in rat tissues such as liver, kidney, small intestine, and testis, but it was not detected in nasal mucosa, skeletal muscle, heart, adrenal gland, brain, or spleen. However, AKR7A1 was inducible by the synthetic antioxidant ethoxyquin in liver, kidney, and small intestine, but not in the other tissues examined. These results show that levels of this important detoxication enzyme vary considerably according to age and sex and that dietary antioxidants can also influence its level in several tissues.

A randomized phase II trial of oral vs. intravenous (i.v.) vinorelbine was designed to determine the efficacy and safety of oral vinorelbine with an intrapatient dose escalation in previously untreated patients with advanced non-small-cell lung cancer (NSCLC).Between December 1997 and April 1999, 115 patients with stage IIIB or IV NSCLC were randomized (2 to 1) to receive either oral vinorelbine at a dose of 60 mg/m2/week for the first three administrations and then increased to 80 mg/m2/week in the absence of severe neutropenia, or i.v. vinorelbine at 30 mg/m2/week.One hundred and fourteen patients (76 in the oral arm and 38 in the i.v. arm) were treated. Ninety-eight patients (86%) were eligible and assessable. The two treatment arms were well-balanced for demographic and prognostic features. After external panel review, the response rates in evaluable patients were 14%, in the oral arm and 12% in the i.v. arm. The median progression-free survival with oral and i.v. vinorelbine was 3.2 months and 2.1 months, respectively, and the median survival 9.3 and 7.9 months, respectively. The most common hematological toxicity was neutropenia, which was severe (grade 3-4) in 46% of patients and for 7% of administrations in the oral arm, and in 62% of patients and for 25% of administrations in the i.v. arm. Non-hematological toxicities including nausea, vomiting, anorexia, weight loss, diarrhea .and constipation were generally mild to moderate.The activity of oral and i.v. vinorelbine in advanced NSCLC appears to be comparable. The safety profiles of both formulations look qualitatively similar. Oral vinorelbine can therefore be considered a good alternative to i.v. administration.

Context The 'Standards, Options and Recommendations' (SOR) project, started in 1993, is a collaboration between the Federation of the French Cancer Centres (FNCLCC), the 20 French cancer centres and specialists from French public universities, general hospitals and private clinics. The main objective is the development of clinical practice guidelines to improve the quality of health care and outcome for cancer patients. The methodology is based on literature review and critical appraisal by a multidisciplinary group of experts, with feedback from specialists in cancer care delivery. Objectives To develop clinical practice guidelines according to the definitions of the Standards, Options and Recommendations project for the management of stage I and II non small cell lung carcinoma treated by radiotherapy alone. Methods Data were identified by searching Medline and personal reference lists of members of the expert groups. Once the guidelines were defined, the document was submitted for review to independent reviewers, and to the medical committees of the 20 French cancer centres. Results The main recommendations for the management of stage I and II non small cell lung carcinoma treated by radiotherapy alone are: 1) The curative external irradiation with a continual course is an alternative to surgery only in the case of medically inoperable tumors or because the patient refuses surgery; 2) The external irradiation of the primary tumor only without the mediastinum could be proposed in peripheral stage IA. In proximal stage IA and IB, external irradiation should be carried out only as part of prospective randomised controlled trials comparing a localised irradiation of the primary tumor with a large irradiation of the mediastinum and the primary tumor. The treated volume must include the macroscopic tumoral volume with or without the microscopic tumoral volume and with a security margin from 1.5 to 2 cm; 3) There is a benefit to delivering a total dose in the primary tumor higher than 60 Gy in so far as the proposed irradiation, taking into account the respiratory function, does not increase the likelihood of severe adverse events due to radiation; and 4) The change in fractionation, the radiochemotherapy combination, the endobronchial brachytherapy with high dose rate alone or with external irradiation could be proposed only as part of prospective controlled trials for tumors classified as stage IB or II.

Preoperative chemotherapy has been intensively studied in stage IIIA non-small cell lung cancer and, to a lesser extent, in stage IIIB. For a considerable time period, early stage non-small cell lung cancer was dropped from studies. For early investigators, shrinking the tumor size, thus allowing complete resection of initially unresectable tumors, appeared as important as destroying micrometastases. Nevertheless, analysis of relapse patterns shows that preoperative chemotherapy appears to act more on micrometastases than on local control. The first randomized studies of preoperative chemotherapy were conducted only among patients with stage IIIA disease. The French Cooperative Oncology Group presented a large randomized study among 373 stage IB, II, and IIIA patients at the American Society of Clinical Oncology meeting in May 1999. A Cox multivariate analysis showed a protective effect of preoperative chemotherapy, and this effect seemed to preferentially involve patients with early stage disease. Ongoing studies of most US and European oncology groups are including early stage tumors, as in the Southwest Oncology Group trial 9901. The new Intergroupe Francophone de Cancérologie Thoracique also is ready to start a preoperative randomized chemotherapy study in stage I and II non-small cell lung cancer, that will compare two different strategies of preoperative chemotherapy in responding patients. Patients will be randomized to two groups: one group will receive chemotherapy before surgery and the other group will receive it before and after surgery.

Contexte. - La Federation nationale des centres de lutte contre le cancer (FNCLCC) et les Centres regionaux de lutte contre le cancer (CRLCC), en collaboration avec des partenaires des secteurs public (CHU, CHG), prive et certaines societes savantes ont entrepris depuis 1993 d'elaborer des recommandations pour la pratique clinique en cancerologie: les « Standards, Options et Recommandations » (SOR). L'objectif de l'operation SOR est d'ameliorer la qualite et l'efficience des soins aux patients atteints de cancer en fournissant aux praticiens une aide a la decision facilement utilisable. La methodologie d'elaboration des SOR repose sur une revue et une analyse critique des donnees de la litterature scientifique par un groupe d'experts pluridisciplinaire, permettant de definir, sur la base du niveau de preuve scientifique et du jugement argumente des experts, des « Standards », des « Options » et des « Recommandations ». Avant publication, les SOR sont revus par des experts independants. Objectifs. - Definir, sur la base d'une revue de la litterature et de l'accord d'experts, des Standards, Options et Recommandations pour la prise en charge des patients atteints de cancer broncho-pulmonaire primitif de stade I ou Il traites par irradiation exclusive. Methodes. - Un groupe de travail multidisciplinaire mis en place par la Federation nationale des centres de lutte contre le cancer (FNCLCC) a revu les donnees scientifiques disponibles concernant la prise en charge des patients atteints de cancer broncho-pulmonaire primitif non a petites cellules de stade I et Il traites par irradiation exclusive. Apres selection des articles, synthese des resultats et redaction des SOR, le document a ete soumis pour relecture et approbation a des relecteurs. Resultats.- Les principales recommandations sont: 1) l'irradiation externe exclusive continue a visee curative, avec un fractionnement conventionnel, n'est une alternative a la chirurgie d'exerese qu'en cas de contre-indications a un acte chirurgical liees au terrain medical ou de refus du malade de tout acte chirurgical; 2) l'irradiation externe du volume tumoral primitif seul, sans le mediastin, peut etre proposee dans les formes classees stade IA, de topographie peripherique. Dans les formes classees stade IA proximal et IB, elle ne peut se concevoir que dans le cadre d'un essai therapeutique prospectif randomise et controle comparant une irradiation localisee au volume tumoral et une irradiation large mediastino-tumorale. Le volume traite doit inclure le volume tumoral macroscopique avec ou sans le volume tumoral microscopique, avec une marge de securite de 1,5 a 2 cm; 3) il y a un benefice a delivrer une dose totale dans le volume tumoral superieure a 60 Gy dans la mesure ou la technique d'irradiation proposee tenant compte de la fonction respiratoire du malade, n'augmente pas la probabilite de risque de complications severes radio-induites; 4) les modifications du fractionnement, l'association radiochimiotherapie concomitante, la curietherapie endoluminale a haut debit de dose seule ou en association a une irradiation externe, ne peuvent etre proposees que dans le cadre d'essais prospectifs controles pour des formes classees de stade IB ou II.

A dose escalation study of paclitaxel in combination with vinorelbine was conducted in 21 patients with previously untreated stage IIIb or IV non-small cell lung cancer (NSCLC). All three patients treated with the initial dose of paclitaxel 135 mg/m2 administered as a 1-h intravenous infusion and vinorelbine 25 mg/m2 experienced dose-limiting toxicity (febrile neutropenia). After modification of the dosing schedule, the MTD of paclitaxel was found to be 115 mg/m2 when combined with vinorelbine 20 mg/m2 on day 1, followed by vinorelbine 20 mg/m2 on day 5. Partial responses were achieved in 24% of patients, with a median duration of response of 126 days (range from 84 to 484 days) and a 1-year survival rate of 42%. In conclusion, haematologic toxicity (febrile neutropenia/neutropenia) severely restricts the dosing schedule of combined paclitaxel and vinorelbine, and possibly limits anti-tumour efficacy.

Background . Although a minimal follow-up with periodic clinic visits and chest radiographs is usually recommended after complete operation for non–small cell lung cancer, the ideal follow-up has not been defined yet. Objectives of this prospective study were to determine the feasibility of an intensive surveillance program and to analyze its influence on patient survival. Methods . Follow-up consisted of physical examination and chest roentgenogram every 3 months and fiberoptic bronchoscopy and thoracic computed tomographic scan with sections of the liver and adrenal glands every 6 months. Influence of patient and recurrence characteristics on survival from recurrence was successively analyzed using the log-rank test and a Cox model adjusted for treatment. Results . Among the 192 eligible patients, recurrence developed in 136 patients (71%) and was asymptomatic in 36 patients (26%). In 35 patients, recurrence was asymptomatic and detected by a scheduled procedure: thoracic computed tomographic scan in 10 (28%) patients and fiberoptic bronchoscopy in 10. Fifteen patients (43%) had a thoracic recurrence treated with curative intent. From the date of recurrence, 3-year survival was 13% in all patients and 31% in asymptomatic patients whose recurrence was detected by a scheduled procedure. Asymptomatic recurrences ( p p p = 0.01), and age 61 years or younger ( p = 0.01) were shown to be significantly favorable prognostic factors. Conclusions . This intensive follow-up is feasible and may improve survival by detecting recurrences after surgery for non–small cell lung cancer at an asymptomatic stage.

Thirty-one previously untreated patients with limited stage small-cell lung cancer (LSCLC) were included in a prospective study, to investigate the feasability and the efficacy of a combined modality treatment using concurrent hyperfractionated chest irradiation and cisplatin (P) plus etoposide (E) chemotherapy. All patients received intravenously P=75 mg/m 2 at day 1, plus E=120 mg/m 2 days 1–3, at 3-week intervals for six cycles. Irradiated patients received 45 Gy in two daily fractions, 5 days a week, from week 4 to week 6. During week 5, prophylactic cranial irradiation was initiated, in one daily fraction of 2.5 Gy for a total dose of 25 Gy. Twenty-nine patients were evaluable for response. Twenty-two (76%) achieved a complete response, five (17%) had a partial response. Five patients are currently alive. The overall response rate was 93% (CI 95% (83.7–100)). The median survival time was 14 months and the 2-year survival rate was 25%. Main toxicities were grade 3–4 esophagitis in half of the patients and myelosuppression. The results are not as optimistic as other studies using a similar regimen.

The present study concerns conjugation of 1-naphthol in primary cultures of rat ovarian cells. Two phase II enzymes catalyzing conjugation, i.e. phenol sulfotransferase (P-SULT) and phenol UDP-glucuronosyltransferase (P-UGT), were measured using 1-naphthol as substrate. The rates of conjugation by the different cell types of the rat ovary were the same at low concentrations and short incubation times. However, after 20 h of incubation the rate of conjugation in cells isolated from ovaries enriched in corpora lutea (CL) exceeded the rate in cells isolated from ovaries enriched in preovulatory follicles. In addition, when the granulosa cells were removed from the preovulatory follicles, the rate of conjugation was 1.7-fold higher, i.e. in the theca/stroma cells. When the cells were incubated with 1-[14C]naphthol and conjugates were subsequently separated by thin-layer chromatography, naphthyl glucuronide was the only conjugate observed. Pentachlorophenol (PCP), a commonly used inhibitor of P-SULT, inhibited 1-naphthol conjugation 50% in cell cultures, as well as in microsomal preparations. alpha-Naphthoflavone (ANF) and ellipticine (ELP), both cytochrome P450 (CYP) inhibitors, affected the conjugation of 1-naphthol in different ways; ANF did not affect P-UGT activity in microsomal preparations, but inhibited 1-naphthol conjugation in cell cultures by as much as 90%. On the other hand, ELP inhibited the conjugation of 1-naphthol up to 99% in the cell cultures, but only 75% in microsomal fractions. Testosterone (TST) and estradiol inhibited this activity approximately equal 50% in both of these experimental systems. Clomiphene citrate (CLF), a drug used to induce ovulation and demonstrating both estrogenic and antiestrogenic effects, did not influence the conjugation of 1-naphthol significantly in the cell cultures. The present findings demonstrate that P-UGT is by far the major enzyme conjugating 1-naphthol in the rat ovary and that commonly used inhibitors of P-SULT and CYPs also inhibit P-UGT activity, either directly or via other mechanisms.

The levels and subcellular distribution of enzymes involved in defenses against reactive oxygen superoxide dismutase (SOD; E.C.1.15.1.1), glutathione peroxidase (GPX; E.C.1.11.1.9), catalase (CAT; E.C.1.11.1.6), and DT-diaphorase (DT; E.C.1.6.99.2) and of the conjugating enzymes glutathione transferase (GST; E.C.2.5.1.18) and p-sulphotransferase (p-ST; E.C.2.8.2.1) in the corpus luteum of ovaries from pregnant and non-pregnant pigs were investigated. In addition, non-protein thiols and glutathione reductase (GRD; E.C.1.6.4.2) were examined in the same manner. The total cytosolic activities of CAT, DT, GRD, and p-ST were significantly increased, whereas total GST activity was decreased in the pregnant corpus luteum compared to the corresponding activities in non-pregnant corpus luteum. In the case of the mitochondrial fraction from pregnant corpus luteum, GPX and GRD displayed significant increases in specific activity. Upon subfractionation of the mitochondrial fraction (i.e. mitoplast preparation), SOD activity was distributed equally between the mitoplasts and the supernatant. CAT and GPX activities were mainly recovered in the supernatant, while the major GRD activity pelleted with the mitoplasts. Microsomes from pregnant corpus luteum demonstrated increased specific GPX activity and decreased SOD activity compared to the non-pregnant corpus luteum. No differences in the non-protein thiol levels in the cytosolic, mitochondrial, or microsomal fractions from the corpus luteum were observed between non-pregnant and pregnant sows.

The expression of different isoenzymes of glutathione transferase (GST), i.e. the cytosolic subunits GSTA1/A2, A3, A4, A5, M1/2, M2 and P1, T2, and the microsomal GST in follicles of different sizes and in corpora lutea from porcine ovary, was investigated by Western blotting. No immunoreactivity was obtained with anti-rat GSTT2 or anti-rat microsomal GST polyclonal antibodies. In contrast, GSTA1/A2, A3, A4, A5, M1/2, M2 and P1 are all expressed in the cytosol from porcine ovaries. In general, the highest levels of these GST isoenzymes were present in the cytosol from corpora lutea, in agreement with measurements of activity towards 1-chloro-2,4-dinitrobenzene. Imunoreactivity with anti-rat GSTP1 was only obtained with follicles. The cytosolic GSTs from follicles and corpora lutea were affinity purified on glutathione–Sepharose and separated by reversed-phase high-performance liquid chromatography in order to quantitate the different subunits. A peak corresponding to the class pi subunit was present in follicles. This peak was also seen with corpora lutea, although at very low level. There were four peaks containing class mu subunits. The remaining peaks were concluded to contain the class alpha subunits, except for two peaks which are suggested to contain proteins other than GSTs. The levels of the different subunits were quantitated on the basis of the areas under the peaks and the relative amounts in follicles of different sizes and in corpora lutea corresponded well with the Western blot analysis.

Osmotic demyelinating syndromes consisting of central pontine and extra-pontine demyelination are very uncommon disorders characterized by non-inflammatory lesions involving the pons and sometimes spreading to other areas. Rapid changes in serum sodium concentration are usually regarded as the main pathophysiological mechanism. We report herein the case of a 23-year-old woman in the 24th week of pregnancy, who demonstrated both central pontine and extra-pontine demyelination occurring at the time of a recently introduced treatment with lithium. The disorder was related to the rapid correction of pregnancy-related hyponatremia, as a consequence of lithium-induced diabetes insipidus. Hence, lithium toxicity is a rare cause of osmotic demyelinating syndromes and appears to correlate with disturbances in sodium homeostasia.