Impact of physical activity on fatigue and quality of life in people with advanced lung cancer: a randomized controlled trial.

BACKGROUND: Physical activity (PA) improves fatigue and quality of life (QOL) in cancer survivors. Our aim was to assess whether a 2-month PA intervention improves fatigue and QOL for people with advanced lung cancer. METHODS: Participants with advanced lung cancer, Eastern Cooperative Oncology Group performance status (PS) ≤2, >6 months life expectancy, and ability to complete six-min walk test, were stratified (disease stage, PS 0-1 versus 2, centre) and randomized (1:1) in an open-label study to usual care (UC) (nutrition and PA education materials) or experimental intervention (EX): UC plus 2-month supervised weekly PA and behaviour change sessions. Assessments occurred at baseline, 2, 4, and 6 months. The primary endpoint was fatigue [Functional Assessment of Cancer Therapy-Fatigue (FACT-F) questionnaire] at 2 months. The study was designed to detect a difference in mean FACT-F subscale score of 6. Analysis was intention-to-treat using linear mixed models. RESULTS: We recruited 112 patients: 56 (50.4%) were randomized to EX, 55(49.5%) to UC; 1 ineligible. Male 55%; median age 64 years (34-80); 106 (96%) non-small cell lung cancer; 106 (95.5%) stage IV. At 2, 4 and 6 months, 90, 73 and 62 participants were assessed, respectively, with no difference in attrition between groups. There were no significant differences in fatigue between the groups at 2, 4 or 6 months: mean scores at 2 months EX 37.5, UC 36.4 (difference 1.2, 95% CI - 3.5, 5.8, P = 0.62). There were no significant differences in QOL, symptoms, physical or functional status, or survival. CONCLUSIONS: Adherence to the intervention was good but the intervention group did not increase their PA enough compared to the control group, and no difference was seen in fatigue or QOL. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry No. ACTRN12609000971235.

Cytokine profiling of docetaxel-resistant castration-resistant prostate cancer.

BACKGROUND: Docetaxel improves symptoms and survival in metastatic castration-resistant prostate cancer (CRPC). However, ∼50% of patients are chemoresistant. This study examined whether changes in cytokine levels predict for docetaxel resistance in vitro and in a clinical cohort. METHODS: PC3 cells or their docetaxel-resistant subline (PC3Rx) were co-cultured with U937 monocytes, with and without docetaxel treatment, and cytokine levels were measured. The circulating levels of 28 cytokines were measured pre-/post cycle 1 of docetaxel from 55 men with CRPC, and compared with prostate-specific antigen (PSA) response. RESULTS: PC3Rx-U937 co-culture expressed more cytokines, chiefly markers of alternative macrophage differentiation, compared with PC3-U937 co-culture. Docetaxel treatment enhanced cytokine production by PC3Rx-U937 co-culture, while reducing cytokine levels in PC3-U937. In patients, changes in the levels of seven circulating cytokines (macrophage inhibitory cytokine 1 (MIC1), interleukin (IL)-1ra, IL-1ß, IL-4, IL-6, IL-12 and IFNγ) after cycle 1 of docetaxel were associated with progressive disease (all P<0.05). The combination of changes in MIC1, IL-4 and IL-6 most strongly predicted PSA response (P=0.002). CONCLUSIONS: In vitro studies suggest docetaxel resistance is mediated, at least in part, by cytokines induced by the interaction between the docetaxel-resistant tumour cells and macrophages. Early changes in circulating cytokine levels were associated with docetaxel resistance in CRPC patients. When considered together, these data suggest a significant role for the inflammatory response and macrophages in the development of docetaxel resistance in CRPC.

Methylated Glutathione S-transferase 1 (mGSTP1) is a potential plasma free DNA epigenetic marker of prognosis and response to chemotherapy in castrate-resistant prostate cancer.

BACKGROUND: Glutathione S-transferase 1 (GSTP1) inactivation is associated with CpG island promoter hypermethylation in the majority of prostate cancers (PCs). This study assessed whether the level of circulating methylated GSTP1 (mGSTP1) in plasma DNA is associated with chemotherapy response and overall survival (OS). METHODS: Plasma samples were collected prospectively from a Phase I exploratory cohort of 75 men with castrate-resistant PC (CRPC) and a Phase II independent validation cohort (n=51). mGSTP1 levels in free DNA were measured using a sensitive methylation-specific PCR assay. RESULTS: The Phase I cohort identified that detectable baseline mGSTP1 DNA was associated with poorer OS (HR, 4.2 95% CI 2.1-8.2; P<0.0001). A decrease in mGSTP1 DNA levels after cycle 1 was associated with a PSA response (P=0.008). In the Phase II cohort, baseline mGSTP1 DNA was a stronger predictor of OS than PSA change after 3 months (P=0.02). Undetectable plasma mGSTP1 after one cycle of chemotherapy was associated with PSA response (P=0.007). CONCLUSIONS: We identified plasma mGSTP1 DNA as a potential prognostic marker in men with CRPC as well as a potential surrogate therapeutic efficacy marker for chemotherapy and corroborated these findings in an independent Phase II cohort. Prospective Phase III assessment of mGSTP1 levels in plasma DNA is now warranted.

Circulating microRNAs are associated with docetaxel chemotherapy outcome in castration-resistant prostate cancer.

BACKGROUND: Docetaxel is the first-line chemotherapy for castration-resistant prostate cancer (CRPC). However, response rates are ∼50% and determined quite late in the treatment schedule, thus non-responders are subjected to unnecessary toxicity. The potential of circulating microRNAs as early biomarkers of docetaxel response in CRPC patients was investigated in this study. METHODS: Global microRNA profiling was performed on docetaxel-resistant and sensitive cell lines to identify candidate circulating microRNA biomarkers. Custom Taqman Array MicroRNA cards were used to measure the levels of 46 candidate microRNAs in plasma/serum samples, collected before and after docetaxel treatment, from 97 CRPC patients. RESULTS: Fourteen microRNAs were associated with serum prostate-specific antigen (PSA) response or overall survival, according to Mann-Whitney U or log-rank tests. Non-responders to docetaxel and patients with shorter survival generally had high pre-docetaxel levels of miR-200 family members or decreased/unchanged post-docetaxel levels of miR-17 family members. Multivariate Cox regression with bootstrapping validation showed that pre-docetaxel miR-200b levels, post-docetaxel change in miR-20a levels, pre-docetaxel haemoglobin levels and visceral metastasis were independent predictors of overall survival when modelled together. CONCLUSIONS: Our study suggests that circulating microRNAs are potential early predictors of docetaxel chemotherapy outcome, and warrant further investigation in clinical trials.

Better estimates of survival for patients considering adjuvant chemotherapy after surgery for early non-small-cell lung cancer.

INTRODUCTION: The aim of this study was to summarise and describe survival data from contemporary randomised trials of platinum-based adjuvant chemotherapy for patients with non-small-cell lung cancer (NSCLC). The goal was to assist clinicians to provide better estimates of survival for patients considering adjuvant chemotherapy following surgical resection for NSCLC. METHODS: Randomised trials of cisplatin-based adjuvant chemotherapy for resected NSCLC were identified. Survival rates at 1, 2, 5, 7 and 10 years and the following percentiles (scenario): 90th (worst case), 75th (lower typical), median, 25th (upper typical) and 10th (best case) were extracted from each overall survival (OS) curve. RESULTS: Thirty-eight OS curves from 19 trials (7042 patients) were analysed. With adjuvant chemotherapy, the median OS rate (interquartile range) at 1 year was 91% (85-95), 2 years was 73% (69-88), 5 years was 61% (45-65) and 7 years was 49% (38-65). With observation only, the median OS rate (interquartile range) at 1 year was 88% (83-92), 2 years was 74% (65-82), 5 years was 55% (42-58) and 7 years was 40% (34-45). In both arms, survival rates at 2, 5 and 7 years were well estimated by raising the 1-year survival rate to the power of two, five and seven respectively. Few trials reported survival rates at 10 years. CONCLUSION: Simple percentages and their powers provide a useful starting point for estimating and describing survival to patients considering adjuvant chemotherapy after surgery for NSCLC.

[Adverse obstetric and perinatal outcome with in vitro fertilization technology: A French nationwide population-based study]. / Risques de morbidité maternelle et périnatale en fécondation in vitro : une étude nationale de cohorte française.

OBJECTIVES: The objective of this study was to quantify the risk of maternal and perinatal morbidity with in vitro fertilization (IVF) technology compared to non-IVF pregnancies in a recent French national cohort. METHOD: The data was extracted from the hospital information data system, including all pregnancies with a delivery from 2013 to 2016. The risks of preterm birth, maternal morbidity (venous and arterial thrombosis, gestational diabetes, vascular disorders, placenta previa, placenta abruption), hypotrophy and congenital malformation were compared in both groups in univariate and multivariate analysis after adjustment on the characteristics of women (age, parity, obesity, tobacco dependence, history of diabetes or high blood pressure), multiple deliveries and sex of children. RESULTS: In all, 2,875,662 pregnancies and 2,922,712 births were analyzed, of which 49,224 were derived from IVF (1.7%). In multivariate analysis, all risks were significantly higher in IVF: premature deliveries (ORajusted=1.28; CI95%=1.24-1.32), maternal morbidity (ORajusted=1.24; CI95%=1.21-2.28), (mainly for thrombosis venous, placenta previa and placenta abruption). The risks of hypotrophy (ORajusted=1.13; CI95%=1.10-1.16) and congenital malformations (ORajusted=1.11; CI95%=1.05-1.17) were slightly increased. CONCLUSION: The results of this study on a large cohort of recent births in France confirm that there was an increased risk of maternal and perinatal morbidities in IVF. These risks were similar to those published in the international literature. This study is the starting point for a forthcoming surveillance.

The CDK inhibitors: potential targets for therapeutic stem cell manipulations?

Therapies involving adult stem cells are dependent upon sufficient expansion of these cells to repopulate or replace the diseased tissue and are consequently hindered by their relatively quiescent phenotype. Cellular proliferation is governed by the cyclin-dependent kinases, which in a complex with a corresponding cyclin, phosphorylate a number of downstream mediators to drive the cell through the cell cycle. In turn, biochemical activities of the cyclin-dependent kinases are regulated by two families of cyclin-dependent kinase inhibitors, which have been shown to be potent cell intrinsic blocks of adult stem cell proliferation in multiple tissue types. In contrast to normal stem cells, inappropriate regulation of the cell cycle in cancer stem cells may underlie tumorigenesis and failure of conventional chemotherapeutics to fully eradicate a tumor. Thus, definition of the roles of the cyclin-dependent kinase inhibitors in normal and cancer stem cells may permit the development of novel strategies for adult stem cell expansion and therapies specifically targeted to cancer stem cells.

Regulation of intracellular pH in tumor cell lines: influence of microenvironmental conditions.

The effect of microenvironmental factors on the regulation of intracellular pH (pHi) in MGH U1 cells and EMT-6 cells was studied using the fluorescent pH probe 2',7'-bis-(2-carboxyethyl)-5-(and-6)-carboxyfluorescein. Na+/H+ exchange and Na(+)-dependent Cl-/HCO3- exchange were found to be present in both cell types. The activity of both exchangers was dependent on pHi, with low levels of activity at neutral pH and an increase in activity as pHi fell. The level of extracellular pH (pHe) also influenced the operation of the exchangers, with a fall in activity as pHe was reduced over the range 7.4-6.6. This effect was more marked for the Na(+)-dependent Cl-/HCO3- exchanger than for the Na+/H+ antiporter, suggesting that under conditions of reduced pHe the Na+/H+ antiporter is the major mechanism for regulation of pHi. Neither 6 h of radiobiological hypoxia nor variations in the extracellular [Ca2+] over the range 1-6 mM had an effect on the regulation of pHi, while extracellular lactate (5-10 mM) caused a small, concentration-dependent decrease in the combined activity of both exchangers. We conclude that under the microenvironmental conditions found in some regions of tumors, Na+/H+ exchange may be the major method of regulation of pHi.

Crosslinking of the surface immunoglobulin receptor in B lymphocytes induces a redistribution of neurofibromin but not p120-GAP.

The activation of Ras proteins is a key step in the signal transduction pathways triggered by ligand-bound cell surface receptors. The GTPase activating proteins (GAPs) p120-GAP and neurofibromin, the neurofibromatosis-type 1 (NF1) gene product, are thought to play an essential role in the regulation of Ras activity by increasing the GTPase activity of wild type, but not activated Ras in vitro. Both GAPs are widely expressed in mammalian tissues thus raising the question of whether or not they have different regulatory functions. In this study, we have analysed the distribution of p120-GAP and neurofibromin in splenic B lymphocytes by immunofluorescent staining. Crosslinking of surface immunoglobulin (slg), the B-lymphocyte antigen receptor, induced the redistribution of neurofibromin. In contrast, no apparent change in the cellular localization of p120-GAP occurred followed the cross-linking of slg. The redistribution of neurofibromin coincided both spatially and temporally with the relocalization of crosslinked slg and was inhibited by the cytoskeletal disrupting agents colchicine and cytochalasin D. These findings indicated that neurofibromin and p120-GAP can be differentially regulated in vivo and suggest that neurofibromin is a component of the signaling pathway initiated by crosslinking of B lymphocyte slg. Furthermore, our observations that cocapping neurofibromin with slg is independent of the p21ras redistribution suggests that the role of neurofibromin in B cells is not solely related to its ability to act as a Ras regulator.

Involvement of Shc and Cbl-PI 3-kinase in Lyn-dependent proliferative signaling pathways for G-CSF.

Granulocyte colony-stimulating factor (G-CSF) is the major hematopoietic factor which controls the production and differentiation of granulocytes. The G-CSF receptor (G-CSFR) belongs to the superfamily of the cytokine receptors, which transduce signals via the activation of cytosolic protein tyrosine kinases (PTK). To determine the role of specific PTK in G-CSF signaling we expressed the human G-CSFR in cell lines derived from DT40 B cells, which lack either the Src-related Lyn or Syk. Wild-type (wt) and syk-deficient cells underwent increased DNA synthesis in response to G-CSF; lyn-deficient cells did not. The purpose of these studies is to identify Lyn's downstream effectors in mediating DNA synthesis. While G-CSF stimulated Ras activity in all cell lines, G-CSF failed to induce the tyrosine phosphorylation of Shc in lyn-deficient cells. G-CSF induced a statistically significant activation of Erk1/Erk2 Kinase or p90Rsk only in the wt cells. G-CSF induced the tyrosine phosphorylation of Cbl and increased activity of PI 3-kinase in wild-type and syk-deficient, but non in lyn-deficient, cells. Inhibition of Shc by over-expression of its SH2 or PTB domains or PI 3-kinase by either treatment with wortmannin or expression of the CblY731F mutant decreased G-CSF-induced DNA synthesis. Thus, the Lyn, Cbl-PI 3-kinase, and Shc/non-Ras-dependent pathways correlate with the ability of cells to respond to G-CSF with increased DNA synthesis.

Ectopic corticotropin syndrome and small-cell carcinoma of the lung. Clinical features, outcome, and complications.

BACKGROUND: Ectopic corticotropin syndrome is a rare complication of small-cell lung cancer (SCLC). There is little information concerning this syndrome available in the literature. We therefore reviewed all cases of ectopic corticotropin syndrome seen at our institution during a 20-year period. METHODS: Cases were identified by searching a computerized database and reviewing the charts of all 840 patients with SCLC seen between 1971 and 1991. Patients were included if they met at least two of the following criteria: spontaneous hypokalemia (potassium level, < 3.2 mmol/L); plasma cortisol level greater than 600 nmol/L; 24-hour urinary free cortisol level greater than 400 nmol/d; and plasma corticotropin level greater than 22 pmol/L. Data were abstracted from the patients' medical records. RESULTS: Of 840 patients with SCLC, 14 (1.6%) had ectopic corticotropin production. This was diagnosed at the time of presentation with SCLC in seven patients and from 3 to 19 months later in the remainder. Five patients had limited disease and nine had extensive disease. One or more features of Cushing's syndrome were observed in 57% of patients, but the entire syndrome occurred rarely. Spontaneous hypokalemia was present in all patients, and 10 patients (71%) had hyperglycemia. There were two complete responses and one partial response to chemotherapy, giving an overall response rate of 21%, and the median survival was 5.5 months. Ten patients died of progressive growth of tumor, while three patients died of infections. In one other patient, infection probably contributed to death. A high rate of nonfatal infections was also seen. CONCLUSIONS: The occurrence of SCLC with ectopic corticotropin syndrome is associated with poor survival, and a high incidence of infective complications, in patients treated with chemotherapy.

New chemotherapeutic agents in the treatment of non-small cell lung cancer: the Australian experience.

The disappointing results obtained with currently available chemotherapy for lung cancer has led to the development of several new agents over the past 5 years. These include paclitaxel, docetaxel, vinorelbine, gemcitabine, and the camptothecins, irinotecan and topotecan. To date, phase I and II clinical trials with paclitaxel, docetaxel, gemcitabine, and combinations containing these drugs have been performed in patients with non-small cell lung cancer in Australia. These trials have produced overall response rates of 10 to 40%, which are similar to the rates obtained in other studies with these agents. In general, the agents have been well tolerated. However, these studies cannot be compared with previous studies employing conventional chemotherapeutic agents, primarily because the results of the former studies may have been skewed due to enrollment of younger, healthier patients and a variable proportion of patients with locally advanced rather than metastatic disease. Randomized controlled trials will be needed to determine whether use of these newer agents is associated with improvements in survival, palliation, and/or toxic reactions when compared with currently used regimens.

Phase II study of paclitaxel and oral etoposide in patients with locally advanced or metastatic non-small cell lung cancer.

The combination of paclitaxel and etoposide was evaluated in a phase II study in patients with locally advanced or metastatic non small-cell lung cancer (NSCLC). Thirty-five patients, median age 61, received treatment with paclitaxel 200 mg/m (2) intravenous over 3 h on day 1, and oral etoposide, 100 mg daily on days 1-5. Cycles were repeated every 21 days for a maximum of nine cycles, or until progression occurred. Twenty-eight patients had stage IV disease, and seven patients had stage IIIA or B disease. There was one complete and seven partial responses (overall response rate, 23%). Two of these responses were in patients with stage III disease (29%) and six in patients with stage IV disease (21%). Median survival was 8.7 months, and 36% of patients were alive at 1 year. There were no treatment-related deaths and little grade 3 or 4 non-haematological toxicity although grade 3 or 4 neutropenia occurred in 60% of patients (33% of cycles). There were four episodes of febrile neutropenia. The combination of paclitaxel and oral etoposide is active in advanced NSCLC and can be delivered with acceptable toxicity.

Active surveillance after orchiectomy for nonseminomatous testicular germ cell tumors: late relapse may occur.

OBJECTIVES: To review the outcome of men with Stage I nonseminomatous germ cell tumors managed with a policy of active surveillance following orchiectomy. METHODS: The clinical records of all men with Stage I nonseminomatous germ cell tumors seen at Royal Prince Alfred Hospital, Australia between 1982 and 1995 were reviewed. Data were obtained concerning the histologic type of tumor, levels of serum tumor markers, relapse and subsequent treatment, and survival. RESULTS: Seventy-seven patients were entered into the active surveillance protocol between 1982 and 1995. With a minimum follow-up of 2 years, 27 (35%) have relapsed, with a median time to relapse of 5 months. Two late relapses occurred at 37 and 57 months after diagnosis. Relapses occurred most commonly in the retroperitoneal lymph nodes, with the lungs the second most common site. Following treatment with chemotherapy and surgery, all patients achieved complete remission, with 1 patient subsequently relapsing and ultimately dying of progressive tumor. One other patient died of acute myeloid leukemia, thought to be secondary to chemotherapy. Overall, 75 patients (97%) remain alive and free of disease. CONCLUSIONS: Active surveillance is a safe and effective approach to the management of Stage I nonseminomatous germ cell tumors. Although most relapses occur within the first 2 years, late relapses may occur.

Bioreductive agents: a clinical update.

Bioreductive agents are drugs that must undergo reduction to form an active cytotoxic species. The existence within solid tumors of regions of hypoxia offers the possibility of using such bioreductive agents to exert tumor-specific cytotoxicity. The only drug with bioreductive properties that is in routine clinical use in mitomycin C. This is a relatively old drug that has cytotoxicity independent of its bioreductive properties. However, the results of recent randomized clinical trials of mitomycin C in combination with radiotherapy have suggested that its bioreductive properties may play an important part in its activity. EO9 is a new bioreductive agent. Phase I and II clinical trials with EO9 have failed to demonstrate any significant antitumor activity. However, the design of these studies was such that activity based on bioreductive properties may have been difficult to demonstrate. Tirapazamine is the lead compound of a novel class of bioreductive agents. It is currently undergoing extensive clinical evaluation alone, combined with radiotherapy, and in combination with other cytotoxic drugs. Although early results of these trials are encouraging, the results of randomized studies will be required before the true value of this drug can be assessed.

Plasma phospholipid fatty acids and urinary excretion of prostaglandins PGE1 and PGE2 in infants during total parenteral nutrition, with continuous or sequential administration of fat emulsion.

During total parenteral nutrition, using an identical supply of fat emulsion (350 mg/kg/24 hr) to correct essential fatty acid deficiency in children, the efficacy of two methods of administration was studied: continuous over 24 hr, or discontinuous 3 hr/day. At the beginning of the study, all the infants (1-4 months old) had proven essential fatty acid deficiency. After at least 1 month of one of the two nutritional protocols (continuous or discontinuous), plasma phospholipid fatty acid composition and PGE1 and PGE2 urinary excretion were measured. The results obtained indicate better utilization of the fat emulsion when it is administered almost every day, in continuous infusion over 24 hr (1 g/kg/24 hr of Intralipid 20%).

[Production of oxygen free radicals in myocardial infarction treated by thrombolysis. Analysis of glutathione peroxidase, superoxide dismutase and malondialdehyde]. / Production de radicaux libres oxygénés au cours de l'infarctus du myocarde traité par thrombolyse. Analyse de la glutathion peroxydase, de la superoxyde dismutase et du malondialdéhyde.

Many enzyme systems such as glutathione peroxidase (GPx) or superoxide dismutase (SOD) neutralise the oxygen derived free radicals produced during myocardial reperfusion by thrombolysis. Erythrocytic SOD, plasma and erythrocytic GPx and their cofactor selenium, substances reacting with thiobarbituric acid (TBARS) were analysed by repeated sampling between T0 and 48 hours in 24 patients treated by thrombolysis for acute myocardial infarction. Angiographic control was undertaken systematically between 60 and 180 minutes after initiating thrombolytic therapy: 18 patients had a patent vessel and 6 patients had an occluded vessel recanalised in 5 cases by angioplasty. Biological analysis was performed in the 23 patients successfully revascularised by thrombolysis, eventually completed by angioplasty. The plasma GPx decreased non-significantly between T0 and 2 hours from 246.8 +/- 53.3 to 233 +/- 39 U/ml with a significant increase between 2 and 48 hours from 233 +/- 39.2 to 294 +/- 76 U/ml, whereas the erythrocytic GPx rose significantly and constantly between T0 and 48 hours from 34.8 +/- 7.1 to 37.6 +/- 7.5 U/gHb with significant consumption of selenium between T0 and 4 hours from 81.2 +/- 14 to 68.5 +/- 12.6 micrograms/l. The erythrocytic SOD increased significantly between T0 and 48 hours from 318.9 +/- 40.8 to 337 +/- 59 U/gHb. Finally, the analysis of plasma TBARS showed a non-significant rise between T0 and 30 minutes from 1.59 +/- 0.30 to 1.71 +/- 1.43 mm/l with a return to the basic line values after about 2 hours. These results show a significant increase in the activity of enzymes protecting against the liberation of oxygen free radicals, such as erythrocyte or plasma GPx and erythrocyte SOD between T0 and 48 hours with consumption of selenium, cofactor of GPx, and an increase in circulating lipid peroxydes in acute myocardial infarction treated by thrombolysis. They also illustrate the oxidative stress which occurs in this situation.

[Screening of essential fatty acid deficiency in children. Respective value of the assay of fatty acids in total lipids and lipid fractions of the serum]. / Dépistage d'une carence en acides gras essentiels chez l'enfant. Intérêt respectif du dosage des acides gras dans les lipides totaux et les fractions lipidiques du sérum.

This study was carried out in metabolically stable infants aged from one to six months receiving artificial food. The lipid serum fraction presenting changes characteristic of essential fatty acid (EFA) deficiency was determined. A preliminary study (n = 13 samples) showed that analysis of total fatty acids (TFA) and of phospholipids (PL) was more discriminatory than analysis of free fatty acids (FFA), triglycerides (TG) or esterified cholesterol (EC). Comparison of TFA and PL (n = 25 samples) confirmed literature data; in particular, C18: 2 n-6 and C20: 4 n-6 decreased whereas C20: 3 n-9 increased. These changes were clearer and significantly greater (p less than 0.001) for C20: 3 n-9 and C20: 4 n-6 of the PL, but were also very significant for the TFA compared to healthy controls. The C20: n-9/C20: n-6 ratio was identical for all fractions. TFA analysis by gas-liquid chromatography is faster and less costly than analysis of lipid fractions and provides sufficient data for screening of EFA deficiency.

[Glutathione peroxidases: value of their determination in clinical biology]. / Les glutathion peroxydases: intérêt de leur dosage en biologie clinique.

The role of glutathione peroxidase in the oxidative metabolism and recent advances in the demonstration of the consequences of the desequilibrium in the proxidant/antioxidant balance on biological molecules oxidation, intracellular signals transduction, apoptosis and necrosis, have led to new approach in the knowledge of many pathological processes. Methods for determining antioxidant capacity have been developed. The measurement of glutathione peroxidase activity is a key step in the study of oxidative stress. Its determination in clinical biology needs optimal conditions for standardised assays which will be used for epidemiological studies aimed to evaluate the role of nutritional factors involved in the pathogeny of diseases caused or accompanied by oxidative stress.

[Multicenter evaluation on different analyzers of three methods for direct HDL-cholesterol assay]. / Evaluation multicentrique sur différents automates d'analyses de trois méthodes de dosage direct du cholestérol-HDL.

Most frequently, in routine laboratories, C-HDL is measured in the supernatant after precipitation of apolipoprotein B-containing lipoproteins by the sodium phosphotungstate/magnesium chloride reagent (PTA). This method involves precipitation, centrifugation and decantation steps which prevent full automation of the measurement and decrease the accuracy of the results. Recently, three direct assays for C-HDL including alpha-cyclodextrin sulphate (alpha-CD), polyanions/detergents (PA-D) or antibodies anti-beta-lipoproteins (AC) have been commercialized, in which all steps are fully managed by automated analyzers. These new methods have been compared to the conventional procedure (PTA), in multicenter studies among six laboratories using different analyzers. The C-HDL values measured by the alpha-CD and PA-D assays correlated well with those of the PTA method (r > 0.98), on most of the analyzers. With the AC assay, only the results obtained with the Hitachi 717 analyzer were correlated with C-HDL values of the PTA method. The linearity and specificity studies were evaluated in the laboratory A on a Kone Specific analyzer. The alpha-CD and PA-D assays were linear for C-HDL values from 0 to 5.56 mmol/l, as observed by increasing amounts of HDL2 + HDL3 or serum without lipoprotein isolated by ultracentrifugation. The specificity of these two methods was evaluated simultaneously, by adding various amounts of lipoproteins isolated by sequential ultracentrifugation. No interference was observed when adding chylomicrons up to 13.4 mmol/l of triglycerides for both methods. Inversely, increased C-HDL values were observed with added VLDL from 6 mmol/l of triglycerides for the PA-D assay and from 8 mmol/l for the alpha-CD assay. No interference was observed with added LDL up to 11.5 mmol/l of C-LDL for the alpha-CD assay and up to 6.7 mmol/l for the PA-D assay. In conclusion, the present multicenter evaluation demonstrates that the new procedures for the direct automation of C-HDL are easy and accurate and most of them correlated well with the classical precipitation method. In addition the study provides arguments for a choice between the different direct C-HDL methods.