[Detection of colorectal findings for cancer prevention by immunochemical stool test with different sensitivity levels]. / Detektion von kolorektalen Befunden zur Darmkrebsprävention mit immunologischem Stuhltest in verschiedenen Empfindlichkeitsstufen.

Immunochemical stool blood tests have a significantly higher sensitivity for the detection of advanced neoplasia and colorectal cancer. Based on national and international studies it has been required to include them into the national cancer screening programme in Germany also. The sensitivity (detection limit) can be set by the manufacturer in order to achieve an optimal and balanced result between sensitivity and specificity. The present study was conducted with 639 patients who have undergone both the screening colonoscopy, as well as the immunochemical stool blood test. The test "immoCARE-C" provided by the company CARE diagnostica Laborreagenzien GmbH was used in the study. The test has been evaluated with seven levels of detection limits between 500  ng/mL and 25  ng/mL. The best sensitivity for detection of advanced lesions was demonstrated by a cut-off of 50 ng/mL and 25  ng/mL. The specificity did not fall below 90  %. These positive results lead to considerations to organise a primary access to such tests in the prevention of colorectal cancer as a kind of filter before offering the screening colonoscopy.

Interactions between antiretroviral therapy and complementary and alternative medicine: a narrative review.

BACKGROUND: The use of complementary and alternative medicine including herbal medicine (phytotherapy), vitamins, minerals and food supplements is frequent among people living with HIV/AIDS (PLWHAs) who take antiretroviral (ARV) drugs, but is often not known by their prescribing physicians. Some drug-supplement combinations may result in clinically meaningful interactions. AIMS: In this literature review, we aimed to investigate the evidence for complementary and alternative medicine interactions with ARVs. SOURCES: A bibliographic search of all in vitro, human studies and case reports of the PubMed database was performed to assess the risk of interactions between complementary and alternative self-medication products and ARVs. The 'HIV drug interaction' (https://www.hiv-druginteractions.org) and 'Natural medicines comprehensive database' (https://naturalmedicines.therapeuticresearch.com) interaction checkers were also analysed. CONTENT: St John's wort, some forms of garlic, grapefruit and red rice yeast are known to have significant interaction and thus should not be co-administered, or should be used with caution with certain ARV classes. Data on other plant-based supplements come from in vitro studies or very small size in vivo studies and are thus insufficient to conclude the real in vivo impact in case of concomitant administration with ARVs. Some polyvalent minerals such as calcium, magnesium, and iron salts can reduce the absorption of integrase inhibitors by chelation. Potential interactions with vitamin C and quercetin with some ARVs should be noted and efficacy and tolerance of the treatment should be monitored. IMPLICATIONS: This review shows the importance of screening all PLWHAs for complementary and alternative medicine use to prevent treatment failure or adverse effects related to an interaction with ARVs. Further human studies are warranted to describe the clinical significance of in vitro interactions between numerous complementary and alternative medicine and ARVs.

Geoidal change and shore-level tilt along holocene estuaries: senegal river area, west Africa.

An expedition under "Projet Rhéomarge" traced marine deposits along the Sénégal estuary. Leveled and dated samples have made it possible to reconstruct portions of paleogeoids of 6500, 5500, and 1800 years before present. The surfaces of these geoids show that the tilt across continental margins predicted by mathematical models is less than 1 meter from the coast to 120 kilometers inland.

Fasting plasma carotenoids concentrations in Crohn's and pancreatic cancer patients compared to control subjects.

Carotenoids are colored molecules that are widespread in the plant kingdom, but animals cannot synthesize them. Carotenes are long, apolar molecules which require fully functioning digestive processes to be absorbed properly. Hence they could be interesting markers of intestinal absorption and digestion. Indeed, only few tests are available to assess these processes and only the D-xylose tolerance test is routinely used. However D-xylose is a sugar that tests only the absorption of water-soluble compounds and it only tests duodenal absorption. In this study, we have evaluated carotenoids as markers of digestion and absorption. We compared fasting plasma carotenoids concentrations in 21 control subjects, 20 patients with Crohn's disease, and 18 patients with pancreatic cancer. Crohn's disease alters intestinal absorption while pancreatic cancer decreases pancreatic enzyme secretion thus impairing digestion. Results show that all carotenoids are significantly lower in Crohn's and cancer patients as compared to control subjects and the multifactorial analysis shows that this decrease is mostly independent of dietary intake. Interestingly, maldigestion as seen in pancreatic cancer more strongly influences plasma lutein and lycopene concentrations while malabsorption in Crohn's disease acts on other carotenoids. Thus carotenoids could be interesting alternatives for testing and following patients that are suspected of having malabsorption or maldigestion syndromes.

Factors influencing blood concentration of retinol, alpha-tocopherol, vitamin C, and beta-carotene in the French participants of the SU.VI.MAX trial.

OBJECTIVES: The data was collected during the inclusion step of the SUpplémentation en VItamines et Minéraux AntioXydants (SU.VI.MAX) study. This article deals with the study's first stage before any supplementation. The collected data shows factors influencing blood vitamin concentrations and may reflect the vitamin status of volunteers. MATERIAL AND METHODS: A total of 12,741 volunteers were enrolled in the SU.VI.MAX study 7,713 women 35-60 years of age and 5,028 men 50-60 years of age. The serum concentrations of retinol, alpha-tocopherol, and beta-carotene were measured by HPLC, and vitamin C concentration was measured by spectrofluorimetry using a Technicon continuous flow analysis apparatus. The volunteers recorded their 24 h diet by means of a specific terminal that was connected to the main central computer of the SU.VI.MAX study. Volunteers recorded the food they consumed daily and estimated its quantity by comparing pictures of dishes. RESULTS: Retinol concentration was significantly higher in older volunteers, and was higher in male than in female volunteers. Smoking had no effect on serum retinol, but the latter was higher in the autumn than in the winter. Serum retinol concentrations were higher in the Southwest region and lower in the Ile-de-France and East-Centre regions. Serum alpha-tocopherol was slightly higher in older volunteers and also higher in male volunteers. Serum alpha-tocopherol was significantly lower in smokers, and former smokers showed intermediate levels. Like retinol, serum alpha-tocopherol was higher in the autumn, and higher in the Southwest as compared to the East-Centre Serum beta-carotene was slightly higher in younger volunteers, and concentrations were higher in female than in male volunteers. Tobacco smoking decreased serum beta-carotene, which was higher in the autumn, and higher in the East, West, and North regions. Serum vitamin C was higher in female volunteers, and was not age related. Serum vitamin C was lower in smokers, was season-dependant, but contrary to fat-soluble vitamins, concentrations were higher in the winter and spring. Serum vitamin C was higher in the Southeast and East-Centre, but lower in the North region. CONCLUSION: These results suggest that serum retinol concentrations depend on gender, age, seasons, and location of residence. Similarly, serum alpha-tocopherol concentrations were slightly influenced by age, but more by tobacco smoking, seasons, dietary intake, and location of residence. Serum concentrations of beta-carotene depend on gender, age, smoking status, dietary intake, and location of residence. Serum vitamin C concentrations depend on gender, age, smoking status, seasons, dietary intake, and location of residence. Contrary to beta-carotene, retinol concentrations were higher in male than in female volunteers. Such a reversed relation suggests a higher beta-carotene-retinol conversion in male volunteers.

Serum concentrations of beta-carotene, vitamins C and E, zinc and selenium are influenced by sex, age, diet, smoking status, alcohol consumption and corpulence in a general French adult population.

OBJECTIVE: To assess relationships between energy, nutrient and food intakes, alcohol consumption, smoking status and body mass index (BMI), and serum concentrations of beta-carotene, alpha-tocopherol, vitamin C, selenium and zinc. METHODS: Data on health status, alcohol consumption, smoking habits, anthropometric data and biochemical measurements were obtained in 1821 women aged 35-60 y and 1307 men aged 45-60 y, participant to the SU.VI.MAX Study. Data on dietary intake were available on a subsample who reported six 24-h dietary records during the first 18 months of the study. RESULTS: Women had higher baseline serum beta-carotene and vitamin C concentrations and lower concentration for serum vitamin E, zinc and selenium than men. In women, younger age was associated with lowered mean concentration of serum beta-carotene, vitamin E and selenium. In men, only differences were observed for serum zinc, which was lower in older men. Current smokers of both sexes had significantly lower concentrations of serum beta-carotene, vitamin C and selenium, and, only in women, of vitamin E, than nonsmokers. Alcohol consumers had lower concentrations of serum beta-carotene and higher selenium concentrations. Serum beta-carotene and vitamin C concentrations were lower in obese subjects. There were positive associations of dietary beta-carotene, vitamin C and E with their serum concentrations. Age, nutrient and alcohol intakes, serum cholesterol, BMI and smoking status explained 15.2% of the variance of serum beta-carotene in men and 13.9% in women, and 10.8 and 10.0% for serum vitamin C, and 26.3 and 28.6% for serum vitamin E, respectively. CONCLUSION: Serum antioxidant nutrient concentrations are primarily influenced by sex, age, obesity, tobacco smoking, alcohol consumption and especially dietary intake of those antioxidant nutrients.

[Recent knowledge about intestinal absorption and cleavage of carotenoids]. / Données récentes sur l'absorption et le catabolisme des caroténoïdes.

Our knowledge about intestinal absorption and cleavage of carotenoids has rapidly grown during the last years. New facts about carotenoid absorption have emerged while some controversies about cleavage are close to end. The knowledge of the absorption and conversion processes is indispensable to understand and interpret the perturbations that can occur in the metabolism of carotenoids and vitamin A. Recently, it has been shown that the absorption of certain carotenoids is not passive - as believed for a long time - but is a facilitated process that requires, at least for lutein, the class B-type 1 scavenger receptor (SR-B1). Various epidemiological and clinical studies have shown wide variations in carotenoid absorption from one subject to another, such differences are now explained by the structure of the concerned carotenoid, by the nature of the food that is absorbed with the carotenoid, by diverse exogenous factors like the intake of medicines or interfering components, by diet factors, by genetic factors, and by the nutritional status of the subject. Recently, the precise mechanism of beta-carotene cleavage by betabeta-carotene 15,15' monooxygenase (EC 1.14.99.36) - formerly called beta-carotene 15,15' dioxygenase (ex EC 1.13.11.21) - has been discovered, and a second enzyme which cleaves asymmetrically the beta-carotene molecule has been found. beta-carotene 15,15' monooxygenase only acts on the 15,15' bond, thus forming two molecules of retinal from one molecule of beta-carotene by central cleavage. Even though the betabeta-carotene 15,15' monooxygenase is much more active on the beta-carotene molecule, a study has shown that it can act on all carotenoids. Searchers now agree that other enzymes that can catalyse an eccentric cleavage of carotenoids probably exist, but under physiological conditions the betabeta-carotene 15,15' monooxygenase is by far the most active, and it is mainly effective in the small bowel mucosa and in the liver. However the conversion of provitamin A carotenoids into vitamin A is only partial, and requires a satisfactory protein status.

5-Hydroxymethyluracil excretion, plasma TBARS and plasma antioxidant vitamins in adriamycin-treated patients.

The thymine oxidative lesion-5-hydroxymethyluracil (HMUra)-was measured in urine collected from cancer patients. These patients all received chemotherapy using Adriamycin. Adriamycin (ADR) intercalates DNA coils and interferes with normal cell metabolism through diverse biochemical mechanisms that may explain its different actions. The anticancer action of ADR could derive from its interaction with topoisomerase II, resulting in DNA nicking followed by DNA fragmentation and apoptosis. Side effects of ADR-mainly its cardiotoxicity-may derive from the fact that ADR generates superoxide and hydroxyl radicals in two ways: redox-cycling and a Haber-Weiss type reaction due to Fe-ADR complexes. The oxygen free radicals, particularly .OH, are thought to be produced by ADR directly in genomic material and attack all its components. 5-Hydroxymethyluracil is a thymine lesion provoked by these attacks, and it has been proposed as a marker of DNA alterations. In this article, we report the results of a study involving 14 cancer patients treated with ADR. We found that urine HMUra is significantly increased by the anticancer therapy (HMUra (nmol/24 h): 74.4 9.46 vs. 96.3 8.74; p < .01), this increase reveals a higher risk of mutagenesis. Our study is the first to show an in vivo alteration of DNA by ADR. Results also show that thiobarbituric acid reactants increase significantly, and that the vitamin levels for retinol and alpha-tocopherol, which are antioxidant vitamins, are lower at the end of chemotherapy. We suggest to supplement these patients with vitamins A and E, and selenium to reduce the side effects of ADR.

Altered antioxidant status and increased lipid peroxidation in children with cystic fibrosis.

Cystic fibrosis often combines an infectious pathology with a syndrome of malabsorption, both potentially capable of favoring the deleterious effects of reactive oxygen species. This study was a simultaneous evaluation of the main antioxidant systems dependent on micronutrients and of lipid peroxidation products in 27 children with cystic fibrosis and 17 healthy children. Plasma of cystic fibrosis patients showed very low concentrations of beta-carotene (0.30 +/- 0.2 vs 1.63 +/- 0.5 mumol/g cholesterol, P < 0.0001) and a lower activity of selenium-dependent glutathione peroxidase (263.6 +/- 42 vs 296.9 +/- 57 U/L, P = 0.028). In parallel, the higher plasma concentrations of organic hydroperoxides (171.5 +/- 54.4 vs 122.6 +/- 23.3 mumol/L, P = 0.001) and of thiobarbituric acid reactants (2.9 +/- 0.6 vs 2.4 +/- 0.3 mumol/L, P = 0.004) reflected oxidative stress in this pathology. In addition, in these patients the major substrates of lipoperoxidation were significantly lower, whether they be linoleic acid (2.26 +/- 0.8 vs 3.60 +/- 0.9 mmol/L, P < 0.0001) or arachidonic acid (0.55 +/- 0.2 vs 0.74 +/- 0.2 mmol/L, P = 0.006). These results suggested that nutritional deficiencies resulting from malabsorption could considerably amplify disorders related to toxicity of reactive oxygen species. These nutritional deficits could also be aggravated by the destruction of antioxidant compounds by the inflammatory process.

Granulomatous hepatitis in Q fever.

Liver lesions in 17 patients with serologically diagnosed Q fever are described. A distinctive granulomatous pattern, with granuloma formation plus a fibrinoid ring, was observed in 14 cases. In two cases the fibrinoid material consisted of fibrillar eosinophilic structures without an annular arrangement, interspersed among epithelioid cells. In only one case was a nonspecific granuloma (devoid of fibrinoid material) noted. We conclude that the association of a granuloma with fibrinoid material is highly indicative of Q fever, but serial sections are often necessary to demonstrate this pattern.

Urinary 8-oxo-7,8-dihydro-2'-deoxyguanosine and 5-(hydroxymethyl) uracil in smokers.

Cigarette smoke is known to generate free radicals by various mechanisms. In this study involving 30 non-smokers and 30 smokers, we show that urinary excretion of 5-(hydroxymethyl) uracil (HMUra) was not different in the two groups (6.54+/-2.07 vs. 6.70+/-1.68 nmol/mmol creatinine). In contrast, 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxo-dGuo) excretion increased by 16% (1.16+/-0.35 vs. 1.35+/-0.50 nmol/mmol creatinine, p = 0.039). Results concerning 8-oxo-dGuo are in agreement with those of previous studies. We observed significant multiple correlations between HMUra and creatinine (r(p) = 0.44), BMI (r(p) = -0.27) and nicotine derivatives (r(p) = 0.26). Multiple correlation analysis showed relations between 8-oxo-dGuo on the one hand, and: creatinine (r(p) = 0.36), nicotine derivatives (r(p) = 0.29), BMI (r(p) = -0.24) on the other.

Urine 8-oxo-7,8-dihydro-2-deoxyguanosine vs. 5-(hydroxymethyl) uracil as DNA oxidation marker in adriamycin-treated patients.

We measured the base 5-(hydroxymethyl) uracil (HMUra) and the nucleoside 8-oxo-7,8-dehydro-2'-deoxyguanosine (8-oxo-dGuo) in urine of adriamycin-treated cancer patients. Adriamycin has been shown to generate oxygen free radicals by various mechanisms. HMUra and 8-oxo-dGuo are two known lesions of DNA, produced by oxygen free reaction on thymine and 2'-deoxyguanosine, respectively. HMUra was measured by GC-MS/isotopic dilution and 8-oxo-dGuo by HPLC/EC, both after prepurification by semipreparative HPLC. Here we report the results of a study involving 20 cancer patients treated with flash doses of ADR. We found that urine HMUra is significantly increased (HMUra (nmol/24h): 80.8 8.44 vs. 98.7+/-6.87; p < 0.01) 24h after administration of the drug, while 8-oxo-dGuo did not show any significant variation. Urine HMUra seems to be a suitable short-term marker of DNA alterations by oxygen free radicals.

Blood and liver lipid peroxide status after chronic ethanol administration in rats.

During the last decades a vast number of reports have aimed at elucidating the mechanisms behind alcohol-related organ injury, but the manner in which ethanol induces, e.g., liver damage is still an enigma. Increased oxidative stress has been put forward as one possible mechanism behind alcohol-related tissue damage. This paper focuses on the effect of chronic ethanol consumption on antioxidant status and lipid peroxide levels in blood and liver of rats. Alcohol was given twice daily in a total dose of 5 g ethanol/kg body wt. per day divided into two 2.5 g ethanol/kg body wt. doses as a 50% water solution, by gavage over 4 weeks. Chronic ethanol ingestion led neither to a significant change in lipid peroxide formation nor to a significant change in enzymatic antioxidant activities. Only concentrations of oxidized glutathione and of other non-enzymatic antioxidant such as vitamin E showed a tendency to decrease after alcohol application. The data presented could serve to emphasize no involvement of free radical-induced lipoperoxidation in the pathogenesis of ethanolic liver diseases.

Longitudinal changes in serum zinc concentration and distribution after acute myocardial infarction.

The authors studied the changes in serum zinc concentration and distribution during the 15 days following acute myocardial infarction in 21 patients. The method is based on ultrafiltration and electrothermal atomic absorption spectrometry. It is rapid and needs only 2.5 ml of serum. Serum and erythrocyte copper and zinc, serum zinc-binding ligands and serum enzyme activities were also determined. Serum zinc (P < 0.00001) and exchangeable zinc (mainly albumin-bound zinc, P = 0.01) declined within the first 3 days and then returned gradually to reference ranges. Exchangeable zinc was correlated with transthyretin (P = 0.00001) and total serum zinc (P < 0.00001). Exchangeable zinc accounted for virtually all of the differences in total serum zinc concentration after myocardial infarction. This result could be related to an increase of zinc uptake by tissues. Therefore, studies are needed to evaluate whether zinc supplementation in the early stages of acute myocardial infarction might improve prognosis.

Protective effect of selenium and zinc on UV-A damage in human skin fibroblasts.

Ultraviolet A radiation participates in cytotoxicity and carcinogenesis of the skin by a mechanism involving the generation of reactive oxygen species. Endogenous antiradical defense systems utilize metalloenzymes including Se-dependent glutathione peroxidase and Cu and Zn superoxide dismutase. The aim of the present work was to determine the protective effect of two trace elements, Se and Zn, on cultured human diploid fibroblasts exposed to UV-A radiation (broad-spectrum source with a maximum intensity at 375 nm). Selenium in the culture medium (0.1 mg/L) in the form of sodium selenite increased the synthesis and activity of glutathione peroxidase by 60.5% in the absence of exposure to UV-A radiation and by 35% after irradiation with 5 J/cm2 (P = 0.043). The presence of this element significantly increased the survival of UV-A-irradiated fibroblasts (P < 0.0001). This confirms the essential role of Se in the detoxifying activity of the enzyme. In addition, thiobarbituric acid-reacting substances (TBAR), which are lipid peroxidation markers, decreased in the presence of exogenous Se: -19% and -22% without irradiation and after irradiation with 5 J/cm2 (P = 0.056). When Zn was added at the dose of 6.5 mg/L as ZnCl2, fibroblasts subjected to oxidizing stress induced by UV-A were protected from cytotoxicity (P < 0.0001). The TBAR production decreased significantly: -33% without irradiation and -34% after irradiation with 5 J/cm2 (P = 0.008). Superoxide dismutase activity, however, decreased after supplementing with Zn: -26% without irradiation and -20% after UV-A irradiation (P = 0.017). The antioxidant properties of Zn are thus apparently independent of superoxide dismutase activity.

Influence of the 'directions for use' on positivity rates of the Hemoccult II test.

OBJECTIVE: A concise, detailed, and complete instruction sheet is indispensable for adequate completion by the users of a product. This sheet should be enclosed in the envelope which contains Hemoccult II slides. The authors found that the instructions provided by the French manufacturer were unsatisfactory. They designed a short and simple notice, adequately detailed to be understandable by all volunteers and to obtain satisfactory stool smears. Positivity rates of Hemoccult II performed with the manufacturer's notice were compared to those obtained with Hemoccult II performed with the authors' instructions. METHODS: This study was made during the third screening campaign carried out by the Office Departemental de Lutte contre le Cancer (ODLC). This screening programme only concerned women 59 to 69 years of age. Six thousand three hundred and ninety-two Hemoccult II containing the manufacturer's instructions were received at the laboratory during March, April, May, June and July 1996, and 2633 Hemoccult II containing the ODLC instructions during March, April, May, June and July 1997. All Hemoccult II were developed and read by one trained technician in the Biochemistry Laboratory (Grenoble University Hospital). RESULTS: The two populations, studied in 1996 and 1997, were strictly comparable in terms of age and number of previous screenings. Out of 6392 Hemoccult II containing the manufacturer's instructions, 157 (2.5%) were found positive, as compared to 36 (1.4%) Hemoccult II out of 2633 which contained the authors' instructions. This difference is highly significant (P = 0.001). CONCLUSION: The directions for use provided with Hemoccult II had a crucial influence on positivity rates, and therefore on the cost of screening. The instruction sheet provided by the French manufacturer is not satisfactory as it contains too much needless information, while several important pieces of advice are missing.

Effects of a combined micronutrient supplementation on maternal biological status and newborn anthropometrics measurements: a randomized double-blind, placebo-controlled trial in apparently healthy pregnant women.

OBJECTIVE: To investigate the possible beneficial effects of a micronutrient supplementation to apparently healthy pregnant women on maternal biological status and new born anthropometric characteristics. SETTING: Departments of Obstetric of the University Hospital of Grenoble (France) and Lyon (France), Laboratoire of Biology of Oxidative Stress, UFR de Pharmacie. Grenoble (France). STUDY DESIGN: Double-blind, randomized placebo-controlled intervention trial. SUBJECTS: A total of 100 apparently healthy pregnant women were recruited at 14+/-2 weeks of gestation to delivery. At the end, they were 65 women to follow out the study. INTERVENTIONS: Daily consumption over gestation of a micronutrients supplement or placebo. MAIN OUTCOME MEASURES: Plasma micronutrient levels and oxidative stress parameters were measured in mothers at 14 and 38 weeks of gestation. New born's anthropometric characteristics were measured at delivery. RESULTS: In the supplemented group, folic acid, vitamin C, E, B2, B6 and beta-carotene levels were higher than in the placebo group. Oxidative stress parameters were not different between the groups. Birth weights were increased by 10% and the number of low newborn weights (<2700 g) decreased significantly when the mother received the supplementation. Maternal plasma Zn levels were positively correlated to the newborn heights. CONCLUSION: A regular intake of a micronutrient supplement at nutritional dose may be sufficient to improve micronutrient status of apparently healthy pregnant women and could prevent low birth weight of newborn.

Assessment of DNA damage by comet assay on frozen total blood: method and evaluation in smokers and non-smokers.

This study was undertaken with the aim to develop an optimised protocol for the evaluation of DNA damage in frozen whole blood. This was achieved by use of the single-cell gel electrophoresis (SCGE) or comet assay in its alkaline version. After collection of blood, the total blood sample was mixed with dimethyl sulfoxide (DMSO), a cryoprotectant commonly used for prevention of freezing-induced damage to living cells, and then stored at -80 degrees C. We observed no statistically significant differences in the level of DNA damage between fresh blood samples and frozen blood samples, as assessed by the comet assay. Considering the absence of effects of the freezing step, a frozen blood sample was included as a control sample in subsequent experiments. Thus the protocol was applied to blood samples of twenty healthy subjects including smokers and non-smokers. The comparative analysis indicated that the level of DNA damage was 56% higher in smokers than in non-smokers (P = 0.01). Altogether, this study strongly suggests that frozen whole blood could be utilised in association with the comet assay in human epidemiological bio-monitoring for the assessment of genetic damage in populations at risk.

"The SU.VI.MAX Study": a primary prevention trial using nutritional doses of antioxidant vitamins and minerals in cardiovascular diseases and cancers. SUpplementation on VItamines et Minéraux AntioXydants.

The "SUpplementation en VItamines et Minéraux AntioXydants" (SU.VI.MAX) Study is a randomized double-blind, placebo-controlled, primary-prevention trial which started in 1994 in France. This epidemiologic study is designed to test the efficacy of a daily supplementation with antioxidant vitamins (vitamin C, 120 mg, vitamin E, 30 mg, and beta-carotene, 6 mg) and minerals (selenium, 100 microg, and zinc, 20 mg) at nutritional doses, in reducing the main causes of premature death (cancers and cardiovascular diseases); 12,735 eligible subjects (women aged 35 to 60 years, and men aged 45 to 60 years) were included in 1994 and and will be followed up for 8 years. Participants undergo a yearly visit consisting, every other year, of either biological sampling or clinical examination. They also regularly provide information on health events and dietary intake by filling out computerized questionnaires using the Minitel Telematic Network. After 2 years of supplementation, biochemical indicators of vitamin and trace element status reach reasonable level without reaching concentrations as high as those observed in intervention studies, which tested relatively high doses of antioxidants, and ended up with higher risk of pathology.

[Hepatic metastasis of unknown primary site]. / Métastases hépatiques de site primitif inconnu.

In this retrospective study, 91 patients (30%) out of a series of 304 with metastatic cancer of unknown primary site were found to have liver metastases. The liver was the only metastatic site in 28 (31%) cases and was associated with other sites in 63 (69%) cases. Median age was 62 yr in 61 male patients and 59 yr in 30 female patients. Thirty patients were submitted to an extensive investigation in search of the primary tumor, including systematic endoscopies: no primary cancer was found in these patients. In 61 other patients, only symptom-oriented investigations were performed and the primary cancer was found in 11 cases. The histologic type was adenocarcinoma in 71 (78%) cases, undifferentiated in 11 (12%) cases, epidermoid in 5 (6%) cases and determined by cytology alone in 4 cases. The median survival was 4 months in patients with metastases in the liver only, and 5 months in the other patients. This difference was not significant, so prognostic factors such as the Karnofsky index, weight loss, CEA and LDH levels were evaluated in the entire group; these factors do not have significant prognostic value. By contrast, when patients were able to receive chemotherapy, median survival was better (4 months) than without (median survival: 1 month; P = 0.005). In addition, in the case of objective response to chemotherapy, the median survival was 9 months versus 3.5 months for patients without objective response (P = 0.001). Seventy-three out of 91 patients (80%) were treated with chemotherapy regimen; 65 patients were evaluable: the objective response rate was 11 +/- 7% (7/65). Different regimens were used. With a non-toxic combination of fluorouracil, vinblastine and cyclophosphamide, 3 partial responses greater than or equal to 50% out of 43 patients (7 +/- 8%) were obtained. No significant advantage was observed when adriamycin was added to FU (4/13): 31 +/- 25%. Second- or third line chemotherapy regimen due to progression of the disease after the first-line combination provided only one objective response out of 36 patients. According to this retrospective study we recommend that overinvestigation be avoided in patients, with liver metastases of unknown primary site and that these patients be treated with non-toxic drug combinations.