[Management of a radiotherapy center during the COVID-19 outbreak: The experience of the Mulhouse hospital centre (France)]. / Organisation d'un service de radiothérapie pendant l'épidémie de COVID-19 : expérience du centre hospitalier de Mulhouse.

The COVID-19 outbreak grows exponentially in our country. Despite most of patients develops benign symptoms, cancer patients are at risk of a severe form of the disease. Radiotherapy centres are a potential contamination place due to the number of patients treated and staff present. Their organization during the outbreak period aims to ensure continuity of care while limiting the risk of death from COVID-19. In the radiotherapy department of Mulhouse hospital (France), we pointed five points out: protection of medical and paramedical staff, protection of patients undergoing treatment, detection of patients suspected of being infected by SARS-CoV-2 and their management, reorganization of the patient circuit and measures regarding the quality management. This reflection, which began at the beginning of the outbreak in our city, allows us to preserve the access to radiotherapy treatments by anticipating the risk of spreading the virus. Through biweekly meetings, we continue to adapt to the epidemic in our department, considering our material resources. The ability to perform diagnostic tests in all suspect patients would also allow us to refine our procedures.

Gas chromatographic separation and mass spectrometric identification of mixtures of oxyphytosterol and oxycholesterol derivatives application to a phytosterol-enriched food.

Pure individual phytosterols were prepared using reversed-phase HPLC in order to obtain the oxidized compounds of sitosterol, campesterol, stigmasterol and brassicasterol. 7-Hydroxy-, 7-keto-, 5,6-epoxy-, 4beta-hydroxy-, 4-ene-6-hydroxy-, 6-keto- and 5alpha,6beta-dihydroxyphytosterols were obtained as well as analogous compounds of cholesterol. The gas chromatographic properties as well as the electronic impact mass spectra of these compounds (as trimethylsilyl ether derivatives) were studied. These data were used to identify oxyphytosterols in a spread enriched in phytosterols: the oxyphytosterols represented no more than 68 microg/g of spread (about 0.08% of phytosterols were oxidised).

Lymphatic absorption of phytosterol oxides in rats.

Two of the main classes of oxyphytosterols (7-keto and epoxides) were synthesized from sitosterol and campesterol and given to mesenteric duct-cannulated adult male rats. Lymph was collected during 24 h and was analyzed for oxysterols. The results showed that the lymphatic recovery of the phytosterol oxides was low: 4.7% of the given dose for epoxy derivatives and 1.5% for 7-keto compounds. The campesterol oxides presented a better absorption than the sitosterol oxides. During the process of absorption, the epoxyphytostanols were also partly transformed in campestanetriol and stigmastanetriol.

Trans isomers of long-chain n-3 polyunsaturated fatty acids in tissue lipid classes of rats fed with heated linseed oil.

The isomerization of linolenic acid into mono- and di-trans isomers takes place during heat treatment. One of these compounds, 18:3 delta 9c, 12c, 15t can be desaturated and elongated to form, in particular, the trans isomers of eicosapentaenoic and docosahexaenoic acids. This study was undertaken to observe the incorporation of these trans long-chain n-3 polyunsaturated fatty acids into the lipid classes of several tissues. Rats were fed for 8 weeks with heated linseed oil containing high levels of trans linolenic acid isomers. The lipid classes of the liver, kidney, heart and adrenals of these rats contained various levels of these compounds. The 20:5 delta 5c, 8c, 11c, 14c, 17t represented between 80 and 90% of the total 20:5 in the phospholipids, but 22:5 delta 7c, 10c, 13c, 16c, 19t and mainly 22:6 delta 4c, 7c, 10c, 13c, 16c, 19t were only present in small quantities. This may indicate that the cis fatty acids are better metabolized in these cases. Among the tissues studied, it was interesting to note a high level of 22:5 delta 19t in the adrenals, particularly in cholesterol esters.

Identification of novel trans isomers of 20:5n-3 in liver lipids of rats fed a heated oil.

Trans polyunsaturated n-3 fatty acids are formed as a result of the heat treatment of vegetable oils. It was demonstrated previously that the 18:3 delta 9cis, 12 cis, 15 trans containing a cis delta 9 ethylenic bond was converted to a geometrical isomer of 20:5n-3, the 20:5 delta 5 cis, 8 cis, 11 cis, 14 cis, 17 trans. In the present study, we have identified two new isomers of eicosapentaenoic acid, the delta 11 monotrans and the delta 11, 17 ditrans isomers in liver of rats fed a heated oil. These are formed as a result of the conversion of two of the main isomers of linolenic acid which are present in refined and frying oils, the 18:3 delta 9 trans, 12 cis, 15 cis and the 18:3 delta 9 trans, 12 cis, 15 trans.

Phase II study of nitrosourea fotemustine as single-drug chemotherapy in poor-prognosis non-small-cell lung cancer.

A phase II study was designed to evaluate objective response rate and toxicity of fotemustine as single-drug chemotherapy in non-small-cell lung cancer. Eighty-seven patients with unresectable non-small-cell lung cancer took part in the study. Seventy-seven were evaluable for response. Of these, 60% had received prior chemotherapy and 74% had metastatic disease. Moreover, 22 patients had central nervous system metastases (of whom 12 were evaluable for this site). Treatment consisted of fotemustine 100 mg m-2 administered on days 1 and 8 followed by a 5 week rest period. Afterwards, responding or stabilised patients received fotemustine 100 mg m-2 every 3 weeks as a maintenance therapy. Toxicity and quality of life were recorded during therapy. Thirteen patients (17%; 95% CI 9-25%) had an objective response (11% for pretreated, 26% for non-pretreated) with a median duration of 22 weeks (range 7-41 weeks). Two objective responses were observed among the 12 patients with evaluable brain metastases. No response was observed among the 14 patients with adenocarcinoma. Haematological, gastrointestinal, hepatic and renal toxicities were mild to moderate and manageable. The most frequent biological adverse reactions were delayed thrombocytopenia and neutropenia. Quality of life did not significantly decrease during the first 6 treatment weeks. Moreover, it remained stable during the study period in patients with response or stabilisation, whereas it significantly decreased in patients who experienced progression of the disease. Fotemustine is feasible for single-drug chemotherapy in non-small-cell lung cancer even though poor prognostic variables such as brain metastases are present. It can be administered on an outpatient basis and toxicity is moderate and manageable. Thus, fotemustine can be considered as a putative drug in further combinations.

Incorporation of trans long-chain n-3 polyunsaturated fatty acids in rat brain structures and retina.

During heat treatment, polyunsaturated fatty acids and specifically 18:3n-3 can undergo geometrical isomerization. In rat tissues, 18:3 delta 9c,12c,15t, one of the trans isomers of linolenic acid, can be desaturated and elongated to give trans isomers of eicosapentaenoic and docosahexaenoic acids. The present study was undertaken to determine whether such compounds are incorporated into brain structures that are rich in n-3 long-chain polyunsaturated fatty acids. Two fractions enriched in trans isomers of alpha-linolenic acid were prepared and fed to female adult rats during gestation and lactation. The pups were killed at weaning. Synaptosomes, brain microvessels and retina were shown to contain the highest levels (about 0.5% of total fatty acids) of the trans isomer of docosahexaenoic acid (22:6 delta 4c,7c,10c,13c,16c,19t). This compound was also observed in myelin and sciatic nerve, but to a lesser extent (0.1% of total fatty acids). However, the ratios of 22:6 trans to 22:6 cis were similar in all the tissues studied. When the diet was deficient in alpha-linolenic acid, the incorporation of trans isomers was apparently doubled. However, comparison of the ratios of trans 18:3n-3 to cis 18:3n-3 in the diet revealed that the cis n-3 fatty acids were more easily desaturated and elongated to 22:6n-3 than the corresponding trans n-3 fatty acids. An increase in 22:5n-6 was thus observed, as has previously been described in n-3 fatty acid deficiency. These results encourage further studies to determine whether or not incorporations of such trans isomers into tissues may have physiological implications.

Utilization of high-performance liquid chromatography as an enrichment step for the determination of cyclic fatty acid monomers in heated fats and biological samples.

A method was developed to determine traces of cyclic fatty acid monomers (CFAM) in oils and animal tissues. This method is a combination of some techniques developed earlier but with the enrichment step being achieved by high-performance liquid chromatography (HPLC) instead of urea inclusion. After transformation of the lipids into methyl esters, the latter were hydrogenated after addition of an internal standard (methyl heptadecanoate or ethyl hexadecanoate). The mixture was enriched in CFAM by HPLC on a semi-preparative C18 reversed-phase column using acetonitrile-acetone (90:10, v/v) at 4 ml/min. The enriched fraction containing the CFAM and the internal standard was then analysed by gas chromatography on a polar column (cyanosilicone phase). This method was developed using known mixtures of CFAM isolated from both heated sunflower and linseed oils. Small amounts of CFAM (50 microg/g of sample) were determined with good reproducibility without any loss during the HPLC enrichment step and with no modification of the relative proportions of the CFAM in the mixture. This method can be applied to either heated fats and oils or biological samples (heart cell culture) that contain only traces of CFAM. Ethyl hexadecanoate (16:0 ethyl ester) can be used as an internal standard for samples containing small amounts of 17:0.

Preferential incorporation of dietary cis-9,cis-12,trans-15 18:3 acid into rat cardiolipins.

Cardiolipins from mitochondria of different rat organs (heart; liver and kidney) appear to be privileged targets for the incorporation of cis-9,cis-12,trans-15 18:3 acid, a compound commonly found in deodorized edible linolenic acid-containing oils. When this acid (together with other linolenic acid geometrical isomers (LAGI)) is fed at high load to rats that had been reared on a fat-free diet since weaned for a few days, it replaces the endogenously synthesized monoenoic acids that had accumulated in cardiolipin during fat deficiency. Although there is no discrimination in deposition of any LAGI in adipose tissue triacylglycerols, a high selectivity of incorporation of the cis-9,cis-12,trans-15 18:3 acid over other isomers (including the all-cis 18:3(n-3) acid) is observed either in diradylphospholipids or in cardiolipins. However, cis-9,cis-12,trans-15 18:3 acid accumulates in cardiolipins at a considerably higher level than in other phospholipids (11 times in liver, 5-7 times in heart and kidney). It reaches 22-24% of total fatty acids in cardiolipins from heart and liver, and 13-14% in kidney. The cis-9,cis-12,trans-15 18:3 acid is esterified to both the 1(1")- and 2(2")-positions of liver mitochondria cardiolipin, with a well-marked selectivity for positions 1(1"). Its 1(1")/2(2") selectivity ratio is about the same as that of 18:2(n-6) acid: 2.1 vs 2.2. It is concluded that the trans-15 ethylenic bond is probably perceived as a single bond by enzymic systems that ensure acylation of cardiolipins. The cis-9,cis-12,trans-15 isomer is able to reverse the fatty acid modifications induced in cardiolipins by a diet devoid of essential fatty acids, in a way similar to that of 18:2(n-6) acid supplementation.

Incorporation of cyclic fatty acid monomers in lipids of rat heart cell cultures.

Primary cultures of newborn rat cardiomyocytes were grown in medium supplemented with cyclic fatty acid monomers (CFAM) which had been isolated from heated linseed oil. The cells were harvested, and lipids were extracted and fractionated using silica cartridges and high-performance liquid chromatography. The CFAM structures isolated from cellular lipids were determined and compared to those that had been supplemented to the medium, using gas-liquid chromatography coupled with mass spectrometry (GC/MS). We found that CFAM were incorporated into phospholipids and neutral lipids of cardiomyocytes. Furthermore, CFAM with a cyclopentyl ring structure were more abundant in cardiomyocytes than were the cyclohexyl ring isomers. Our data suggest that CFAM of the 5-carbon and 6-carbon ring series are metabolized differently in newborn rat cardiomyocytes.

Separation of 20:4n-6 and 20:4n-7 by capillary gas-liquid chromatography.

The use of a capillary column coated with 100% cyanopropyl polysiloxane (CP(TM)Sil 88) allows the separation of several fatty acids associated with fat deficiency. Starting with liver mitochondrial phospholipids of weanling rats fed a fat-free diet, an unusual fatty acid was isolated, along with 20:4n-6, by thin-layer chromatography on AgNO3-impregnated silica gel plates. After partial hydrazine reduction of these acids, the resulting monoenes were isolated and subjected to ozonolysis in BF3/methanol. The resulting monomethyl and dimethyl esters were identified by gas chromatography/mass spectrometry. Our data indicate that the unusual component corresponds to 20:4n-7. Based on published biochemical and analytical studies and on our own chromatographic retention data, some of the other unusual fatty acids were tentatively identified as 18:2n-7, 20:2n-7 and 20:3n-7. The CP(TM)Sil 88 column appears to be a simple and useful tool for the separation of fatty acids of the palmitoleate series.

Trans n-3 eicosapentaenoic and docosahexaenoic acid isomers exhibit different inhibitory effects on arachidonic acid metabolism in human platelets compared to the respective cis fatty acids.

N-3 trans geometrical isomers of 20:5 n-3 and 22:6 n-3 were isolated from rats fed heated linseed oil. The ability of these acids to inhibit 20:4 n-6 metabolism by human platelets was examined. The concentrations required to inhibit 50% of platelet aggregation (IC50) induced by 2.5 microM 20:4 n-6 were higher for the 20:5 delta 17t isomer compared to all cis 20:5 n-3; means 29.2 and 7.6 microM, respectively (P less than 0.05). There were no significant differences in IC50 between 22:6 delta 19t and all cis 22:6 n-3; means 4.3 and 5.6 microM, respectively (P greater than 0.05). Inhibition of action of cyclooxygenase on 20:4 n-6 was similar for 20:5 delta 17t and 20:5 n-3 when examined at their IC50s, but comparison at equal concentrations indicated that 20:5 n-3 was a significantly better inhibitor (P less than 0.05). The ability to inhibit platelet aggregation was paralleled by cyclooxygenase inhibition as determined by thromboxane B2 and 12-hydroxyheptadecatrienoic acid formation. 22:6 delta 19t appeared to inhibit cyclooxygenase more completely than 22:6 n-3, examined at their IC50s or at similar concentrations (P less than 0.05). Isomers of 20:5 n-3 and 22:6 n-3 having an n-3 cis or trans bond appear to have similar modes of action, although levels required for effectiveness are different for the C20 acids.

Occurrence of geometrical isomers of eicosapentaenoic and docosahexaenoic acids in liver lipids of rats fed heated linseed oil.

Mono trans geometrical isomers of 20:5 n-3 and 22:6 n-3 were detected in liver lipids of rats fed heated linseed oil. The isomers were identified as being 20:5 delta 5c,8c,11c,14c,17t and 22:6 delta 4c,7c,10c,13c,16c,19t. These fatty acids were isolated as methyl esters by preparative high-performance liquid chromatography (HPLC) on reversed phase columns followed by silver nitrate thin layer chromatography (AgNO3-TLC). The structures were identified using partial hydrazine reduction, AgNO3-TLC of the resulting monoenes, oxidative ozonolysis of each monoene band, and gas-liquid chromatography (GLC) of the resulting dimethyl esters and monomethyl esters. Fourier-transform-infrared spectrometry confirmed the trans geometry in isolated 20:5 and 22:6 isomers. The isomers of eicosapentaenoic and docosahexaenoic acids in liver lipids probably resulted from desaturation and elongation of 18:3 delta 9c,12c,15t, a geometrical isomer of linolenic acid present in the heated dietary oil.

Induction of hepatic drug-metabolizing enzymes by cyclic fatty acid monomers in the rat.

The effects of cyclic monomers on the activities of several drug-metabolizing enzymes were evaluated. Female Wistar rats were fed, for 4 wk, a semi-synthetic diet containing different quantities of cyclic monomers isolated from linseed oil heated at 275 degrees C for 12 hr under nitrogen. Microsomal proteins and cytochrome c were significantly increased in rats fed a diet containing 0.1 or 1% cyclic monomers. Aminopyrine demethylation, a model reaction preferentially induced by phenobarbital, was increased by this treatment. NADPH-cytochrome P-450 reductase was also stimulated. Moreover, ethoxyresorufin deethylation, known to be greatly increased by methylcholanthrene-type inducer was only increased threefold by this treatment. The activity of p-nitrophenol UDP-glucuronosyl transferase decreased while the conjugation of bilirubin was stimulated. These results suggest that cyclic monomers isolated from heated linseed oil show some characteristics of phenobarbital-type inducers.

Quantitative analyses of polar components in frying oils by the iatroscan thin-layer chromatography-flame ionization detection technique.

Frying oils collected in restaurants were fractionated into a polar and a non-polar fraction by the Iatroscan thin-layer chromatography-flame ionization detection (TLC-FID) system on Chromarod S II using hexane-diethyl ether-acetic acid (97:3:1) as the solvent system. The FID responses for Iatroscan analyses of the polar and the non-polar fraction isolated from a frying oil by column chromatography on a 5% hydrated silicic acid were studied at Chromarod load levels ranging from 1 to 16 micrograms, relative to methyl heptadecanoate as the internal standard. The correction factors were relatively constant in the range 10-16 micrograms, but increased in the range 1-5 micrograms. The amount of polar material in ten commercial frying oil samples was quantitated by the Iatroscan TLC-FID technique. Good correlations were found between the results and data obtained by column chromatography and silica gel Sep-Pak cartridges.

[Do inguinal lymph node metastases of germinal tumors of the testis exist?]. / Les métastases ganglionnaires inguinales des tumeurs germinales du testicule existent-elles?

Abdomino-aortic glands are usually involved by regional extension of germinal tumors of testis. Inguinal gland extension may occur from alteration of lymphatic circulation due to inguinoscrotal surgery and post-orchidectomy scrotal contamination. Among 140 patients treated in Val-de-Grâce Army Hospital between 1978 and 1985, only one patient with a pure non-seminoma germinal tumor developed inguinal gland metastases. Causes of inguinal gland extension are analyzed based on past history of this patient, involving repair of inguinal hernia and orchidopexy. Proposed therapy includes inguinoscrotal radiotherapy for seminoma, surveillance or chemotherapy for a pure non-seminoma germinal tumor.

[Identification of an atypical polyunsaturated fatty acid present in the liver of rats after the ingestion of heated linseed oil]. / Identification d'un acide gras polyinsaturé atypique présent dans le foie de rats ayant ingéré de l'huile de lin chauffée.

A C20:5 fatty acid with a trans delta 17 ethylenic bond was identified in liver lipids of rats fed with heated linseed oil. This component was isolated using a combination of high performance liquid chromatography on a reverse phase column and AgNO3 thin layer chromatography (TLC). This fatty acid was identified after hydrazine reduction, methoxy-bromomercuric adducts fractionation, AgNO3-TLC and ozonolysis in BF3-MeOH. It could be a metabolite of one trans isomeric linolenic acid formed during the heat treatment of linseed oil.

[Detoxification by the rat of compounds formed during thermal polymerization of linseed oil. II. Effects of discontinuous administration of the heated oil on the urinary excretion of glucuronides, liver weight and the tissue content of cyclic monomers]. / Détoxification par le rat des composés formés au cours de la thermopolymérisation de l'huile de lin. II.--Effets d'une administration discontinue d'huile chauffée sur l'excrétion urinaire de glucuronides, le poids du foie et les teneurs tissulaires en monomères cycliques.

During four successive periods of 9 days each, adult rats were fed alternatively fresh or hermopolymerized linseed oil in their diet. As compared to the control animals, the rats fed with the thermopolymerized oil showed increased urinary glucuronide excretion and higher liver weight, as well as a rise in the cyclic monomer content in that organ and, to a lesser degree, in the fat tissue. When fresh oil was substituted for heated oil in the diet, these animals recovered the levels of urinary glucuronides and liver monomers observed in the control rats. On the contrary, the rise in liver weight still observed can be considered as an indication of diet toxicity.

[Recent research on the physiological effects of various types of compounds present in heated fats]. / Recherches récentes sur les effets physiologiques de différents types de composés présents dans les corps gras chauffés.

Combe, Constantin and Entressangles's work on the intestinal absorption of various new compounds formed during the heating of fats revealed that most of these compounds may pass through the intestinal mucosa, but that the absorption rate varies from a type of compound to another one. Among all the compounds present in the heated fats, the fraction of cyclic monomers was the most studied; previous works revealed that this fraction was toxic. However recent result of Iwaoka and Perkins seem to indicate that cyclic monomers are well tolerated by rats and induce only a slight effect on lipid metabolism; these surprising results may be due to the fact that the cyclic monomers are well tolerated by rats and induce only a slight effect on lipid metabolism; these surprising results may be due to the fact that the cyclic monomers used by Iwaoka and Perkins included only cyclohexadienic and aromatic compounds; Saito and Kaneda indeed obtained marked toxic effects with cyclic monomers including in particular compounds with cyclohexanic, cyclohexenic and cyclohexyl 1,2 diylidene structures; on the other hand, Potteau, Dubois and Rigaud identified after hydrogenation not only cyclohexanic compounds but also compounds with disubstituted cyclopentanic and hexahydroindane structure, in thermopolymerizated or thermally oxidized oils, which proved to be toxic to experimental animals, in particular in breeding experiments. Some experimental facts suggest a system of detoxification consisting in particular in the urinary glucuronide excretion. The apolar thermic polymers (cyclic or not) are little absorbed and produce few or no physiological effect; however they can be found again in appreciable amounts in adipose tissue (Billek and Rost) or in liver (Perkins and Taubold). Very little is known on the other fractions present in the heated fats, except that the fraction of oxidized acids can globally prove to be toxic. Alexander's work does not seem quite convincing to us: the statement according which oils rich in monoenic fatty acids would be more toxic after heating than the oils rich in polyunsaturated fatty acids is not based on reliable experimental results.