Support practices by an interdisciplinary team in a palliative-care unit for relatives of patients in agonal phase.

BACKGROUND: In the absence of extant recommendations, the aim of this study was to formalise support practices used by an interdisciplinary team in a palliative-care unit (PCU) for the relatives of patients in the agonal phase preceding death. The secondary objective was to understand the expectations of relatives during this phase in terms of the support provided by professionals and volunteers. METHODS: Thirty-two people took part in this study; all were interviewed through focus groups (FGs). Each FG comprised one category of individuals working in the PCU: nurses, care- assistants, doctors, psychologists, other professionals, palliative-care volunteers, and relatives. Groups were surveyed using an interview guide, and the interviews were recorded and transcribed to enable identification and characterization of all practices. Care practices were classified into four categories: current consensual practices (i.e. performed by all team members), occasional consensual practices, non-consensual practices (performed by one or a few participants), and practices to be developed. RESULTS: In total, 215 practices were mentioned by professionals and palliative-care volunteers: 150 current consensual practices, 48 occasional consensual practices, 1 non-consensual practice, 16 practices yet to be developed, and 29 practices for relatives. Many practices were mentioned by different categories of participants; thus, after cross-checking, the number of practices decreased from 215 to 52. A list of practices deemed desirable by all was drawn up and then validated by the entire interprofessional team. These practices were organised around four themes: providing care and ensuring comfort; communicating, informing, and explaining; interacting; and mobilising interdisciplinary skills. CONCLUSIONS: These results underline the importance of the quality of care provided to patients, the attention given to the relatives themselves, and they highlight the importance of the helping relationship. Following this study, which established a list of varied practices aimed at supporting the relatives of patients in agonal phase, it will be important to set up a broader study seeking to establish a consensus on these practices with an interprofessional group of experts from other PCUs using broad surveys and an adapted methodology. Such studies will make it possible to develop training modules for teams working with relatives.

[Research ethics: French regulations and applications in radiation oncology]. / Éthique de la recherche : réglementations françaises et applications en oncologie radiothérapie.

French regulations about research ethics are based on the so-called Jardé law, which defines researches involving human beings. Researches involving human beings require the submission of research protocols to a committee for protection of persons with a precise list of documents to submit for a favourable opinion. This law describes different categories of researches and determines the ethical procedures to apply before setting up a research protocol. This issue of categorisation is central and must be taken into account by researchers from the beginning of the research process. Researches considered as not involving human beings also require a set of ethical precautions focused on patients' information and the collection of their non-opposition (due to the application of the General Data Protection Regulation adopted by the European Parliament). Thus, many regulations exist and they require a real work for researchers to meet these requirements in research ethics. This article aims to summarise French regulations. Selected examples are specifically taken into the field of radiation oncology research.

Exploring the religious and spiritual coping experience of cases via cancer: A qualitative research.

Objective: Lately, the spiritual and religious (S/R) aspect of health behave has been receiving an increased attention in the scientific literature. The study aims to show the components of R/ S coping in cases of cancer in Iran. Method: The design of the current research is according to a qualitative research using content analysis. Sixteen patients with various kinds of cancer take part in the research. Data was produced though in-depth discussions and the gratified investigation utilized to discover categories and sub-themes. Results: Three categories combined from the information investigation: 1) Maintaining/ improving self-esteem, 2) Positive appraisal/ Being optimistic, and 3) Self-sustaining. In the participants' view, the general category realized to be the "improving calmness". Conclusions: Positive R/S coping strategies were used by the patients and most cancer patients tried to achieve calmness through R/ S coping. The findings of the research can be used to plan medical and nursing approach towards increasing the R/S quality care both in the acute and the long-term settings.

Management program decreases postoperative nausea and vomiting in high-risk and in general surgical patients: a quality improvement cycle.

BACKGROUND: Preventing postoperative nausea and vomiting (PONV) is a major priority for postsurgical patient care. Our objective was to assess the efficacy of a multimodal postoperative nausea and vomiting (PONV) approach, which was associated with a continuous quality improvement program, in maintaining a low PONV incidence in the PACU. METHODS: Consecutive adult patients scheduled for surgery (ambulatory surgery or not) were prospectively included. PONV data were recorded in the PACU and over a 24-hour period. The management program was based on a multimodal approach with both changes in anesthetic techniques and anti-emetics, and on a three-stage protocol including: 1) phase I: institutional practice phase based on prospective observational study; 2) protocol implementation; 3) phase II: prospective observational study associated with feedback, scientific session and evaluation to guideline adherence. We used the Apfel risk scoring system to identify patients at high risk of PONV. Feedback with audit results and didactic sessions were scheduled quarterly in the Phase II. RESULTS: Thirty-seven/395 (9.4%) and 151/3864 (3.9%) patients experienced PONV in the PACU during Phase I and Phase II respectively (P<0.001). Among the patients with an Apfel risk score that included at least two risk factors, 16.6% and 4.2% experienced PONV in the PACU during Phase I and Phase II respectively (P<0.001). CONCLUSION: We highlight the association with a sharp decrease in PONV incidence over a one-year period and a multimodal PONV approach using feedback to clinicians associated with continuous quality improvement program.

Operative treatment and outcome of unstable distal radial fractures using a palmar T-miniplate at a non-specialized institution.

Treatment options for displaced distal radial fractures are still a controversial topic of discussion. Although good results for the palmar plating of high-volume centers have been published, evidence of its successful use in smaller institutions is still lacking. We report the clinical and radiological results of the treatment for 84 distal radial fractures with a single 2.4-mm T-miniplate in an institution performing <30 procedures per year. According to the AO classification system, there were 30 A, 5 B, and 49 C fractures with a patients mean age of 64 years. After a minimum of 12-month follow-up, we found very good and good results according to the Gardland and Sarmiento scores and a DASH of 5.6. Only five patients were classified as having a moderate outcome. A remaining intra-articular step-off of more than 1 mm was seen in 15 patients. In a comparison of grip strength between the injured and uninjured hands, we saw a difference of 6.8 % less on the injured side. We saw two instances of tendon rupture and one of tendon irritation due to prominent dorsal screws and necessitating revision surgery. Flexor tendon irritation was noted in one patient, requiring a second operation. Modern treatment for distal radial fractures can be performed successfully and with good clinical outcome in smaller institutions. Based on the high and increasing incidence of distal radial fractures, there is no need to transfer these patients into high-volume centers. Level of evidence Case study, Level IV.

[Changes of heat shock proteins content in the gill epithelium cells of mussel Mytilus edulis L. depending upon the salinity of medium].

The composition and the level of heat shock (stress) proteins content were studied by the method of immunobloting in the gill epithelium cells of mussels Mytilus edulis L. from the White sea, treated by water of different salinities. Stress proteins of about 70 and 40 kDa were revealed at Western blots. After long-term (11-14 days) acclimation to 14 and 35 per thousand the level of Hsp70 in gill epithelium cells increased to compare with that in control mussels. Hsp70 induction was observed in the cells of isolated gills after salinity shock at 14 per thousand during 3 and 24 hours.

Nutritional risk score is not sensitive enough to predict weight loss in diseased elderly subjects.

OBJECTIVES: malnutrition is highly prevalent in diseased elderly people, especially in hospital departments, and weight loss also occurs during hospital stays. Among the tools proposed to define malnutrition and to screen persons at risk of malnutrition, the nutritional risk score (NRS) has been suggested as a simple tool. DESIGN AND PARTICIPANTS: the aim of the present study was to test the validity of the NRS to predict weight changes 3 months after discharge. NRS and visual analogue scales for hunger, early satiety, thirst, fatigue and pain were performed in 106 patients aged 65 yrs and over, 67 treated for cancer, without overt malnutrition. RESULTS: forty six patients lost more than 1 kg. None of the parameters tested was correlated with weight changes, except NRS which was weakly correlated (r=-0.22, P=0.037). However a 0 score at NRS was associated with weight changes ranging -9 to +5 kg. Furthermore, the 11 patients with a high NRS score and weight loss were in a clinical situation that made it very likely that they would lose weight. In conclusion, NRS is not a valid score to predict weight change.

Clinical experience with 99mTc-MIBI scintimammography in patients with breast microcalcifications.

The aim of this study was to evaluate whether 99mTc-MIBI scintimammography can improve the diagnostic value of mammography for the differentiation of benign and malignant breast microcalcifications. In 41 women presenting 45 clusters of microcalcifications, a 99mTc-MIBI scintimammography was performed before open biopsy. There were 24 malignant lesions (53%). The sensitivity (SE) and specificity (SP) of 99mTc-MIBI scintimammography were 58.3% and 81%, and the positive and negative predictive values (PPV, NPV) were 78% and 63%, respectively. SE and PPV increased for lesions over 10 mm and for the younger patients (under 50 years). No correlation was found between true positive uptake and breast cancer invasiveness: 69% (9/13) for invasive lesions and 45% (5/11) for noninvasive lesions (P = 0.48). 99mTc-MIBI scintimammography was more often positive in high grade than in low- or intermediate-grade ductal carcinoma in situ (P = 0.03). The results were analysed according to the morphologic aspect of the microcalcifications. 99mTc-MIBI scintimammography could not be used for routine evaluation of all the microcalcifications detected by mammography.

Characterisation of alpha1B-adrenoceptors linked to inositol phosphate formation and calcium mobilisation in human astrocytoma U373 MG cells.

The human U373 MG astrocytoma cell line has been widely used as a model system for the investigation of astrocyte function. The aim of this study was to establish which alpha1-adrenoceptors are present on these cells. The specific binding of [3H]prazosin to membranes of U373 MG cells (Bmax 32+/-3 fmol mg(-1) protein, Kd 0.27+/-0.03 nM) was inhibited in a monophasic manner by alpha1-antagonists that have different affinities for alpha1A-, alpha1B- and alpha1D-adrenoceptors. Estimates for pKi values were: prazosin 9.69+/-0.06, 5-methylurapidil 7.10+/-0.21; (+)-niguldipine 7.06+/-0.26; WB 4101 8.26+/-0.16; and BMY 7378 6.60+/-0.21. The specific binding of [3H]prazosin was reduced to low levels by pretreatment of cells with 10 microM chloroethylclonidine for 15 min. In the presence of 30 mM LiCl, 100 microM noradrenaline stimulated [3H]inositol phosphate accumulation by 2.1+/-0.1-fold of basal after 30-min incubation. The EC50 for the accumulation of [3H]IP1, the major product detected (85+/-2% of total [3H]IP1 + [3H]IP2 + [3H]IP3), was 0.38+/-0.05 microM. Noradrenaline-induced [3H]IP1 accumulation was also inhibited by alpha1-antagonists. Estimates for pKi values were: 5-methylurapidil 6.95+/-0.01; WB 4101 8.31+/-0.07; and BMY 7378 6.71+/-0.28. The accumulation of [3H]IP1 in response to 100 microM noradrenaline was not significantly affected by raising the extracellular Ca2+ concentration from 1.3 to 4 mM. Noradrenaline (100 microM) also produced an increase in intracellular Ca2+ (mean peak 86+/-5 nM above basal). Pretreatment with chloroethylclonidine (10 microM, 15 min) abolished noradrenaline-induced [3H]IP1 accumulation and Ca2+ mobilisation. Activation of the alpha1B-adrenoceptors by 10 microM phenylephrine increased [3H]thymidine uptake to 140+/-5% of control uptake. Taken together, these results indicate that U373 MG cells express a single class of alpha1-adrenoceptors, the alpha1B-subtype, which are coupled to phosphoinositide hydrolysis and calcium mobilisation, and which mediate a mitogenic response to alpha1-agonists.

[Abdominal and pelvic segmented T1-weighted echo-planar imaging and MRI. Comparison with T1-TSE and T2-UTSE sequences]. / Echo-planar segmentaire pondéré T1 en IRM abdominale et pelvienne. Comparaison avec les séquences T1 TSE et T2 UTSE.

PURPOSE: To assess, quantitatively and qualitatively, the diagnostic value of a segmented EPI T1W sequence compared to T1W and T2W TSE sequences. MATERIAL AND METHODS: A prospective analysis of abdominal and pelvic MRI examinations of 70 patients (44 women, 26 men, mean age of 61 years), was performed on a 0.5 T supraconductive magnet with 15 mT/m gradients. The sequences were randomized and compared in a blinded fashion by 3 independent reviewers: TSE T1W (TR/TE = 500/12 ms, NSA = 6, turbo factor 5, 3:49 min), EPI T1W (TR/TE = 500/30 ms, NSA = 6, EPI factor = 7, 2:13 min) and UTSE T2W (TR/TE = 1600-2500/100, NSA = 6, turbo factor = 31, 2:20 min). RESULTS: Quantitatively, no significant difference was found between T1W sequences for signal to noise ratio. The EPI T1W sequence had lower signal but stronger enhancement after gadolinium injection. Qualitatively, EPI T1W had significantly less flow artefacts (p < 0.001, wilcoxon test), and more chemical shift artifact (p < 0.01). For lesion detection, differences were not statistically significant between T1W sequences or between paired T1W and T2W sequences (sensitivity and specificity 84 and 86% for TSE T1W 76 and 86% for EPI T1W, 78 and 79% for UTSE T2W, 90 and 65% for TSE T1W-UTSE T2W, 88 and 65% for EPI T1W-UTSE T2W). Kappa concordance test (0.686) and Mac Nemar symmetry test (3.55) were high between T1W sequences. CONCLUSION: The segmented EPI T1W sequence used had equivalent results compared to the TSE T1W sequence, it allows a 40% reduction in acquisition time and this without difference in the diagnostic performances of the reviewers.

Adhesion of mammalian cells to polymer surfaces: from physical chemistry of surfaces to selective adhesion on defined patterns.

The study of the adsorption of type I collagen from a solution containing Pluronic F68 has shown that the latter prevents collagen adsorption on polystyrene and does not prevent it on surface-oxidized polystyrene. This explains the control of mammalian cell adhesion by substrate surface hydrophobicity and composition of pre-conditioning solution. On that basis, selective adhesion of different types of mammalian cells (PC12 pheochromocytoma, MSC80 schwannoma, Hep G2 hepatoblastoma, rat hepatocytes) on patterned surfaces was achieved. Therefore tracks (width in the range of a few tens of microm) of reduced hydrophobicity were produced on polystyrene by photolithography and oxygen plasma treatment. After conditioning by a solution containing both Pluronic F68 and extracellular matrix protein (collagen, fibronectin), the latter adsorbed selectively on these paths thus allowing selective adhesion of the cells.

Unselected brain 0.5-T MR imaging: comparison of lesion detection and characterization with three T2-weighted sequences.

PURPOSE: To compare the diagnostic values of three T2-weighted sequences in unselected brain 0.5-T magnetic resonance (MR) imaging examinations. MATERIALS AND METHODS: MR imaging was performed in 102 patients because of neurologic symptoms or the follow up "previously known disease." The protocol comprised three T2-weighted sequences: turbo spin-echo (SE), turbo fluid-attenuated inversion-recovery (FLAIR), and gradient and SE (GRASE) sequences. In a prospective, blinded analysis, sequences were compared quantitatively and qualitative by three independent readers for lesion detection and characterization. RESULTS: Twenty-four patients had normal findings, and 78 had abnormal findings, with 121 final diagnoses. Quantitatively, the "white" cerebrospinal fluid (CSF) sequences, turbo SE and GRASE, had higher contrast-to-noise ratios (CNRs) than the "black" CSF sequence, FLAIR, with respect to the signal intensity of white manner, but lower CNRs than FLAIR with respect to the signal intensity of CSF. Qualitatively, for lesion detection, sensitivity and accuracy were significantly higher for FLAIR than for turbo SE or GRASE (P < .05); there was no statistically significant difference between turbo SE or GRASE. FOR lesion characterization, FLAIR was significantly superior to GRASE and turbo SE for white matter disease (P < .05), superior to only turbo SE (P < .05) for vascular disease, and not superior to GRASE or turbo SE for tumors. CONCLUSIONS: The black CSF T2-weighted turbo FLAIR sequence is a useful adjunct to the usual white CSF T2-weighted sequences in unselected brain 0.5-T MR imaging.

Evidence for a role for bulbospinal pathways in the spinal antinociceptive effect of systemically administered vapreotide in normal rats.

Numerous neurotransmitters are involved in nociceptive transmission or regulation. Several reports have shown the analgesic effects of somatostatin and its analogues. Somatostatin, when given intrathecally, markedly reduced pain in cancer patients. Somatostatin analogues that possess a longer half-life time are more convenient for therapeutic use. Vapreotide, a somatostatin analogue, was shown to induce a long-lasting antinociceptive effect in rats. We studied the site and the mechanism of action of vapreotide in rats using the paw pressure test. Intrathecal administration of vapreotide induced no antinociception. Systemically administered vapreotide-induced antinociception was inhibited by several intrathecal (i.t.) administered antagonists (yohimbine, naloxone and to a lesser degree tropisetron). These results show a lack of spinal effect and suggest a supraspinal site of action with an involvement of noradrenergic and to a lesser degree serotonergic bulbospinal pathways. In addition, spinal opioid receptors also seen to be involved.

Convex hull test for ordered categorical data.

When testing for stochastic order in ordered 2 x J contingency tables, it is common to select the cutoff required to declare significance so as to ensure that the size of the test is exactly alpha conditionally on the margins. It is valid, however, to use the margins to select not only the cutoff but also the form of the test. Linear rank tests, which are locally most powerful and frequently used in practice, suffer from the drawback that they may have power as low as zero to detect some alternatives of interest when the margins satisfy certain conditions. The Smirnov and convex hull tests are shown, through exact conditional power calculations and simulations, to avoid this drawback. The convex hull test is also admissible and palindromic invariant and minimizes the required significance level to have limiting power of one as the alternative moves away from the null in any direction.

[Bladder adenomyomatosis. Apropos of a case of segmental involvement. Correlation ultrasonography-MRI]. / L'adénomyomatose vésiculaire. A propos d'un cas d'atteinte segmentaire. Corrélation échographie-IRM.

Adenomyomatosis of the gall bladder is a classical but seldom recognized cause of gallbladder wall thickening. The authors review the imaging features of this disease and emphasize the value of ultrasound and MRI. Although considered a benign disease, some recently described cases of neoplastic transformation may warrant surgery.

Iron repletion attenuates the protective effects of iron deficiency in DMBA-induced mammary tumors in rats.

Mammary tumor incidence, natural killer (NK) cell activity, and tumor necrosis factor-alpha (TNF-alpha) activity were measured in iron (Fe)-deficient and iron-replete rats treated with the carcinogen 7,12-dimethylbenz[a]anthracene (DMBA). Female weanling rats were fed AIN-76 diets: the iron-deficient group was fed 5 mg Fe/kg diet; the control group was fed 50 mg Fe/kg diet; the food-restricted group was fed 50 mg Fe/kg diet in the amount consumed by the iron-deficient group; and the replete group was fed 5 mg Fe/kg diet for 45 days and then 50 mg Fe/kg diet. After six weeks of feeding, the rats were given a single intragastric dose of DMBA. Feeding the iron-deficient diet for 20 weeks reduced hematocrit, hemoglobin, liver iron, and tumor iron values and increased spleen weight. Dietary iron repletion for 14 weeks reversed these effects of iron deficiency. Splenic NK cell cytotoxicity against YAC-1 cells was highest in the control group. Repleting rats with 50 mg Fe/kg diet corrected iron deficiency but did not restore NK cell cytotoxicity. No significant differences in macrophage TNF-alpha bioactivity were found among groups. Cumulative tumor incidence over all weeks was lowest in the iron-deficient rats. Iron repletion during the promotion phase of tumorigenesis attenuates the protective effects of iron deficiency. Food restriction to the extent present in the iron-deficient group did not protect against tumorigenesis. The iron-deficient group had the lowest tumor burden and delayed onset of tumors. Iron deficiency significantly reduces tumor incidence in DMBA-treated rats by mechanisms other than NK cell cytotoxicity, TNF-alpha activity, and food restriction.

Calcium-dependence of histamine- and carbachol-induced inositol phosphate formation in human U373 MG astrocytoma cells: comparison with HeLa cells and brain slices.

1. Histamine (1 mM) induced an accumulation of inositol monophosphate ([3H]-IP1) in the U373 MG human astrocytoma cell line which increased with time in the presence of 30 mM Li+. After a 30 min incubation period with 1 mM histamine [3H]-IP1 was the major product detected (84 +/- 1% of total [3H]-IPx) and was present at a level 11 (+/- 1) fold of basal accumulation. 2. Concentration-response curves for histamine-induced [3H]-IP1 accumulation in U373 MG cells (EC50 5.4 +/- 0.5 microM) were shifted to the right in a parallel fashion by mepyramine (slope of a Schild plot 0.99 +/- 0.08), yielding a Kd for mepyramine of 3.5 +/- 0.3 nM, consistent with the involvement of histamine H1-receptors. 3. The temelastine-sensitive binding of [3H]-mepyramine to a membrane fraction from U373 MG cells was hyperbolic and had a mean Kd of 2.5 +/- 1.0 nM. The maximum amount of temelastine-sensitive binding was 86 +/- 19 pmol g-1 membrane protein. 4. Carbachol also induced [3H]-IP1 accumulation in U373 MG cells, 2.8 (+/- 0.1) fold of basal with 1 mM carbachol, with an EC50 of 48 +/- 8 microM. Pirenzepine shifted carbachol concentration-response curves to the right (slope of Schild plot 0.89 +/- 0.07) giving a Kd for pirenzepine of 0.10 +/- 0.01 microM, suggesting that phosphoinositide hydrolysis in U373 MG cells is mediated by the M3-, rather than the M1-, muscarinic receptor subtype. 5. [3H]-IP1 accumulation induced by both 1 mM histamine and by 1 mM carbachol increased when the Ca2+ concentration of the medium was increased from 'zero' (no added Ca2+) to 0.3 mM. Histamine-stimulated [3H]-IP1 accumulation was further increased, although not so markedly, as the Ca2+ was raised to 4 mM. The same pattern was apparent with histamine-induced accumulations of [3H]-IP2 and [3H]-IP3. In contrast, [3H]-IPx accumulation in response to carbachol increased between 0.3 and 1.3 mM, but thereafter remained unchanged ([3H]-IP1) or declined ([3H]-IP2 and [3H]-IP3). 6. In HeLa cells, [3H]-IP1 accumulations induced by 1 mM histamine and 1 mM carbachol showed the same pattern of Ca2+ dependence and were independent of extracellular Ca2+ above 0.3 mM (histamine) or 1.3 mM (carbachol). The response to carbachol appeared to be mediated by an M3-muscarinic receptor (apparent Kd for pirenzepine 0.09 microM). 7. In cross-chopped slices of guinea-pig cerebral cortex and guinea-pig cerebellum, [3H]-IPI accumulation induced by 1 mM histamine in the presence of 10 mM Li+ increased as the extracellular Ca2+ was increased from 0.3 to 2.5 mM, but a further increase to 4 mM had no further effect. In contrast the response to histamine in rat cerebral cortex increased markedly between 1.3 and 4 mM Ca2+. Accumulations of [3H]-IP1 induced by carbachol in guinea-pig or rat cerebral cortical slices were not increased as extracellular Ca2+ was raised from 0.3 to 4 mM.8. Nimodipine (100 nM) and w-conotoxin (3 microM) had no significant effect on histamine-induced [3H]-IP1accumulation in rat cerebral cortical slices or in U373 MG cells. 9. We conclude that histamine-induced [3H]-IP1 accumulation in U373 MG cells does appear to have a component dependent on the extracellular Ca2+ concentration. The degree of Ca2+-dependence approaches that observed in guinea-pig cerebral cortex but is much less than in rat cerebral cortex.Whether U373 MG cells will be of use as a model system for the apparent Ca2+-entry component observed in guinea-pig or rat brain slices remains to be established.

Generation of free radicals during the reductive metabolism of the nitroaromatic compound, nilutamide.

Incubation of the antiandrogen nilutamide with rat liver microsomes and NADPH, under anaerobic conditions, led to the formation of the nitro anion free radical, as indicated by electron spin resonance spectroscopy. The steady-state concentration of the nitro anion free radical was not decreased by SKF 525-A, carbon monoxide or metyrapone (3 inhibitors of cytochrome P-450) but was decreased by NADP+ or p-chloromercuribenzoate (2 inhibitors of NADPH-cytochrome P-450 reductase). Under aerobic conditions, the nitro anion free radical was reoxidized by oxygen, and the electron spin resonance signal was not detected. This redox cycle was associated with NADPH oxidation, consumption of oxygen, and formation of superoxide anion, hydrogen peroxide and glutathione disulfide. Under anaerobic conditions, nilutamide was further reduced to chemically reactive metabolites. Anaerobic incubation of [3H]nilutamide (0.1 mM) with rat liver microsomes and a NADPH-generating system resulted in the in vitro covalent binding of [3H]nilutamide metabolites to microsomal proteins; covalent binding required NADPH; it was decreased in the presence of NADPH-cytochrome P-450 reductase inhibitors (methylene blue, 2'-adenosine monophosphate) or in the presence of the nucleophile glutathione, but was unaffected by cytochrome P-450 inhibitors (SKF 525-A, CO). Covalent binding was decreased markedly under aerobic conditions. We conclude that nilutamide is reduced by microsomal NADPH-cytochrome P-450 reductase into a nitro anion free radical. In the presence of oxygen, this nitro anion free radical undergoes redox cycling with oxygen, and forms reactive oxygen species. In anaerobiosis, it is reduced further to covalent binding species.