Accidental overdose among injecting drug users in Dorset, UK.

AIMS: To establish the prevalence and frequency of non-fatal accidental overdose among Dorset injecting drug users (IDUs), map their response to it and their beliefs about protective and risk behaviours. DESIGN: Survey of a community sample of IDUs. SETTING: Ten Dorset towns. PARTICIPANTS: Two hundred and twelve IDUs, recruited through multisource sampling, who had injected in the 2 months before interview. MEASUREMENTS: Structured interview, SDS and LDQ. FINDINGS: In the previous year, 30% of interviewees had overdosed and 58% had witnessed another do so. Most (79%) had had a personal acquaintance die from an accidental overdose. Interviewees commonly attributed their own most recent overdose(s) to excessive consumption of drugs, mixing drugs and low tolerance, believed that these factors generally increased risk and described a repertoire of protective behaviours. Those who had overdosed in the previous year had significantly greater involvement with drug injecting. Virtually all who had witnessed another's overdose described peoples' attempts to help: many were appropriate, some dangerous. Avoiding seeking medical help was common. Half (52%) demonstrated the rudiments of putting people into the recovery position, and a minority (31%) cardio-pulmonary resuscitation. Most interviewees (55%) said that they would "probably" or "definitely" attend a workshop on Overdose Aid. CONCLUSIONS: There is potential for preventing overdose by promoting protective behaviours. Since IDUs often witness overdose, training them in first aid may be valuable, and tackling the reasons that delay their seeking help is crucial.

Personality and religion among female drug misusers.

Fifty female drug misusers completed the Eysenck Personality Questionnaire and the Francis scale of attitude towards Christianity on entry to a Christian residential rehabilitation programme. The data confirm the deviant personality profile of drug misusers, who score high on psychoticism and neuroticism and low on extroversion and the lie scale, and demonstrate that the general findings relating religious attitudes to the Eysenckian dimensions of personality among normal populations also hold good among this deviant group, thereby confirming the generalisability of the conclusion that it is psychoticism, rather than neuroticism or extroversion, which is fundamental to religiosity. The practical relevance of these findings is discussed for rehabilitation programmes which include spiritual or religious components.

Cognitive-behavioural treatments for obesity.

The effects of the original behavioural treatment have been studied exhaustively and the limits of this very useful approach have been delineated. Further developments have largely come from combining it with other modes of treatment or from delivering it in more intensive ways. The knowledge base has been limited to operant psychology, despite the fact that study of the psychology of appetite has developed extensively in the two decades since Stuart's original paper of 1967 (Stuart RB. Behavioral control of overeating. Behav Res Ther 1967; 5: 357-365). Many fundamental processes such as the role of conditioning in the development of satiety, and the effects of monotony and variety, have important implications for the treatment of obesity which have yet to be explored.

Dropping out of treatment for obesity.

This study compared the pre-treatment characteristics of participants in three weight reduction programmes who either completed treatment or dropped out. The three programmes each lasted for 16 weeks, selected subjects on the same criteria, and offered the same dietary advice. The first two programmes were run by the same psychologist in the same community setting. In each study a different set of characteristics significantly separated completers from dropouts, and discriminant function analysis assessed how well this separation was achieved. The discriminant function from the first study correctly identified 75% of the subjects on which it was based. When applied to the second study it correctly identified 64% of subjects, showing limited generalisability. There were also significant differences between early dropouts and late drop-outs, but the nature of these varied between studies. In discussing the implications of these results it was argued that further research might more fruitfully focus on psychological processes involved in drop-out rather than continue to search for correlates of drop-out.

Synthesis and immunomodulating activity of 5H-thiazolo[2,3-b]quinazolin-3(2H)-one.

The synthesis and immunomodulating activity of 5H-thiazolo[2,3-b]quinazoline-3(2H)-one (7) are described. When tested in the Kennedy plaque assay, 7 exerted immunosuppressive activity on IgM production in female C3H mice sensitized with sheep erythrocytes.

CT derived Patlak images of the human kidney.

This study aimed to produce Patlak images of the kidney from dynamic CT data and to determine whether such images are substantially affected by fluid movement between renal tubular segments. Renal permeability was measured in 31 kidneys by applying Patlak analysis to time-density data from kidney and aorta during dynamic CT. Permeability parameters were correlated against plasma urea. The renal region (cortex or medulla) with the greatest permeability was determined from parametric images generated using pixel by pixel analysis. The mean value for whole kidney permeability was 517.5 microliters min-1 ml-1. A correlation was found between whole kidney permeability and plasma urea (p < 0.01). Permeability values were highest in the renal medulla in 24 (77%) kidneys. The higher medullary values of permeability are artefactual, resulting from movement of fluid and contrast medium between cortex and medulla. Although Patlak images do not reflect true intrarenal permeability values, the apparent medullary permeability may provide diagnostically useful information about the concentrating ability of the kidney. CT measurements of whole kidney permeability reflect filtration function but the apparent intrarenal variations in permeability will result in measurement errors dependent upon the relative amounts of renal cortex and medulla included in the CT slice studied.

Serohematologic alterations in broiler chicks on feed amended with Fusarium proliferatum culture material on fumonisin B1 and moniliformin.

Two hundred twenty-eight male broiler chicks (Columbia x New Hampshire) were given feed amended with autoclaved culture material of Fusarium proliferatum containing fumonisin B1 (FB1) at 61, 193, and 546 ppm, fumonisin B2 (FB2) at 14, 38, and 98 ppm, and moniliformin at 66, 193, and 367 ppm in 3 separate feeding trials (amounts of toxin in each trial, respectively). Birds were started on amended rations at days 1, 7, and 21 and continuing for 14 days. Of serum chemistry parameters, only glucose was significantly decreased. Significant increases were noted in serum cholesterol, sodium, alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, and gamma-glutamyl transferase. Of the hematologic parameters, significant decreases were noted in red blood cell counts, hemoglobin, packed cell volume, and white blood cell counts. Immunologic changes included impaired anti-Newcastle disease antibody hemagglutination inhibition titers associated with relative decreases in total serum globulins and increases in albumin/globulin ratios. The changes were noted in all treatment groups when compared to controls.

The individual and combined effects of the Fusarium mycotoxins moniliformin and fumonisin B1 in turkeys.

Fumonisin B1 (FB1) and moniliformin (M) were supplied by Fusarium moniliforme M-1325 and Fusarium fujikuroi M-1214 culture material, respectively. Turkeys were fed a control ration, or rations containing 200 mg FB1/kg, 100 mg M/kg, or a combination of both 200 mg FB1/kg and 100 mg M/kg feed from 1 to 21 days of age. These rations contained 0, 3.8, 1.0, and 4.8% culture material, respectively. In comparison to controls, turkeys fed FB1 had increased relative liver weights. Both aspartate aminotransferase and lactate dehydrogenase were increased in poults fed FB1. Turkeys fed M had decreased feed intake and body weight gains and increased relative heart weights in comparison to controls. Poults fed FB1 had moderate diffuse hepatocellular hyperplasia and poults fed moniliformin had a loss of cardiomyocyte cross striations. Turkeys fed the ration containing both M and FB1 had all the above changes; however, no additive or synergistic effects were evident for any single parameter measured. No treatment-related morbidity or mortality was observed in the study.

A sudden death syndrome induced in poults and chicks fed diets containing Fusarium fujikuroi with known concentrations of moniliformin.

A sudden death syndrome was induced in chicks and poults fed diets containing Fusarium fujikuroi, formulated to contain 0-330 mg/kg moniliformin (M) with or without the maximum recommended therapeutic concentration of monensin. Lesions of monensin toxicosis were not observed. Clinical signs were referable to cardiac dysfunction (sudden death, dyspnea, cyanosis, depression). Poults and chicks dying early in the study had no gross lesions or had lesions of right ventricular dilation. Treated poults and chicks dying late in the study or euthanatized at termination of the study had lesions of bilateral myocardial hypertrophy, usually concentric. Absolute heart weights and relative heart weights, expressed as a percentage of body weight, were significantly greater in treated birds than controls (P < 0.05), whereas body weights were significantly less (P < 0.05). Microscopically, lesions progressed from acute myocardial degeneration to necrosis, fibrosis, and hypertrophy. Ultrastructural findings were consistent with the gross and microscopic lesions. Serum pyruvate concentrations were a useful indicator of M-induced cardiotoxicosis. Concentrations of serum pyruvate increased with increased concentration of dietary M, but were not affected by addition of monensin to the diet. In chicks ingesting 40-300 mg/kg M, serum pyruvate concentrations were significantly greater (P > 0.05) than those in controls (controls, 0.28 +/- 0.08 mmol/liter; exposed 0.38 +/- 0.11-0.55 +/- 0.13 mmol/liter). Poults ingesting 80-330 mg/kg M had significantly greater serum pyruvate concentrations than controls (controls 0.33 +/- 0.09 mmol/liter; exposed 0.43 +/- 0.13-1.00 +/- 0.006 mmol/liter). The Vetronics System was used to evaluate electrocardiographic alterations in a limited number of chicks and poults surviving to the end of the feeding trial. Electrocardiographic alterations in poults and chicks fed diets containing > or = 40 mg/kg and > or = 160 mg/kg M, respectively, were consistent with ventricular hypertrophy, myocardial injury, and hypoxia. Electrocardiographic alterations were more striking in poults than in chicks. Altered myocardial metabolism due to M toxicosis, in conjunction with the unusual susceptibility of domestic poultry to altered cardiac metabolism, is believed to be the cause of the organ-specific lesions in these birds. These findings suggest that cardiac injury with subsequent alterations in cardiac electrical conductance may be a cause of the sudden deaths observed in poultry chronically intoxicated with dietary M.

Expectations in the treatment of obesity.

The initial efficacy expectations and outcome expectations held by 147 women participating in two weight reduction programmes were assessed and found to be partially related to drop-out and the weight loss attained. Expectations were revised as treatment progressed, but changes were not closely correlated with changes in weight over the same period. Initial outcome expectations were associated with higher weight, and lower social class and verbal ability, but not the number of previous attempts to lose weight.

An evaluation of self-instructional training in the treatment of obesity.

An experimental evaluation of a cognitive self-instructional procedure for increasing self-control of eating was carried out in a weight reduction programme for obese women. All subjects received a 'core', 16 week long treatment programme of nutritional advice and encouragement provided by five group meetings and one individual session. Subjects were randomly assigned to receive only the core programme, or the core programme plus seven individual sessions of one of three types of treatment. Thus there were four treatment conditions: (a) Cognitive Rehearsal (Self-instructional training attempting to teach subjects to resist temptation through the self-directing power of inner speech), (b) Insight Control (teaching subjects to become aware of, but not to change, unhelpful cognitions), (c) Individual Contact Control (encouragement and nondirective discussion of dieting) and (d) Group Contact Control (core programme only). Of the 94 subjects entering the programme 74 completed the 16 weeks of treatment and 69 were followed up a year later. There were no significant differences between treatments in obesity reduction either at the end of treatment or at followup. There were significant reductions in anxiety and depression and in initially unrealistically high outcome expectations. Initial weight loss, an apparently important variable, predicted subsequent losses.

Cognitive rehearsal in the treatment of obesity: a comparison against cue avoidance and social pressure.

The effects of a cognitive (cognitive rehearsal) in the treatment of obesity were evaluated in a 16-week weight reduction programme by comparison against two other treatments, cue avoidance, and social pressure. Fifty-three obese females, categorised (on the basis of their weight loss after 3 weeks of dieting) as either high losers or low losers, were randomly assigned to one of these three treatments. Posttreatment weight losses were significantly greater for high losers than low losers, and for subjects in cue avoidance than those in social pressure. Those in cue avoidance went over their diet less often than others, and reported greater changes in eating habits, and in the cognitive domain. Neither subject type nor treatment type has a significant effect on weight change during the follow-up year. High losers adhered to the diet more initially, but also, throughout treatment, lost more weight for the same degree of dietary adherence. Behavioural and physiological characteristics underlying this important dimension of individual differences were discussed.

Analysis of fumonisin B1 in corn by capillary electrophoresis.

Intact fumonisins contain two tricarballylic acid groups and can therefore acquire a net negative charge. The anionic nature of the fumonisins is the basis behind the widely used method for cleanup of corn with strong anion exchange (SAX) columns. This property also enables the fumonisins to be separated by electrophoretic techniques which, until now, have not been applied to the analysis of fumonisins in corn. Fumonisin B1, extracted from corn with 80/20 (v/v) methanol/water and isolated with a commercially available affinity column, was derivatized with fluorescein isothiocyanate for analysis by capillary zone electrophoresis with laser-induced fluorescence detection (CZE-LIF). Recoveries from corn fortified with 0.25 to 5.0 ppm FB1 averaged 89% (range 71 to 102%). As little as 0.05 ppm FB1 could be detected in corn. For corn naturally contaminated with FB1, the CZE-LIF method compared favorably to established SAX/HPLC and C18/HPLC methods. Capillary electrophoresis can be used for quantitation of FB1 in corn, with minimal use of organic solvents and provides an additional tool for confirming fumonisin contamination.

Distribution of fumonisins in food and feed products prepared from contaminated corn.

The fate and distribution of the fumonisins B1 (FB1) and B2 (FB2) were determined in products obtained from naturally contaminated corn used for ethanol fermentation and wet milling operations. Fumonisins are stable to the conditions used in ethanol fermentations and tend to concentrate in the distillers dried grain, a fraction generally used for animal feed. No toxin was found in the ethanol. Starch from wet milling of corn, naturally contaminated at 13.9 micrograms fumonisin B1/g, was free of detectable toxin. The other fractions contained fumonisins at the following levels: gluten (5.1-5.8 micrograms FB1/g, 4.7-4.9 micrograms FB2/g); fiber (2.7-5.7 micrograms FB1/g, 2.1-3.1 micrograms FB2/g); and germ (1.3-3.1 micrograms FB1/g, 0.7-1.6 micrograms FB2/g). The steep water and process water contained 22% of the recoverable fumonisins. A combination of analytical methodologies was required to determine fumonisins in the different products from the wet milling process.

Analysis of naturally occurring mycotoxins in feedstuffs and food.

Aflatoxins, zearalenone, deoxynivalenol, fumonisins, and their respective metabolites require specific procedures for their determination because of their diverse chemistry and occurrence in complex matrices of feedstuffs and foods. Major sources of error in the analysis of these mycotoxins arise from inadequate sampling and inefficient extraction and cleanup procedures. The determinative step in the assay for each of these toxins is sensitive to levels below those that are considered detrimental to humans and animals. Aflatoxins can be determined in grains and animal fluids and tissues by TLC, HPLC, gas chromatography-mass spectrometry (GC-MS), and ELISA procedures. Zearalenone, an estrogenic mycotoxin, can readily be determined in cereal grains and foods by HPLC (50 ng/g) and by TLC (300 ng/g). No incurred levels of zearalenone or its metabolites have been detected in animal tissues destined for human consumption. Deoxynivalenol can be determined in wheat and corn at 300 ng/g by a rapid TLC procedure and at 325 ng/g by a GC method. Although not tested collaboratively, an HPLC procedure and an ELISA screening procedure are capable of detecting deoxynivalenol at low (nanograms/gram) levels in feedstuffs and foods. The recently characterized fumonisins can be detected by TLC, HPLC, and GC-MS at levels below those now considered harmful. Thin-layer chromatography and HPLC (with fluorescence detection of derivatives) procedures can detect fumonisins at approximately 100 ng/g; GC-MS is required for detection at lower levels.

Enzyme-linked immunosorbent assay for detection of zearalenone in corn, wheat, and pig feed: collaborative study.

A direct competitive enzyme-linked immunosorbent assay (ELISA) screening method for zearalenone in corn, wheat, and feed at 500 ng/g was evaluated by 23 collaborators (22 laboratories) in an international collaborative study. Eighteen samples of spiked or naturally contaminated corn, wheat, and pig feed were prepared by the sponsoring laboratory and sent for testing with complete test kits to participating collaborators in Canada, Italy, Sweden, The Netherlands, and the United States. Test samples were extracted with methanol-water solution (70 + 30) by shaking on a wrist-action shaker for 3 min. A portion of the extract was mixed with an equal volume of zearalenone-enzyme conjugate, and the mixture was incubated with zearalenone-specific monoclonal antibodies coated onto microtiter wells. All test samples were assayed in duplicate. One of 52 (2%) blanks was reported positive. Thirty-nine of the 52 (75%) samples that were spiked at 500 ng/g were reported as positive. Forty-nine of the 51 (96%) samples with concentrations at or above 1000 ng/g were reported as positive. The overall incidence of false negatives was 6.0% and the incidence of false positives was 22.7% by the ELISA method. Only one (3.4%) false negative was reported for samples containing > or = 800 ng/g. In the spectrophotometric method, 8 collaborators determined approximate levels of zearalenone in test samples from standard curves constructed from spiked extracts (0-3000 ng/g of each commodity tested). This method gave and overall incidence of false negatives of 5.7% and false positives of 17.8%. Average relative standard deviations, RSDr (repeatability) and RSDR (reproducibility), were 11.6 and 25.1% for spiked samples and 11.7 and 33.1% for naturally contaminated samples, respectively. Standard curves were constructed with each set of samples assayed. Comparison of absorbance values from these standard curves indicate the performance of reagents and antibody used in the assay. The ELISA method has been adopted first action by AOAC INTERNATIONAL as a screening method for zearalenone at > or = 800 ng/g in corn, wheat, and pig feed.

An optimized MTT bioassay for determination of cytotoxicity of fumonisins in turkey lymphocytes.

In vitro cytotoxicity assays have been performed for detection and quantitation of fumonisins, as possible alternatives for whole animal testing. This study was undertaken to establish optimal in vitro conditions using turkey lymphocytes. Turkey lymphocytes were isolated from peripheral blood by Percoll gradient centrifugation. Cytotoxicity of fumonisin B1 (FB1) and B2 (FB2) was determined by exposing lymphocytes to FB1 or FB2 at concentrations of 0.01-25 micrograms/mL for 24, 48, or 72 h at 39 degrees C. The MTT bioassay was used to measure cell viability and proliferation. In metabolically active cells, the tetrazolium salt, MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide], was reduced to MTT formazan. Turkey lymphocytes that had been exposed in vitro to FB1 and FB2 for 48 and 72 h showed inhibition of cell proliferation that was dose-dependent. The 50% inhibitory dose for FB1 and FB2 was 0.4-5 micrograms/mL. Cells exposed to FB1 or FB2 exhibited high levels of cytoplasmic vacuolization and were unable to proliferate, whereas proliferation of control lymphocytes was observed at 48 and 72 h. FB2 was 3- to 4-fold more cytotoxic than FB1.

Effects of feeding Fusarium fujikuroi culture material, containing known levels of moniliformin, in young broiler chicks.

An experiment was conducted with 270 male broiler chicks to evaluate the effects of a Fusarium fujikuroi M-1214 culture material containing moniliformin (M) on broiler chicks. Day-old chicks were allotted randomly to dietary treatments containing 0, .24, .48, .72, .96, 1.44, 1.92, 2.40, and 2.88% M culture material (MCM). These levels of MCM supplied 0, 25, 50, 75, 100, 150, 200, 250, or 300 mg M/kg of feed. Each dietary treatment was fed to six pen replicates of five chicks per pen for 21 d. Significant mortality (P < .05) occurred in chicks fed 200 (8 out of 30), 250 (17 out of 30), and 300 (25 out of 30) mg M/kg feed. Chicks fed > 100 mg M/kg had lower (P < .05) feed intakes and smaller BW gains (P < .05) than controls. Increased heart weights (P < .05) were observed in chicks fed > 50 mg M/kg, and increased liver weights (P < .05) in chicks fed > 100 mg M/kg. Gross lesions of M toxicity included generalized cardiomegaly with dilation of the right ventricle. Histopathology revealed a high incidence of large and variably shaped cardiomyocyte nuclei and a generalized loss of cardiomyocyte cross striations in chicks fed > 75 and 200 mg M/kg, respectively. Results indicated that F. fujikuroi culture material containing M is toxic to young broiler chicks.