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In this communication we report on the self-organising properties of a novel asymmetric bolaphile composed of sugar and steroidal units. The material was found to exhibit unusual phase changes in that it formed a cubic phase upon heating, whereas upon cooling it formed a lamellar phase. This change in property was ascribed to kinetic versus thermodynamic behaviour at the phase transition to the liquid.

This ecological study aimed, through the analysis of 1,146 wards in the South West of England (1998-2002), firstly, to examine whether chemical incidents and public casualties are more likely near complex industry (emissions to land, air or water: Integrated Pollution Control industry, IPC) or industry with emissions to air only (Local Air Pollution Control industry, LAPC). Secondly, the study examined whether industry, incidents and casualties are found close to deprivation. Social inequalities were examined across quintiles of wards. Fifty-two wards (4.5%) contained an IPC industry and 712 (62.1%) an LAPC. Incidents occurred in 132 wards (11.5%), with casualties in 59 (5.1%). Chemical incidents occurred more frequently in wards with LAPC (152, IPC 20); the same was true of casualties (211, 12). With each additional LAPC site in a ward, the risk of an incident rose by 22% (95% confidence interval [CI] 8-38%), suggesting a dose-response relationship. No clear social inequalities were found. In the South West of England, the public are more likely to be affected by an incident occurring at a simple LAPC site rather than a complex IPC site. This has implications for emergency planning which, at present, focusses most attention on the larger, more complex IPC sites.

Synthetic C-terminal amidated cationic ferrocenoyl peptide bioconjugates Fc-Orn-Orn-Orn (1) and Fc-Tyr-Orn-Orn-Orn (2) were rationally designed as superoxide dismutase (SOD) mimics based on the structure of the iron SOD from Escherichia coli. Ferrocenoyl peptide bioconjugates 1, 2 and ferrrocenecarboxylic acid (4) were subsequently evaluated as SOD mimics and as inhibitors of peroxynitrite-mediated tyrosine nitration. Due to their cationic character, ferrocenoyl peptide bioconjugates 1 and 2 exerted an acceptable SOD activity (EC(50)=575 microM and 310 microM, respectively) in comparison with 4 (EC(50)=1.4mM). The C-terminal amidated cationic peptide Ac-Tyr-Orn-Orn-Orn (3), designed as marker of peroxynitrite, was used to evaluate the inhibitory activity of 1 and 4 towards peroxynitrite-mediated tyrosine nitration. Both compounds proved to inhibit the nitration especially the cationic ferrocenoyl peptide bioconjugates 1. The ferrocene moiety of conjugate 2 displayed a strong inhibitory activity of peroxynitrite-mediated nitration of the neighboring tyrosine.

The D816V-mutated variant of Kit triggers multiple signaling pathways and is considered essential for malignant transformation in mast cell (MC) neoplasms. We here describe that constitutive activation of the Stat5-PI3K-Akt-cascade controls neoplastic MC development. Retrovirally transduced active Stat5 (cS5(F)) was found to trigger PI3K and Akt activation, and to transform murine bone marrow progenitors into tissue-infiltrating MCs. Primary neoplastic Kit D816V(+) MCs in patients with mastocytosis also displayed activated Stat5, which was found to localize to the cytoplasm and to form a signaling complex with PI3K, with consecutive Akt activation. Finally, the knock-down of either Stat5 or Akt activity resulted in growth inhibition of neoplastic Kit D816V(+) MCs. These data suggest that a downstream Stat5-PI3K-Akt signaling cascade is essential for Kit D816V-mediated growth and survival of neoplastic MCs.

In the context of the use of carbohydrates obtained from agricultural crops, the search for amphiphilic derivatives is one of the most developed aspects. Indeed, due to the high polarity and the functional richness of sugars, many different structures can be targeted, with a wide range of physicochemical properties, either for large scale products of industrial interest, or for fine applications at the chemistry-biology interface. Among carbohydrates arising from agricultural resources, sucrose is especially interesting because of its very large production scale in the world (ca. 160Mt/year, ca. 20Mt/year of which in the European Community). Here, we describe the research accomplished in our group dealing with the synthesis and the study of the properties of amphiphilic derivatives prepared from sucrose as well as from another very available disaccharide, isomaltulose.

New N-acyl homoserine lactone analogues, N-acyl-3-amino-5H-furanone derivatives and some 4-halogeno counterparts, were synthesised and tested for their ability to modulate LuxR-dependent bacterial quorum sensing. Both types of analogues proved to be inhibitors, the halogenated compounds being significantly more active. Molecular modelling suggested that the conjugated enamide group induces two preferential conformations leading to specific binding modes. In addition, the presence of the halogen atom could enhance the fitting of the lactone ring through specific interactions with strictly conserved or conservatively replaceable residues in the LuxR protein family, namely Asp79, Trp94 and Ile81.

Amino acid sequence alignments of the transcriptional regulator AfeR, which is involved in type 1 quorum sensing (QS) in Acidithiobacillus ferrooxidans bacteria, with other acyl homoserine lactone (AHL)-dependent QS regulators, revealed the presence of strictly or highly conserved residues located in the active site of these proteins. As a consequence, a model of AfeR was constructed to study the binding mode of long-chain AHLs using molecular dynamics and subsequent rigid ligand docking. This study, performed on the tetradecanoyl homoserine lactone C14-AHL, showed that the binding mode involved a curved conformation. Based on these results, the binding mode of tetradec-7-Z enoyl homoserine lactone, an AHL that is conformationally constrained due to the presence of the cis double bond, was investigated. This mono-unsaturated AHL with its preferential curved shape conformation was found to be particularly well adapted to the active site of AfeR. These results should be helpful in the rational design of QS modulators with potential biotechnological applications and especially in the improvement of industrial bioleaching from ores.

A series of 9 homoserine lactone-derived sulfonylureas substituted by an alkyl chain, some of them bearing a phenyl group at the extremity, have been prepared. All compounds were found to inhibit the action of 3-oxo-hexanoyl-L-homoserine lactone, the natural inducer of bioluminescence in the bacterium Vibrio fischeri, the aliphatic compounds being more active than their phenyl-substituted counterparts. Molecular modelling studies performed on the most active compound in each series suggest that the antagonist activity could be related to the perturbation of the hydrogen-bond network in the ligand-protein complexes.

Objective: To aid the interpretation of the trends in prostate cancer mortality, which declined in the UK in the early 1990 s for unknown reasons, by investigating prostate cancer death rates, incidence and treatments in England and Wales in 1975-2004., Methods: Join-point regression was used to assess secular trends in mortality and incidence (source: Office of National Statistics), radical prostatectomy and orchidectomy (source: Hospital Episode Statistics database) and androgen-suppression drugs (source: Intercontinental Medical Statistics)., Results: Prostate cancer mortality declined from 1992 (95% confidence interval, CI, 1990-94). The relative decline in mortality to 2004 was greater and more sustained amongst men aged 55-74 years (annual percentage mortality reduction 2.75%; 95% CI 2.33-3.18%) than amongst those aged >or=75 years (0.71%, 0.26-1.15%). The use of radical prostatectomy increased between 1991 (89 operations) and 2004 (2788) amongst men aged 55-74 years. The prescribing of androgen suppression increased between 1987 (33,000 prescriptions) and 2004 (470,000)., Conclusions: The decrease in prostate cancer mortality was greater amongst men aged 55-74 years than in those aged >or=75 years, but pre-dated the substantial use of prostate-specific antigen screening and radical prostatectomy in the UK. An increase in radical therapy amongst younger groups with localized cancers and screen-detected low-volume locally advanced disease as a result of stage migration, as well as prolonged survival from increased medical androgen suppression therapy, might partly explain recent trends.

Objective: To investigate the morbidity and mortality after radical prostatectomy (RP) in relation to the numbers of RPs carried out at individual hospitals, as recent studies of complex surgery report worse outcomes in low-volume hospitals, and there has been a large increase in RPs for localized prostate cancer., Methods: We analysed hospital episode statistics data for all 18 027 RPs in English National Health Service hospitals between 1997 and 2004., Results: In multivariate analysis, there was a U-shaped association of hospital volume with mortality (P for nonlinear trend, 0.004), but this finding was based on only 59 (0.3%) deaths. The mean length of stay was 6 days and decreased by 2.96% (95% confidence interval, CI, 1.98-3.92; P < 0.001) per quintile increase in hospital volume. In all, 16.1% of men had 30-day in-hospital complications; 20.3% were readmitted with complications within a year. The odds of 30-day in-hospital wound/bleeding complications decreased by 6% (95% CI 1-11; P = 0.02), and miscellaneous medical complications decreased by 10% (0-19; P = 0.04) per increase in hospital volume quintile. For re-admissions within a year, the hazard of vascular complications decreased by 15% (6-22; P = 0.001), wound/bleeding complications decreased by 8% (2-13; P = 0.01) and genitourinary complications decreased by 5% (2-8; P = 0.002), per increase in hospital volume quintile., Conclusion: In men undergoing RP the length of hospital stay and rates of some short- and long-term postoperative complications afterward are lower in high-volume hospitals. The magnitudes of these effects on the outcomes studied may be too small and inconsistent to indicate a policy of selective referral to high-volume hospitals. Quality of life and oncological outcomes, however, could not be investigated in this dataset.

Objectives: To investigate recent trends in in-patient admissions in England for assaults that involve a stabbing. Design and data source Time-series analysis of the NHS Health and Social Care Information Centre's Hospital Episode Statistics (HES) database. Setting England, April 1997 to March 2005. Main outcome measure All completed hospital admissions with a mention of assault by sharp object (International Classification of Diseases, Tenth Revision, code X99) in the relevant diagnosis fields in HES., Results: In the eight years between 1st April 1997 and 31st March 2005 the number of people admitted to hospital reportedly following an assault involving a sharp object rose by 30%, from 3770 patients in 1997/8 to 4891 in 2004/5. One hundred and fifty-four of these people died (0.5%). Forty-two percent (14 220) of admissions were on a Saturday or Sunday. Males accounted for 90% (males 30 464 and females 3406) of admissions. Forty-nine percent (14 786) of the men, and 41% (1383) of the women, had injuries to the head, neck or thorax., Conclusions: The number of recorded hospital admissions from stabbing assaults increased between 1997 and 2005. Approximately 13 people a day are currently admitted to hospital for treatment after being stabbed. Further research is required to identify effective interventions to reduce the number of stabbings.

The ERETIC method has been used to determine precise concentrations of aqueous solutions of sucrose and sugar surfactants, namely octyl glucoside and fatty acid sucrose esters by (1)H NMR spectroscopy. The effects of NMR tuning, acquisition parameters, and spectrum processing on the measurement have been assessed in these particular cases. The linearity upholds over the whole concentration range, with both sucrose and octyl glucoside, whatever the physicochemical phenomena occurring, either an increasing viscosity or the micellization of the surfactant. For sucrose solutions, an accuracy of 2% is measured for concentrations between 0.1 and 200 mmol/L, which is consistent with literature data.

Three families of mono-substituted sucrose fatty acid esters were prepared by enzymatic and classical synthetic procedures, and their self-assembly and self-organizational properties were investigated by thermal polarised light microscopy, differential scanning calorimetry and X-ray diffraction. The properties were evaluated as a function of the fatty acid chain length. For the lower homologues of the series columnar liquid-crystalline stacking structures were found, whereas for the higher homologues, lamellar phases predominated. A model for the columnar stacking arrangement, consisting of a unique arrangement of the molecules which could lead to the creation of multiple internal ion channels between the hydrophobic interior and the hydrophilic exterior of the columns, is suggested.

The micellization of pure monosubstituted sucrose fatty acid esters in water, namely sucrose octanoate, sucrose decanoate, sucrose laurate, sucrose dodec-5-cis-enoate, sucrose myristate, and sucrose palmitate, has been investigated by means of two NMR methods, pulsed field gradient spin-echo NMR (PFGSE-NMR), giving access to the self-diffusion coefficients of free molecules and micelles in solution, and the ERETIC method (electronic reference to access in vivo concentrations) for the measurement of concentrations by external calibration of a synthetic NMR signal. The early micellar regions and, when possible, the premicellar regions were investigated. By this method, we obtained the hydrodynamic radii of micelles, displaying a linear progression in relation to the chain length and an accurate determination of critical micellar concentration (CMC) for each sucrose ester. The effect of the regiochemistry of fatty chain grafting has been investigated, showing special behavior for 1'-O-sucrose palmitate.

Background: The assessment and reporting of national patterns of psychiatric hospital admissions is important for strategic service development and planning., Aims: To investigate patterns of psychiatric hospital admissions of patients aged 16-64 years in England., Method: We used the Department of Health's national Hospital Episode Statistics data on admissions to National Health Service hospitals in England between April 1999 and March 2000, to investigate patterns by region, gender, age and diagnosis., Results: The annual admission rate for England was 3.2 per 1000 population. There were marked regional variations and rates were higher in males than in females. Depression and anxiety together were the most common (29.6%) reason for admission. Length of stay exceeded 90 days in 9.2% of admissions and 1 year in 0.9% (highest in London and for psychoses)., Conclusions: Depression and anxiety together were the most frequent diagnoses leading to hospitalisation. There has been a reversal of the previously reported predominance of female admissions. Regional variations in activity and the significant numbers of patients remaining for long periods in'acute' inpatient care have important policy implications.

Rapid-eye movement sleep (REMS) in the rat occurs in the form of episodes separated by long (>3 min: isolated REMS episodes, IREMSEs) and short (<3 min: sequential REMS episodes, SREMSEs) intervals. The mechanism clustering SREMSEs is thought to be better suited to increase the amount of REMS when its drive is high. We tested this hypothesis in a new situation by transiently augmenting this drive with a moderate psychogenic stress. After a 90-min immobilization stress, REMS increased by 54% over the rest of the dark phase. This increase was associated with a modest increase in IREMSEs (+40%), but a massive increase in SREMSEs (+300%). Thus, the mechanism that clusters REMS episodes operates in response to a moderate psychogenic stress imposed in standard laboratory conditions and not preceded by sleep deprivation.

Investigations of the thermotropic liquid-crystalline properties of 6,6'-di-O-stearoylsucrose show, for the first time, that glycolipids can exhibit phase transitions within the smectic A phase.

The effects of a nocturnal exposure to a cool environment on daytime recovery sleep was studied in eight young (20-25 years old) healthy volunteers. A set of standardized clothing (KSU ensemble type) was provided to each individual (estimated total thermal resistance: 0.6 clo). The subject kept awake was passively exposed from 22.30 to 07.30 hours to environments perceived as neutral (N) and comfortable or slightly cold (C) and uncomfortable. They were then allowed to sleep ad libitum (light out at 08.00 hours) under thermoneutral conditions (air temperature: 21 degrees C to 22 degrees C; clothing: cotton tee-shirt and pajama-pants; covering: one cotton sheet and one wool blanket). Sleep was recorded and scored according to the Rechtchaffen and Kales standard procedures. Esophageal temperature (T(es)) was recorded from 21.30 hours until the end of sleep. The nocturnal drops in T(es) were significantly different between N and C (p<0.01), this difference disappearing during sleep. No statistical difference was found between conditions for most of the sleep variables. Compared to N however, C resulted in a significant increase in rapid eye movement (REM) sleep duration (+35%, p<0.01) during the subsequent daytime sleep. It is hypothesized that the REM-sleep increase induced by the exposure to moderate cold is due to the thermal discomfort stress consciously perceived by the subject.

The metabolizable energy content of low-digestible carbohydrates does not correspond with their true energy value. The aim of the present study was to determine the tolerance and effects of two polyols on digestion and energy expenditure in healthy men, as well as their digestible, metabolizable and net energy values. Nine healthy men were fed for 32 d periods a maintenance diet supplemented either with dextrose, Lycasin HBC (Roquette Frères, Lestrem, France), or the hydrogenated polysaccharide fraction of Lycasin HBC, at a level of 100 g DM/d in six equal doses per d according to a 3 x 3 Latin square design with three repetitions. After a 20 d progressive adaptation period, food intake was determined for 12d using the duplicate meal method and faeces and urine were collected for 10 d for further analyses. Subjects spent 36 h in one of two open-circuit whole-body calorimeters with measurements during the last 24h. Ingestion of the polyols did not cause severe digestive disorders, except excessive gas emission, and flatulence and gurgling in some subjects. The polyols induced significant increases in wet (+45 and +66% respectively, P<0.01) and dry (+53 and +75 % respectively, P<0.002) stool weight, resulting in a 2% decrease in dietary energy digestibility (P<0.001). They resulted also in significant increases in sleeping (+4.1%, P<0.03) and daily energy expenditure (+2.7 and +2.9% respectively, P<0.02) compared with dextrose ingestion. The apparent energy digestibility of the two polyols was 0.82 and 0.79 respectively, their metabolizable energy value averaged 14.1 kJ/g DM, and their net energy value averaged 10.8 kJ/g DM, that is, 35 % less than those of sucrose and starch.

The tactile arousal threshold of sleeping birds has not been investigated to date. In this study, the characteristics of this threshold were assessed by stimulating either the upper back or a foot of two groups (one cutaneous site per group) of 60 sleeping king penguins (Aptenodytes patagonica) in the breeding colony of Baie du Marin (Crozet Archipelago). Increasing weights were put onto one of the feet or the upper back of individuals that had been sleeping for more than 5 min until they showed behavioural signs of arousal (head raising). The weight applied to the upper back that was needed to awaken a sleeper (837 +/- 73 g) was 20 times greater than that applied to a foot (38 +/- 6 g). In terms of pressure, the difference remained five times higher for the back (209 +/- 18 g/cm(2)) than the foot (40 g +/- 7 g/cm(2)). Because the king penguin incubates its single egg and rears its young chick on its feet, the low threshold measured at this level could be viewed as an adaptation against progeny predation. Sleepers are frequently bumped by conspecifics walking through the colony. The increased arousal threshold associated with tactile stimulation of the back may help to preserve sleep continuity under these conditions.

We studied the influence of a nocturnal environment perceived as warm on the subsequent daytime sleep of healthy human subjects (20-25 years old). From 00:00 to 8:00, they were kept awake and exposed to either a thermoneutral and comfortable (CN) or a warm and uncomfortable (EW) environment, as assessed by the predicted mean vote/percentage of persons dissatisfied questionnaire (PMV/PPD). The subjects then slept from 8:00 to 14:00 in a thermoneutral environment. Sleep was scored according to the Rechtschaffen and Kales criteria. Rectal temperature was recorded from 22:00 to the end of the sleep period. Compared to CN, a significant but moderate hyperthermia (0.3-0.4 degrees C) occurred rapidly in EW, and was maintained throughout the night. This modest difference disappeared during subsequent sleep spent at thermal comfort. Exposure to a warm uncomfortable environment before bedtime significantly increased the duration (+37%) and percentage of rapid eye movement sleep (REMS). This hypnic response could be due to interactions occurring between thermoregulatory, circadian, and sleep mechanisms. It could also be ascribed to synergic actions of the neurophysiological (among others, involving the hypothalamo-pituitary-adrenal axis) and psychological (involving memory processing) processes developed when the organism faces a moderate stress.

The growing interest in combinatorial chemistry has led to a new source of compounds from which a large number of leads has emerged over recent years. Parallel synthesis, in particular, allows a quick production of a wide number of individual compounds. A rapid analytical control is needed to determine their quality. A strategy using automated, fast reversed-phase C18 high-performance liquid chromatography with diode-array detection (LC-DAD-MS) followed by atmospheric pressure chemical ionisation mass spectrometry (APCI-MS) and NMR has been developed for their characterisation and purity control. Complementary NMR analyses are done on selected compounds to provide a better structural characterisation of the expected compounds and their potential side-products. Validated libraries are then registered in ISIS databases using automated procedures.

Neurological disorders, such as stroke, trauma, tardive dyskinesia, Alzheimer's and Parkinson's diseases, may be partially attributed to excessive exposition of the nervous tissue to oxygen-derived radicals. A novel water-soluble alpha-tocopherol analogue, 2,3-dihydro-2,2,4,6,7-pentamethyl-3-(4-methylpiperazino) methyl-1-benzofuran-5-ol dihydrochloride (MDL), is a potent radical scavenger. Following subcutaneous administration to mice, MDL inhibited the lipid peroxidation induced in the 100-fold diluted brain homogenates, with an ID50 of 8 mg/kg. Rapid brain penetration, within 30-60 min postadministration, and even distribution into different brain areas were observed. MDL was also detected after oral administration. In brain homogenate undergoing lipid peroxidation, MDL prevented the consumption of an equal amount of alpha-tocopherol, while inhibiting the concomitant malondialdehyde formation. The radical scavenging capacity of MDL was superior to that of alpha-tocopherol, although the peak and half-peak potentials were not significantly different. However, MDL was much less lipophilic, the partition coefficient (log P) at the octanol/water interface being 1.91. Although it is yet unknown, whether the applied criteria sufficiently predict its usefulness, beneficial effects of MDL may be expected in the above mentioned disorders.

To determine the potential prognostic value of epithelial cadherin (E-cadherin), a Ca(2+)-dependent cell-cell adhesion molecule, we have analysed its immunoreactivity and cellular localisation in 67 transitional cell carcinomas (TCC) using an avidin-biotin immunoperoxidase technique on formalin-fixed, paraffin-embedded tissues. These results were correlated with histopathological grade, tumour stage, presence of metastases and survival. In addition, 10 cystitis and 11 normal bladder biopsies were evaluated as controls. E-cadherin was expressed in a normal membranous pattern in all normal and 7 of 10 cystitis biopsies. Loss of normal surface E-cadherin expression was found in 3 of 15 superficial tumours and in 48 of 52 invasive cancers. Abnormal immunoreactivity was strictly related to tumour differentiation and stage. Fifteen of 20 well-differentiated (grade I) tumours showed preserved membranous E-cadherin immunoreactivity, while 46 of 47 moderate and poorly differentiated tumours (grades II and III) demonstrated abnormal staining patterns. Loss of membranous E-cadherin immunoreactivity was also associated with advanced tumour stage. There was a significantly higher 5-year survival rate for patients with preserved membranous staining compared with patients with abnormal staining.

Analogues of alpha-tocopherol and ascorbic acid with permanently cationic substituents, i.e., phosphonium (8, 9), sulfonium (11), acylhydrazinium (13, 14), and ammonium (1, 16, 21), were synthesized, and the 2R and 2S enantiomers of the alpha-tocopherol analogues 1, 8, 11, and 13 were separated. The compounds were found to scavenge lipoperoxyl and superoxide radicals in vitro and accumulate in heart tissue (cardioselectivity) as demonstrated by measurement of ex vivo inhibition of lipid peroxidation in mouse heart homogenates and confirmed by HPLC determination of drug concentrations for 1 and 11. The 2R and 2S enantiomers of 1 inhibited ex vivo lipid peroxidation to an equal extent. Thus the in vivo uptake into myocytes (cardioselectivity) is independent of the geometry at the chiral center and common to permanently cationic compounds.

A series of alpha-tocopherol analogues was synthesized with potential therapeutic value for such pathological conditions as stroke and trauma. A set of criteria such as the inhibition of in vitro lipid peroxidation, superoxyl radical scavenging, and brain penetration, as measured by ex vivo inhibition of lipid peroxidation, was applied to select the most effective compound. 2,3-Dihydro-2,2,4,6,7-pentamethyl-3-[(4-methylpiperazino)methyl]-1 - benzofuran-5-ol dihydrochloride (22) was selected because of its superior antioxidant properties and better brain penetration. This compound also protected mice against the effects of head injury. The criteria thus turned out to be useful for the characterization of a neuroprotective analogue of alpha-tocopherol.

In the UK, compliance with conventional faecal occult blood (FOB) tests such as Haemoccult is about 50% in the general population. It has been postulated that characteristics of the performance of conventional tests, in particular the need for dextrous gathering and manipulation of faeces, delay in receiving results, and the recommended dietary restrictions, may all diminish compliance. New FOB tests have been developed, popularly termed 'magic toilet paper' tests, which not only minimize faecal manipulation but are also self-reported. Compliance rates with two self-administered faecal occult blood tests (Early Detector and Coloscreen Self-Test) were compared with Haemoccult in a randomized trial involving 1,842 subjects aged 40-74 years. Use of self-administered FOB tests did not increase compliance significantly, with rates of 52.1% for Early Detector, 50.6% for Coloscreen and 49.1% for Haemoccult. Moreover, dietary restriction did not reduce compliance significantly (restricted 49.3%, unrestricted 51.8%). A wide variation (from 1.3% to 21.4%) in positivity rates was observed which was dependent on which of the three tests was used and whether dietary restrictions were applied. Since the physical aspects of test performance do not appear to determine an individual's decision to be screened, self-administered tests will not overcome the problem of poor compliance with FOB screening.

To determine the relative importance of health beliefs and the characteristics of different methods of faecal occult blood screening in predicting acceptance of the test a self completed questionnaire was offered to 590 patients registered with a practice in an Oxfordshire market town. The patients were an age-sex stratified random sample of those who had been offered screening as part of a trial in which one of three different faecal occult blood screening tests, two of which were self-reported, had been offered. The overall adjusted response rate was 70.1%. Those who complied with the test had more positive attitudes to the implications of a positive test, to treatment and to the value of screening in general. The experience of a close relative or friend with bowel cancer was associated with an increased likelihood of compliance [odds ratio = 15.2 (9.4-24.3)]. Three were marked differences between the tests in the proportions of patients finding them 'messy' or 'disgusting' (Haemoccult 72.0%, Coloscreen 48.0%, Early Detector 55.4% chi 2 Haemoccult vs. self-reported = 5.05 P less than 0.05), and the odds of finding the procedure disgusting were significantly higher among patients who did not complete the test [odds ratio 6.9 (3.1-15.5)].

A survey was conducted to study the experiences of patients with false positive results for colorectal cancer. The study patients were participants in a randomized trial of compliance with different methods of colorectal cancer screening by faecal occult blood testing. Fifty four out of fifty six patients (96.4%) with false positive results agreed to be interviewed. An age and sex matched control group of 112 patients with negative test results was identified --92 (82.1%) returned questionnaires. Thirteen of the patients with false positive results (24.1%) and 19 controls (20.7%) were to some extent distressed by the initial letter inviting them to participate in the screening programme. Thirty seven of the patients with false positive results (68.5%) felt some degree of distress at the initial positive test result and 19 (35.2%) some distress because of delays experienced in the process of being screened. Ten false positive patients had colonoscopy and the median waiting time for this procedure was 10 days--half of the patients found this wait distressing. Nevertheless, 53 of the patients with false positive results (98.1%) felt that it had been worthwhile to have had the test. Generally, colorectal screening was as acceptable to the patients who experienced false positive results as to those with negative results.

Differences of A cell reactions in Langerhans islets can be explained by variations of the activity of a same cell. Resting of this cell by injection of glucagone or glucose makes it argyrophilic and abolishes tryptophan reaction. Stimulation of A cells by fasting or injection of insulin suppresses argyrophilism and makes the tryptophane reaction positive. A1 and A2 cells cannot be opposed. Variations of glucagone production explains diversity of the reactions in A cells.

We report an unusual and severe vasculitic disorder following co-trimoxazole, given orally for a urinary tract infection. The vasculitis was manifest solely as thrombophlebitis migrans and involving only veins without evidence of polyarteritis nodosa, or underlying malignancy.

Addition of lithium salts to cultures of hepatocytes increases glycogen in these cells. Glycogenolytic action of glucagone or AMPc becomes slow. Toxic action of paraquat is suppressed.

The toxicant action on hepatocytes of "paraquat" introduced at very low concentrations in an in vitro culture of such cells is here established. Mitoses are slowed down and moreover, the lysosomial system is impaired, thus inducing a decrease in its enzymic reactions and the proliferation of very large vesicles.

Embryonic liver cells of chicken have been cultivated in medium more or less supplemented with serum. With a rich medium mitochondria become larger and often ramify. Their fundamental structure remains normal. It is only a hypertrophic condition correlated to an increase of mitochondrial material synthesis, limited to liver mitochondria.