Dermatology outpatient case-mix survey for all Welsh Trusts, 2007.

Background In 2006 a U.K. government White Paper recommended making NHS care in England more accessible by shifting services from secondary care into community settings. There is a shortage of contemporary activity data for U.K. dermatology units to allow benchmarking for service development. This study will not only provide useful comparative data for the future in Wales, but will also serve to highlight the impact of changes made in England. Objective To provide an overview of 1 week's dermatology outpatient activity for the whole of Wales. Methods All dermatology units in Wales collected data for 1 week in early 2007. The case mix, appropriateness of referral, requirement for surgery or second-line therapies and follow-up requirements were all determined. Results A total of 2142 patients were seen. Of new patients, 21% had skin cancer. Seventeen per cent of skin cancers had no diagnosis suggested by the general practitioner (GP) and 10% of basal cell carcinomas, 33% of squamous cell carcinomas and 17% of malignant melanomas were inappropriately diagnosed. In all, 26% of new patients had benign lesions, and this group caused the greatest diagnostic difficulty for GPs. Seventy-one per cent of these patients were diagnosed, reassured and discharged at their first visit without the need for biopsy or surgery. Thirty-seven per cent of new patients required surgery, of which 21% required complex intervention. Twenty-six per cent of follow-up patients were receiving second-line therapies. The new to follow-up ratio varied considerably according to diagnosis, the mean ratio being 1 : 0.21 for benign lesions through to 1 : 5.53 for psoriasis. This highlights the inappropriate nature of a 'one fits all' ratio. The majority of follow-up patients in secondary care required this level of input for monitoring of cancer, complex second-line therapies or surgery. Conclusions This study provides evidence to support logical planning of dermatological services and to assess the impact of proposed changes on different healthcare systems in the U.K.

First Report of Wheat streak mosaic virus on Wheat in New Zealand.

In August of 2005, seeds of wheat (Triticum aestivum) breeding line 6065.3 tested positive for Wheat streak mosaic virus (WSMV; genus Tritimovirus) by a WSMV-specific reverse transcription (RT)-PCR assay (2). The sequence of the 200-bp amplicon (GenBank Accession No. FJ434246) was 99% identical with WSMV isolates from Turkey and the United States (GenBank Accession Nos. AF454455 and AF057533) and 96 to 97% identical to isolates from Australia (GenBank Accession Nos. DQ888801 to DQ888805 and DQ462279), which belong to the subclade D (1). As a result, an extensive survey of three cereal experimental trials and 105 commercial wheat crops grown on the South Island of New Zealand was conducted during the 2005-2006 summer to determine the distribution of WSMV. Wherever possible, only symptomatic plants were collected. Symptoms on wheat leaf samples ranged from very mild mosaic to symptomless. In total, 591 leaf samples suspected to be symptomatic were tested for WSMV by a double-antibody sandwich (DAS)-ELISA (DSMZ, Braunschweig, Germany). Of the 591 symptomatic samples, 81 tested positive. ELISA results were confirmed by RT-PCR with novel forward (WSMV-F1; 5'-TTGAGGATTTGGAGGAAGGT-3') and reverse (WSMV-R1; 5'-GGATGTTGCCGAGTTGATTT-3') primers designed to amplify a 391-nt fragment encoding a region of the P3 and CI proteins. Total RNA was extracted from the 81 ELISA-positive leaf samples using the Plant RNeasy Kit (Qiagen Inc., Chatsworth, CA). The expected size fragment was amplified from each of the 81 ELISA-positive samples. The positive samples represent 30 of 56 wheat cultivars (54%) collected from 28 of 108 sites (26%) sampled in the growing regions from mid-Canterbury to North Otago. These results suggest that WSMV is widespread in New Zealand both geographically and within cultivars. WSMV is transmitted by the wheat curl mite (Aceria tosichella) (3), which had not been detected in New Zealand despite repeated and targeted surveys. WSMV is of great economic importance in some countries, where the disease has been reported to cause total yield loss (3). Although WSMV is transmitted by seeds at low rates (0.1 to 0.2%) (4), it is the most likely explanation of the spread of the disease in New Zealand. References: (1) G. I. Dwyer et al. Plant Dis. 91:164, 2007. (2) R. French and N. L. Robertson. J. Virol. Methods 49:93, 1994. (3) R. French and D. C. Stenger. Descriptions of Plant Viruses. Online publication. No. 393, 2002. (4) R. A. C. Jones et al. Plant Dis. 89:1048, 2005.

Improved survival in patients with end-stage cancer treated with coenzyme Q(10) and other antioxidants: a pilot study.

This pilot study evaluated the survival of patients with end-stage cancer who received supplements of coenzyme Q(10) and a mixture of other antioxidants (e.g. vitamin C, selenium, folic acid and beta-carotene). During a period of 9 years, 41 patients who had end-stage cancer were included. Forty patients were followed until death and one patient was lost to follow-up and presumed dead. Primary cancers were located in the breast, brain, lungs, kidneys, pancreas, oesophagus, stomach, colon, prostate, ovaries and skin. The median predicted survival time was calculated from Kaplan-Meier curves for each patient at inclusion. Median predicted survival was 12 months (range 3 - 29 months), whereas median actual survival was 17 months (1 - 120 months), which is > 40% longer than the median predicted survival. Mean actual survival was 28.8 months versus 11.9 months for mean predicted survival. Ten patients (24%) survived for less time than predicted, whereas 31 (76%) survived for longer. Treatments were very well tolerated with few adverse effects.

Noble gases confirm plume-related mantle degassing beneath Southern Africa.

Southern Africa is characterised by unusually elevated topography and abnormal heat flow. This can be explained by thermal perturbation of the mantle, but the origin of this is unclear. Geophysics has not detected a thermal anomaly in the upper mantle and there is no geochemical evidence of an asthenosphere mantle contribution to the Cenozoic volcanic record of the region. Here we show that natural CO2 seeps along the Ntlakwe-Bongwan fault within KwaZulu-Natal, South Africa, have C-He isotope systematics that support an origin from degassing mantle melts. Neon isotopes indicate that the melts originate from a deep mantle source that is similar to the mantle plume beneath Réunion, rather than the convecting upper mantle or sub-continental lithosphere. This confirms the existence of the Quathlamba mantle plume and importantly provides the first evidence in support of upwelling deep mantle beneath Southern Africa, helping to explain the regions elevation and abnormal heat flow.

Ethologically-based animal models of anxiety disorders.

An overview of ethologically-based animal models suitable for investigating the pharmacological treatment of anxiety disorders is presented. The DSM-IIIR classification provides a framework for the discussion. The limitations of the models in current use are considered. It is suggested that there is a need for a greater emphasis on animal models of anxiety with an etiological basis.

Environmental assessment of mercury contamination from the Rwamagasa artisanal gold mining centre, Geita District, Tanzania.

This study presents the results of an environmental assessment of mercury (Hg) contamination in the Rwamagasa artisanal gold mining area, northwest Tanzania, and the potential downstream dispersion along the River Malagarasi to Lake Tanganyika. At the time of sampling, generally low concentrations of Hg (<0.05 mg/kg) occurred in most cultivated soils although higher Hg (0.05-9.2 mg/kg) was recorded in urban soils and vegetable plot soils where these are impacted by Hg-contaminated water and sediment derived from mineral processing activities. Hg in vegetable and grain samples is mostly below the detection limit of 0.004 mg/kg Hg, apart from 0.007 and 0.092 mg/kg Hg in two yam samples and 0.011 to 0.013 mg/kg Hg in three rice samples. The standardized (i.e., standardized to 10 cm length) Hg concentrations in Clarias spp. increase from about 0.01 mg Hg/kg for the River Malagarasi delta to 0.07, 0.2, and 1.6 mg/kg, respectively, for the Rwamagasa 'background', moderately and most contaminated sites. For piscivorous (Lates, Brycinus, and Hydrocynus spp.), insectivorous (Barbus spp.), and planktivorous (Haplochromis spp.) fish species, the 10-cm standardized Hg concentrations increase from about 0.006 mg/kg for the River Malagarasi-Lake Tanganyika area to 0.5 and 3.5 mg/kg, respectively, for the Rwamagasa moderately and most contaminated sites. The low concentrations of Hg in fish from the Malagarasi River delta and Lake Tanganyika indicate that Hg contamination from the Rwamagasa area does not have a readily discernible impact on the biota of Lake Tanganyika. Many of the fish samples from Rwamagasa exceed guidelines for human consumption (0.5 mg/kg) as well as the WHO recommended limit for vulnerable groups (0.2 mg/kg). Tissue total Hg (THg) of all fish collected from the River Malagarasi-Lake Tanganyika subarea is well below these guidelines. Potential human exposure through consumption of 300 g/day of rice grown on Hg-contaminated soils is 5.5 microg/week. Consumption of 250 g Nile perch (Lates spp.), 500 g tilapia (Oreochromis spp.), and 250 g of catfish (Clarias spp.) each week would result in an intake of 65 microg Hg/week for people consuming only fish from the Mara and Mwanza regions of Lake Victoria and 116 microg Hg/week for people in the Rwamagasa area consuming tilapia and Nile perch from Lake Victoria and catfish from mining-impacted streams. This is lower than the Provisional Tolerable Weekly Intake (PTWI) of 300 microg for Hg in the diet set by the WHO and the FAO. Inadvertent ingestion of soil containing 9 mg Hg/kg at a rate of 80 mg/day would give an additional estimated weekly intake of 5 microg THg, whereas the persistent and purposeful consumption of soil (geophagia) at a rate of 26 g soil/day would produce an additional chemical exposure of 230 microg Hg/day.

The amnesic action of benzodiazepines in man.

A qualitative description of the amnesia produced by the benzodiazepines in man is presented. The benzodiazepines exert their greatest effects in tests of long-term episodic memory in which they cause a dose-related impairment in the acquisition of new information, do not appear to affect retention and may facilitate retrieval. Benzodiazepines do not appear to impair semantic memory or the acquisition of skills. Although state-dependent learning may be observed with benzodiazepine treatment it is a small effect and cannot account for most of the observed impairments. The amnesia appears to be characteristic of all benzodiazepines and may be related to the sedative action of these compounds but evidence on the latter point is inconclusive. The importance of the amnesic action in a population of clinically anxious outpatients taking benzodiazepines over an extended period remains to be investigated. The benzodiazepines may provide the cognitive psychologist with a useful tool to investigate the mechanisms of normal memory.

Psychobiological modeling of age-related memory changes.

Useful models of age-related human and animal memory changes should simulate specific features of cognitive impairment associated with aging. It is necessary but not sufficient to demonstrate that manipulations such as those produced by lesions and drugs cause impairments in some cognitive function such as memory. A useful model should be able to reproduce a pattern of cognitive changes in which islands of spared versus impaired functioning resemble those associated with aging and differ from those produced by other conditions. This requires the use of research strategies utilizing multivariate treatment and dependent measure designs. The papers in this section illustrate the value of such a research approach.

Arabidopsis thaliana ferrochelatase-I and -II are not imported into Arabidopsis mitochondria.

Using in vitro import assays into purified mitochondria and chloroplasts we found that Arabidopsis ferrochelatase-I and ferrochelatase-II were not imported into mitochondria purified from Arabidopsis (or several other plants) but were imported into pea leaf chloroplasts. Other dual targeted proteins could be imported into purified mitochondria from Arabidopsis. As only two ferrochelatase genes are present in the completed Arabidopsis genome, the presence of ferrochelatase activity in plant mitochondria needs to be re-evaluated. Previous reports of Arabidopsis ferrochelatase-I import into pea mitochondria are due to the fact that pea leaf (and root) mitochondria appear to import a variety, but not all chloroplast proteins. Thus pea mitochondria are not a suitable system to either study dual targeting, or to distinguish between isozymes present in mitochondria and chloroplasts.

Dissociation of the acute effects of alcohol on implicit and explicit memory processes.

The effects of alcohol (0, 0.3 and 0.6 g/kg) on learning and memory were assessed in independent groups of male student volunteers. Subjects were shown a list of words and asked to form an image of a scene involving each word 1 hr after drinking an alcohol-containing beverage. Alcohol consumption impaired the ability of subjects to explicitly remember the words in a test of free recall. However, no impairment was observed if memory for the same material was assessed implicitly using a backwards-reading or word-completion task. That is, both alcohol-and placebo-treated subjects showed similar degrees of priming. The data indicate that alcohol's effects on memory are selective.

Effects of ethanol on fight- or swim-stressed mice in Porsolt's swim test.

The effects of ethanol in Porsolt's swim test on mice preexposed to fight- or swim-stressors were investigated. The control mice did not change their behavior in the swim test after an acute injection of 0.4 or 0.8 g/kg ethanol; 1.2 g/kg ethanol increased their immobility in one but not in another experiment. The mice exposed to continuous fight-attacks in their home cage by one dominant mouse shortened immobility after 0.8 g/kg ethanol as well as tended to shorten it after 0.4 g/kg ethanol. The mice that were forced to swim in the water twice before the actual swim test responded to 0.4 g/kg ethanol by shortening immobility; 0.8 g/kg tended to have the same effect; 1.2 g/kg ethanol just failed to lengthen immobility of the fight-stressed mice and had no effect on the swim-stressed mice. Because antidepressant drugs decrease and stressors increase immobility in the swim test, the test may serve as a putative animal model of depression. The present findings showed that low doses of ethanol reverse lengthened immobility of mice preexposed to a stressor. This suggests that ethanol either has antidepressant-like properties, or it improves animal's ability to cope with a stressful situation, or both.

Do the reductions in social interaction produced by picrotoxin and pentylenetetrazole indicate anxiogenic actions?

The effects of picrotoxin (2 and 4 mg/kg) and of pentylenetetrazole (PTZ 5, 10 and 20 mg/kg) were examined in a social-interaction test of anxiety. Picrotoxin (2 mg/kg) caused a significant reduction in active social interaction, without a concomitant reduction in motor activity, indicating an anxiogenic action. Picrotoxin (4 mg/kg) and pentylenetrazole (20 mg/kg) reduced social interaction by more than 75% and motor activity by 40%. Although it is likely that the reduction in motor activity is secondary to the very low levels of social interaction, an unambiguous interpretation of an anxiogenic effect is not possible. Increased concentrations of corticosterone in plasma following administration of picrotoxin were consistent with the drug being anxiogenic. Chlordiazepoxide (5 mg/kg) significantly reversed the reductions in social interaction and locomotor activity following injection of picrotoxin (4 mg/kg) and PTZ (20 mg/kg).

beta-CCE and chlordiazepoxide reduce exploratory head-dipping and rearing: no mutual antagonism.

Intravenous injection of ethyl beta-carboline-3-carboxylate (beta-CCE, 2 mg/kg) significantly reduced exploratory behaviour in a holeboard and 1 & 2 mg/kg markedly reduced the number of rears made. These effects were similar to those found with chlordiazepoxide (5 mg/kg). When they were given together the two drugs neither counteracted each other's effects, nor were their combined effects additive. We suggest that beta-CCE and the benzodiazepines might both act at one class of benzodiazepine receptor, as agonists to produce the same behavioural effects. The results are also discussed with reference to other intrinsic actions of these compounds.

Alcohol, the chloride ionophore and endogenous ligands for benzodiazepine receptors.

Considerable evidence suggests that at least some of the effects of ethanol are mediated by an action on the GABAA receptor chloride channel complex. More speculative is the suggestion that ethanol might interact with endogenous ligands for the benzodiazepine receptor on the complex. This paper considers the evidence for such interactions.

Interactions of alpha 2-adrenoceptor antagonists with medetomidine and with ethanol in a holeboard test.

The effects of two selective alpha 2-adrenoceptor agonists (clonidine and medetomidine) and antagonists (atipamezole and idazoxan) were examined in the holeboard test. The interactions of the two antagonists with ethanol were also investigated. Atipamezole (0.1-3.0 mg/kg) and idazoxan (0.01-0.3 mg/kg) were without effect on either directed exploration or locomotor activity in the holeboard test, whereas clonidine (0.003-0.1 mg/kg) and medetomedine (0.003-0.1 mg/kg) were sedative. Atipamezole (1-3 mg/kg) and idazoxan (0.3-1.0 mg/kg) reversed the behavioral effects of 0.1 mg/kg of medetomidine. When administered with ethanol (2 g/kg), atipamezole (1-3 mg/kg) showed a significant antagonism of the ethanol-induced reduction in exploratory head-dipping: no change in the locomotor stimulant properties of ethanol was seen. A similar trend was seen for exploration after a combination of idazoxan (1-3 mg/kg) with 2 g/kg ethanol; however, the 3 mg/kg dose attenuated the locomotor stimulant effect. Both antagonists caused a dose-related reduction in the increase in head-dipping seen after administration of 1 g/kg of ethanol, without any effect on the locomotor stimulant effect of this dose. These results suggest mediation of alpha 2-adrenoceptors in some of the behavioral effects of ethanol.

Intrinsic behavioural actions of n-propyl beta-carboline-3-carboxylate.

The behavioural effects of n-propyl beta-carboline-3-carboxylate (beta-CCP) were assessed in the social interaction test of anxiety and in the holeboard test of exploratory behaviour. n-Propyl beta-carboline-3-carboxylate (2 mg/kg) significantly reduced the time spent in social interaction without affecting locomotor activity, indicating an anxiogenic action. This reduction was not significantly reversed by chlordiazepoxide (3 mg/kg). In the holeboard, beta-CCP (4 mg/kg) reduced exploratory head-dipping and rearing; neither of these effects was significantly reversed by chlordiazepoxide (5 mg/kg). The actions of beta-CCP in these two tests are similar to those of the structurally-related compound ethyl beta-carboline-3-carboxylate.

The anxiogenic action of benzodiazepine antagonists.

Two benzodiazepine antagonists were tested in an animal model of anxiety, the social interaction test. Ethyl beta-carboline-3-carboxylate (1 and 2 mg/kg) had a potent anxiogenic action; the imidazodiazepine RO 15-1788 (4-10 mg/kg) had a weak anxiogenic effect that with a larger dose (20 mg/kg) disappeared and RO 15-1788 (10 mg/kg) significantly counteracted the anxiogenic effect of the beta-carboline (1 mg/kg). The implications of these results for the understanding of the pharmacological basis of anxiety and for the existence and nature of an endogenous ligand for the benzodiazepine binding site are discussed.

Interactions of the imidazodiazepine Ro 15-4513 with chemical convulsants.

1. The proconvulsant effects of the imidazodiazepine Ro 15-4513, were investigated in mice by use of intravenous infusion of a variety of convulsant drugs. 2. Dose-response and time course studies of Ro 15-4513 against gamma-aminobutyric acid (GABA) antagonists were performed. On the basis of these studies a maximally effective dose of 5 mg kg-1 was administered 5 min before the determination of seizure thresholds in subsequent experiments. 3. Ro 15-4513 (5 mg kg-1) significantly lowered seizure thresholds to pentylenetetrazole, bicuculline and the convulsant benzodiazepine Ro 5-3663, but failed to alter seizure thresholds to picrotoxin, strychnine, caffeine and quipazine. 4. Ro 15-4513 significantly raised seizure threshold to the benzodiazepine receptor inverse agonist methyl 6,7-dimethoxy-4 ethyl-beta-carboline-3-carboxylate (DMCM). 5. These results are discussed in relation to other studies investigating the proconvulsant and alcohol-antagonizing effects of Ro 15-4513.