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Background: The main indication for carotid endarterectomy (CEA) is severity of carotid artery stenosis, even though most strokes in carotid disease are embolic. The relationship between carotid plaque volume (CPV) and symptoms of cerebral ischaemia, and the measurement of CPV by minimally invasive tomographic ultrasound imaging, were investigated. Methods: The volume of the endarterectomy specimen was measured using a validated saline suspension technique in patients undergoing CEA. Time from last symptom and severity of stenosis measured by duplex ultrasonography were recorded. Middle cerebral artery emboli were counted using transcranial Doppler imaging (TCD) in a subset of patients. Results: Some 339 patients were included, 270 with symptomatic and 69 with asymptomatic carotid stenosis. Mean(s.d.) CPV was higher in symptomatic than in asymptomatic patients (0·97(0·43) versus 0.74(0·41) cm3; P < 0·001). CPV did not correlate with severity of carotid stenosis (P = 0·770). Mean CPV was highest at 1·03(0·46) cm3 in the 4 weeks following cerebral symptoms, declining to 0·78(0·36) cm3 beyond 8 weeks. Among 33 patients who had TCD, mean CPV was 1·00(0·48) cm3 in the 27 patients with ipsilateral cerebral emboli compared with 0·67(0·16) cm3 in those without (P = 0·142). There was excellent correlation between CPV measured by tomographic ultrasound imaging and the endarterectomy specimen in 34 patients (r = 0·93, P < 0·001). Conclusion: CPV correlated with symptoms of cerebral ischaemia, but not carotid stenosis. It could be a potential indicator for CEA. [ABSTRACT FROM AUTHOR]

Background Delay in presentation contributes to poorer survival of older women with breast cancer. Research has shown the effectiveness of the promoting early presentation (PEP) intervention when delivered by radiographers in the NHS Breast Screening Programme. This paper investigates the effectiveness of the intervention when delivered by practice nurses in general practice. Methods The Breast Cancer Awareness Measure was used to compare participants' awareness of breast cancer before, 1 month after and 12 months after the delivery of the PEP intervention. Five hundred and fifty-six women aged over 70 years took part, 308 of whom returned all three surveys. Results The intervention was associated with increased awareness of non-lump breast symptoms and reported breast check frequency. There was a marked increase in breast cancer awareness which persisted for 12 months. Less than 5% of women were classified as 'breast cancer aware' before the intervention, rising to over 25% 1 month afterwards. This percentage dropped slightly after 1 year to just below 20%. Conclusion Delivery of the PEP intervention in general practice was very effective at raising the awareness of breast cancer among older women. Primary care settings are well placed to enhance the reach of this kind of intervention to at-risk women. [ABSTRACT FROM AUTHOR]

Background Fumaric acid esters ( FAEs) have been used for over 30 years in the management of psoriasis. Objectives To determine drug survival of FAEs in patients with psoriasis, treatment-limiting adverse drug events and the range of effective drug doses. Methods A retrospective, single-centre study assessing all patients commenced on FAEs between October 2003 and July 2012. Demographic data, length of treatment, reasons for discontinuation of FAEs, side-effects and range of doses were recorded. Results Two hundred and forty-nine patients [160 (64%) male] were included. The mean age at which FAEs were commenced was 44·5 years (range 17-82 years). The mean length of treatment was 28 months (range 1 week to 106 months). In patients who were commenced on FAEs ≥ 4 years before inclusion in this study, the 4-year drug survival was 60% (64/107). FAEs were discontinued in 146/249 patients (59%); this was due to lack of efficacy in 59/146 (40%) and gastrointestinal upset in 39/146 (27%). A very low dose of FAEs (< 240 mg daily) was successful in maintaining control of psoriasis in 26 (10%) patients. The mean treatment duration of these patients was 64 months (range 32-106 months). Conclusions Fumaric acid esters have a 4-year drug survival rate of 60%, which compares favourably with reported 4-year survival rates of 40% for etanercept and adalimumab and 70% for infliximab. Longer drug survival is more likely in the significant subgroup of patients in whom a very low dose of FAEs is sufficient to control disease. The reasons for this are unclear. [ABSTRACT FROM AUTHOR]

Background Anti-tumour necrosis factor ( TNF)-α therapies have revolutionized the treatment of psoriasis; however, up to 50% of patients do not respond satisfactorily. Identification of pharmacogenetic markers of treatment response is an important stop in the development of individually tailored treatment. The objective of this study was to assess the association of human leucocyte antigen ( HLA)- C, killer immunoglobulin receptor ( KIR) and vitamin D receptor ( VDR) genotypes with response to treatment by etanercept and adalimumab. Methods This was a study of 138 patients with severe chronic plaque psoriasis who were treated with etanercept and/or adalimumab. Patients were classified as responders if they achieved a 75% reduction in PASI ( PASI75) or were almost clear of psoriasis after 24 weeks of therapy. The frequencies of HLA- C and KIR haplotypes and VDR polymorphisms were compared in responders and nonresponders. The frequency of all HLA- C and KIR genotypes were compared between the 138 patients with psoriasis and 247 healthy donors. Results The number of patients classified as responders was 46 of 94 (49%) in the etanercept group and 50 of 76 (66%) in the adalimumab group. None of the HLA- C, KIR or VDR genotypes examined was predictive of treatment response. Compared with healthy controls, patients with psoriasis were more likely to have the HLA- C*06 genotype ( P < 0.001) and less likely to have the HLA- C*07 genotype ( P < 0.001), whereas there was no significant difference in frequencies of any KIR subtype. Conclusions Using the candidate gene approach to identify biomarkers of treatment response in psoriasis may have limited utility. This was a small study with limited power. Future larger studies are needed to further examine these findings and to explore alternative approaches to identify predictors of treatment response to biological agents. [ABSTRACT FROM AUTHOR]

Moderate to severe psoriasis is associated with increased alcohol intake and excessive mortality from alcohol-related causes. Alcohol biomarkers provide an objective measure of alcohol consumption. Carbohydrate-deficient transferrin (CDT) is the single most sensitive and specific alcohol biomarker. To assess alcohol consumption in a cohort of patients with moderate to severe psoriasis using standard alcohol screening questionnaires and biomarkers. We investigated whether there was an association between alcohol intake, anxiety, depression and disease severity. Consecutive patients with chronic plaque psoriasis were recruited and completed a range of anonymized assessments. Psoriasis severity, anxiety and depression, and the impact of psoriasis on quality of life were assessed. Alcohol screening questionnaires were administered. Blood specimens were taken and γ-glutamyltransferase (γGT) and CDT were measured. A total of 135 patients completed the study. Using validated questionnaires, between 22% and 32% had difficulties with alcohol. Seven per cent had CDT > 1·6% indicating a heavy alcohol intake. The Alcohol Use Disorders Identification Test (AUDIT) questionnaire was superior to other validated questionnaires in detecting alcohol misuse. There were no significant associations between measures of excessive alcohol consumption and disease severity. Excessive alcohol intake as measured by the CAGE questionnaire was associated with increased depression ( P = 0·001) but other measures of alcohol excess did not correlate with psychological distress. Men had significantly more difficulties with alcohol than women ( P < 0·001). Alcohol misuse is common in patients with moderate to severe psoriasis. Screening with the AUDIT questionnaire and CDT may allow the identification of patients who are misusing alcohol and allow appropriate intervention. [ABSTRACT FROM AUTHOR]

There is considerable variability in the number of exposures of narrowband ultraviolet B (NB-UVB) needed to clear psoriasis and in the duration of remission. We assessed clinical parameters as predictors of the number of exposures needed to clear psoriasis and of the duration of remission. The influence of genetic polymorphisms of the vitamin D receptor (VDR) on treatment response was also evaluated. This was a prospective study of 119 patients with chronic plaque psoriasis treated with NB-UVB until clearance was achieved. They were then followed for up to 1 year or until relapse occurred. The frequency of the Fok1, Apa1, Bsm1, Taq1 and rs4516035 polymorphisms of the VDR gene was assessed in 93 of the 119 patients. Of the 119 patients, 105 completed the course of phototherapy. Using an intention to treat analysis, 83% of the initial cohort (99 of 119 patients) achieved clearance, in a median of 26 exposures (interquartile range 19-35) with a median remission duration of 16 weeks (interquartile range 9-22). Factors significantly associated with a lower number of exposures to clearance included a lower baseline Psoriasis Area and Severity Index ( P = 0·004), lower baseline Dermatology Life Quality Index ( P = 0·047), female sex ( P =0·043), lower body weight ( P = 0·008), and a higher number of previous courses of TL-01 ( P = 0·005). The only clinical factor influencing remission duration was number of exposures ( P = 0·0009), with a decreased remission duration in those who required a greater number of exposures to clear. The Taq1 VDR polymorphism (rs731236) also significantly predicted remission duration ( P = 0·038). Patients homozygous for the C allele, which is associated with decreased activity of the VDR, had a shorter remission duration than those heterozygous for the allele ( P = 0·026) and those homozygous for the T allele ( P = 0·013). This study highlights the fact that both genetic and clinical parameters are important in determining treatment outcomes in psoriasis. [ABSTRACT FROM AUTHOR]

Aim. To assess the efficacy and safety profile of adalimumab in patients with severe, recalcitrant chronic plaque psoriasis, and to assess short-term overlapping of other systemic treatment with adalimumab to prevent flaring of disease. Methods. This was a retrospective study comprising 39 patients with chronic plaque psoriasis treated with adalimumab between October 2005 and January 2008. All had failed treatment with other systemic agents, including biological therapies in 59% of patients. Patients were started on adalimumab 40 mg weekly or fortnightly, as clinically indicated. Severity of psoriasis was assessed by the Psoriasis Area and Severity Index (PASI). Therapeutic response was assessed by 75% improvement on PASI (PASI 75). All adverse events were recorded. Results. Results were analysed separately for those treated with adalimumab only and those on combination treatment. PASI 75 was achieved in 38% (8 of 21 patients at week 16), 62% (13 of 21 patients) at week 24, 69% (9 of 13 patients) at week 48% and 71% (5 of 7 patients) at week 72 in the adalimumab-only group, compared with 56% (5 of 9 patients) at week 16, 50% (4 of 8 patients) at week 24, 80% (4 of 5 patients) at week 48% and 67% (2 of 3 patients) at week 72 in the combined group. Of the 39 patients, 15 (38%) achieved a PASI of 0 at some point in their treatment. Adalimumab was well tolerated; 38% of patients experienced side-effects, which were generally mild. Conclusion. Adalimumab was effective in a group of patients with psoriasis refractory to other systemic therapies, including biological treatments, and was well tolerated. [ABSTRACT FROM AUTHOR]

Background The safety and efficacy of etanercept have been demonstrated in patients with rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis. Placebo-controlled trials have indicated the efficacy of etanercept in moderate to severe psoriasis. Objectives To observe the efficacy and safety profile of etanercept in patients with severe psoriasis resistant to other systemic agents over a 2-year period. Methods In this retrospective study, 49 patients were treated with etanercept between March 2004 and March 2006. All patients were screened for tuberculosis with tuberculin test and a chest X-ray. Thirty-nine patients started on etanercept 25 mg twice weekly (BIW) and 10 started at 50 mg BIW when judged to be clinically indicated. In 19 of those on 25 mg BIW, the dose was increased to 50 mg BIW because of poor response and psoriasis flaring. Response to treatment was assessed by Psoriasis Area and Severity Index (PASI) and static Physician Global Assessment (PGA). Patients were reviewed at 8-week intervals, when clinical response and adverse effects were noted. Results Forty-four patients (90%) had chronic plaque psoriasis, two (4%) were suberythrodermic, one (2%) had palmoplantar pustular psoriasis and two (4%) had acrodermatitis continua of Hallopeau. At least 75% reduction in PASI was achieved in 47% of patients at week 24 and 66% at week 48. At week 24, 44% had a PGA score of excellent, and at week 48, 58% scored excellent. In 12 who cleared, etanercept was stopped. Ten of these relapsed and etanercept was recommenced, while two remained in remission (mean 12·5 weeks). One patient developed extrapulmonary tuberculosis. Conclusions Etanercept was effective in severe psoriasis recalcitrant to other systemic medication. The drug was well tolerated. Development of tuberculosis in one patient underlines the need for rigorous tuberculosis screening. [ABSTRACT FROM AUTHOR]

Background. Fumaric acid esters (FAEs) offer an effective alternative to patients with psoriasis in whom other systemic agents are contraindicated or have failed. Objective. We assessed the efficacy and side effect profile of FAEs in a group of patients with psoriasis. Methods. A retrospective study was carried out on patients treated with FAEs over 21 months. Information was gathered from patients' notes. Dosage, response and side effects were recorded. Results. In total, 31 patients were included. The mean age was 46.8 years. All patients had been treated with other modalities and 61.5% had received previous systemic treatment. There was good to excellent response in 58.6% of patients. Subjective side-effects were common (87.1%), and lymphopenia occurred in 61.3%. The drug was not tolerated by one-fifth of patients. Conclusion. The relatively low toxicity and absence of hepatotoxicity makes FAEs a reasonable first-line systemic treatment in selected patients with difficult psoriasis. [ABSTRACT FROM AUTHOR]

Eastwood, P. D., Mills, C. M., Aldridge, J. N., Houghton, C. A., and Rogers, S. I. 2007. Human activities in UK offshore waters: an assessment of direct, physical pressure on the seabed. – ICES Journal of Marine Science, 64: 453–463.Integrated assessments (IA) and marine spatial planning (MSP) are becoming major drivers for the assessment and management of human activities at sea. To be successful, both require an understanding of the distribution of the pressures caused by human activities. We used spatial data for the major human activities operating in the England and Wales sector of UK waters in 2004 to provide an assessment of direct, physical pressure on the seabed from multiple human activities. Pressure was estimated as the spatial extent of each of the activities; the intensity, longevity, and impacts arising from the pressures were not considered. Estimates of spatial extent were assigned to three pressure categories, subdivided into six pressure types. We estimated that four of the six pressure types affected < 1% of the seabed of England and Wales in 2004, whereas selective extraction caused by demersal trawling affected a minimum of 5.4%, rising to a possible maximum of 21.4%, of the total area of the seabed. This was a greater area than all other pressure types combined. The assessment process described here can be used as the framework for reporting human pressures at regular time intervals and feed into both IA and MSP for regional seas. [ABSTRACT FROM PUBLISHER]

Elucidating the genetic architecture of population divergence may reveal the evolution of reproductive barriers and the genomic regions implicated in the process. We assembled genetic linkage maps for the dwarf and Normal lake whitefish species complex and their hybrids. A total of 877 AFLP loci and 30 microsatellites were positioned. The homology of mapped loci between families supported the existence of 34 linkage groups (of 40n expected) exhibiting 83% colinearity among linked loci between these two families. Classes of AFLP markers were not randomly distributed among linkage groups. Both AFLP and microsatellites exhibited deviations from Mendelian expectations, with 30.4% exhibiting significant segregation distortion across 28 linkage groups of the four linkage maps in both families (P < 0.00001). Eight loci distributed over seven homologous linkage groups were significantly distorted in both families and the level of distortion, when comparing homologous loci of the same phase between families, was correlated (Spearman R = 0.378, P = 0.0021). These results suggest that substantial divergence incurred during allopatric glacial separation and subsequent sympatric ecological specialization has resulted in several genomic regions that are no longer complementary between dwarf and Normal populations issued from different evolutionary glacial lineages. [ABSTRACT FROM AUTHOR]

Background Survivin, an inhibitor of apoptosis protein (IAP), has been implicated in endothelial cell stability, through inhibition of apoptosis and in cell proliferation. Objectives To evaluate the effect of antitumour necrosis factor (TNF)- α therapy on survivin expression in psoriasis skin at 0, 2 and 12 weeks after infliximab therapy. Methods Skin biopsies were obtained from 16 patients; 11 also had arthritis with active skin/joint disease. Clinical scores [Psoriasis Area and Severity Index (PASI), involved body surface area (BSA), Disease Activity Score (DAS28) and Health Assessment Questionnaire] were recorded. Inflammatory infiltration and survivin protein expression were examined and graded by immunohistochemical staining, and mRNA levels were determined by real-time polymerase chain reaction. Results Survivin mRNA and protein were demonstrated in all baseline lesional biopsies. Survivin mRNA and protein expression was significantly greater in lesional compared with nonlesional baseline skin ( P < 0·05). Differential cellular localization of survivin was demonstrated with cytoplasmic survivin protein expression localized to the perivascular/endothelial regions and strong nuclear staining localized in the basal layer of the epidermis. Infliximab produced a dramatic clinical response in skin and joints ( P < 0·05), paralleled by significant reduction in the inflammatory infiltrate and survivin protein expression ( P < 0·05) which was reflected at the mRNA level where expression was significantly reduced by week 12 ( P < 0·01). Survivin protein levels before and after treatment significantly correlated with PASI ( r = 0·478, P < 0·05) and BSA scores ( r = 0·528, P < 0·024). PASI strongly correlated with BSA ( r = 0·949, P < 0·0001) and DAS28 ( r = 0·717, P < 0·002) scores. Conclusions Survivin correlates with disease activity in patients with psoriasis and is significantly downregulated following anti-TNF- α treatment. Understanding the role of IAPs in cell survival/antiapoptosis and proliferation mechanisms may provide important insights into downstream therapeutic targeting in inflammation. [ABSTRACT FROM AUTHOR]

Understanding the genetic architecture of reproductive barriers and the evolutionary forces that drove their divergence represents a considerable challenge towards understanding speciation. The objective of this study was to determine the genetic basis of intrinsic and extrinsic post-zygotic isolation in diverging populations of dwarf and normal lake whitefish with allopatric glacial origins. We found that the rate of embryonic mortality was 5.3–6.5 times higher in dwarf-normal hybrid backcrosses during development than in F1 dwarf and normal crosses. When comparing embryos that died during development against larvae that successfully hatched, patterns of Mendelian segregation at 101 loci whose linkage is known identified 13 loci distributed over seven linkage groups that exhibited significant shifts in segregation ratios leading to significant segregation distortion at these loci in the surviving progeny. Controlled crosses and quantitative trait loci analysis revealed a significant genetic basis for developmental time until emergence, a trait critical to fish larval survival in nature. Hatching backcross progeny exhibited asynchronous emergence and transgressive segregation, suggesting that extrinsic post-zygotic isolation may select against hybridization in specific environmental contexts. Evidence of a genetic basis for increased embryonic mortality followed by asynchronous emergence indicated that intrinsic and extrinsic mechanisms are not mutually exclusive in the formation and maintenance of reproductive isolation, but may be jointly promoting population divergence and ultimately speciation. [ABSTRACT FROM AUTHOR]

Background. In this retrospective study, we report our experience with infliximab for recalcitrant psoriasis. Methods. Twelve patients were treated between September 2001 and April 2005. Infliximab 5 mg/kg was given at 0, 2 and 6 weeks followed by 5 mg/kg at 8-week intervals. When two patients developed resistance to treatment, methotrexate was added at a dose of 5–7.5 mg weekly for all patients. Response to treatment was assessed with physician global assessment with a score of excellent, good, moderate, poor and failure. Ten patients had chronic plaque psoriasis, one had pustular palmoplantar psoriasis and one had acrodermatitis continua of Hallopeau. Results. Nine patients, including the patient with acrodermatitis continua, showed an excellent response. Two patients initially showed good response but became resistant to treatment. One patient failed to respond, and treatment was discontinued. With time, six patients with excellent response and two with good response developed side-effects that necessitated stopping treatment. Conclusions. We have found infliximab to be very impressive, both in efficacy and speed of action, in severe psoriasis. Its use, however, is limited, as it requires hospital admission and by the need for concomitant methotrexate. Because of its powerful immunosuppressive action, the possibility of activating tuberculosis and inducing lymphoma remains a concern. [ABSTRACT FROM AUTHOR]

Background Streptococcal throat infections and HLA Cw6 (Cw*06) have been implicated in the pathogenesis of psoriasis, particularly in the guttate form. Objectives To study 105 Irish patients with psoriasis to investigate the relationship between streptococcal infections and Cw*06. Methods The patients were divided into two groups: those with guttate psoriasis or guttate flare (guttate group, GG, n = 64) and those with chronic plaque psoriasis (chronic plaque group, CPG, n = 41). Results The incidence of Cw*06 was 86% in the GG and 73% in the CPG, which was not significantly different ( P = 0·1725) but the incidence in both groups was significantly higher than in an Irish control group (18%) ( P < 0·0001 vs. GG and P < 0·0001 vs. CPG). Evidence for streptococcal infection was higher in the GG (56%) than in the CPG (32%) ( P = 0·0231). Of those patients with evidence of streptococcal infection, 30 of 36 GG (83%) and nine of 13 CPG (69%) patients possessed the Cw*06 genotype. Conclusions Thus, not all patients with streptococcal-related psoriasis carry Cw*06. The role of Cw*06 in psoriasis, if any, has yet to be determined. [ABSTRACT FROM AUTHOR]

Patients receiving long-term methotrexate for psoriasis are at risk of developing hepatic fibrosis. Repeated liver biopsy has long been regarded as the only reliable method of detecting this and it is still recommended by the American Academy of Dermatology (AAD). More recently, monitoring by serum procollagen III aminopeptide (PIIINP) measurement (Orion Diagnostica, Espoo, Finland) has been advocated as a means of significantly reducing the need for liver biopsy.To assess the validity of guidelines developed in Manchester for the use of PIIINP to monitor patients with psoriasis receiving long-term methotrexate; to assess the anticipated benefits to patients of introducing this change in practice, including reduction in requirement for liver biopsy; and to determine the impact of its introduction on healthcare costs.A multicentre audit was conducted over a 24-month period to compare the healthcare costs and outcomes of two intervention groups from centres where serial PIIINP measurement was employed with those of two control groups from centres in which AAD guidelines were followed.A sevenfold reduction in the need for liver biopsy was observed in the two intervention groups (n = 166; 0·04 and 0·02 biopsies/patient/year, respectively) compared with the two control groups (n = 87; 0·26 and 0·30 biopsies/patient/year, respectively). Abnormalities of sufficient severity to influence management were identified in one in five patients biopsied in the main intervention group compared with one in 16 in the control groups. The overwhelming majority of patients surveyed expressed a preference for being monitored by methods that would minimize the need for liver biopsy. The adoption of PIIINP for monitoring would result in significant cost savings.This audit has shown that patients managed by the Manchester protocol using serial PIIINP measurement and selective liver biopsy were not disadvantaged in comparison with those managed according to AAD guidelines; they were subjected to sevenfold fewer liver biopsies without evidence that important liver toxicity was missed in the process. If PIIINP monitoring were widely adopted, methotrexate would become a more acceptable option for many patients who are dissuaded from considering it because of the threat of repeated liver biopsy; it would also result in significant savings to the healthcare budget. [ABSTRACT FROM AUTHOR]

Summary Background A multicentre, randomized, double-blind, vehicle-controlled, parallel-group study was carried out to study the effect of the addition of calcipotriol ointment to methotrexate (MTX) therapy in patients with psoriasis vulgaris. Objectives To investigate whether the addition of calcipotriol to treatment with MTX has an MTX-sparing effect, and whether the combination of treatments is safe. Additionally, to compare the effect of calcipotriol or vehicle on the duration of the relapse-free interval after cessation of MTX. Methods Patients on maintenance therapy with MTX with controlled psoriasis were selected. The study was divided into three phases: (i) an MTX-free phase with double-blind treatment with either calcipotriol ointment or vehicle; (ii) an MTX titration phase with open MTX treatment and additional double-blind treatment with either calcipotriol or vehicle until target response; and (iii) follow-up phase: in a group of 97 patients, psoriasis was assessed using the modified psoriasis severity score, patients' assessment and safety parameters were monitored as well. Results The combined use of calcipotriol with MTX resulted in an MTX-sparing effect of 3·4 mg week-1 (phase (II) and 2·6 mg week-1 (phase I and II taken together), while still maintaining efficacy. Calcipotriol treatment increased the time to relapse of psoriasis following discontinuation of MTX: 113 days vs. 35 days. A decrease in aspartate aminotransferase and alanine aminotransferase was seen during the study of 8% (calcipotriol) and 12% (vehicle). Conclusions The combination of calcipotriol and MTX was safe and well tolerated. The combination resulted in lower cumulative dosages of MTX compared with MTX and vehicle. Therefore the risk of side-effects is substantially decreased. [ABSTRACT FROM AUTHOR]

Summary This report examines the dosimetry of ultraviolet (UV) radiation applied to dermatological treatments, and considers the definition of the radiation quantities and their measurement. Guidelines are offered for preferred measurement techniques and standard methods of dosimetry. The recommendations have been graded according to the American Joint Committee on Cancer classification of strength of recommendation and quality of evidence (summarized in Appendix 5). [ABSTRACT FROM AUTHOR]

Summary The use of cyclosporin A (CSA) for the treatment of severe psoriasis is well established. However its use is limited by its adverse effects, especially nephrotoxicity. We reviewed 28 patients treated with CSA for severe psoriasis over an 11-year period. All patients were on long-term CSA treatment (median duration 55.5 months). Twenty patients developed renal impairment which required discontinuation of treatment in seven. Twelve patients' renal function stabilized on dose reduction and one improved. Sixteen patients developed hypertension. For this small group of patients with severe psoriaisis, recalcitrant to other treatments, CSA afforded better quality of life which they otherwise could not enjoy. Although this comes at a cost with the development of renal impairment we feel that such patients can be continued on CSA provided that they are under the combined care of a dermatologist and a nephrologist. [ABSTRACT FROM AUTHOR]

Catches of demersal fish from research vessel surveys in three areas around the British Isles from 1901 to 1907 were compared with survey catches in the same areas from 1989 to 1997. Mesh size and other characteristics of the trawls used suggested that some of these data were comparable, and could be used to describe changes in demersal fish assemblages over the last 80 years. In Start Bay (NW English Channel) and the Irish Sea, species diversity was the same in both periods, although the most abundant species in each period were not the same. In English coastal regions of the southern North Sea, fish populations became more diverse, as plaice Pleuronectes platessa and whiting Merlangius merlangus became less abundant, and the relative abundance of several non-target species such as dragonet Callionymus spp., bib Trisopterus luscus, and bull-rout Myoxocephalus scorpius increased. The proportion in the catch of small fish species (maximum body length <30 cm), which would be least vulnerable to capture by commercial trawls, increased between the two survey periods in Start Bay and the southern North Sea. None of these small species was commercially exploited. The proportions of larger teleosts (maximum body length >30 cm) in catches decreased in all regions during the time period, except in the Irish Sea where plaice replaced grey gurnard Eutrigla gurnardus as a dominant species. There was a decline in abundance of large sharks, skates and rays, including the common skate, Raja batis, white skate R. alba and the angel shark Squatina squatina. During historic surveys, 60% of the elasmobranch fauna consisted of thornback ray Raja clavata, whereas in contemporary surveys the lesser spotted dogfish Scyliorhinus canicula was the most abundant elasmobranch. Changes in length-frequency distribution of fish in both target and non-target categories, and other observed changes, were thought to be a response to commercial exploitation, and corresponded to similar observations recorded elsewhere. [ABSTRACT FROM PUBLISHER]

Focuses on an article published in the 'Clinical and Experimental Dermatology' periodical, which described a clinical case of dermatomyositis-like eruption and leg ulceration caused by hydroxyurea in a patient with psoriasis. Pathogenesis; Characterization of the disease condition.

Loss of heterozygosity (LOH) had been widely used to assess genetic instability in tumours and a high LOH on chromosome arms 3p, 9p and 17p has been considered to be a common event in squamous cell carcinoma of the head and neck (SCCHN). We have investigated LOH in 52 SCCHN using a range of microsatellite markers. LOH was observed in 69% of individuals on 17p using seven markers, in 64% of individuals on 3p using 17 markers and in 61% of individuals on 9p using 11 markers. Fractional allele loss (FAL) has been calculated for each tumour (FAL is the number of chromosomal arms showing LOH divided by the number of informative chromosomal arms) and a median FAL value of 0.25 was obtained in the 52 SCCHN studied. The LOH data were examined on the basis of FAL scores: low FAL (LFAL), 0.00–0.19; medium FAL (MFAL), 0.20–0.32; high FAL (HFAL), 0.33–0.88. HFAL tumours demonstrated a significantly higher LOH on chromosome arms 3p, 9p and 17p, with 94% LOH on 3p, 94% on 9p and 100% on 17p compared with LFAL tumours. Six of the 16 patients in the LFAL group were found to have no LOH on 3p, 9p or 17p and of these four had LOH at other sites, on chromosomes 2p25–p24, 5q21–22, 7pter–p22, 8q13–q22.1, 11q23.3, 13q32, 17q, 18p11.21, 18q21.31 and 19q12–q13.1. These results indicate that LFAL patients form a subset of SCCHN tumours with distinct molecular initiating events which may represent a discrete genetic population. [ABSTRACT FROM PUBLISHER]

Background and Purpose. The purpose of this study was to compare exercise during dry-land bicycle ergometry and running in water with a flotation device in individuals with rheumatoid arthritis. Subjects. Eight individuals with adult-onset rheumatoid arthritis, between the ages of 30 and 40 years (X=35.88, SD=2.85), participated. Methods. Each subject did a graded maximal exercise test on a stationary bicycle and in the water wearing a flotation device, while oxygen uptake (VO2), heart rate (HR), pain, rating of perceived exertion (RPE), minute ventilation (VE), respiration rate, tidal volume (VT), and respiratory exchange ratio (R) were monitored. Results. Higher maximum RPE and R were seen during water running, whereas higher VE and VT were seen during bicycle riding. Heart rate, R, and plateauing VO2 data indicated that a true physiological peak VO2 was reached during the bicycle test. Peak VO2 and HR were similar for either water or bicycle exercise. These findings show that with both forms of exercise, subjects were able to reach training levels as set by the American College of Sports Medicine. Conclusion and Discussion. The water exercise, therefore, provides a means of exercising for individuals with rheumatoid arthritis. It allows them to reach the needed training levels in a comfortable aquatic environment. [ABSTRACT FROM AUTHOR]

Pre-treatment plaque thickens determined the rate at which psoriasis responded to PUVA treatment, taking longer with thicker plaques. For dithranol, the rate of response to treatment was independent of pre-treatment plaque thickness. Plaques of psoriasis that showed the greatest evaporative water loss before treatment took longest to clear with PUVA. At the time of clinical clearing the water loss had returned to that of adjacent, uninvolved skin. With dithranol the evaporative water loss did not return to normal levels but remained considerably elevated when the plaque was clinically clear. [ABSTRACT FROM AUTHOR]

Skin thickness measured by the Harpenden skin-fold caliper showed that the uninvolved or non-lesional skin thickness in psoriasis does not differ significantly from that of normal skin. It is thinner in females than in males under 65 years and decreases with age in both sexes. It is thinner in those with fair skin compared to those who tan easily. Uninvolved skin thickness in psoriasis appears to influence the thickness of an adjacent psoriatic plaque. [ABSTRACT FROM AUTHOR]

Forty patients with psoriasis treated with methotrexate (MTX) are reviewed. MTX was particularly effective in controlling erythrodermic and generalized pustular psoriasis. The treatment was discontinued in seven patients due to nausea in two and because of abnormal laboratory tests in five. Two patients developed toxic epidermal necrolysis (TEN) and died. Patients under 60 years of age had a liver biopsy before treatment and repeat biopsy after each cumulative MTX dose of 1500 mg. We consider that MTX is the drug of choice of treating difficult psoriasis. [ABSTRACT FROM AUTHOR]

A randomized controlled trial has been set up to examine the effect of diet on the secondary prevention of myocardial infarction, involving 2033 men. The trial has a factorial design, subjects being randomized independently to receive advice or no advice regarding three dietary factors: 1. a reduction in total fat and an increase in polyunsaturatedfat intake; 2. an increase in fatty fish intake; 3. an increase in cereal fibre intake. Nearly half the men under 70 years of age who survived myocardial infarction during the recruitment period entered the trial, the commonest reason for exclusion being that the subject was already eating (or intended to eat) a diet which included one or more of the regimens being investigated. Detailed dietary questionnaires were completed by each subject after 6 months in the trial. The results suggest that compliance with the advice is reasonably good. The differences between the diets of the groups given and not given advice on fish and fibre were substantial; the difference attributable to advice on fat has been somewhat less than anticipated, partly because of failure to comply with advice and partly because of spontaneous changes in the diets of control subjects. [ABSTRACT FROM PUBLISHER]

A 1 year, prospective multicentre study was performed to investigate the efficacy and safety of intermittent treatment with cyclosporin in psoriasis vulgaris. Subjects received cyclosporin (Neoral®) 5 mg/kg per day until achieving 90% reduction in area affected, or for a maximum of 12 weeks. Those failing to demonstrate a satisfactory response were withdrawn. When further treatment was required, cyclosporin was recommenced. This cycle was repeated up to three times. Psoriasis activity was recorded using the area affected and sign scores for erythema, scaling and infiltration. Overall assessments of response and tolerability were recorded. Forty-one subjects, mean age 36, mean PASI 12.8, entered the first treatment period. Thirty-three received a second period of treatment and 16 a third. Eighteen failed to complete the study as planned: five were withdrawn due to adverse events, four due to treatment failure and nine due to protocol violations. At the end of each treatment period, significant improvements were seen in all efficacy parameters. Overall response was graded as `considerable improvement' or `minimal or no symptoms', by over 80% of subjects and investigators. Median intervals to relapse for subjects remaining in the study were 72 days (range 28-329) and 53 days (range 14-141) after periods 1 and 2, respectively. There were significant increases in mean serum creatinine and blood pressure during each treatment period. However, there were no significant differences in either parameter between baseline and the final follow-up visit. At the end of each treatment period, overall tolerability of the treatment was considered `good' or `very good' by over 80% of subjects and investigators. [ABSTRACT FROM AUTHOR]

A prospective, open, multicentre study was performed to investigate the efficacy and safety of longterm treatment with cyclosporin in adults with severe atopic dermatitis. Subjects were treated for a maximum of 48 weeks. For the first 8 weeks, cyclosporin was administered at 2.5 mg/kg per day. The dose was then adjusted according to response. Disease activity was monitored using the six-area, six-sign score and the proportion of skin involved. Pruritus and sleep disturbance were assessed using four-point scales. Response was further evaluated on a five-point scale. Adverse events, blood pressure and serum biochemistry were monitored. Tolerability was assessed on a live-point scale. One hundred subjects were enrolled and 65 completed 48 weeks of treatment. Withdrawals occurred due to remission (three), inadequate response (seven), protocol violations (11) and adverse events (14, of which seven were probably treatment related). Cyclosporin produced rapid and highly significant improvements in all indices of disease activity. Sixty-five subjects considered that they had shown a considerable improvement or complete clearance of disease. Most patients relapsed after cessation of treatment, but neither signs nor symptoms had returned to baseline severity 8 weeks later. Blood pressure and serum creatinine levels increased slightly, and in one subject renal impairment was a major factor contributing to withdrawal of the drug. Overall, 85 subjects rated the tolerability of cyclosporin as good or very good. The results indicate that cyclosporin has a place in the long-term treatment of severe atopic dermatitis provided that appropriate patients are selected and careful monitoring is performed. [ABSTRACT FROM AUTHOR]

Eleven elderly patients (mean age 83 years; range 75–90) with microbiologically proven urinary tract infections were given 400 mg lomefloxacin as a single daily dose for up to seven days. On the first and final day of treatment blood was taken at timed intervals and drug concentration-time curves plotted. Blood was also taken immediately before each of the other doses for assay of pre-dose concentrations. The mean (± s.n.) peak serum concentration of lomefioxacin on the first day was 4.8 mg/l (± 1.5) observed at a mean of 156 min (±88) and on the final day was 6.3 mg/l (± 2.5) at a mean of 119 min (± 68). The mean serum half-life on the first day was 10.0 h (±2.8) and on the final day 10.3 b (±2.5). The daily pre-dose serum concentrations of lomefloxacin showed no accumulation of the drug. No serious adverse events were reported and all patients were cured although two had persistent pyuria. It is suggested that a once daily dose of 400 mg lomefloxacin is suitable for the elderly and that no dosage modification is needed in this patient group. [ABSTRACT FROM PUBLISHER]

224 patients with widespread plaque psoriasis were randomly allocated to treatment with PUVA or dithranol. 103 of the 113 patients treated with PUVA (91.2%) cleared satisfactorily compared with 91 out of 111 patients treated with dithranol (82%). However, dithranol cleared psoriasis significantly faster than PUVA (20.4 ± 0.9 days compared to 34.4 ± 1.8 days). Photochemotherapy produced no evident short-term adverse effects on the bone marrow, liver, or kidneys. [ABSTRACT FROM AUTHOR]

The 2 m beam trawl and 1.5 m push net were used to sample the small epibenthic fish assemblage during September on the east and south coasts of England. Fishing stations were distributed along the entire coast within four depth bands to 20 m. A total of 104 species were caught between 1973 and 1995, and these included infrequent Lusitanean species such as the big-scale sand-smelt (Atherina boyeri), and the undulate ray (Raja undulata), and infrequent boreal species such as the Norway haddock (Sebastes viviparus). Fifty-four taxa were selected as representative of the small, demersal inshore fish community that would be most vulnerable to capture by the two sampling gears, and were used in subsequent analyses of community structure. The north-east coast assemblage was the least diverse (H′=1.58) and least even (J′=0.47). It also supported the least number of species (55), and the variation in catch of the only dominant genus, Pomatoschistus spp., was partly responsible for large year-to-year variations in diversity and in the total population abundance of selected demersal species. On the east and south-east coasts, both diversity (H′=1.78 and 1.93) and evenness (J′=0.50 and 0.51) were greater than in the north, as a result of larger numbers of species available to the gears, and several species with relatively high catch density, such as Pomatoschistus spp., dab (Limanda limanda), solenette (Buglossidium luteum), and dragonet (Callionymidae). As a result, the fish assemblages of these coasts showed lower inter-annual variation in evenness and diversity. Trends in mean catch density of some species were correlated with the mean surface water temperature and salinity, especially for species which were near the edge of their normal geographic distribution in the southern North Sea. In addition, mean surface water temperatures were positively correlated with the total number of Lusitanean species on the south coast. These data provide evidence that during a period of more than 20 years, hydrographic factors have not only affected species abundance, but, at low density, also their presence or absence in catches. [ABSTRACT FROM PUBLISHER]

This in-vitro study was designed to investigate the effects of commonly prescribed antibiotics on sperm movement characteristics, viability and the ability of spermatozoa to undergo the acrosome reaction. Spermatozoa were obtained by swim-up from normozoospermic semen and cultured for 24 h with increasing concentrations of cotrimoxazole, erythromycin, amoxycillin, tetracycline and chloroquine. Tetracycline at concentrations as low as 2.5 μg/ml led to a significant dose-dependent inhibition in percent rapid-moving spermatozoa, mean path velocity (VAP), straight-line velocity (VSL) and curvilinear velocity (VCL), but at 50 μg/ml tetracycline all spermatozoa were static. Erythromycin had significant effects on rapid movement, VAP, VSL and VCL only at concentrations >100 μg/ml. In contrast, percent rapid-moving spermatozoa was significantly enhanced at low concentrations of chloroquine (5 μg/ml), but significantly inhibited by higher concentrations. Co-trimoxazole did not adversely affect percent rapid-moving spermatozoa below 500 μg/ml, at which concentration movement was decreased by 34%. The mean lateral head displacement (ALH) was significantly enhanced by 5 μg/ml co-trimoxazole and reduced at 1 mg/ml erythromycin. The effects of these drugs were mostly irreversible. Amoxycillin had no effect on sperm movement characteristics over the dose range used, though it inhibited viability at high doses. Viability was significantly reduced at concentrations of all drugs which affect rapid sperm movement; these concentrations of drugs did not appear to affect the ability of spermatozoa to undergo the acrosome reaction. The results from this study, when combined with known effects on spermatogenesis, should facilitate the choice of drugs for the treatment of both genitourinary and unrelated infections in men who are attempting to conceive. [ABSTRACT FROM PUBLISHER]

The classification of PsA is controversial. Two recent papers have suggested new subgroup classifications, however both have served only to expand the controversy. In this study the clinical and radiologic features of 100 patients with PsA are recorded in order to examine possible clinical or radiologic features which may be associated with functional disability and to examine the usefulness of recent reclassification proposals in our patient population. Results indicate that an asymmetric oligoarthritis (AO) pattern of disease is most common occurring in 43%. A symmetric polyarthritis (SP) was present in 33%, and this subgroup had the highest number of erosions and deformities, and a higher proportion of patients with grade III/IV ARA functional disability. While the DIP joints were involved in 46%, predominant DIP joint disease occurred in 16%. As the DIP group had the shortest duration of arthritis, it may be that this group represents recent onset PsA which will evolve into one of the other subgroups Sacroiiiitis was a feature in 14% with predominant spondylitis (SPON) in 4%. Arthritis mutilans (AM) was rare occurring in only 2% of this population, perhaps representing patients with end-stage SP disease. Finally, 2% of patients had features of the synovitis-acnepustulosis- hyperostosis-osteomyelitis (SAPHO) syndrome. A classification comprising just three subgroups (AO, SP, SPON) is proposed as being of most use clinically though a long-term prospective study is needed for verification. [ABSTRACT FROM PUBLISHER]

The most frequent PUVA treatment regimen in current use is three times weekly, using skin typing to estimate the starting dose. Recently, it was suggested that twice-weekly treatment, using the minimal phototoxic dose (MPD) to calculate suberythemal starting doses of UVA, achieved similar clearance rates with fewer treatments and a lower cumulative UVA dose. We have carried out a trial on 83 patients, comparing twice-weekly MPD-PUVA with three times-weekly skin typing-PUVA, in order to test this hypothesis. Although clearance rates were comparable between the two regimens, there was no overall significant difference in the number of treatments or in the cumulative UVA doses at clearance. However, for patients with skin types I and II the cumulative UVA dose was significantly higher using the twice-weekly MPD regimen (70.0J/cm2 vs. 55.8J/cm2; P<0.05). Our results do not confirm that there is a reduction in cumulative UVA dosage with twice-weekly MPDPUVA. [ABSTRACT FROM AUTHOR]

Adhesion molecule expression in synovial membrane obtained from patients with psoriatic arthritis (PA) has previously been compared with rheumatoid arthritis (RA).1 Although expression of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) was similar in both psoriatic and rheumatoid synovium, in contrast, little or no endothelial leucocyte adhesion molecule-1 (ELAM-1) was observed in psoriatic synovium. In the present study, the expression of ICAM-1, ELAM-1 and VCAM-1 was examined in the involved and uninvolved skin from patients with PA (n = 15), patients with psoriasis (Ps) but no arthritis (n = 5) and in normal skin (n=4). ICAM-1 was intensely expressed on endothelium and keratinocytes of involved skin from patients with Ps with or without arthritis. There was constitutive expression of ICAM-1 on endothelium only in uninvolved and normal skin. In contrast, ELAM-1 expression was restricted to endothelial cells; it was widespread and intense in involved skin, but was minimal in uninvolved and normal skin. VCAM-1 was expressed on endothelium, and also on some dendritic cells in involved psoriatic skin. There was minimal VCAM-1 staining on endothelial cells in uninvolved and normal skin. In conclusion, in involved psoriatic skin from patients with and without arthritis ICAM-1, ELAM-1 and VCAM-1 expression is up-regulated on vascular endothelium, and ICAM-1 is expressed on keratinocytes. However, ELAM-1 and VCAM-1 expression seen in dermal vessels is not found in psoriatic synovial vessels. These differences suggest a mechanism for controlling cellular traffic in Ps and in PA. [ABSTRACT FROM AUTHOR]

Presents several letters to the editor regarding various recent studies in the field of dermatology. Information regarding findings of two case studies of basal cell carcinoma and its association with cystic fibrosis; Findings of a immunopharmacological study of dapsone-induced agranulocytosis; Information regarding a survey-based clinical study revealing the association of Erythema nodosum and arthritis with food poisoning bacteria, Salmonella enteritidis.

Forty-four patients with chronic plaque psoriasis were randomly allocated to treatment with bath-water- delivered 8-methoxypsoralen (bath 8-MOP) or oral 8-methoxypsoralen (oral 8-MOP) PUVA therapy. There was a significant reduction in extent of the lesions and psoriasis area and severity index (PASI) after 20 treatments with each modality. There was a fourfold reduction in cumulative ultraviolet A (UVA) dose in the bath group. Side-effects of erythema and nausea were less with bath therapy. [ABSTRACT FROM AUTHOR]

Short-contact treatment with dithranol (anthralin) is a widely used treatment for chronic plaque psoriasis. Although effective, it causes staining and irritation, and is therefore inconvenient. Calcipotriol is a recently developed vitamin D analogue which is effective and easy to use. To evaluate the relative efficacy, safety and acceptability of these treatments a multicentre, open, randomized, parallel-group comparison was performed. Four hundred and seventy-eight patients with chronic plaque psoriasis were randomized to use one Of the two treatments for 8 weeks. One group applied calcipotriol ointment (50 μ/g) twice daily. The other used a single application for 30 min each day of Dithrocream® in the highest concentration tolerated. Severity of psoriasis was assessed by modified PASI score at baseline, and after 2, 4, and 8 weeks of treatment. A five-point scale was used by subjects and by investigators as an additional assessment of overall response, and a similar scale was used by subjects to grade acceptability. Total serum calcium was monitored at baseline and after 2 and 8 weeks on treatment. The mean PASI score fell from 9.1 to 4.7 after 8 weeks on dithranol (P<0.001), and from 9.4 to 3.4 on calcipotriol (P<0.001). The difference between the two treatments was significant in favour of calcipotriol at 2 weeks (P<0.001), and remained so at subsequent assessments. At 8 weeks the difference between mean improvements in scores for the two groups was 1.6 (95% confidence interval 0.5–2.7). Efficacy grading by subjects and investigators, and acceptability grading by subjects, were all significantly better for calcipotriol. The mean serum calcium showed no increase in either group. Calcipotriol was more effective and better accepted than short-contact dithranol. Both treatments appeared free from serious adverse effects. [ABSTRACT FROM AUTHOR]

Cutaneous xanthogranulomatous inflammation is usually regarded as a primary disease process. We describe two patients with xanthogranulomatous pyelonephritis and nephro-cutaneous fistulae, one patient with xanthogranulomatous cholecystitis and a chole-cutaneous fistula and one patient with xanthogranulomatous appendicitis and appendiceal-cutaneous fistula. After the first case, awareness that cutaneous xanthogranulomatous inflammation can be secondary to related internal disease played a vital diagnostic role in the subsequent cases. [ABSTRACT FROM AUTHOR]

The article discusses a study that examined the effect of body mass index (BMI), abdominal obesity and insulin resistance on the severity of psoriasis in patients receiving phototherapy. Topics discussed include the results of tests performed on subjects including Framingham risk, BMI and Psoriasis Area and Severity Index (PASI), correlation between BMI and PASI in patients before phototherapy and association of abdominal obesity with diabetes.

Primary varicella infection is caused by varicella-zoster virus (VZV). It is a common childhood infection, which is usually benign but can occasionally cause morbidity and mortality. In immunosuppressed adults, atypical presentation and disseminated disease can occur with significant morbidity and mortality. A VZV vaccine is available. This study was designed to measure the prevalence of immunity to VZV and to determine the predictive value of a self-reported history of varicella infection in a population of dermatological patients receiving systemic immunosuppressant therapy. We sought to assess the need for routine serological testing for varicella-zoster immunity in this cohort. Serological testing for VZV immunity was done on 228 patients receiving systemic immunosuppressive treatment for a dermatological condition. Information regarding a history of previous primary VZV infection was obtained from each patient. Two hundred and twenty-eight patients had VZV serology performed. The mean age of the patients was 49·6 years. The prevalence of VZV seropositivity in this cohort was 98·7%. One hundred and two patients (44·7%) reported having a definite history of primary VZV. The sensitivity of a self-reported history of VZV infection was 45·3% with a specificity of 100%. The positive and negative predictive values of a self-reported history of VZV for serologically confirmed immunity were 100% and 2·3%, respectively. The prevalence of VZV IgG antibodies in our cohort of Irish dermatology patients receiving immunosuppressive therapy is 98·7%. A recalled history of varicella infection is a good predictor of serological immunity. This study has shown that there are VZV-susceptible individuals within our cohort. These patients did not have a clear history of previous infection. We recommend serological testing of patients without a clear history of infection prior to the commencement of immunosuppressive therapy and vaccination of patients with negative serology. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented which offers information on the treatment of acrodermatitis continua of Hallopeau with adalimumab.

A patient developed toxic epidermal necrolysis (TEN), which was triggered by sun exposure while the patient was on long-term hydroxychloroquine. Phototoxic and photoallergic reactions are known to occur with hydroxychloroquine, but, to our knowledge, this is the first reported case of photo-induced TEN associated with the drug. [ABSTRACT FROM AUTHOR]

PUVA is known to be carcinogenic when used in the treatment of psoriasis. To date skin cancer has not been demonstrated after PUVA treatment of vitiligo. We report a patient in whom multiple squamous cell carcinomata and keratoses developed in vitiligo areas after a prolonged course of PUVA. [ABSTRACT FROM AUTHOR]