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Objectives To screen novel small molecule compounds for inhibition of Mycoplasma bovis growth and to characterize their activity in terms of dose-dependency and ability to function in milk. Methods Using a tetrazolium salt cytotoxicity assay, 480 natural compounds were screened to determine which of the small molecules have the potential to become therapeutic options for M. bovis prevention and treatment. The dose response was determined in broth culture and in fresh quarter milk for a subset of compounds shown to be capable of inhibiting M. bovis growth. Results Data suggest that 32 of the 480 compounds tested were able to inhibit growth of M. bovis using a tetrazolium salt assay. Methanesulphonic acid, 3-[(2E)-3-(3,4-dihydroxyphenyl)prop-2-enoyloxy](1S,3R,4R,5R)-1,4,5-trihydroxycyclohexane carboxylic acid, S-carboxymethyl-l-cysteine, l-aspartic acid, dihydrotachysterol, eriodictyol and (+)-α-tocopherol acid succinate were selected for further concentration-dependent studies and testing in fresh quarter milk. Each compound demonstrated a dose response in broth culture and at 3 h and 24 h in fresh quarter milk. Conclusions Small molecule natural compounds are capable of inhibiting the growth of M. bovis in both a pleuropneumonia-like organism (PPLO) medium and in fresh quarter milk. Results suggest that the compounds are mycoplasmastatic in a dose-dependent manner. By inhibiting M. bovis, small molecule natural compounds offer the potential for prophylactic or therapeutic use on organic and natural farms as a viable alternative to traditional antimicrobial agents. [ABSTRACT FROM PUBLISHER]

Background Little is known about the pathophysiology of localized scleroderma (skin fibrosis, also termed ‘morphoea’), although it is likely that microvascular dysfunction is a contributing factor. Objectives Our aim was to investigate different components of blood flow in morphoea using infrared thermography and dual-wavelength laser Doppler imaging (LDI). Methods Eight plaques of morphoea (in eight patients) were studied. Skin temperature and blood flow were assessed in both affected (within plaque) and adjacent unaffected (perilesional) skin. Results Skin temperature (representing blood flow) was higher in all areas of morphoea when compared with uninvolved skin. Perfusion within the plaques was found to be increased, when compared with uninvolved skin; in all cases as imaged by red wavelength (633 nm) LDI (representing blood flow through large, thermoregulatory vessels) and in six of eight cases by green wavelength (532 nm) LDI (representing nutritive capillary blood flow). The median (range) skin temperature difference between plaque and perilesional skin was 1·1 (0·7–2·2) °C and the median (range) ratios of plaque/perilesional perfusion as measured by red and green wavelength LDI were 1·3 (1·1–1·9) and 1·1 (0·8–1·5) arbitrary perfusion units, respectively. Conclusions Microvascular perfusion is increased within morphoea plaques and the increased response detected by both thermography and red wavelength LDI, as compared with green wavelength LDI, suggests that the increase in perfusion is more marked in deeper, larger, rather than in superficial, smaller vessels. [ABSTRACT FROM AUTHOR]

SUMMARY In mice, the roles of cytokines in the initiation of epidermal Langerhans’ cell (LC) migration are well documented; however, the mechanism of this response in humans is less well defined. The purpose of the present investigation was to examine the contribution of interleukin (IL)-1β to human epidermal LC migration and to define further the mechanisms of this response. We demonstrate here that homologous recombinant IL-1β administered intradermally to healthy human volunteers provides a stimulus for LC migration, with significant (P < 0·01) reductions in LC densities being observed at both 2 h and 4 h following treatment. At the later time-point of 4 h, injection of IL-1β was also accompanied by activation of those LC remaining in the epidermis. Analysis of fluid aspirated from suction blisters formed at injection sites revealed significant (P < 0·01) tumour necrosis factor (TNF)-α production (2·99 ± 1·18 pg TNF-α /mg protein; mean ± s.d. of n = 10) in response to IL-1β treatment compared with saline control injections (0·90 ± 1·05 pg TNF-α /mg protein). Prior topical application of human recombinant lactoferrin (LF), an iron-binding protein found in exocrine secretions and skin, inhibited IL-1β -mediated LC migration and also compromised the production of TNF-α protein as measured in suction blister fluids derived from each of the treatment sites. Taken together, these data demonstrate that IL-1β is associated with both the stimulation of human epidermal LC migration and local TNF-α production. Topical treatment with LF compromises both these responses. These data suggest that topical LF may potentially represent a novel therapeutic in the treatment of skin inflammation where TNF-α is an important mediator. [ABSTRACT FROM AUTHOR]

Summary An understanding of the molecular basis of angiogenesis is key to the appreciation of many of the advances made in the field of neovascularization over the past two decades. The sequence of events involved in angiogenesis includes: (i) increased vascular permeability and leakage; (ii) degradation of basement membrane; (iii) endothelial cell proliferation and migration through the surrounding extracellular matrix; and (iv) maturation and stabilization of the newly formed vessel bed. This review provides an update on the molecular basis of such pathways in the skin, with particular emphasis on the endothelial cell-specific vascular endothelial growth factor and angiopoietins as modulators of angiogenesis that can be targeted in therapy of cutaneous disease. [ABSTRACT FROM AUTHOR]

Summary Background Skin-homing, memory T lymphocytes play an important role in the pathogenesis of psoriasis by interacting with the vascular addressin, E-selectin and trafficking into lesional skin. Thus an attractive option for targeted therapy of the disease would be blockade of skin-homing T cells with an antibody directed at E-selectin. Objective We performed a multicentre, randomized, placebo-controlled trial to investigate the clinical efficacy and side-effect profile of a humanized monoclonal antibody to E-selectin, CDP850, in the treatment of moderate to severe chronic plaque psoriasis. Methods Patients with moderate/severe chronic plaque psoriasis were selected for study. Nine male subjects (mean age 37 years, range 25–47) were given 20 mg kg-1 CDP850 intravenously as a single dose and four subjects (three males, one female; mean age 40 years, range 23–50) received placebo infusion. Clinical response to treatment was assessed using the psoriasis area and severity index (PASI). Skin biopsies were taken for immunohistochemical analysis at the baseline, pretreatment, visit and also at day 2 and weeks 1 and 4 postinfusion. Results The treatment was well-tolerated with a minimal side-effect profile. Plasma E-selectin levels were significantly decreased in those subjects who received CDP850 compared with those who had placebo for the entire study period. At the end of study (8 weeks postinfusion), there was no significant reduction in PASI from baseline for either the CDP850 or placebo-treated groups. Immunohistochemical analysis of biopsies taken from lesional psoriatic skin showed that 2 days after dosing with CDP850, staining for E-selectin was decreased, although not absent, on dermal vascular endothelial cells when compared with baseline (P < 0·01). This decrease in E-selectin expression was maintained 4 weeks after infusion (P < 0·05). It was not, however, accompanied by a significant reduction in numbers of... [ABSTRACT FROM AUTHOR]

Summary Background Langerhans cells (LCs) play essential roles in the initiation and regulation of cutaneous immune responses mediated through their successful migration from the epidermis to draining lymph nodes while carrying antigen. Tumour necrosis factor (TNF)-α, a keratinocyte-derived cytokine, has recently been shown to play an important role in the mobilization of LCs from human epidermis. Although it is known that with age the immune system changes, the influence of increasing age on the function of human LCs has not been defined clearly. Objectives To examine the influence of age on the ability of TNF-α to induce LC migration. Methods Ten elderly (six men, four women; mean age 76 years, range 72–79) and 10 young (six men, four women; mean age 23 years, range 18–35) volunteers received intradermal injections of 200 U of human recombinant TNF-α diluted in sterile saline, and control injections of sterile saline alone, at each of two paired sites identified on photoprotected buttock skin. Two hours later, paired injection sites were excised by punch biopsy. One set of paired biopsies was processed for assessment of the frequency and morphology of epidermal LCs, following preparation of epidermal sheets and immunofluorescence staining for the LC marker CD1a. The remaining paired biopsies were processed in formalin and the inflammatory response to TNF-α was assessed by standard histological examination. Results Mean ± SEM baseline values for LC frequency within epidermal sheets were significantly different between young (1156·3 ± 38·5 cells mm-2 ) and elderly subjects (835·7 ± 48·2 cells mm-2 ; P < 0·01). Intradermal injections of 200 U of TNF-α caused a significant reduction in the frequency of LCs in both elderly and young subjects (P < 0·01). However, the extent of TNF-α-induced LC migration was substantially different between the two groups,... [ABSTRACT FROM AUTHOR]

Background Palmoplantar pustular psoriasis (PPP) is a chronic, relapsing condition often recalcitrant to therapy. Synthetic retinoids have been found to be efficacious in the treatment of PPP, but their use is limited by side-effects. Liarozole is an imidazole-like compound that inhibits the retinoic acid (RA) 4-hydroxylase-mediated breakdown of all-trans RA, causing elevation of plasma and cutaneous levels of RA. Thus liarozole acts as a retinoid-mimetic drug. Liarozole has already been found to be effective in the treatment of retinoid-responsive conditions such as chronic plaque psoriasis and ichthyoses. Objectives To assess the efficacy and side-effect profile of liarozole in the treatment of PPP. Methods We performed a double-blind, randomized, placebo-controlled trial of oral liarozole 75 mg twice daily for 12 weeks in the treatment of PPP. The trial was conducted at two centres and involved 15 patients. Results Using the PPP Area and Severity Index we found a statistically significant (P = 0·02) improvement in PPP in subjects on liarozole (median 3, range 1·8–14·1) as compared with placebo (median 12·1, range 5–18) by the end of the treatment phase. There was also a statistically significant difference (P = 0·006) in the number of fresh pustules after treatment for the two study groups (liarozole median 2, range 0–18; placebo median 38, range 2–75). The severity of disease (on a scale of 0–8) between the two groups was significantly different at the end of treatment (liarozole median 1, range 1–5; placebo median 3, range 2–6; P = 0·04). No patients withdrew from the trial because of adverse events. The most commonly reported side-effects were pruritus, cheilitis and xerosis but these were rarely severe and resolved rapidly on discontinuation of treatment. Laboratory results, including haematology, liver function tests and serum cholesterol and triglycerides were not... [ABSTRACT FROM AUTHOR]

We describe a case of carcinoma cuniculatum of the foot assessed by magnetic resonance scanning. The potential use of this imaging technique in the management of this condition is discussed. [ABSTRACT FROM AUTHOR]

Comments on several issues related to dermatology. Role of T lymphocytes within normal human epidermis; Cause of hypertrophy of the skin; Factors influencing the emigration of Langerhans cells.

We present a brief account of the life and times of Dr Henry Grundy Brooke, a Manchester dermatologist and key figure in British dermatology in the nineteenth century. Our report highlights the achievements of a man whose contributions to dermatology continue to be of relevance in the new millennium. [ABSTRACT FROM AUTHOR]

Changes in the microvasculature are considered to play an important part in the pathogenesis of psoriasis and its associated arthritis. The novel method of nailfold video capillaroscopy is an extension of the technique of widefield nailfold microscopy which has been of diagnostic and predictive use in the in vivo study of the microcirculation in systemic sclerosis and other connective tissue disorders. However, similar studies in patients with psoriasis and psoriatic arthritis and/or nail changes have produced conflicting results. We tested the hypothesis that any abnormalities in nailfold capillaries of either a quantitative or qualitative nature might be observed more readily in subjects with pathology adjacent to the nailfold, i.e. distal interphalangeal (DIP) joint changes and/or nail dystrophy, when using this technique. Forty-four patients with psoriasis were recruited (21 males, 23 females). Twelve patients had psoriasis alone, 13 had psoriasis and nail changes, six had DIP joint involvement with changes of psoriasis elsewhere, and 13 had psoriasis, DIP arthritis and nail changes. Capillary density and standard capillary dimensions were studied and compared with those of 44 age- and sex-matched control subjects. There was a significant (P < 0·05) decrease in capillary loop density in patients with either psoriasis plus nail disease (14·5 ± 5·7 capillaries per 3 mm field) or psoriasis plus nail and DIP joint disease (14·3 ± 5·0) when compared with controls (19·2 ± 3·8). In patients with psoriatic arthritis affecting the DIP joints, there was a statistically significant (P < 0·05) decrease in arterial and venous capillary limb diameters, and this was also seen in those with arthritis associated with nail changes. However, there was no difference in capillary dimensions between patients with psoriasis and/or nail changes when compared with normal controls. Morphological abnormalities previously described in the literature were not noted in any of our four patient groups. Our findings of diminution in both nailfold capillary bed density and dimensions of the arterial and venous capillary limbs suggest that vascular injury, previously noted in ultrastructural studies, may play a part in the pathogenesis of psoriatic arthritis. However, in contrast to previous studies, we found no specific pattern of a morphological nature of nailfold capillaries in patients with psoriasis with or without nail changes, when compared with normal controls. [ABSTRACT FROM AUTHOR]

We describe a case presenting as atypical granuloma annulare where the underlying diagnosis, confirmed by lymph node biopsy, was lymphoepithelioid cell lymphoma (Lennert’s lymphoma). Lennert’s lymphoma is a peripheral T-cell lymphoma which may follow a variable course and transform into an aggressive phase. Cutaneous manifestations of this condition have only rarely been reported in the literature. The presence of granulomas in the skin may have either obscured the lymphoma infiltrate or may have reflected a more generalized immune response to the underlying malignancy. [ABSTRACT FROM AUTHOR]

We have developed, tested and validated a new scoring system for psoriasis: the Salford Psoriasis Index (SPI). The SPI incorporates the current clinical extent of psoriasis based on the Psoriasis Area and Severity Index (PASI), a score indicating psychosocial disability, and past severity based on treatment history. The resultant three-figure SPI (signs, psychosocial disability, interventions) is a similar paradigm to the TNM (tumour, nodes, metastasis) classification used for cancer staging. The first figure transforms the PASI into a number from 0 to 10 reflecting extent of psoriasis. The second assesses the psychosocial impact of psoriasis on each patient using a 0–10 visual analogue scale. The third figure reflects historical severity of disease as judged by the need for systemic treatment, admission to hospital and number of episodes of erythroderma. The SPI was prospectively employed in assessing 150 consecutive patients with psoriasis. Furthermore, in a separate cohort of 100 patients we tested the Psychosocial Impact Score against a recognized self-report psoriasis-specific measure, the Psoriasis Disability Index. There was a strong correlation between the two (r = 0·59, P < 0·001). However, the Psychosocial Impact Score correlated poorly with clinical extent scores such as the PASI (r = 0·28, P < 0·05) and the Self-administered PASI in 72 patients tested (r = 0·19, P = 0·1). There was a high correlation between all six observers in 20 patients for both PASI (r = 0·71; 95% confidence interval, CI 0·51–0·86) and the Extent Score (r = 0·70; 95% CI 0·56–0·89). We believe that the SPI will be more relevant to real-life categorization of psoriasis severity in that it takes an holistic approach based not only on physician assessment but also psychological disability and treatment resistance. [ABSTRACT FROM AUTHOR]

Examines the role of cytokines and chemokines in the initiation and regulation of epidermal Langerhans cell (LC) mobilization. Interaction with appropriate receptors expressed by LC; Induction of cutaneous immune responses; Inducement of LC migration by the molecules.

Neovascularization appears to play an early and important part in the evolution of psoriatic plaques. We studied the distribution and production of two known angiogenesis factors, endothelial cell stimulating angiogenesis factor (ESAF) and vascular endothelial growth factor (VEGF), in the skin of patients with chronic plaque psoriasis and normal control subjects. Our results showed that tissue levels of ESAF and VEGF were significantly elevated in involved as compared with normal control skin (P = 0·006 and P < 0·0001, respectively). Tissue levels of ESAF and VEGF were also raised in involved skin as compared with uninvolved skin in patients with psoriasis (P = 0·001 and P < 0·0001, respectively). Tissue levels of ESAF and VEGF in plaques of psoriasis correlated closely with the clinical severity of psoriasis (r = 0·6 and r = 0·9, respectively). Serum levels of ESAF and VEGF were significantly raised in patients with psoriasis as compared with control subjects (P = 0·001 and P = 0·02, respectively). In vitro culture studies revealed that ESAF is produced by both keratinocytes and fibroblasts in approximately equal quantities in normal skin, whereas VEGF is secreted predominately by keratinocytes. A similar pattern is seen in both involved and uninvolved skin of patients with psoriasis. However, there is increased secretion of both factors in keratinocytes and fibroblasts from involved and uninvolved skin as compared with normal control skin (P < 0·001). The increased levels and secretion in plaques of psoriasis of two molecules, ESAF and VEGF, known to promote new blood vessel formation, suggest a pathogenetic role for them in this disease. [ABSTRACT FROM AUTHOR]

Reports on a case of a girl who was presented with a history of a hypopigmented, sclerotic linear band affecting her left inner thigh. Description of the clinical features of the girl with scleroderma or systemic sclerosis; Role of lymphocytes in the pathogenesis of systemic sclerosis; Examination of the patient's responses to ciclosporin.

Examines the correlation between eczema craquele and acute oedema. Description of the development of bullae; Relevance of eczema craquele on tense blisters; Components of dermatitis.

Background The development of bullae accompanying acute oedema is a commonly observed clinical sign but has been rarely reported in the literature. Objectives To document the clinical features and increase awareness of this entity. Methods Retrospective case note review of 13 inpatient consultation cases seen in two dermatology departments. Results Oedema blisters appear to be related to the speed of development rather than the degree of oedema, and respond rapidly to the reduction of the underlying oedema. Conclusions Recognition of oedema blisters is important as they respond quickly and completely to treatment of the underlying oedema. [ABSTRACT FROM AUTHOR]

Reports on a case of 30-year-old man with complex partial seizures who had prolonged toxic epidermal necrolysis due to the anticonvulsant drug, Lamotrigine. Development of painful ulcerations despite discontinuation of therapy; Stabilization of patient's condition with high flow oxygen, fluid boluses, vasopressor therapy and parenteral analgesia; Application of topical clobetasol propionate cream for treatment.

We report a patient with multiple glomus tumours and Coats' disease of the retina, an association not previously described. We discuss the possible pathogenesis of these conditions in view of the finding of elevated serum levels of basic fibroblast growth factor. [ABSTRACT FROM AUTHOR]

Examines the ability of interleukin-1 beta to induce epidermal Langerhans cell migration in young and elderly research volunteers. Comparison of results to previously reported responses to tumor necrosis factor; Use of intradermal injections of homologous recombinant interleukin-1beta from Insight Biotechnology Ltd.; Results of punch biopsies.

Responds to comments made by F.A. Bahmer on the authors' research article regarding the enumeration of the frequency of Langerhans cells in epidermis, published in the volume 147, 2002 edition of the periodical 'British Journal of Dermatology.' Need for procedures to eliminate statistical bias; Effect of the possible specimen shrinkage as a result of age.