Rapid decompression in the EA-6B

BACKGROUND AND OBJECTIVE: In recent years, many reports have suggested an active role of neuropeptides in the pathogenesis of psoriasis. Increased numbers of neuropeptide-containing nerves positive for substance P (SP), vasoactive intestinal polypeptide (VIP), and calcium gene-related peptide (CGRP) have been reported in psoriatic tissue. As psoriatic epidermis has a larger mass/volume, however, it is expected to have more nerves and a higher number of neuropeptergic fibers. Therefore, instead of demonstrating a larger number of neuropeptergic fibers, a more significant study is to investigate whether the neuropeptergic fibers are denser in psoriatic tissue. In this study, we applied a double labeled immunofluorescence technique. This method allows the identification of the total number of nerve fibers and the number of nerves positive for specific neuropeptides. MATERIALS AND METHODS: We obtained biopsies from nine lesional and seven non-lesional psoriatic skins and six normal controls. Biopsies were snap frozen and then cut into 14 microm cryosections. The tissues were first treated with anti-microtubule associated protein (MAP)2 antibody to stain the nerves. This was followed by a second set of stainings for SP, VIP, and CGRP. Primary antibodies were used in dilutions of 1:200 for anti-MAP2, 1:200 for anti-SP, 1:800 for anti-VIP, and 1:400 for anti-CGRP. RESULTS: We found that the percentage of SP-positive fibers was twofold greater and the percentage of CGRP-positive fibers was 2.5 times greater in the psoriatic epidermis than in the epidermis of normal skin. Psoriatic epidermis had 30.1 +/- 3.9% SP-positive nerve fibers compared with 15.7 +/- 3.7% in the normal control. The corresponding values for CGRP-positive nerve fibers were 30.1 +/- 3.9% and 12.0 +/- 4.2%. CONCLUSIONS: The results of our study suggest that SP- and CGRP-containing neuropeptide nerve fibers are more dense in the psoriatic epidermis. Both SP and CGRP are chemotactic to neutrophils and mitogenic to keratinocytes and endothelial cells. In addition, SP activates T lymphocytes and induces adhesion molecules on the endothelial cells. Our observations suggest that neuropeptides may play a significant role in the inflammatory and proliferative process of psoriasis.     

Cataract-glaucoma combined surgery: comparison between phacoemulsification combined with deep sclerectomy, or trabeculectomy

Stereological quantification of mast cell numbers was applied to sections of punch biopsies from lesional and nonlesional skin of atopic dermatitis patients and skin of healthy volunteers. We also investigated whether the method of staining and/or the fixative influenced the results of the determination of the mast cell profile numbers. The punch biopsies were taken from the same four locations in both atopic dermatitis patients and normal individuals. The locations were the scalp, neck and flexure of the elbow (lesional skin), and nates (nonlesional skin). Clinical scoring was carried out at the site of each biopsy. After fixation and plastic embedding, the biopsies were cut into 2 microns serial sections. Ten sections, 30 microns apart, from each biopsy were examined and stained alternately with either toluidine blue or Giemsa stain and mast cell profile numbers were determined. The study yielded the following results: (1) in atopic dermatitis lesional skin an increased number of mast cell profiles was found as compared with nonlesional skin, (2) comparing atopic dermatitis skin with normal skin, a significantly increased number of mast cell profiles per millimetre squared was found in specimens from the neck, (3) staining with toluidine blue yielded a lower number of mast cell profiles than Giemsa staining, (4) the use of Carnoy's fixative resulted in a lower mast cell profile count than the use of formaldehyde, and (5) there was no statistically significant correlation between the clinical score and the number of mast cell profiles per millimetre squared. Using stereological techniques, this study indicated that mast cells might participate in the inflammatory process in skin leading to atopic dermatitis.     

Mast cells of psoriatic and atopic dermatitis skin are positive for TNF-alpha and their degranulation is associated with expression of ICAM-1 in the epidermis

The release of cytokines from cutaneous cells may be of major importance in the initiation and development of many inflammatory skin disorders. For example, tumor necrosis factor-alpha (TNF-alpha), which in healthy skin is found preformed only in mast cells, is able to induce the expression of several adhesion molecules including intercellular adhesion molecule-1 (ICAM-1). Increased expression of ICAM-1 occurs in keratinocytes in lesional skin of psoriasis and atopic dermatitis (AD) and it is considered to be an important initiator of leucocyte/keratinocyte interactions in skin inflammation. We counted the mast cells showing TNF-alpha immunoreactivity using a double-staining method in nonlesional and lesional skin sections from 12 patients with AD and 12 patients with psoriasis. The percentage of TNF-alpha+ mast cells in lesional and nonlesional AD skin was 36 +/- 22% and 21 +/- 15% (P < 0.018, paired t-test), respectively, and in psoriatic skin was 16 +/- 25% and 15 +/- 15%, respectively (P < 0.89, paired t-test). We also cultured whole skin biopsies taken from the healthy-looking skin of psoriatic and AD patients in the presence of mast cell degranulator compound 48/80, which resulted in focal expression of ICAM-1 in the epidermis. In cultured keratinocytes, both histamine and an extract of a human mast-cell line (HMC-1) induced ICAM-1 immunostaining only in occasional cells, but the combination of histamine and the HMC-1 extract resulted in intense ICAM-1 staining in numerous cells. This enhancement of ICAM-1 staining was abolished by preincubation of the HMC-1 extract with anti-TNF-alpha antibody. These results suggest that the degranulation of mast cells induces the expression of ICAM-1 in keratinocytes probably via TNF-alpha and histamine.     

Epidermal nerve fiber density: normative reference range and diagnostic efficiency

BACKGROUND: The sensitivity of neuron-specific antibodies permit the identification of the small unmyelinated nerve fibers within the skin. OBJECTIVES: To develop a reference range of epidermal nerve fiber density in humans, and to evaluate their diagnostic efficiency for sensory neuropathies. METHODS: Ninety-eight normal controls (age range, 13-82 years) were examined with both directed neurologic examinations and quantitative sensory testing. The diagnostic utility was examined in 20 patients with sensory neuropathies. Each subject had 2 punch biopsies performed at each site in the thigh and distal part of the leg (total of 392 biopsies). After formalin fixation, 50-microm-thick free-floating sections were stained with a polyclonal antibody to neuron-specific ubiquitin hydrolase, anti-protein gene product 9.5. We enumerated intraepidermal nerve fibers per millimeter to derive a "linear density." The linear density technique was validated against a stereological technique that used the fractionator to measure the total length of intraepidermal nerve fibers per 3-mm punch. RESULTS: The biopsy technique was well tolerated, with no notable complications. The linear density quantitation was rapid and had high intraobserver and interobserver reliability. We determined that the density of intraepidermal fibers in normal controls was 21.1+/-10.4 per millimeter (mean +/- SD) in the thigh (fifth percentile, 5.2 per millimeter), and was 13.8+/-6.7 per millimeter at the distal part of the leg (fifth percentile, 3.8 per millimeter). Significantly higher intraepidermal fiber densities were seen in the youngest group (P = .004), and we observed no significant effect of race, sex, height, or weight. The density at the thigh was significantly correlated with that at the distal part of the leg (P = .01) and was consistently higher by about 60%, a reflection of the normal proximal-distal gradient. The results obtained with stereology and the linear density correlated significantly (P=.001), providing internal validation for the technique. Epidermal nerve fiber density was significantly reduced (P = .001) in patients with sensory neuropathies. With a cutoff derived from the fifth percentile of the normative range for the distal part of the leg, the technique had a positive predictive value of 75%, a negative predictive value of 90%, and a diagnostic efficiency of 88%. CONCLUSIONS: We have established a reference range for intraepidermal nerve fiber density in normal humans by means of a simple quantitation method based on enumeration of individual intraepidermal nerve fibers on vertical sections of punch skin biopsy specimens stained with the sensitive panaxonal marker anti-protein gene product 9.5. The utility of the density measurement was confirmed for sensory neuropathy with a diagnostic efficiency of 88%. Skin biopsies may be useful to assess the spatial distribution of involvement in peripheral nerve disease and the response to neurotrophic and other restorative therapies.     

IL-10 levels are decreased in psoriatic lesional skin as compared to the psoriatic lesion-free and normal skin suction blister fluids

IL-10 is a cytokine produced by B and T-cells, monocytes and keratinocytes with pleiotropic effects, some of which are directed towards suppressing monocyte activities (anti-inflammatory cytokine). No information at the protein level is available concerning IL-10 in suction blister fluids from psoriatic skin, even if contrasting data have been reported on IL-10 mRNA of psoriatic biopsies and on the cytokine patterns of the T-cell clones, isolated from psoriatic skin. The IL-10 blister fluid concentrations in psoriatic lesions were compared to those found in the non-lesional skin of 14 patients effected with plaque-type psoriasis, and to those found in the skin of healthy controls (9 subjects sharing sex ratio and age with psoriatic patients). No difference in the IL-10 levels was found between non-lesional and control skin. In contrast, lower IL-10 levels were observed in blister fluids obtained from lesional psoriatic skin (p < 0.0005). The possible meanings of these results have been evaluated in the context of the mechanisms activating or maintaining the chronic inflammatory components of psoriasis.     

Localization of sphingomyelinase in lesional skin of atopic dermatitis patients

Because it has been suggested that the majority of the activity hydrolysing [N-methyl-14C] sphingomyelin is due to sphingomyelin acylase in the lesional skins of atopic dermatitis (AD), in this study we used immunologic techniques to localize and quantitate sphingomyelinase in AD lesional and normal skin. A polyclonal antibody raised against a synthetic polypeptide corresponding to a portion of the amino acid sequence deduced from the cDNA of human acid sphingomyelinase, cross-reacted with a 58 kDa, pI 5.8 human epidermal protein in an immunoblot analysis. The 58 kDa protein-rich fraction, partially purified by immunoprecipitation, converted [N-methyl-14C]-sphingomyelin to 14C-phosphorylcholine and ceramides. The reaction products were immunohistochemically observed in the intercellular domain from the upper spinous cell layer to the upper stratum corneum cell layers in the lesional skin of AD patients. Immunoelectron-microscopically, gold particles appeared to be concentrated in the intercellular domains of the granular-upper stratum corneum cells in the lesional skin of AD patients. The total amount of the 58 kDa protein in a 7 mm2 area of the skin was measured by quantitative immunoblot analysis; and was slightly increased in the lesional skin samples [3.5 +/- 0.3 microg per 7 mm2 (n = 7)], as compared with the nonlesional skin samples of AD patients [2.8 +/- 0.19 microg per 7 mm2 (n = 10)] and with the normal skin samples [2.7 +/- 0.22 microg per 7 mm2 (n = 10)]. This difference (between the lesional skin of AD and the nonlesional skin of AD or the normal control) was significant (nonpaired student's t test, p < 0.05).     

Effects of incubation temperature on the energetics of embryonic development and hatchling morphology in the Brisbane river turtle Emydura signata

AIMS: To investigate the malignant potential of lichen sclerosus, a study using the cell proliferation marker Ki67 comparing lichen sclerosus with and without associated squamous cell carcinoma was performed. METHODS AND RESULTS: Formalin-fixed, paraffin-embedded slides of 13 cases of lichen sclerosus with associated carcinoma, and 31 cases without associated carcinoma, including 16 random cases, seven with epidermal thickening and eight with epidermal thinning, were examined by the immunoperoxidase technique for Ki67, a cell proliferation marker. Ki67 reactivity was mostly seen in the basal and parabasal cells in both groups of lichen sclerosus and this pattern was similar to normal skin, squamous cell hyperplasia and analogous to that of one form of squamous cell carcinoma. There was a mean of 50 Ki67 positive cells per 100 basal cells in lichen sclerosus with associated squamous cell carcinoma; however, in squamous cell hyperplasia adjacent to carcinoma this rose to 90 Ki67 positive cells per 100 basal cells. In lichen sclerosus without associated carcinoma, the random cases had a count of 53 per 100 basal cells, those with epidermal thickening 53 and those with thinning 42. Non-genital normal skin had a count of 71 per 100 basal cells. CONCLUSION: The lack of qualitative differences of Ki67 expression in normal skin, in lichen sclerosus with and without carcinoma, in squamous cell hyperplasia and in one form of squamous cell carcinoma indicates that these conditions share a common localized pattern of cell proliferation and does not support or deny the malignant potential of lichen sclerosus. The higher Ki67 count in squamous cell hyperplasia adjacent to carcinoma could indicate premalignancy or a reaction to the carcinoma. In patients without carcinoma, the higher Ki67 count in thickened lichen sclerosus compared to thinned suggests that some or all of the cases of thickened lichen sclerosus were lichen sclerosus with squamous cell hyperplasia or that lichen simplex chronicus superimposed on lichen sclerosus has a higher Ki67 expression or that the distinction between squamous cell hyperplasia and lichen simplex chronicus is only one of terminology.     

Immunohistochemical characterization of the plasminogen activator system in psoriatic epidermis

The relative topographical distribution of urokinase-type plasminogen activator (uPA), tissue-type PA (tPA), PA-inhibitor-1 (PAI-1), PA-inhibitor-2 (PAI-2), plasmin(ogen), alpha 2-antiplasmin, and alpha 2-macroglobulin was studied in lesional epidermis of psoriasis vulgaris, and in normal epidermis, by immunohistochemistry. In psoriatic epidermis, tPA predominated, although uPA was found in some biopsies. PAs were not detected in normal epidermis. PAI-1 was not detected in normal epidermis and was only present in a proportion of biopsies of psoriatic lesions. PAI-2 was found in normal and psoriatic epidermis. Plasmin(ogen) was confined to the basal cell layer of normal epidermis, whereas in lesional psoriatic skin it was scattered throughout the epidermis. Alpha 2-antiplasmin and alpha 2-macroglobulin were not found in the epidermis of normal skin. In psoriatic epidermis alpha 2-antiplasmin was confined to the subcorneal layer, whereas staining for alpha 2-macroglobulin was found only in a proportion of biopsies, in the upper epidermis. Our immunohistological findings indicate that colocalization of tPA and its substrate plasminogen may allow efficient generation of plasmin, and that the focal absence of plasmin inhibitors may then favour the persistence of plasmin activity.     

Neuropeptides in the skin: interactions between the neuroendocrine and the skin immune systems

The interaction between components of the nervous system and multiple target cells in the cutaneous immune system has been receiving increasing attention. It has been observed that certain skin diseases such as psoriasis and atopic dermatitis have a neurogenic component. Neuropeptides released by sensory nerves that innervate the skin and often contact epidermal and dermal cells can directly modulate functions of keratinocytes, Langerhans cells (LC), mast cells, dermal microvascular endothelial cells and infiltrating immune cells. Among these neuropeptides the tachykinins substance P (SP) and neurokinin A (NKA), calcitonin gene-related peptide (CGRP), vasoactive intestinal peptide (VIP) and somatostatin (SOM) have been reported to effectively modulate skin and immune cell functions such as cell proliferation, cytokine production or antigen presentation under physiological or pathophysiological conditions. Expression and regulation of their corresponding receptors that are expressed on a variety of skin cells as well as the presence of neuropeptide-specific peptidases such as neutral endopeptidase (NEP) or angiotensin-converting enzyme (ACE) determine the final biological response mediated by these peptides on the target cell or tissue. Likewise, skin cells like keratinocytes or fibroblasts are a source for neurotrophins such as nerve growth factor that are required not only for survival and regeneration of sensory neurons but also to control responsiveness of these neurons to external stimuli. Therefore, neuropeptides, neuropeptide receptors, neuropeptide-degrading enzymes and neurotrophins participate in a complex, interdependent network of mediators that modulate skin inflammation, wound healing and the skin immune system. This review will focus on recent studies demonstrating the role of tachykinins, CGRP, SOM and VIP and their receptors and neuropeptide-degrading enzymes in mediating neurogenic inflammation in the skin.     

Pattern of distribution of neuropeptides in the camel lacrimal gland

The pattern of distribution of neuropeptides, including neuropeptide-Y (NPY), vasoactive intestinal polypeptide (VIP), neurotensin (NT), serotonin (5-HT), galanin (GAL), leucine-enkephalin (LEU-ENK) and calcitoningene-related-peptide (CGRP), in the nerves of the camel lacrimal gland was investigated using immunohistochemical techniques. Fresh lacrimal gland segments, obtained from adult camels slaughtered in the local abattoir, were used for the immunohistochemical techniques. NPY and LEU-ENK immunoreactivity was observed in the nerve cell bodies and nerve fibers of the camel lacrimal gland. VIP, GAL and CGRP were demonstrated predominantly in fine varicose nerve fibers lying on the basolateral surfaces of the lacrimal acinar cells. NT and 5-HT were identified mainly in neurons situated in the periacinar regions, close to the basal surfaces of the acinar cells. It is concluded that the camel lacrimal nerves contain several neuropeptides including NPY, VIP, NT, 5-HT, GAL, LEU-ENK and CGRP which may modulate lacrimal fluid and protein secretion.     

Intrapulpal temperature during preparation with the Er:YAG laser compared to the conventional burr: an in vitro study

A total of 149 elderly men and women with pruritic skin problems were selected for study at the dermatological clinic in the Department of Medicine, Rajavithi General Hospital, Bangkok, Thailand, from 26 November 1996 to 10 January 1997. There were 62 men (41.6%) and 87 women (58.4%). The average age was seventy years. Among these elderly patients, pruritic skin disease was the most common problem, found in about 41%. Xerosis (senile pruritus) was the most common problem at 38.9%. Other pruritic skin diseases found were inflammatory eczema (22.8%), lichen simplex chronicus (12.1%), skin infections (11.4%), psoriasis vulgaris (6.7%), urticaria (4.7%), drug rash (2%), insect bite (0.7%), and anogenital pruritus (0.7%). Xerosis usually occurred with increased bathing frequency and use of strong soaps and detergents. The causes of inflammatory eczema were seborrheic dermatitis, allergic contact dermatitis, dyshidrosis, and stasis dermatitis. Statistical analysis of xerosis and inflammatory eczema by gender showed no difference, but there was more inflammatory eczema among females.     

Nerve growth factor in normal and psoriatic skin equivalent models

Our objective was to determine the pattern and time course of nerve growth factor expression in an established skin equivalent model that we have used in the past to study wound healing and psoriasis phenotypes. Skin equivalents were constructed in triplicate using normal neonatal foreskin keratinocytes plated on collagen gels containing fibroblast lines. These lines were derived from five specimens of psoriatic lesions, three specimens of normal skin from patients with psoriasis, and three specimens of eyelid skin from normal donors. Immunohistochemistry and a monoclonal nerve growth factor-b antibody were used to determine the pattern of protein staining over 2 weeks. We looked at the wound healing phenotype using the skin equivalent model for 7-14 days. When keratinocytes invaginate into the dermis of skin equivalents (beginning at around 7 days of growth), dark staining of nerve growth factor was seen under the basal membrane zone, suggesting that nerve growth factor serves in the development of the basal membrane zone and the epidermis, and may influence the migration of nerves through the basal membrane zone into the regenerated skin.     

Do children with repaired low anorectal malformations have normal bowel function?

To determine the association of Epstein-Barr virus (EBV) with primary cutaneous amyloidosis (PCA), a retrospective study was conducted on skin tissue from 27 Chinese patients with lichen amyloidosus and macular amyloidosis. In situ hybridization with oligonucleotide probes was used to detect the expression of EBV-encoded RNAs (EBERs). Eleven of 27 cases (40.7%) were found to contain the EBV genome. No EBV genome was detected in the skin of the control groups, including three cases of secondary cutaneous amyloidosis, two cases of primary systemic amyloidosis, and four cases of lichen simplex chronicus. Our study showed no correlation between the presence of EBV in PCA patients and the patients' age, sex, clinical type or severity of the skin lesions. Although our results suggest that EBV may be associated with some cases of PCA, the true aetiological role of EBV in PCA remains unknown.     

Cardiac extension of intravenous leiomyomatosis with successful resection

The density and fine structure of the peripheral nerve system in various skin lesions of 64 patients with atopic dermatitis (AD) was quantitatively analyzed by immunohistochemical staining with antibodies directed against protein gene product (PGP) and substance P (SP). The density of PGP-positive peripheral nerves was 2.5 x 10(3) microns2/delta s (delta s = 0.24 mm2 selected area) in early acute lesions, 3.8 x 10(3) microns2/delta s in subacute lesions, 4.9 x 10(3) microns2/delta s in lichenified lesions and 7.1 x 10(3) microns2/delta s in prurigo lesions of AD. The density of nerve fibers in subacute, lichenified and prurigo lesions was significantly higher than in uninvolved skin of AD patients (2.0 x 10(3) microns2/delta s). Electron microscopically, bulging of axons with many mitochondria and a loss of their surrounding sheath of Schwann cells suggests that the free nerve endings in skin lesions of AD are in an active state of excitation. Many pinocytotic vesicles in the periphery of basal keratinocytes facing nerve endings which contained many neurovesicles suggests reciprocal effects between keratinocytes and nerve endings. The number of SP-positive nerve fibers in AD lesions was far less than one-tenth of the number of PGP-positive nerve fibers.     

Suicide with psychotropic drugs in Switzerland

Factor XIIIa+ "dendrocytes", normal residents of the submucosa and dermis, are a morphologically and phenotypically distinctive subset of the monocyte-macrophage system. Because these cells are believed to participate in the regulation of immune responses, we postulated that they may play a role in the pathogenesis of lichen planus, a condition of immune dysregulation. Tissue sections of oral lichen planus were evaluated immunohistochemically for evidence of differences in dendrocyte populations in lesional and non-lesional areas from the same patient. In addition to factor XIIIa, sections were stained for antigens (CD68, S-100 protein, CD36) that may be expressed by other cells that occasionally exhibit dendritic profiles. CD18 (found on leukocytes and dendrocytes) and its ligand ICAM-1 (intercellular adhesion molecule) were also identified in sections to determine if these antigens are operative in lichen planus. Results showed that XIIIa+ dendrocytes were significantly increased in number (and size) in lichen planus. The mean number of dendrocytes in connective tissue subjacent to basement membrane (0.064 mm2) was 27 in lichen planus as compared to 10 in adjacent unaffected tissue. Similar increases were also evident in connective tissue deep to this zone (mean of 20 dendrocytes vs. mean of 8). CD68+ macrophages were also abundant in the lichen planus infiltrate, and S-100+ connective tissue cells were frequently seen. CD36+ dendritic cells were seen in relatively small numbers in the same sites where dendrocytes were found. ICAM-1+ connective tissue dendritic cells of undetermined lineage were also evident in the diseased areas.(ABSTRACT TRUNCATED AT 250 WORDS)     

Successful ultraviolet B treatment of psoriasis is accompanied by a reversal of keratinocyte pathology and by selective depletion of intraepidermal T cells

Skin irradiation with ultraviolet B (UVB) is a common and often durable treatment for psoriasis and other inflammatory skin disorders. We studied the effects of UVB on keratinocytes and leukocytes in psoriatic tissue and in culture. In nine patients treated repetitively, most of the cellular and molecular changes that typify the psoriatic epidermis reverted to normal. Keratinocyte hyperplasia, assessed by expression of the Ki-67 cell cycle antigen, decreased by 70%, and residual cell proliferation was appropriately confined to the basal layer. Epidermal thickening was reduced by 60%, and a granular layer reformed. Expression of keratin 16, as well as suprabasal integrin alpha 3 and insulin-like growth factor-1 receptors, was eliminated, whereas filagrin increased markedly. UVB also depleted > 90% of the CD3+, CD8+, and CD25+ T cells from the psoriatic epidermis, whereas dermal T cells were only minimally depressed. The latter finding parallels the known inability of these doses of UVB to penetrate the dermis. In tissue culture, UVB was antiproliferative and cytotoxic toward T cells and keratinocytes, but the T cells were 10-fold more sensitive. Furthermore, low doses of UVB induced apoptosis in lymphocytes but not keratinocytes, as detected by the TUNEL (TdT-mediated dUTP-biotin nick end labeling) technique. The selective effects of UVB on intraepidermal T cells in situ and in culture support the hypothesis that epidermal alterations in psoriasis can be normalized by a depletion of activated intraepidermal T cells.     

Simulated postaggression metabolism in healthy subjects: metabolic changes and insulin resistance

BACKGROUND: Psoriasis vulgaris can be effectively treated with trimethylpsoralen (TMP) bath PUVA therapy (psoralen plus UVA), but no data exist on the extent to which psoriatic pathology is affected by this treatment, or on its cellular mechanism of action. OBSERVATIONS: Eleven patients with recalcitrant psoriasis vulgaris were treated with TMP bath PUVA therapy and observed through clinical and histological measures. Clinical resolution of psoriasis was achieved in 10 of 11 patients. Histopathological resolution of epidermal hyperplasia (marked by keratin 16 expression) was achieved in 90% of individuals treated with TMP bath PUVA. Epidermal acanthosis was reduced by 40% at 2 weeks and 66% by the end of treatment. Epidermal improvement correlated best with reduction in intraepidermal T lymphocytes, which were reduced by 76% at 2 weeks of treatment and 93% at the end of treatment. Furthermore following TMP bath PUVA therapy, the numbers of epidermal CD1a+ Langerhans cells were markedly reduced, and CD86+ cells were eliminated. Through in vitro assays, TMP was found to be about 10,000-fold more active as a lymphotoxic agent compared with 8-methoxypsoralen (8-MOP). Additionally, at physiologic concentrations, lymphocytes were killed more readily by TMP PUVA (TMP plus UVA) than were keratinocytes. CONCLUSIONS: Treatment with TMP bath PUVA was effective in treating moderate to severe psoriasis, even in darker pigmented individuals. It is likely that this treatment ameliorates psoriasis through direct effects on activated leukocytes in lesional skin.     

Renal artery dissection causing renal infarction in otherwise healthy men

Considerable evidence indicates that the microvascular changes observed in psoriasis are a result of angiogenesis. Vascular proliferation is driven by the local production of molecules which have angiogenic activity. Platelet-derived endothelial cell growth factor/thymidine phosphorylase (PDECGF/TP) is a potent angiogenic factor active in in vivo angiogenesis assays and overexpressed in several tumour types. We have demonstrated by ribonuclease protection analysis a consistently high degree of PDECGF/TP mRNA production in lesional psoriatic skin, while immunohistochemical studies revealed strong PDECGF/TP immunoreactivity in lesional epidermis, with nuclear staining present in basal keratinocytes and cytoplasmic immunoreactivity in suprabasal layers. Non-lesional skin showed minimal PDECGF/TP mRNA production and weak epidermal immunostaining. These results indicate a potential role for PDECGF/TP in the pathophysiology of psoriasis, and reveal a target for antiangiogenesis therapy in the treatment of this disease.