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Biomedical subjects

A V Powles

Publications and source records attributed to A V Powles.

At least 19 recordsLinked to original sources
PubMed1999

Unusual giant comedo naevus.

Comedo naevi are usually well circumscribed, and although extensive cases have been reported individual lesions crossing the midline are rare. Associated neurological, skeletal and ophthalmological abnormalities are also recognized. thus, the patient now reported is unusual in that she had an extensive systematized comedo naevus with crossing of the midline but no associated abnormalities. Topical tretinoin was helpful in improving the texture and appearance of the comedones, and various larger lesions responded to curettage.

Adult↗
PubMed1998

Renal function after 10 years' treatment with cyclosporin for psoriasis.

Renal function was assessed by measuring serum creatinine and glomerular filtration rate (GFR) in two groups of patients with chronic plaque psoriasis who had been treated with cyclosporin A (CyA), average dose 2.8 mg/kg per day (range 1-5 mg/kg per day). Group I was our original cohort of nine patients, seven of whom had received CyA for an average period of 10 years (range 9.5-11 years). These seven patients showed a persistent increase in serum creatinine > 30% from baseline measurement and four of the seven had persistent increases > 50%. The GFR, which was first measured after 2.5 years of treatment, showed at 10 years a decrease of > 30% in two patients and of > 50% in one patient. Three of the seven showed stable renal function while two had repeat renal biopsy because of deteriorating renal function and histology showed further evidence of CyA nephrotoxicity compared with that after 5 years' treatment. Two of the nine patients in group I had discontinued CyA 5 years previously after 5 years of treatment because of CyA nephrotoxicity on renal biopsy and impaired renal function. This impairment of renal function showed improvement during the 5 years of follow-up, implying reversibility of CyA nephrotoxicity. The second group of 20 patients had received CyA for an average duration of 6 years (range 5-8 years). Nine of the 20 patients showed persistent increases in serum creatinine of > 30% from baseline and five showed persistent increases of > 50%. The GFR showed a persistent decrease of > 30% in seven patients and of > 50% in two patients. This study has shown that nephrotoxicity is associated with long-term treatment with CyA. However, there is patient variation as to when nephrotoxicity commences and its speed of progression. On discontinuing CyA the impairment of renal function improves with time. Providing renal function is monitored with GFR and renal biopsy in addition to serum creatinine then long-term (5-10 years) CyA treatment can be justified in severe psoriasis not responsive to other treatments.

Adult↗
PubMed1996

Cytokine expression in psoriatic skin lesions during PUVA therapy.

To determine whether an improvement in skin lesions as a result of PUVA therapy may be correlated with changes in cytokine patterns, RT-PCR amplification was used to compare the levels of IL-2, IL-6, IL-8, IL-10, TNF-alpha and IFN-gamma cytokine mRNA expression in serial biopsies from three chronic plaque psoriatic patients. In each case, 3-mm punch biopsies were taken from lesional skin before and during 2-28 days of treatment with PUVA. Total mRNA was extracted from each biopsy, cDNA synthesized, and then amplified by 35 cycles of PCR using cytokine-specific primers. The specificity of the PCR products was confirmed by the Southern blot technique. Substantial levels of specific mRNA for each of the cytokines studied was present in the lesions prior to treatment. In two of the three patients who responded well to PUVA, a reduction in all the cytokines including IL-10 was observed compared with baseline levels. In contrast, PUVA proved to be ineffective in clearing the psoriasis of the third patient whose skin lesions worsened during the course of treatment. This was accompanied by an increase in IFN-gamma but not of the other cytokines investigated, above the pretreatment level. This study showed an association between PUVA-induced resolution and decreases in the levels of various cytokines highly expressed in psoriatic lesions.

Adult↗
PubMed1995

A comparison of the stimulatory effects of cytokines on normal and psoriatic keratinocytes in vitro.

Keratinocytes from normal and psoriatic skin were tested for their in vitro proliferative response to a range of concentrations of rIL-6, rTGF alpha, rIL-8 and rGM-CSF using a serum-free culture system. With one exception, all normal cultures (11/12) were stimulated by 1000 ng/ml IL-6 (P < 0.001). Six out of ten psoriatic keratinocyte cultures were also stimulated at this concentration, but this just failed to reach significance (P = 0.05). As a group, the response by psoriatic keratinocytes to IL-6 was significantly less than that of normal keratinocytes (P = 0.02). TGF alpha at 1 ng/ml induced proliferation in approximately 60% of both normal (8/12, P < 0.05) and psoriatic (6/10, P < 0.01) keratinocyte cultures; there was no significant difference between the responses of the two groups to this cytokine. In addition, small numbers of both normal and psoriatic cultures responded to TGF alpha over a concentration range of 0.1 to 100 ng/ml. Approximately half of the normal and psoriatic cultures were stimulated by 10-1000 ng/ml IL-8. However, the effect was not significant for the group at any of the concentrations tested. GM-CSF had minimal to no effect on most of the normal and psoriatic cultures tested. This study showed that psoriatic keratinocytes are equally responsive to the stimulatory effects of TGF alpha and IL-8, but are less susceptible to IL-6 compared to keratinocytes from normal skin. These findings are consistent with a role for these cytokines in the maintenance of a hyperproliferative epidermis in psoriasis.

Adult↗
PubMed1994

Decreased T cell reactivity to trypsinized group A, type M22 streptococci in psoriasis.

The proliferative responses of peripheral blood mononuclear cells from patients with guttate and chronic plaque psoriasis to streptococcal M protein were investigated using whole and trypsinized group A M22-positive streptococci. Peripheral blood mononuclear cell responses to whole type M22 group A streptococci were significantly increased in guttate, but not chronic plaque, psoriasis patients compared to 17 non-psoriatic controls (p < 0.05; n = 17). A significant reduction of this response was observed in both guttate (p < 0.001; n = 17) and chronic plaque (p < 0.01; n = 27) psoriatic patients, but not in the control group, after repeated trypsinization to remove M protein from the streptococci. Furthermore, the difference between the peripheral blood mononuclear cell response to untrypsinized and trypsinized streptococci was significantly greater in the guttate patients than in the controls (p < 0.02). This preliminary study has shown an increased reactivity of T lymphocytes with specificity for trypsin-sensitive protein expressed by type M22 streptococci in the peripheral blood of patients with psoriasis.

Adolescent↗
PubMed1993

Restricted T-cell receptor V beta gene usage in the skin of patients with guttate and chronic plaque psoriasis.

A strong association between acute guttate psoriasis and group A, beta-haemolytic streptococcal infections is well established. Furthermore, streptococcal M proteins and toxins have been shown to act as superantigens, stimulating subpopulations of T lymphocytes expressing particular V beta families. We have therefore studied the possible role of streptococcal superantigens in psoriasis by staining peripheral T lymphocytes and skin sections from patients with guttate or chronic plaque psoriasis for the expression of nine TCR V beta families, using a range of monoclonal antibodies. A marked over-representation of V beta 2+ T lymphocytes was observed in the dermis and epidermis of patients in both groups, when compared with T lymphocytes in their peripheral blood. A less marked dermal increase in V beta 5.1+ T lymphocytes was also observed in these patients. These findings are consistent with the involvement of a superantigen, possibly streptococcal, in the pathogenesis of psoriasis.

Acute Disease↗
PubMed1993

Renal function and biopsy findings after 5 years' treatment with low-dose cyclosporin for psoriasis.

Renal biopsies were performed in eight patients with chronic plaque psoriasis who had been treated with low-dose cyclosporin (CyA) (range 1-6 mg/kg/day; average dose 3.3 mg/kg/day) for an average period of 5 years. In six of the eight patients biopsies showed features consistent with CyA nephrotoxicity. Tubular atrophy and arteriolar hyalinosis were present in all six, four had an increase in interstitium, and two showed an increased incidence of glomerular obsolescence. Two of the patients showed all of these features, two patients had three features, and the remaining patients had two features. Renal function was assessed by glomerular filtration rate (GFR) and serum creatinine. Both a fall in the GFR and a rise in the serum creatinine correlated with the severity of the features of CyA nephrotoxicity seen on biopsy. However, the best predictor of the biopsy findings was a failure of renal function to show significant improvement when CyA was discontinued for a month. CyA has been discontinued in two of the eight patients who had the most severe features of CyA nephrotoxicity on renal biopsy. In both patients there has been improvement of renal function after 1 year of follow-up.

Adult↗
PubMed1993

Normal response to tumor necrosis factor-alpha and transforming growth factor-beta by keratinocytes in psoriasis.

Normal and chronic plaque psoriatic keratinocyte cultures were tested for their in vitro response to 2-200 ng/ml TNF-alpha and 0.1-10 ng/ml TGF-beta in a serum-free culture system. All normal and lesional psoriatic epidermal cell cultures showed a dose- and time-dependent inhibition of growth in response to TNF-alpha and TGF-beta. Inhibition in individual cultures was first seen at a concentration of 2 ng/ml for TNF-alpha and 0.1 ng/ml for TGF-beta at day 2, but became significant at 20 ng/ml and 1 ng/ml for TNF-alpha and TGF-beta respectively at days 2-6. This effect was statistically significant at days 3-4 for the group of normal (TNF-alpha and TGF-beta, n = 10, p < 0.01) and psoriatic cultures (TNF-alpha, n = 9, p < 0.01; TGF-beta, n = 7, p < 0.05). Epidermal cells from normal and psoriatic skin were inhibited to the same extent at the same optimal concentrations by each cytokine. Inhibition was abolished by the addition of specific antibody to each cytokine, whilst antibody to a different cytokine had no effect. Nuclear and/or nuclear membrane staining was observed with antibody to the p55 TNF receptor both in cultured keratinocytes and in the upper epidermal layers of both normal and psoriatic skin. In contrast, plasma membrane and cytoplasmic expression of the p55 TNF receptor was observed on macrophages and lymphocytes infiltrating psoriatic dermis. This study has shown that the growth of normal and psoriatic keratinocytes was equally inhibited by TNF-alpha and TGF-beta in vitro.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Is epidermal cell proliferation in psoriatic skin grafts on nude mice driven by T-cell derived cytokines?

Plasminogen activity and DNA synthesis by epidermal cells have been reported to be doubled in psoriatic skin grafts compared with grafts of normal skin 6 weeks after transplantation to nude mice. In our study human lymphocytes disappeared from such grafts within 48 h whilst some DR-positive human dendritic cells were retained in the grafts for up to 4 weeks. However, the grafts were infiltrated by Thy 1.2+ mouse lymphocytes within 6 days and this infiltration persisted at a moderate level throughout the observation period. It consisted of perivascular aggregates, scattered dermal and papillary T cells, and some mouse T cells were also found in the epidermal compartment. Grafts of psoriatic and non-psoriatic control skin were infiltrated to a similar extent, suggesting a low-grade rejection response against the human xenografts. These findings raise the possibility that psoriatic keratinocytes are responding abnormally to inflammatory cytokines released by mouse lymphocytes reacting against the skin grafts.

Animals↗
PubMed1991

Altered cell-mediated immunity to group A haemolytic streptococcal antigens in chronic plaque psoriasis.

The proliferative lymphocyte response to sonicated group A, beta-haemolytic streptococci (Strep-A) was measured by thymidine incorporation in 78 patients with psoriasis (guttate, chronic plaque or both). Lymphocytes from 72 of these patients were also cultured with streptokinase/streptodornase (SK/SD), and 20 of the patients with chronic plaque psoriasis were further tested with PPD, Candida albicans and sonicated Streptococcus mutans, a bacterial type not associated clinically with psoriasis. The median stimulation index (SI) of the psoriasis group to the Strep-A preparation was significantly higher than that of a group of 27 non-psoriatic individuals (P less than 0.05). Within this group, only the patients with chronic plaque psoriasis (n = 42) showed a significantly increased proliferative response compared to the non-psoriatic controls (median SI = 123.8 and 31.9, respectively, P less than 0.01). Although the lymphocyte response of the chronic plaque group to SK/SD was also markedly higher than that of the control group, this difference did not reach statistical significance. In addition, these patients did not show significantly increased responses to any of the other antigens tested, including S. mutans. No correlation was observed between the degree of proliferation to Strep-A and disease extent or activity. Similarly, ASO titres, which were raised in 11 out of 23 guttate and three out of nine chronic plaque psoriasis patients tested, did not correlate with the proliferative responses observed.

Adolescent↗
PubMed1991

Soluble IL-2 receptor and CD25 cells in psoriasis: effects of cyclosporin A and PUVA therapy.

A study was conducted to quantify soluble IL-2 receptor (sIL-2R) levels in sera of 57 chronic plaque psoriasis patients and correlate these measurements with disease activity and the number of IL-2R-positive (CD25+) lymphocytes in lesional biopsies of 11 cyclosporin A (CsA) and 13 psoralen plus ultraviolet radiation (PUVA) treated patients. Levels of sIL-2R showed a strong correlation with the psoriasis area and severity index (PASI). CsA and PUVA significantly reduced the PASI and sIL-2R levels to a similar degree after 4 weeks of treatment. Although the majority of CsA-treated patients who were biopsied showed reductions in lesional CD25+ cells, these did not reach statistical significance; in five patients biopsied who had PUVA treatment, no consistent effect on the numbers of CD25+ cells was observed. A significant correlation was found between CD25+ cells in lesional biopsies and the PASI score.

Adult↗
PubMed1990

Four years of experience with cyclosporin A for psoriasis.

Forty-four patients with severe psoriasis have been treated with cyclosporin A (CyA) for 2-50 months (mean 17 months). During the study, 31 (70%) of these patients achieved a greater than 70% reduction in PASI score, 39 (88%) achieved a greater than 60% reduction and 42 (95%) a greater than 50% reduction. The mean initial dose of CyA was 3 mg/kg/day and the mean dose was 3.3 mg/kg/day throughout the study. Twenty-five (57%) patients were maintained on less than or equal to 3 mg and six (14%) required greater than 5 mg/kg/day for limited periods to obtain significant improvement. In three of these patients, this was achieved with 6 mg/kg/day but, of the remainder, one required 7 mg and two required 10 mg/kg/day. Of the 44 patients, 32 (73%) are still taking CyA. Patients were discontinued because of: side-effects directly attributable to treatment (n = 4); remission of psoriasis (n = 4); death (n = I); defaulting (n = I); infrequent attendance (n = I); high doses of NSAID were necessary for arthritis (n = I). Before starting CyA, 39 patients were normotensive; 21 (54%) developed mild hypertension. In 28 patients where the GFRs were estimated before and during treatment, there was a 16% reduction (P less than 0.0001) during a mean period of 8 months. Two patients developed malignancies. The incidence of hypertension and percentage decrease in GFR were strongly correlated with the dose required to control the psoriasis.

Adult↗
PubMed1990

Renal function after long-term low-dose cyclosporin for psoriasis.

Two groups of patients receiving cyclosporin A (CyA) for psoriasis had their renal function assessed by measurement of glomerular filtration rate (GFR) and effective renal plasma flow (ERPF). The first group comprised 13 patients who had taken low dose (average 3 mg/kg per day) CyA for an average period of 2.5 years. Seven of the 13 had a normal GFR of 108 (77-121) ml/min (median; range). In the other six patients the GFR was low at 63 (50-77) ml/min and CyA was discontinued for periods ranging from 3 to 17 weeks. The GFR rose in all six patients, to 79 (60-91) ml/min; this change was significant (P less than 0.05). The six patients restarted CyA because their psoriasis recurred and after a mean interval of 15 weeks the GFR had fallen in all six to 63 (46-80) ml/min (P less than 0.05) and the ERPF decreased from 339 (231-414) ml/min to 244 (177-321) ml/min (P less than 0.05). In the second group of 11 patients measurements were made prior to starting CyA and after taking CyA for a mean of 9 weeks. The GFR fell in eight out of 11 subjects, the GFR for the 11 patients being 117 (72-128) ml/min before taking CyA and 97 (51-122) ml/min after CyA (P less than 0.02). The ERPF was measured in nine of the 11 patients and fell in seven of the nine. The ERPF for the nine patients before CyA was 490 (296-642) ml/min and for the 11 patients after CyA was 410 (195-543) ml/min (P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

Intradermal antigen tests in psoriasis.

To assess whether elicitation of delayed hypersensitivity may be superior to trauma in inducing the Koebner reaction in psoriasis, 12 affected patients and 9 control subjects were tested with 0.1 ml intradermal injections of streptokinase/streptodornase (20 mu/5 mu per 0.1 ml), PPD (1 in 1000) and saline control solutions in a double-blind study; Koebner status was also established in the psoriatic patients. Injected sites were examined at 48 h and 7, 14, 21 and 28 days for local development of psoriasis, erythema and induration (diameter). One patient was Koebner-positive and developed psoriasis at all three injection sites. The other, Koebner-negative psoriatic subjects did not develop psoriasis locally. However, compared with non-psoriatic controls they showed a marked delay in resolution of the delayed hypersensitivity reaction to the PPD antigen and a similar but less marked phenomenon was observed for streptokinase/streptodornase. These findings indicate that intradermal antigen, of the nature and amount used in this study, is no more effective in inducing the Koebner phenomenon than injury alone. However, the ability of psoriasis patients to switch off cell-mediated immune reaction appears to be impaired.

Adult↗