摘要:

rasmutations have been reported as an early event in some human malignancies and in the mouse skin model of multistep carcinogenesis; early studies in human non‐melanoma skin cancers have reported variable rates ofrasmutations. A recent study, however, has reported a high frequency of activating mutations of the Harvey‐rasproto‐oncogene in non‐melanoma skin cancers, and the site specificity of the mutation at the second position of codon 12 prompted us to re‐examine the importance of Ha‐rascodon 12 mutations as an early event in the development of these tumours, using a combination of PCR and restriction fragment polymorphism of codon 12 of the Ha‐rasgene. Dilution experiments confirmed that the method was sensitive and capable of detecting mutations at this codon when only 4% of the total alleles are mutated. We were surprised to find no mutations in the 40 basal cell carcinomas. 12 squamous cell carcinomas and 12 cases of Bowen's disease studied. We conclude that Ha‐rascodon 12 mutations are rare events in human non‐melanoma skin cancer in the U.K. The marked differences in the frequency of codon 12 Ha‐rasmutations in published studies may relate to either technical artefacts, or differences in the molecular epidemiology between areas of low an

ISSN:0007-0963    

DOI:10.1111/j.1365-2133.1993.tb15137.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

Fifty‐one white Caucasian patients from the west of Scotland, with stage I primary malignant melanoma arising on the plantar surface were studied. Subungual lesions were excluded from the study. Clinical and pathological features were related to survival, and compared with a group of 239 cases of clinical stage 1 melanoma of the lower limb, excluding the foot, collected in the same geographical area over the same period of time (1979–84). The average age of patients with plantar melanoma was 67 years and was significantly older than those with leg melanomas, in whom the mean age was 53 years.Twenty patients with plantar lesions had superficial spreading melanomas, 27 had acral lentiginous melanomas, and four had nodular lesions. The female: male ratio was 3:2 which was significantly different from the 7:1 female:male ratio for leg lesions. Plantar melanomas were more commonly ulcerated (57%) than were melanomas on the leg (29%) [P<0.001]. There was no significant difference between the mean thickness of melanomas on the plantar surface and those on the leg. Nine (17%) of the patients with plantar melanomas gave a clinical history of pre‐existing naevus and in 27% there was pathological evidence of a pre‐existing naevus.Disease‐free survival at 5 years for the population with plantar melanomas was 82, 51 and 0%, respectively, for melanomas 0–1.49,1.5–3.49 and over 3–5 mm in thickness. This compares with 95, 71 and 46%, respectively, for leg lesions. In each thickness category patients with leg melanomas have a significantly better survival. In analysis of multiple prognostic features using a stepwise proportional hazards model, tumour thickness was the major prognostic indicator, and thickness alone provided all prognostic information on recurrence of stage I plantar melanoma. For survival, however, ulceration complemented tumour thickness. These were the only two significant factors for modelling time of death

ISSN:0007-0963    

DOI:10.1111/j.1365-2133.1993.tb15138.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

We have studied the prevalence of hepatitis C virus antibodies (anti‐HCV) in 13 patients suffering from sporadic porphyria cutanea tarda. The sera were tested by Abbott second‐generation enzyme immunoassay; seropositivity was confirmed by Ortho second‐generation recombinant immunoblot assay. Ten cases (76.1%) were anti‐HCV positive; one patient was also seropositive for HIV. This preliminary study suggests that HCV could be a frequent triggering factor for sporadic porphyria cutane

ISSN:0007-0963    

DOI:10.1111/j.1365-2133.1993.tb15139.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

Soluble interIeukin‐2 receptor (sIL‐2R) serum levels were evaluated in Sézary syndrome (SS). mycosis fungoides. non‐epidermotropic T‐cell lymphomas. inflammatory skin diseases (eczema, psoriasis and lichen planus) and benign erythroderma. All groups displayed mean values significantly higher than controls, and values in SS were also significantly higher than those in the other diseases investigated. Follow‐up of 17 SS patients showed that serum SIL‐2R correlated with the clinical course of the disease and with other haematologicai parameters (ahsolute numher of circulating Sézary cells, lactic dehydrogenase). Culture experiments demonstrated that, in contrast with other haematoiogical disorders, highly enriched resting Sézary cells were unahle to release sII‐2R. and failed to release normal amounts even after mitogen stimulation. Nevertheless, the leukaemic burden, together with the activation and consequent CD25 expression of leukaemic lymphocytes infiltrating the skin, may justify the hypothesis of a neoplastie sIL‐2R source. To further support this hypothesis, the highest sIT.‐2R values were found in patients with advanced disease, in which normal reactive lymphocytes were

ISSN:0007-0963    

DOI:10.1111/j.1365-2133.1993.tb15140.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

This study assesses the variability of two non‐invasive methods of measuring stratum corneum barrier functionin vivo. Transepidermal water loss (TEWL), and the vascular response to hexyl nicotinate (HN) penetration as determined by laser‐Doppler flowmetry, were measured in a group of 21 healthy volunteers. Each time profile of the vascular response to HN penetration was analysed using the following parameters: the baseline cutaneous blood flow, the lag‐time between application and initial response (to), the time between application and maximum response (tmax.), the maximum response, and the slope of the curve. TEWL measured on the left volar forearm showed a normal range of 3.9–7.6 g/m2h and a small inter‐individual variability [coefficient of variation (CV) 19–4%]. TEWL values at three other forearm sites did not show differences of clinical importance compared with the left volar forearm. The parameters of the vascular response to HN penetration spanned a wider normal range than the TEWL values (CV between 33 and 52%). Repeat measurements after a 1–2 month interval showed highly reproducible individual TEWL values. The mean difference between first and second measurements was only 0.03 g/m2h: the relative difference 0.6%. The intra‐individual reproducibility of toand tmaxfor HN penetration was also high (relative differences of 2.8 and 3.1%, respectively). The other vascular response parameters were less reproducible (relative differences of 6.9–18.6%). We conclude that TEWL and selected parameters of HN penetration, as non‐invasive tests of the stratum corneum barrier function, yield reproducible results and are hence useful for investigations assessing the skin barrier function i

ISSN:0007-0963    

DOI:10.1111/j.1365-2133.1993.tb15141.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

Post‐occlusive reactive hyperaemia is the temporary increase of blood flow in a tissue following transient vascular obstruction, and has recently heen proposed as anin vivomethod for ranking topical corticosteroid potency. We investigatedin vivovascular reactions before and during postocclusive hyperaemia using laser‐Doppler flowmetry and reflectance spectroscopy (RS). RS enables resolution ofin vivoerythema into deoxygenated (venous) [DOH] and oxygenated (arterial) haemoglobin (OH) components (expressed in arbitrary units. All). Using a randomized 24‐h occlusive exposure in 10 healthy volunteers the effects of a corticosteroid (betamethasone‐1 7‐valerate). a non‐steroidal anti‐inflammatory drug (NSAID) [indomethacin], an antihistamine (diphenydramine), or vehicle, were studied before and during post‐occlusive hyperaemia.The 24‐h vehicle exposure decreased total haemoglobin (composed of a small increase in OH [P<0.001] and a greater decrease in DOH[P<0.005]. [OH.0.23±0.18 AU: DOH. 0.28±0.12 AU]). The blood flow increased 7.1% to 28±8 AU (P

ISSN:0007-0963    

DOI:10.1111/j.1365-2133.1993.tb15142.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

Thirty‐two drugs, including some in use for a variety of clinical disorders, were examined for their ability to inhibit calmodulin activityin vitro. From these. 10 drugs were selected for their inhibition of calmodulin activity and examined for their ability to inhibit proliferation of rapidly dividing human keratinocytes. A significant correlation between antiproliferative activity and calmodulin antagonist potency was found. Of these drugs there were several, including miconazole. dequalininm chloride, bromocriptine and tamoxifen, whose use is well established and well documented. The potential use of these drugs (and others identified in this way) as antipsoriatic agents is discusse

ISSN:0007-0963    

DOI:10.1111/j.1365-2133.1993.tb15143.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

Guttate psoriasis may be precipitated by acute streptococcal infection, usually of the upper respiratory tract. We have studied the immune response to streptococci in 26 patients presenting with a first or recurrent episode of acute guttate psoriasis (AGP), using immunoblotting. Eighteen of 26 patients studied had a demonstrable response to a wide range of streptococcal antigens using this approach, compared with 14 of 26 patients who demonstrated a response using more conventional anti‐streptococcal antibody tests. Patients with AGP had a significantly higher antibody detection score using immunoblotting than did control subjects (P<0.005). We conclude that immunoblotting is a useful technique in studying this condition and may be of benefit in exploring the immunopathogene‐sis of

ISSN:0007-0963    

DOI:10.1111/j.1365-2133.1993.tb15144.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

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 liltration rate (CFR) 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 foliow

ISSN:0007-0963    

DOI:10.1111/j.1365-2133.1993.tb15145.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

In the U.K., PUVA treatment for psoriasis is usually given three times weekly, with the starting dose of UVA chosen according to the skin type of the patient. Observations on the time‐course and dose response characteristics of PUVA erythema suggest that larger doses of UVA could be used safely, provided that the frequency of PUVA treatment is reduced. We have examined this by treating 100 patients with chronic plaque‐type psoriasis with a PUVA protocol in which treatment using oral 8‐methoxypsoralen was given twice weekly, with the starting dose of UVA based on each patient's minimal phototoxic dose, and with weekly UVA dose increments calculated as a percentage of the dose used in the previous treatment.Clearance of psoriasis was achieved in 92% of patients. The median number of treatments required for clearance was 12, and the median cumulative UVA dose for clearance was 52 J/cm2Although erythema occurred at some stage during the course of PUVA in 48% of patients, in only 16% of cases was the erythema of sufficient intensity to result in more than one treatment being missed.These results compare favourably with previous studies in which treatment was given three or four times weekly. Thus, twice weekly PUVA treatment for psoriasis is at least as effective as treatment given more frequently, and may be safer, as lower cumulative UVA doses are required for clearance. It also allows for more efficient operation of a PUVA unit and is more convenient for pat

ISSN:0007-0963    

DOI:10.1111/j.1365-2133.1993.tb15146.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY