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W J Cunliffe

Publications and source records attributed to W J Cunliffe.

At least 19 recordsLinked to original sources
PubMed2003

Antibiotic-resistant acne: lessons from Europe.

BACKGROUND: Propionibacterium acnes and P. granulosum are widely regarded as the aetiological agents of inflammatory acne. Their proliferation and metabolism are controlled using lengthy courses of oral and/or topical antibiotics. Despite numerous reports of skin colonization by antibiotic-resistant propionibacteria among acne patients, accurate prevalence data are available only for the U.K. OBJECTIVES: To determine the prevalence of skin colonization by antibiotic-resistant propionibacteria among acne patients and their contacts from six European centres. METHODS: Skin swabs were collected from 664 acne patients attending centres in the U.K., Spain, Italy, Greece, Sweden and Hungary. Phenotypes of antibiotic-resistant propionibacteria were determined by measuring the minimum inhibitory concentrations (MIC) of a panel of tetracycline and macrolide, lincosamide and streptogramin B (MLS) antibiotics. Resistance determinants were characterized by polymerase chain reaction (PCR) using primers specific for rRNA genes and erm(X), followed by nucleotide sequencing of the amplified DNA. RESULTS: Viable propionibacteria were recovered from 622 patients. A total of 515 representative antibiotic-resistant isolates and 71 susceptible isolates to act as control strains were characterized phenotypically. The prevalence of carriage of isolates resistant to at least one antibiotic was lowest in Hungary (51%) and highest in Spain (94%). Combined resistance to clindamycin and erythromycin was much more common (highest prevalence 91% in Spain) than resistance to the tetracyclines (highest prevalence 26.4% in the U.K.). No isolates resistant to tetracycline were detected in Italy, or in Hungary. Overall, there were strong correlations with prescribing patterns. Prevalence of resistant propionibacteria on the skin of untreated contacts of the patients varied from 41% in Hungary to 86% in Spain. Of the dermatologists, 25 of 39 were colonized with resistant propionibacteria, including all those who specialized in treating acne. None of 27 physicians working in other outpatient departments harboured resistant propionibacteria. CONCLUSIONS: The widespread use of topical formulations of erythromycin and clindamycin to treat acne has resulted in significant dissemination of cross-resistant strains of propionibacteria. Resistance rates to the orally administered tetracycline group of antibiotics were low, except in Sweden and the U.K. Resistant genotypes originally identified in the U.K. are distributed widely throughout Europe. Antibiotic-resistant propionibacteria should be considered transmissible between acne-prone individuals, and dermatologists should use stricter cross-infection control measures when assessing acne in the clinic.

Acne Vulgaris↗
PubMed2003

Comedogenesis: some aetiological, clinical and therapeutic strategies.

Hypercornification is an early feature of acne and usually precedes inflammation. It is associated with ductal hyperproliferation, and there are many controlling factors such as androgens, retinoids, sebum composition and cytokines. Cycling of normal follicles and of comedones may explain the natural resolution of comedones and, in the longer term, resolution of the disease itself. There is a need to tailor treatment according to comedonal type. Suboptimal therapy can often result from inappropriate assessments of comedones, especially microcomedones, sandpaper comedones, submarine comedones and macrocomedones. Macrocomedones can produce devastating acne flares, particularly if patients are inappropriately prescribed oral isotretinoin. Gentle cautery under topical local anaesthesia is a useful therapy in the treatment of such lesions. The newer retinoids and new formulations of all-trans-retinoic acid show a better benefit/risk ratio.

Acne Vulgaris↗
PubMed2002

Prevalence of antibiotic-resistant propionibacteria on the skin of acne patients: 10-year surveillance data and snapshot distribution study.

BACKGROUND: Cutaneous propionibacteria are implicated in acne pathogenesis, although their exact role in the genesis of inflammation is still poorly understood. Agents, including antibiotics, that reduce the numbers of propionibacteria on skin are therapeutic. Resistance in the target organism is a well-recognized consequence of antibiotic therapy for acne but formal prevalence and distribution data are lacking. OBJECTIVES: To monitor the prevalence of skin colonization by antibiotic-resistant propionibacteria in acne patients attending the dermatology out-patient clinic at Leeds General Infirmary over a 10-year period beginning in 1991, and to examine the distribution of resistant strains on acne-prone skin and in the nares. METHODS: Propionibacterial samples were obtained from the skin surface of the worst affected site (usually the face) of 4274 acne patients using a moistened swab. The swab was used to inoculate agar plates with and without selective antibiotics. After anaerobic incubation at 37 degrees C for 7 days, the amount of growth in the presence of each antibiotic was scored on a scale from 0 to 5+. A small number of patients (72) were selected for more detailed quantitative sampling at six different sites to examine the distribution of resistant propionibacteria on acne-prone skin and in the anterior nares. RESULTS: The proportion of patients carrying strains resistant to one or more commonly used antiacne antibiotics rose steadily from 34.5% in 1991 to a peak of 64% in 1997. The prevalence dropped to 50.5% during 1999 and then rose again to 55.5% in 2000. Resistance to erythromycin was the most common and the majority of erythromycin-resistant strains were cross-resistant to clindamycin. Resistance to tetracyclines was less common in all years and with little increase over time. The more detailed quantitative study in 72 patients showed that population densities of resistant propionibacteria varied considerably between sites and between individuals. Almost invariably, patients were colonized with resistant strains at multiple sites, including the nares. CONCLUSIONS: Skin colonization with antibiotic-resistant propionibacteria is much more common now than a decade ago. Resistant propionibacteria are widely distributed on acne-prone skin and in the nares. This suggests that they will be very difficult to eradicate using existing therapeutic regimens, especially from the nasal reservoir.

Acne Vulgaris↗
PubMed2001

Use of the monoclonal antibody DAKO-ERbeta (8D5-1) to measure oestrogen receptor beta in breast cancer cells.

BACKGROUND: Oestrogen receptor beta (ERbeta) is highly homologous with the classical ER (known now as ERalpha). The exact role of ERbeta in breast cancer and its contribution in influencing patient response to endocrine therapy remains unclear. The aim of this study was to develop and evaluate a flow cytometric method for the detection of ERbeta in breast cancer cells using the DAKO monoclonal anti-ERbeta 8D5-1 antibody. METHODS: MCF7 cells were used as a positive control and U937 as a negative control for titration of the antibody. Cell lines and tumour samples were fixed with 1% paraformaldehyde and permeabilised with 0.5% saponin prior to flow cytometric analysis. RESULTS: A ten fold difference in expression of ERbeta within the different breast cell lines studied was found. Confirmation of antibody specificity against ERbeta protein by Western blot analysis detected a single band at approximately 65kDa. ERbeta immunopositive nuclei were identified in MCF7 cells by immunohistochemistry. CONCLUSIONS: DAKO ERbeta 8D5-1 antibody is specific for ERbeta protein and does not cross react with ERalpha protein. Using this antibody, ERbeta can be detected and accurately quantified in cell lines and solid breast tumours by flow cytometry.

Antibodies, Monoclonal↗
PubMed2001

Rectal retroflexion: an essential part of lower gastrointestinal endoscopic examination.

PURPOSE: Retroflexion of the endoscope during rectal examination may increase diagnostic yield but is not routinely performed because of concerns about safety and a lack of appreciation of its importance. The purpose of this study was to examine the yield, safety, and tolerance of endoscopic rectal retroflexion. METHODS: Prospective cohorts of subjects undergoing unsedated screening flexible sigmoidoscopy were examined with and without routine retroflexion. Pain scores were recorded. RESULTS: A total of 526 subjects (mean age 60 (range, 55-66) years) underwent flexible sigmoidoscopy in the first period when the endoscope was not routinely retroflexed. Of these, 480 (mean age 60 (range, 55-66) years) were subsequently examined with routine retroflexion. Retroflexion was impossible in 17 subjects (3.5 percent) because of discomfort. In the second group, 12 subjects (2.5 percent) had polyps in the lower rectum seen only on retroflexion. Of these, eight had metaplastic and four had adenomatous polyps (3 tubular <5 mm, 1 tubulovillous 15 mm). There was no difference in mean pain scores between the groups (no retroflexion = 2.13, retroflexion = 2.18). CONCLUSION: With an adenoma pick-up rate of 8 to 12 percent for screening flexible sigmoidoscopy, retroflexion increases adenoma detection by approximately 1 percent without adverse effects and should be an integral part of flexible sigmoidoscopy.

Adenoma↗
PubMed2001

MUC1 expression in primary breast cancer: the effect of tamoxifen treatment.

This was a non-randomised single institution retrospective study. Forty-six banked frozen tumour specimens were obtained from a group of patients who had undergone 3 weeks of neoadjuvant treatment with tamoxifen between biopsy and surgery. Fifty-one comparison specimens were randomly selected from a group of concomitantly treated primary breast cancer patients who did not receive neoadjuvant tamoxifen. Specimen selection was not based on prognostic factors: hormone receptor status, patient age, or menopausal status. MUC1 expression and cell cycle distribution were assessed by flow cytometry. S-phase fraction of MUC1 positive and MUC1 negative cells were compared. A lower percentage of cells expressed MUC1 following 3-week tamoxifen treatment 18.2% versus 28.5% (p = 0.03, Mann-Whitney) and lower levels of MUC1 expression were seen following tamoxifen treatment 31,519 molecules/cell versus 39,387 (p = 0.04, Mann-Whitney). MUC1 positive cells, irrespective of treatment group, had a greater proportion of cells in S-phase of the cell cycle 27.9% versus 16.8% (p = 0.0004, Mann-Whitney) and demonstrated more cases of aneuploidy 80.65% versus 42.6% (p < 0.0001). MUC1 levels in primary tumours treated neoadjunctively with 3 weeks of tamoxifen were lower than a comparison group which did not receive tamoxifen. MUC1 should be explored further as an intermediate biomarker for assessment of treatment and prognosis.

Aged↗
PubMed2001

Expression, candidate gene, and population studies of the melanocortin 5 receptor.

In mouse the melanocortin 5 receptor is known to regulate sebaceous gland function. To clarify its role in man, we have studied melanocortin 5 receptor expression in skin, and allelic variation at the melanocortin 5 receptor locus in diverse human populations and candidate disease groups. Melanocortin 5 receptor protein and mRNA expression were studied by immunohistochemistry and reverse transcriptase polymerase chain reaction. Melanocortin 5 receptor mRNA was detected in normal skin and cultured keratinocytes but not in cultured fibroblasts or melanocytes. Immunohistochemistry revealed melanocortin 5 receptor immunoreactivity in the epithelium and appendages, including the sebaceous gland, eccrine glands, and apocrine glands, as well as low level expression in the interfollciular epidermis. In order to screen for genetic diversity in the melanocortin 5 receptor that might be useful for allelic association studies we sequenced the entire melanocortin 5 receptor coding region in a range of human populations. One nonsynonymous change (Phe209Leu) and four synonymous changes (Ala81Ala, Asp108Asp, Ser125Ser, and Thr248Thr) were identified. Similar results were found in each of the populations except for the Inuit in which only the Asp108Asp variant was seen. The apparent "global distribution" of melanocortin 5 receptor variants may indicate that they are old in evolutionary terms. Variation of melanocortin 5 receptor was examined in patients with acne (n = 21), hidradenitis supprativa (n = 4), and sebaceous gland lesions comprising sebaceous nevi, adenomas, and hyperplasia (n = 13). No additional mutations were found. In order to determine the functional status of the Phe209Leu change, increase in cAMP in response to stimulation with alpha-melanocyte-stimulating hormone was measured in HEK-293 cells transfected with either wild-type or the Phe209Leu variant. The variant melanocortin 5 receptor was shown to act in a concentration-dependent manner, which did not differ from that of wild type. We have therefore found no evidence of a causative role for melanocortin 5 receptor in sebaceous gland dysfunction, and in the absence of any association between variation at the locus and disease group, the pathophysiologic role of the melanocortin 5 receptor in man requires further study.

Acne Vulgaris↗
PubMed2001

Human beta defensin-1 and -2 expression in human pilosebaceous units: upregulation in acne vulgaris lesions.

A rich residential microflora is harboured by the distal outer root sheath of the hair follicle and the hair canal - normally without causing skin diseases. Although the basic mechanisms involved in the development of inflammation during acne vulgaris remain unclear, microbial agents might play an important role in this process. In this study we have analyzed by in situ hybridization and immunohistochemistry the expression patterns of two antimicrobial peptides, human beta defensin-1 and human beta defensin-2, in healthy human hair follicles as well as in perilesional and intralesional skin of acne vulgaris lesions such as comedones, papules, and pustules. Strong defensin-1 and defensin-2 immunoreactivity was found in all suprabasal layers of the epidermis, the distal outer root sheath of the hair follicle, and the pilosebaceous duct. Marked defensin-1 and defensin-2 immunoreactivity was also found in the sebaceous gland and in the basal layer of the central outer root sheath including the bulge region. The majority of acne biopsies displayed a marked upregulation of defensin-2 immunoreactivity in the lesional and perilesional epithelium - in particular in pustules - and a less marked upregulation of defensin-1 immunoreactivity. The upregulation of beta-defensin expression in acne vulgaris lesions compared to controls suggests that beta-defensins may be involved in the pathogenesis of acne vulgaris.

Acne Vulgaris↗
PubMed2001

Cell-mediated immunity to the mycelial phase of Malassezia spp. in patients with pityriasis versicolor and controls.

BACKGROUND: Malassezia is the aetiological agent of pityriasis versicolor. The mycelial phase of the organism predominates in lesions of pityriasis versicolor. OBJECTIVES: To evaluate the cell-mediated immune (CMI) response to the mycelial phase of Malassezia in patients with this disease, which has not previously been studied. METHODS: The CMI status of 12 patients with pityriasis versicolor and 12 age- and sex-matched controls to mycelial antigen(s) of the organism was examined. The responses to the mycelial form of three strains of the organism were assessed using lymphocyte transformation and leucocyte migration inhibition assays. RESULTS: The transformation responses of the lymphocytes from both patients and controls gave transformation indices < or = 3, although the responses of lymphocytes from patients with pityriasis versicolor to the mycelial form of Malassezia strains were generally higher than those of the controls. In the leucocyte migration inhibition assay, leucocytes from patients with pityriasis versicolor and controls responded to the mycelial antigens of three different Malassezia strains; however, there was no significant difference in leucocyte response between patients with pityriasis versicolor and controls. CONCLUSIONS: Patients with pityriasis versicolor do not therefore have a CMI deficiency to Malassezia mycelial antigens but fail to generate a protective CMI response to mycelial antigens over and above that of control individuals during active disease.

Adult↗
PubMed2001

Phenotypic and genotypic characterization of antibiotic-resistant Propionibacterium acnes isolated from acne patients attending dermatology clinics in Europe, the U.S.A., Japan and Australia.

BACKGROUND: Propionibacterium acnes is the target of antimicrobial treatments for acne vulgaris. Acquired resistance to erythromycin, clindamycin and tetracyclines has been reported in strains from diverse geographical loci, but the molecular basis of resistance, via mutations in genes encoding 23S and 16S rRNA, respectively, has so far only been elucidated for isolates from the U.K. OBJECTIVES: To determine whether similar or different resistance mechanisms occur in resistant P. acnes isolates from outside the U.K. METHODS: The phenotypes and genotypes of 73 antibiotic-resistant strains of P. acnes obtained from the skin of acne patients in the U.K., U.S.A., France, Germany, Australia and Japan were compared. Antibiotic susceptibilities were determined by minimum inhibitory concentration (MIC) measurements, and polymerase chain reaction and DNA sequencing were used to identify mutations in genes encoding rRNA. RESULTS: Most erythromycin-resistant isolates (MIC(90) > or = 512 microg mL(-1)) were cross-resistant to clindamycin but at a much lower level (MIC(90) > or = 64 microg mL(-1)). As in the U.K., resistance to erythromycin was associated with point mutations in 23S rRNA in 49 of 58 strains. An A-->G transition at Escherichia coli equivalent base 2058 was present in 24 strains. This gave a unique cross-resistance phenotype against a panel of macrolide, lincosamide and type B streptogramin antibiotics. Two further point mutations (at E. coli equivalent bases 2057 and 2059) were identified (in three and 22 isolates, respectively) and these were also associated with specific cross-resistance patterns originally identified in isolates from the U.K. However, nine of 10 erythromycin resistant-strains from Germany did not exhibit any of the three base mutations identified and, in six cases, cross-resistance patterns were atypical. Consistent with previous U.K. data, 34 of 38 tetracycline-resistant strains carried a base mutation at E. coli 16S rRNA equivalent base 1058. Tetracycline-resistant isolates displayed varying degrees of cross-resistance to doxycycline and minocycline, but isolates from the U.S.A. had higher MICs for minocycline (4--16 microg mL(-1)) than isolates from other countries and, in particular, Australia. All the P. acnes isolates resistant to one or more of the commonly used antiacne antibiotics were sensitive to penicillin, fusidic acid, chloramphenicol and the fluoroquinolone, nadifloxacin. All but one isolate (from the U.K.) were sensitive to trimethoprim. CONCLUSIONS: This study shows that 23S and 16S mutations identified in the U.K. conferring antibiotic resistance in P. acnes are distributed widely. However, resistant strains were isolated in which mutations could not be identified, suggesting that as yet uncharacterized resistance mechanisms have evolved. This is the first report of high-level resistance to minocycline and is of concern as these strains are predicted to be clinically resistant and are unlikely to remain confined to the U.S.A. Epidemiological studies are urgently required to monitor how resistant strains are selected, how they spread and to ascertain whether the prevalence of resistance correlates with antibiotic usage patterns in the different countries.

Acne Vulgaris↗
PubMed2001

A clinical and therapeutic study of 29 patients with infantile acne.

BACKGROUND: Infantile acne is a relatively uncommon condition; there are few data in the literature on the optimum treatment for this disorder. OBJECTIVES: To review treatment results in infantile acne. METHODS: We performed a retrospective review of 29 patients (24 boys and five girls) treated over a 25-year period. RESULTS: The age at onset was 6-16 months (median 9). The acne was mild in 24%, moderate in 62% and severe in 14%. The type of acne was predominantly inflammatory (59%), but was comedonal in 17%, showed a mixed pattern in 17% and was nodular in 7%. No infants had any clinically obvious endocrinopathy. Patients with mild acne responded well to topical treatment (benzoyl peroxide, erythromycin and retinoids). All but two infants with moderate acne responded well to oral (paediatric) erythromycin 125 mg twice daily and topical therapy. Patients with erythromycin-resistant Propionibacterium acnes required trimethoprim 100 mg twice daily. Most patients were able to stop oral antibiotics within 18 months. In 38% of children, long-term oral antibiotics (> 24 months) were required. The time for clearance of the acne was 6-40 months (median 18). One patient required oral isotretinoin that cleared the acne in 4 months. Five patients (17%) were left with scarring. CONCLUSIONS: This study confirms the male predominance of infantile acne. Treatment is similar to that of adult acne, with the exclusion of the use of tetracyclines. When necessary, oral isotretinoin can be used.

Acne Vulgaris↗
PubMed2000

Sebum excretion rates in mothers and neonates.

As neonates have a high sebum production compared with 6-month-old babies, we wished to investigate the relationship of sebum production in mother and neonate. The sebum excretion rate (SER) was therefore measured in 10 mothers prenatally, and in each mother and baby as soon after birth as possible, and again 5-12 weeks postnatally. There was a significant correlation between the maternal and neonatal SER perinatally. The perinatal SER in the babies was markedly higher than the postnatal sample. These observations suggest an important role for the maternal hormonal environment on the infant sebaceous glands. There is animal evidence which suggests that the endocrine environment of the neonate influences the sebaceous gland development in puberty, but it is not known whether babies with a high SER are more prone to seborrhoea and acne in later life.

Acne Vulgaris↗