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Biomedical subjects

J J Leyden

Publications and source records attributed to J J Leyden.

At least 19 recordsLinked to original sources
PubMed2005

Efficacy of oral isotretinoin in the control of skin and nasal colonization by antibiotic-resistant propionibacteria in patients with acne.

BACKGROUND: Skin colonization by antibiotic-resistant propionibacteria is commonplace among acne patients globally. Increasing attention is now being paid to how resistance rates might be reduced to preserve the future efficacy of antibiotics, especially erythromycin and clindamycin in acne therapy. OBJECTIVE: To assess the efficacy of oral isotretinoin in the control of antibiotic-resistant propionibacteria. METHODS: Acne patients (72 in the U.K., 62 in the U.S.A.) colonized with high numbers of antibiotic-resistant propionibacteria were sampled before, during and 12 weeks after oral isotretinoin therapy. Propionibacterial samples were collected from five acne-prone skin surface sites using a detergent scrub method and from the anterior nares using moistened swabs. Total and antibiotic-resistant propionibacteria were enumerated by viable counting on media with and without selective antibiotics. RESULTS: After 16 weeks of oral isotretinoin therapy, mean population densities of viable propionibacteria and variants resistant to erythromycin, clindamycin or tetracycline had fallen by more than 90% at all skin sites and in the nares. The sole exception was a smaller reduction in tetracycline-resistant strains on the lower back. In general, greater reductions were observed on skin than in the nares. By the end of the treatment period only three patients (all in Philadelphia) yielded no antibiotic-resistant strains from any site. Post-treatment, propionibacterial counts remained well below pretreatment levels but had begun to recover on the face and in the nares. The recovering propionibacterial population included both susceptible and resistant strains. Changes during and post-treatment at the two centres were similar but not identical. CONCLUSIONS: Oral isotretinoin effectively reduced skin and nasal colonization by antibiotic-resistant propionibacteria. However, viable populations of resistant isolates persisted post-treatment at multiple sites. Novel methods are required to eradicate antibiotic-resistant propionibacteria completely, especially from the nasal reservoir.

Acne Vulgaris↗
PubMed2005

Colonisation rates of Streptococcus pyogenes and Staphylococcus aureus in the oropharynx of a young adult population.

There are very few reports on the rates of oropharyngeal colonisation by Streptococcus pyogenes and Staphylococcus aureus in young adults. The present study found colonisation rates of 9.6% and 26.2%, respectively. These rates are two-fold higher than historical rates, indicating that these organisms may be more prevalent than thought previously. This finding may have important clinical consequences in certain populations, and requires further investigation.

Adolescent↗
PubMed2003

Propionibacterium acnes resistance: a worldwide problem.

Antibiotic therapy directed against Propionibacterium acnes has been a mainstay of treatment for more than 40 years. Despite years of widespread use of systemic tetracyclines and erythromycin, change in P. acnes sensitivity to antibiotics was not seen until the early 1980s. The first clinically relevant changes in P. acnes antibiotic sensitivity were found in the USA shortly after the introduction of topical formulations of erythromycin and clindamycin. By the late 1980s, P. acnes strains with very high MIC levels for erythromycin and elevated MICs for tetracycline were increasingly found in the UK and the USA. Mutations in the genes encoding the 23S and 16S subunits of ribosomal RNA were first identified in the UK and also seen in a recent survey from clinics in Europe, Japan, Australia and the USA. In addition, strains were found in which these known mutations could not be identified, indicating that as yet unidentified resistance mechanisms have evolved. These findings indicate the need to develop strategies to minimize the use of antibiotics in acne therapy.

Acne Vulgaris↗
PubMed2002

Scrotal temperatures do not differ among young boys wearing disposable or reusable diapers.

BACKGROUND/AIMS: This study investigated the effect of specific, commonly used diaper types on scrotal temperatures in normal healthy, young boys. These included both modern disposable and reusable diapers as well as various types of protective outer coverings that are in common use in both North America and Europe METHODS: Scrotal and skin surface temperatures were continuously monitored in healthy, young males using a computerized data-logging system based on temperature probes specifically designed for paediatric studies. These systems could be used either tethered to the PC or made completely portable depending upon the age and activity of the child being measured. Based on our results from several pilot studies, it became clear that the best way to determine if disposable and reusable diapers differ with regard to their impact on scrotal temperatures is to run these comparisons under controlled laboratory conditions where "diaper type" was the primary variable. A 2-h time period was chosen to ensure that sufficient time had elapsed for thermal equilibrium to be established under the diapers. We also felt it necessary to study the impact of urination and simulated this condition over the last 15 min using standardized methods. In addition to the skin surface temperatures, we also measured the temperature of the tympanic membrane using an infrared thermometer as an estimate of "core" temperature for each individual at various times during the session. RESULTS AND CONCLUSIONS: In this study, we have clearly shown that scrotal temperatures are the same whether the child is wearing disposable or reusable cloth diapers with a protective cover. The only situation in which scrotal temperatures were found to be lower is when the cloth diaper is used alone without a protective cover but this is not representative of how these products are actually used. We also found that on average scrotal temperatures are significantly lower than core for each diaper type. Occasionally, we did see individuals in which the maximal scrotal temperatures approached core temperatures but in every case the thermal sensors were soiled by a bowel movement. We also found that skin surface temperatures increased not only when covered by a diaper but also due to the thermal insulation provided by outer garments and blankets.

Body Temperature↗
PubMed2001

Tazarotene cream for the treatment of facial photodamage: a multicenter, investigator-masked, randomized, vehicle-controlled, parallel comparison of 0.01%, 0.025%, 0.05%, and 0.1% tazarotene creams with 0.05% tretinoin emollient cream applied once daily for 24 weeks.

OBJECTIVE: To assess the safety and efficacy of 4 concentrations of tazarotene cream in the treatment of facial photodamage. DESIGN: Prospective weekly multicenter, investigator-masked, randomized, parallel-group study. SETTING: University hospitals and clinical research centers. PATIENTS: Three hundred forty-nine subjects with facial photodamage. INTERVENTION: Daily topical application of tazarotene cream (0.01%, 0.025%, 0.05%, and 0.1%) compared with its vehicle and with 0.05% tretinoin emollient cream. RESULTS: Tazarotene cream and tretinoin cream significantly improved mottled hyperpigmentation and fine wrinkles. At week 24, treatment success rates based on global responses were 67% (39 of 58 subjects) with 0.1% tazarotene, 52% (30 of 58 subjects) with 0.05% tazarotene, 36% (21 of 58 subjects) with 0.025% tazarotene, 41% (24 of 59 subjects) with 0.01% tazarotene, 55% (32 of 58 subjects) with 0.05% tretinoin, and 22% (13 of 58 subjects) with vehicle. Local adverse events, although more frequent with tazarotene at higher concentrations, were generally mild to moderate. CONCLUSIONS: Tazarotene in a cream formulation is safe and is associated with positive changes in the treatment of photodamaged facial skin.

Administration, Cutaneous↗
PubMed2001

Sodium dodecyl sulfate induces plasminogen activator inhibitor type 2 expression in epidermal keratinocytes in vivo and in vitro.

The detergent sodium dodecyl sulfate is a well-known inducer of irritant contact dermatitis. In this study we show that sodium dodecyl sulfate induces the serine proteinase inhibitor, plasminogen activator inhibitor type 2, in epidermal keratinocytes. The enhancement in plasminogen activator inhibitor type 2 mRNA and antigen is observed both when sodium dodecyl sulfate is applied topically to normal human skin as well as when it is added to the growth medium of cultured human keratinocytes. In vitro, plasminogen activator inhibitor type 2 mRNA is increased within 4-8 h after addition of the detergent, and the increase in plasminogen activator inhibitor type 2 antigen occurs slightly later. The enhancing effect of sodium dodecyl sulfate on plasminogen activator inhibitor type 2 is not related to nonspecific cell lysis nor is it secondary to induction of tumor necrosis factor alpha. Similarities between our in vitro and in vivo findings lead us to hypothesize that sodium dodecyl sulfate may exert its effect on epidermal plasminogen activator inhibitor type 2 via interaction with the keratinocyte.

Cells, Cultured↗
PubMed2001

Current issues in antimicrobial therapy for the treatment of acne.

This review summarizes current information regarding the use of antimicrobial agents for the treatment of patients with inflammatory acne. A number of drugs have been used effectively as topical or systemic therapy, often in combination with benzoyl peroxide or a retinoid. Propionibacterium acnes exhibits high in vitro sensitivity to a wide range of antimicrobials, including ampicillin, clindamycin, erythromycin, tetracycline, doxycycline, nadifloxacin, ofloxacin, minocycline, cephalexin, and gentamycin. However, not all of these drugs are equally effective in penetrating the lipid-filled microcomedo and reducing numbers of P. acnes in the skin. Antimicrobial therapy, particularly systemic treatment, may be complicated by the potential for drug-drug interactions. Historically, the potential for antimicrobials to reduce the effectiveness of oral contraceptives has been a concern in the treatment of acne. However, there is evidence to suggest that such an interaction does not take place in patients being treated with the antimicrobials most often used in dermatological practice. Antimicrobial therapy for acne has also been complicated by the emergence of antibiotic-resistant strains of P. acnes. Increasing P. acnes resistance can be combated by judicious use of retinoids in combination with antibiotics to reduce inflammation and infection, and employment of retinoids for maintenance therapy.

Acne Vulgaris↗
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

The evolving role of Propionibacterium acnes in acne.

Propionibacterium acnes is a member of the resident cutaneous flora. Sebaceous follicles involved in acne are characterized by the accumulation of abnormally desquamated corneocytes and excess sebum-the microcomedo. This environment provides ideal growth conditions for P acnes. Several orders of magnitude level of P acnes are found in microcomedos. P acnes produces a variety of chemotactic factors and proinflammatory molecules that are responsible for the inflammatory phase of acne. Antibiotic therapy works by reducing the viable number of P acnes as well as by reducing the production of inflammatory stimuli. Antibiotic therapy has been a mainstay of treatment for more than 30 years. In the last decade, decreased sensitivity to antibiotics has developed and clinical resistance has been described. This development threatens the usefulness of antibiotic therapy in the future.

Acne Vulgaris↗
PubMed2001

A randomized trial of the efficacy of a new micronized formulation versus a standard formulation of isotretinoin in patients with severe recalcitrant nodular acne.

BACKGROUND: Isotretinoin is very frequently the drug of choice for the management of severe recalcitrant nodular acne. Recently, a new micronized and more bioavailable formulation of isotretinoin has been developed that permits once-daily administration in lower doses than usually used with standard isotretinoin (Accutane), regardless of whether it is taken with or without food. OBJECTIVE: Our purpose was to determine whether micronized isotretinoin and standard isotretinoin are clinically equivalent. METHODS: In this multicenter, double-blind, double-dummy study, 600 patients with severe recalcitrant nodular acne were treated with either 0.4 mg/kg of micronized isotretinoin once daily without food (n = 300) or 1.0 mg/kg per day of standard isotretinoin in two divided doses with food (n = 300). Lesion counts were monitored over 20 weeks. RESULTS: Both treatment groups in this well-controlled clinical trial experienced an equivalent reduction in the number of total nodules (facial plus truncal). In addition, an equivalent proportion of patients achieved 90% clearance of the total number of nodules. Both formulations had similar results for other efficacy variables. CONCLUSION: Once-daily use of the micronized and more bioavailable formulation of isotretinoin under fasted conditions is clinically equivalent to the standard twice-daily formulation under fed conditions in the treatment of severe recalcitrant nodular acne.

Acne Vulgaris↗
PubMed2001

Safety of a new micronized formulation of isotretinoin in patients with severe recalcitrant nodular acne: A randomized trial comparing micronized isotretinoin with standard isotretinoin.

BACKGROUND: Isotretinoin is a very effective drug for treating severe recalcitrant nodular acne. A new micronized formulation of isotretinoin has been shown to be clinically equivalent to standard isotretinoin with improved bioavailability and minimal food effect. The safety profile of the micronized formulation has not been described previously. OBJECTIVE: The objective of this article is to report the incidence and intensity of adverse events found in a comparative, double-blind efficacy study that showed clinical equivalence of the new micronized formulation of isotretinoin and the standard isotretinoin formulation (Accutane). METHODS: Six hundred patients with severe recalcitrant nodular acne were treated with micronized isotretinoin (n = 300) under fasted conditions or standard isotretinoin (n = 300) under fed conditions. One cohort received single daily doses of 0.4 mg/kg of micronized isotretinoin without food and the other cohort received 1.0 mg/kg per day of standard isotretinoin in two divided doses with food. Adverse events were monitored during 20 weeks of drug therapy. RESULTS: The proportion of adverse events in most body systems was generally lower in patients receiving micronized isotretinoin than in those receiving standard isotretinoin. CONCLUSION: Micronized isotretinoin appears to have a safety profile similar to that of standard isotretinoin and to carry a lower risk of mucocutaneous events and hypertriglyceridemia.

Acne Vulgaris↗
PubMed2001

Comparison of the efficacy and safety of a combination topical gel formulation of benzoyl peroxide and clindamycin with benzoyl peroxide, clindamycin and vehicle gel in the treatments of acne vulgaris.

BACKGROUND: Topical clindamycin and benzoyl peroxide have each demonstrated clinical efficacy in the treatment of acne vulgaris. When used in combination, they promise greater efficacy than either individual agent used alone and the combined use of benzoyl peroxide with topical antibacterial has been shown to decrease the emergence of antibacterial resistant species. OBJECTIVE: The objective was to determine the efficacy and safety of a combination benzoyl peroxide plus clindamycin in a gel formulation compared with each of its 2 active constituents in gel vehicle, and gel vehicle given alone in the treatment of acne vulgaris. METHODS: In this 10-week, multicenter, double-blind trial, 480 patients with moderate to moderately severe acne were randomized to receive twice-daily treatment with 5% benzoyl peroxide plus 1% clindamycin, 5% benzoyl peroxide, 1% clindamycin, or vehicle. RESULTS: Significantly greater reductions in the number of inflammatory and total lesions were demonstrated in patients using combination therapy compared with those using any of its 3 individual components. Likewise, both physicians' and patients' global evaluations showed significantly greater improvements with the combination therapy than with its individual components. The most frequent adverse effect, dry skin, occurred to a similar extent in the combination and benzoyl peroxide treatment groups. CONCLUSION: The improved efficacy obtained with the combination therapy was accompanied by a tolerability profile similar to that of benzoyl peroxide alone, making this new combination product an alternative antimicrobial therapy for acne vulgaris.

Acne Vulgaris↗
PubMed2000

Concomitant administration of vitamin E does not change the side effects of isotretinoin as used in acne vulgaris: a randomized trial.

BACKGROUND: Isotretinoin treatment is frequently associated with reversible, dose-related side effects. Recent studies claimed that combining vitamin E with high-dose isotretinoin ameliorated isotretinoin-induced side effects. OBJECTIVE: The purpose of this double-blind, randomized study was to determine the effects of a fixed dose of vitamin E on the side effects of isotretinoin for treatment-resistant acne vulgaris. METHODS: One hundred forty subjects were randomly assigned to one of two treatment programs with isotretinoin (1 mg/kg) together with either vitamin E (800 IU/day) or a vitamin E placebo for 20 weeks. The incidence, severity, and duration of the side effects (eg, dry eyes, dry lips) were assessed. RESULTS: A fixed 800 IU/day dose of vitamin E did not improve the incidence, severity, or duration of side effects associated with isotretinoin (1 mg/kg per day). CONCLUSION: Vitamin E did not significantly ameliorate retinoid side effects when combined with 1 mg/kg of isotretinoin in the treatment of acne.

Acne Vulgaris↗
PubMed2000

Cutaneous microenvironment of human immunodeficiency virus (HIV)-seropositive and HIV-seronegative individuals, with special reference to Staphylococcus aureus colonization.

A cross-sectional quantitative study of cutaneous bacterial and yeast flora at seven body sites in 99 human immunodeficiency virus-seropositive and 50 seronegative military personnel was performed. Statistically significant differences in carriage rates were only observed for Staphylococcus aureus on the foreheads of seropositive individuals. Seronegative individuals demonstrated staphylococcal carriage rates 1.3 to 2 times as great as those of historical controls (defined as healthy individuals not receiving any medications) at five of six body sites. We conclude that seropositive military personnel do not exhibit statistically significant elevations in densities and carriage rates of the microorganisms examined (except Staphylococcus aureus), relative to seronegative individuals. Seropositive individuals may be predisposed to staphylococcal carriage. The elevated staphylococcal carriage rates of military personnel undergoing basic training warrants a formal evaluation of the impact of training exercises on cutaneous flora. The information gained may serve to limit the spread of infection during training exercises and battlefield conditions.

Adolescent↗
PubMed1998

Identification and immunohistochemical localization of protein precursors to human axillary odors in apocrine glands and secretions.

OBJECTIVES: To determine the cellular localization in male and female axillary tissue for apocrine secretion odor-binding proteins 1 (ASOB1) and 2 (ASOB2) and the electrophoretic pattern of female apocrine proteins and to begin characterization of the ASOB1 protein. DESIGN: Immunohistochemical techniques were used with biopsy samples from axillary tissue of male and female subjects. Immunological techniques and microsequencing were used to characterize several of the proteins in male and female apocrine secretions. SETTING: A university medical center. PARTICIPANTS: Healthy male and female volunteers who donated apocrine secretions and/or axillary tissue. RESULTS: Specific immunoreactivity was localized only to the apocrine glands in both sexes. Furthermore, only preabsorption with a mixed apocrine secretion sample eliminated all immunoreactivity. The electrophoretic pattern of proteins in female apocrine secretions is similar to that in male secretions. Western blotting of the separated proteins from female samples using serum samples containing antibodies to ASOB1 and ASOB2 yielded identical results to those found with separated proteins from male samples. Partial sequence data obtained from the N-terminus of ASOB1 suggested that it shares homology with the alpha-chain of apolipoprotein J (Apo J). Apocrine secretion odor-binding protein 1 is not immunologically similar to ApoJ, but 2 other apocrine secretion proteins are. CONCLUSIONS: Male and female subjects appear to have the same glycoprotein carriers for (E)-3-methyl-2-hexenoic acid localized to the apocrine glands. The N-terminal sequence for ASOB1 may be homologous to Apo J, but it is not immunologically similar to it. However, 2 other proteins in the apocrine secretion appear to be the monomer and dimer forms of Apo J.

Adult↗