Investigation of the mechanism of action of nonablative pulsed-dye laser therapy in photorejuvenation and inflammatory acne vulgaris.

BACKGROUND: Nonablative lasers are widely used for treatment of wrinkles, atrophic scars and acne. These lasers stimulate dermal remodelling and collagen production, but the early molecular stimulus for this is unknown. The mechanism of nonablative lasers in inflammatory acne is variously suggested to be damage either to sebaceous glands or to Propionibacterium acnes. Their effects on cytokine production are unknown. OBJECTIVES: To assess the in vivo effects of a short pulse duration nonablative pulsed-dye laser (NA-PDL) previously used for photorejuvenation and treatment of acne, on cytokine production, P. acnes colonization density and sebum excretion rate (SER). METHODS: We examined the effect of NA-PDL (NliteV; Chromogenex Light Technologies, Llanelli, U.K.) on P. acnes colonization before and after laser therapy using a scrub-wash technique and culture at 0 and 24 h (n = 15), on SER using absorptive tape at 0, 2, 4, 8 and 12 weeks (n = 19) and on cytokine mRNA using reverse transcription-polymerase chain reaction from skin biopsies at 0, 3 and 24 h (n = 8). Results NA-PDL had no effect on P. acnes or SER. Transforming growth factor (TGF)-beta1 mRNA increased fivefold after 24 h and 15-fold in two subjects (P = 0.012). CONCLUSIONS: TGF-beta is known to be a potent stimulus for neocollagenesis and a pivotal immunosuppressive cytokine which promotes inflammation resolution. Its upregulation by NA-PDL provides a possible unifying molecular mechanism linking stimulation of dermal remodelling in photorejuvenation with inhibition of inflammation in acne. Damage to P. acnes or sebaceous glands cannot explain the effect of this device in acne.

Treatment of xanthoma disseminatum with cyclophosphamide.

Xanthoma disseminatum is a rare non-Langerhans cell (class II) histiocytosis, which is often resistant to treatment. We describe an illustrative case with extensive mucocutaneous, ocular, laryngeal, pituitary and central nervous system involvement, which responded to treatment with cyclophosphamide. The presentation, course and treatment of the condition are reviewed. Many of the non-Langerhans cell histiocytoses represent a spectrum of diseases of dermal dendrocytes ranging from self-limiting and benign conditions to multisystem progressive diseases that respond poorly to treatment and severely impair quality of life. We suggest that chemotherapy should be considered at an early stage in the more aggressive subtypes of non-Langerhans cell histiocytoses.

Pulsed-dye laser treatment for inflammatory acne vulgaris: randomised controlled trial.

BACKGROUND: Low-fluence (low irradiation energy density) pulsed-dye lasers (PDLs) have been used for atrophic acne scarring, and anecdotal experience suggests that long-term improvements in inflammatory acne can be seen after one PDL treatment. Our aim was to compare the efficacy and tolerability of such PDL treatment with sham treatment in patients with facial inflammatory acne in a double-blind, randomised controlled trial. METHODS: We recruited 41 adults with mild-to-moderate facial inflammatory acne. We randomly assigned patients to PDL (n=31) or sham treatment (n=10). Treatment was given at baseline and patients were seen after 2, 4, 8, and 12 weeks. Assessors and participants were unaware of treatment allocations. Primary outcome measures were acne severity after 12 weeks and adverse events at any time. Secondary measures were change in lesion counts after 12 weeks and change in acne severity with time. Analysis was by intention-to-treat. FINDINGS: After 12 weeks, acne severity (measured by Leeds revised grading system) was reduced from 3.8 (SD 1.5) to 1.9 (1.5) in the PDL group and 3.6 (1.8) to 3.5 (1.9) in the sham group (p=0.007). Treatment was well tolerated. Total lesion counts fell by 53% (IQR 19 to 64) in PDL patients and 9% (-16 to 38) in controls (p=0.023), and inflammatory lesion counts reduced by 49% (30 to 75) in PDL patients and 10% (-8 to 49) in controls (p=0.024). The most rapid improvements were seen in the first 4 weeks after treatment. INTERPRETATION: PDL therapy improves inflammatory facial acne 12 weeks after one treatment with no serious adverse effects.

Pregnancy and use of oral contraceptives reduces the biotransformation of proguanil to cycloguanil.

OBJECTIVE: To determine the effects of late pregnancy and also oestrogen supplementation on the CYP2C19-mediated biotransformation of proguanil (PG) to its active antifol triazine metabolite cycloguanil (CG). METHODS: Case control study conducted on the NW border of Thailand; a single dose of PG (4 mg/kg) was administered to Karen women in late pregnancy and a single blood and urine sample taken 6 h later. Women were studied in late pregnancy (>36 weeks) and restudied 2 months after delivery. A separate cohort of Karen women newly attending a birth-control clinic were studied before and 3 weeks into their first course of oral contraceptives (OCP: levonorgestrel 0.15 mg and ethinyloestradiol 0.03 mg). Forty-five pregnant women and forty-two healthy OCP users were studied. RESULTS: The results were similar in both groups; pregnancy and OCP use were both associated with reduced formation of cycloguanil (CG). Impaired PG biotransformation was seen in women with the "extensive metaboliser" phenotype (urine PG/CG ratio <10). CG levels, adjusted for dose, were a median (range) 73% (-59 to 420%) higher following the pregnancy than during the pregnancy in women characterised as extensive metabolisers ( P<0.001). CG levels in women characterised as extensive metabolisers were 34% (-54 to 323%) higher before than while taking the OCP ( P<0.01). CONCLUSION: Late pregnancy and OCP use impair biotransformation of the active antimalarial metabolite CG from the parent PG. This may be mediated by oestrogen inhibition of CYP2C19 activity. The dose of PG should be increased by 50% in these groups.

Presence and recovery of Ascaridia dissimilis ova on the external shell surface of turkey eggs.

Ascaridia dissimilis, a roundworm in turkeys, has been noted with increased frequency in commercial turkeys. Because infected turkeys can shed A. dissimilis ova in their feces, the potential exists for the external surface of turkey eggshells to be contaminated with A. dissimilis ova. The objectives of this study were to determine the presence of and recover A. dissimilis ova on the external surface of the turkey egg. In Experiment 1, turkey eggs were collected from naturally infected flocks, and eggs were processed by a sodium hydroxide procedure to recover any A. dissimilis ova on the external egg surface. In Experiment 2, the external surface of the turkey eggs was inoculated with 116 A. dissimilis ova/g feces, and eggshells were sampled every 3 days until 28 days of incubation to assess the recovery of A. dissimilis ova from the eggshell. In Experiment 1, of the 36 eggs examined from a flock naturally infected with A. dissimilis, one egg had an A. dissimilis ovum on its external eggshell surface. Experiment 2 demonstrated that A. dissimilis ova can be recovered from the external egg surface after a 28-day incubation period in the incubator. Ova recovery declined from an average of 62 A. dissimilis ova/turkey egg at day 2 of incubation to an average of 3 A. dissimilis ova/turkey egg at day 28 of incubation.

Photon pharmacology of an iron-sulphur cluster nitrosyl compound acting on smooth muscle.

1. The mechanisms of action on smooth muscle of the iron-sulphur cluster nitrosyl compound, heptanitrosyl-tri-mu 3-thioxotetraferrate (1-), (RBS), a photosensitive nitric oxide donor, have been investigated in the guinea-pig taenia caeci (coli) in vitro. 2. After exposure to RBS (50 microM) for 30 min, and subsequent washout, a sustained contraction was recorded in the absence of light to either the agonist carbachol (50 microM) or a depolarizing concentration of KCl (23.5 mM). Photon irradiation (> 400 nm) caused a prompt relaxation of precontracted RBS-treated muscle, the magnitude of which depended upon the intensity (1.1 x 10(3) to 1.1 x 10(5) lux), duration (30 s to 20 min) and wavelength (400 to 800 nm), of the incident illumination. 3. Repeated periods of illumination at 1.1 x 10(4) lux produced a reversible relaxation of both carbachol and KCl-evoked tone in muscle pretreated with RBS (50 microM). These photorelaxations were reproducible at 10 min intervals for several hours with a maximal relaxation amounting to 80 to 90% that of the tone produced by carbachol (50 microM). 4. The nitric oxide synthase inhibitor, NG-nitro-L-arginine (60 microM), caused no inhibition of the photon-induced relaxation of RBS-treated muscle. In contrast, N-methylhydroxylamine (2 mM), L-cysteine (10 mM), DL-dithiothreitol (2 mM), methylene blue (30 microM), and haemoglobin (20 microM), all reversibly but significantly inhibited (P < 0.001) the photorelaxation response. However, neither the aminothiol N-acetyl-L-cysteine (10 mM) nor the tripeptide glutathione (10 mM) blocked the RBS-induced photorelaxation. 5 The photolytic cleavage of RBS depended on the intensity and duration of illumination; it was accompanied by a corresponding decrease in absorbance and by the liberation of NO as measured by the Griess diazo reaction with sulphanilic acid. L-Cysteine (10 mM) prevented the decrease in absorbance and the photolytic liberation of NO.6 It is concluded that (i) sequestered or bound RBS, when photon-activated, liberates NO by a process which can be controlled by the wavelength, intensity and duration of the incident light, (ii) the photon-released NO rapidly relaxes the smooth muscle cells of the taenia coli primarily via cyclic GMP-dependent pathways which can be blocked by use of appropriate inhibitors, and (iii) the RBS-induced photorelaxation effect does not involve the activation of NO synthase. RBS is therefore a valuable photosensitive NO donor for establishing the functional and pharmacological significance of NO.

Suspect value of non-CSF viral cultures in the diagnosis of enteroviral CNS infection in young infants.

Laboratory criteria used for presumptive diagnosis of enteroviral meningitis were evaluated as predictors of cerebrospinal fluid (CSF) infection. Records were retrospectively analysed of infants under four months of age admitted to hospital between 1977 and 1987 with viral CSF cultures: those with enteroviruses isolated from CSF (group 1) were compared with those with enteroviruses isolated only from non-CSF sites (group 2). Predictive value computations demonstrated that no single or combined non-CSF culture accurately predicted isolation of enteroviruses from the CSF. These results suggest that CSF viral culture is imperative in establishing the diagnosis of enteroviral meningitis in young infants.