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Biomedical subjects

R Bissonnette

Publications and source records attributed to R Bissonnette.

At least 19 recordsLinked to original sources
PubMed2006

Multiple large surface photodynamic therapy sessions with topical methylaminolaevulinate in PTCH heterozygous mice.

BACKGROUND: Photodynamic therapy (PDT) combines the administration of a photosensitizer with its subsequent activation by light of the appropriate wavelength. Methylaminolaevulinate (MAL) is a photosensitizer precursor, transformed by cells into protoporphyrin IX. The PTCH gene plays a central role in the genesis of basal cell carcinoma (BCC). The PTCH transgenic mouse develops microscopic BCCs when chronically exposed to ultraviolet (UV) or ionizing radiation. OBJECTIVES: The aim of this study was to explore the ability of multiple large surface MAL-PDT to prevent BCC, using the PTCH heterozygous mouse as a model. METHODS: Thirty-five mice were exposed to UV radiation for a total of 20 weeks. Group 1 (20 mice) was exposed only to UV whereas group 2 (15 mice) was exposed to UV and weekly to MAL-PDT. At 28 weeks the mice were killed and the skin of the back processed for standard histopathology. Assessment was blind and any slide showing the presence of BCC was counted as a single BCC. The number of mice in groups 1 and 2 showing BCC were compared using Fisher's exact test. RESULTS: Nineteen BCCs in nine mice from group 1 were found, but no BCCs in mice from group 2. The difference was statistically significant (P = 0.001). CONCLUSIONS: Weekly suberythematous PDT sessions with topical MAL were able to delay the development of microscopic BCCs in PTCH mice chronically exposed to UV radiation.

Aminolevulinic Acid↗
PubMed2006

Etanercept for the treatment of psoriasis.

Etanercept has recently been approved for the treatment of moderate-to-severe plaque psoriasis at a dose of 50mg twice per week for 12 weeks followed by a maintenance dose of 50mg once weekly thereafter. Clinical studies have shown excellent efficacy and a good safety profile in patients with psoriasis. Extensive information on etanercept safety is available as this biological agent has been used for many years for other indications such as rheumatoid arthritis, and psoriatic arthritis.

Drug Administration Schedule↗
PubMed2004

Irradiance and light dose influence histological localization of photodamage induced by photodynamic therapy with aminolaevulinic acid.

BACKGROUND: Photodynamic therapy (PDT) with aminolaevulinic acid (ALA) is used in many countries for the treatment of actinic keratoses. OBJECTIVES: The objectives of the current study were to evaluate the influence of irradiance and light dose on the localization and extent of photodamage to mouse skin following ALA-PDT. METHODS: In this study we evaluated the influence of irradiance and light dose on epidermal photodamage following ALA-PDT. Groups of hairless mice received an intraperitoneal injection of ALA followed 2 h later by exposure to 12 J cm(-2), 24 J cm(-2) or 48 J cm(-2) of unfiltered light from a slide projector. For each of these fluences, groups of mice were exposed at the following irradiances: 5 mW cm(-2), 20 mW cm(-2) or 40 mW cm(-2). Skin biopsies were performed 24 h and 72 h later. RESULTS: Histological localization of photodamage was influenced by irradiance and light dose. At high irradiance and low fluence, PDT photodamaged cells were mostly located in the upper area of the epidermis whereas at lower irradiance and high fluence the complete epidermis was necrotic and often absent 24 h after light exposure. Protoporphyrin IX (PpIX) fluorescence intensity was similar in the upper and lower region of the epidermis 2 h after ALA injection. The decrease in PpIX fluorescence intensity immediately after light exposure was also similar in both regions of the epidermis. CONCLUSIONS: The localization of photodamage following ALA-PDT is influenced by irradiance and light dose. This phenomenon cannot be explained by differences in PpIX intensity in the epidermis either before or after light exposure.

Aminolevulinic Acid↗
PubMed2002

A new calcipotriol/betamethasone dipropionate formulation (Daivobet) is an effective once-daily treatment for psoriasis vulgaris.

BACKGROUND: Topical corticosteroids and calcipotriol have been used separately for many years to treat psoriasis. A new combination ointment has been formulated, which contains both calcipotriol and the corticosteroid betamethasone dipropionate. OBJECTIVE: To compare the combination ointment with betamethasone dipropionate ointment, calcipotriol ointment and ointment vehicle in patients with psoriasis vulgaris. METHODS: 1,603 patients were randomised to one of the 4 double-blind treatments used once daily for 4 weeks. RESULTS: The mean percentage change in the PASI at the end of treatment was -71.3 (combination), -57.2 (betamethasone), -46.1 (calcipotriol) and -22.7 (vehicle). The mean difference of combination minus betamethasone was -14.2 (95% CI: -17.6 to -10.8, p < 0.001), of combination minus calcipotriol -25.3 (95% CI: -28.7 to -21.9, p < 0.001) and of combination minus vehicle -48.3 (95% CI: -53.2 to -43.4, p < 0.001). 6.0% of patients (combination) reported local adverse reactions compared to 4.9% (betamethasone), 11.4% (calcipotriol) and 13.6% (vehicle). CONCLUSION: Calcipotriol/betamethasone dipropionate combination ointment used once daily is well tolerated and more effective than either active constituent used alone.

Administration, Topical↗
PubMed2002

Prevention of polymorphous light eruption and solar urticaria.

Polymorphous light eruption (PLE) and solar urticaria (SU) are two photodermatoses that are induced by ultraviolet radiation and sometimes by visible light. This article will review the various means of preventing PLE and SU with an emphasis on the role of sunscreens.

Humans↗
PubMed2001

Fenofibrate raises plasma homocysteine levels in the fasted and fed states.

The effect of fenofibrate (FEN), compared with placebo (PL), on total plasma homocysteine (tHcy) levels in the fasted and fed states has been examined. Twenty men with established coronary artery disease (CAD) or with at least two cardiovascular risk factors, who had elevated plasma triglyceride levels (> 2.3 mmol/l) and reduced HDL-C levels (< 0.91 mmol/l), and in whom a fibric acid derivative was clinically indicated were studied. The study was a randomized, PL controlled, double-blind study designed to test the effect of micronized FEN on postprandial lipemia. Plasma tHcy levels were investigated as a post-hoc analysis. After a 4-week dietary stabilization period, patients were randomized to PL or FEN (200 mg/day) for 8 weeks, followed by an 8-h postprandial study, consisting of 1 g fat/kg body weight (35% cream). The methionine content of cream was approximately 0.53 mg/ml. A 5-week washout period was then followed by a second 8-week treatment period (FEN or PL), at the end of which a second postprandial study was undertaken. Blood was sampled in the fasted state (0 h) and postprandially at 2, 4, 6 and 8 h. Plasma was stored at -80 degrees C for homocysteine, vitamins B(6), B(12) and folate measurements. FEN caused a marked decrease in all triglyceride-rich lipoprotein parameters, no change in LDL-C, and an increase in HDL-C levels. Fen treatment was associated with an increase in fasting tHcy (PL: 10.3+/-3.3 micromol/l to FEN: 14.1+/-3.8 micromol/l, 40.4+/-20.5%, P < 0.001) and fed tHcy levels 6 h post-fat load (PL: 11.6+/-3.3 micromol/l vs. FEN: 17.1+/-5.4 micromol/l, P < 0.001). Homocysteine levels were increased by the fat load; PL: 14% (P < 0.001) and FEN: 21%, P < 0.001 at the 2, 4, 6 and 8 h time points. Change in tHcy level on FEN was not associated with changes in plasma levels of folate, vitamins B(6) or B(12) or creatinine. Amino acid analysis revealed that methionine and cysteine were significantly increased on FEN (P < 0.005). The incidence of hyperhomocysteinemia (defined as tHcy level >14 micromol/l) was PL: 2/20 (10%) and FEN: 9/20 (45%) (chi(2) = 4.51, P = 0.034). There was no correlation between changes in plasma triglyceride levels and tHcy levels. Since tHcy is considered an emerging cardiovascular risk factor, the ability of FEN to increase plasma tHcy levels could potentially mitigate the potential of this drug to protect against cardiovascular disease.

Adult↗
PubMed2001

Systemic photodynamic therapy with aminolaevulinic acid delays the appearance of ultraviolet-induced skin tumours in mice.

BACKGROUND: Photodynamic therapy (PDT) with topical aminolaevulinic acid (ALA) has recently been approved by the US Food and Drug Administration for the treatment of actinic keratoses. OBJECTIVES: To determine whether weekly systemic suberythemogenic ALA-PDT could prevent the appearance of ultraviolet (UV) -induced skin tumours in hairless mice. METHODS: One group of 20 mice received daily UV radiation from FS 20 tubes, and weekly intraperitoneal injections of ALA 40 mg kg(-1), each followed 3 h later by 12 J cm(-2) of white light (ALA-PDT). Control groups consisted of mice exposed only to UV, to UV and ALA without white light, or UV and white light without ALA, as well as untreated mice. RESULTS: The tumour-free survival was significantly longer for mice exposed to daily UV and weekly ALA-PDT as compared with the control groups. Neither the mortality nor the incidence of large skin tumours was higher in the UV/ALA-PDT group than in mice exposed only to UV. In vivo fluorescence spectroscopy showed that the 635-nm fluorescence emission within tumours was lower than in normal skin 3 h after ALA administration. This was also confirmed by quantitative fluorescence microscopy. CONCLUSIONS: Systemic ALA-PDT can delay the appearance of UV-induced skin tumours in mice without increasing mortality or the incidence of large tumours.

Animals↗
PubMed2001

The treatment of moderate to severe psoriasis with a new anti-CD11a monoclonal antibody.

BACKGROUND: Anti-CD11a (hu1124) is a humanized monoclonal antibody directed against the CD11a subunit of LFA-1. This study investigated whether treatment with anti-CD11a antibody provides clinical benefit to patients with moderate to severe plaque psoriasis. METHODS: This was a double-blind, placebo-controlled, phase II, multicenter study. In total, 145 patients with minimum Psoriasis Area and Severity Index scores of 12 and affected body surface area of 10% or more were sequentially enrolled into low-dose (0.1 mg/kg, n = 22) or high-dose (0.3 mg/kg, n = 75) groups. Within groups, patients were randomized to treatment or placebo (n = 48) in a 2:1 ratio. Drug was administered intravenously at weekly intervals for 8 weeks. RESULTS: The percentage of subjects achieving more than 50% improvement in physician's global assessment at day 56 (1 week after final dose) was 15% and 48% for placebo and 0.3 mg/kg of drug, respectively (P =.002). A physician's global assessment of excellent (>75% improvement) was greater in the 0.3 mg/kg group versus placebo (25% vs 2%, P =.0003). Average Psoriasis Area and Severity Index scores at day 56 were 13.9 +/- 7.5 (placebo) and 10.9 +/- 8.4 (0.3 mg/kg) (P <.0001). Epidermal thickness was reduced in the 0.3 mg/kg group compared with the placebo group (37% vs 19%, P =.004). Treatment was well tolerated; mild to moderate flu-like complaints were the most common adverse events. White blood cell counts and lymphocyte counts transiently increased. Depletion of circulating lymphocytes did not occur. CONCLUSIONS: Anti-CD11a antibody administered intravenously in 8 weekly doses of 0.3 mg/kg was well tolerated and induced clinical and histologic improvements in psoriasis.

Adult↗
PubMed2001

Oral aminolevulinic acid induces protoporphyrin IX fluorescence in psoriatic plaques and peripheral blood cells.

Photodynamic therapy (PDT) with topical aminolevulinic acid (ALA) has been shown in previous studies to improve psoriasis. However, topical ALA-PDT may not be practical for the treatment of extensive disease. In order to overcome this limitation we have explored the potential use of oral ALA administration in psoriatic patients. Twelve patients with plaque psoriasis received a single oral ALA dose of 10, 20 or 30 mg/kg followed by measurement of protoporphyrin IX (PpIX) fluorescence in the skin and circulating blood cells. Skin PpIX levels were determined over time after ALA administration by the quantification of the 635 nm PpIX emission peak with in vivo fluorescence spectroscopy under 442 nm laser excitation. Administration of ALA at 20 and 30 mg/kg induced preferential accumulation of PpIX in psoriatic as opposed to adjacent normal skin. Peak fluorescence intensity in psoriatic and normal skin occurred between 3 and 5 h after the administration of 20 and 30 mg/kg, respectively. Ratios of up to 10 for PpIX fluorescence between psoriatic versus normal skin were obtained at the 30 mg/kg dose of ALA. Visible PpIX fluorescence was also observed on normal facial skin, and nonspecific skin photosensitivity occurred only in patients who received the 20 or 30 mg/kg doses. PpIX fluorescence intensity was measured in circulating blood cells by flow cytometry. PpIX fluorescence was higher in monocytes and neutrophils as compared to CD4+ and CD8+ T lymphocytes. PpIX levels in these cells were higher in patients who received higher ALA doses and peaked between 4 and 8 h after administration of ALA. There was only a modest increase in PpIX levels in circulating CD4+ and CD8+ T lymphocytes. In conclusion oral administration of ALA induced preferential accumulation of PpIX in psoriatic plaques as compared to adjacent normal skin suggesting that PDT with oral ALA should be further explored for the treatment of psoriasis.

Administration, Oral↗
PubMed2000

Topical photodynamic therapy with 5-aminolaevulinic acid does not induce hair regrowth in patients with extensive alopecia areata.

BACKGROUND: Photodynamic therapy (PDT) is a new modality involving the administration of a photosensitizer, or photosensitizer precursor, followed by its activation with light to generate a therapeutic effect. 5-Aminolaevulinic acid (ALA) is a photosensitizer precursor that is transformed by cells into protoporphyrin IX (PpIX), which can in turn be activated by red light. OBJECTIVES: To investigate the effect of PDT in alopecia areata (AA). METHODS: In six patients with extensive AA, topical ALA lotion at 5%, 10% and 20% as well as the vehicle lotion alone were applied separately to different scalp areas, followed 3 h later by exposure to red light at each treatment session. RESULTS: No significant hair growth was observed after 20 twice-weekly treatment sessions. A significant increase in erythema and pigmentation was observed for the three concentrations of ALA lotion vs. the vehicle, implying that a phototoxic PDT effect was achieved in the skin. In vivo fluorescence spectroscopy in one patient showed an increase in red PpIX fluorescence 3 h after ALA application followed by a decrease after light exposure. On fluorescence microscopy, bright red fluorescence was present in the epidermis and sebaceous glands, but not in the inflammatory infiltrate surrounding the hair follicle following ALA application. CONCLUSIONS: PDT was ineffective in the treatment of AA.

Adult↗
PubMed2000

Comparison of UVA protection afforded by high sun protection factor sunscreens.

UVA protection afforded by 6 different sunscreens with a sun protection factor of 21 or more was compared by means of the persistent pigmentation darkening method. Colorimetric and visual assessment showed significant differences in UV radiation-induced pigmentation at 2 hours. The labeled sun protection factor of the tested sunscreens was not predictive of UVA protection level.

Administration, Topical↗
PubMed1999

Treatment of refractory solar urticaria with plasma exchange.

BACKGROUND: Solar urticaria is a photodermatosis that can be very disabling for patients who are highly sensitive to light and can also be very resistant to therapy. OBJECTIVE: To correlate the results of serial phototesting in a patient with severe and refractory solar urticaria before and after treatment with plasma exchange. METHODS: Plasma exchange was performed five times over a period of 10 days. Phototesting to ultraviolet A (UVA) irradiation and visible light was performed with fluorescent ultraviolet tubes and an incandescent lamp. RESULTS: The urticaria that developed after very low light doses during baseline phototesting could not be provoked following plasma exchange. The patient is now almost symptom-free, with only occasional and transient hives more than 21 months after her last plasma exchange. CONCLUSIONS: Plasma exchange is a therapeutic modality to consider in highly light-sensitive patients when other treatments have failed.

Adult↗
PubMed1998

Psoriatic plaques exhibit red autofluorescence that is due to protoporphyrin IX.

In evaluating the autofluorescence properties of normal and diseased skin we discovered that psoriatic plaques can emit a distinct red fluorescence when illuminated with UVA or blue light. Using a macrospectrofluorometer equipped with a 442 nm excitation laser, a sharp in vivo fluorescence emission peak around 635 nm could be demonstrated within the plaques of 34 of 75 (45%) patients with psoriasis. This peak was absent from normal appearing skin of psoriatic patients and also from the skin of 66 patients with other dermatologic diseases. A microspectrofluorometer coupled with the same excitation laser was used to obtain emission spectra of separated epidermal sheets and dermis from plaques demonstrating macroscopic red autofluorescence. An emission peak around 635 nm was observed in all three patients thus studied, but only on spectra obtained from the epidermis. Additional spectra of vertical microscopic sections of intact psoriatic skin from five other patients revealed that the peak originated from the stratum corneum. Emission spectra from other microlocations including the mid-epidermis and dermis of psoriatic and normal skin, as well as the stratum corneum of normal skin, failed to demonstrate a 635 nm peak. The excitation and emission fluorescence spectra of acid extracts of psoriatic scale from five patients were all similar to those of protoporphyrin IX in acid solution. High performance liquid chromatography identified the presence of protoporphyrin IX in the acid extracts from psoriatic scale of the same patients. We conclude that native psoriatic plaques can exhibit red autofluorescence that is due to elevated levels of protoporphyrin IX within scales.

Fluorescence↗
PubMed1997

Bruton's tyrosine kinase regulates apoptosis and JNK/SAPK kinase activity.

Mast cells derived from Bruton's tyrosine kinase (Btk)-defective xid or btk null mice showed greater expansion in culture containing interleukin-3 (IL-3) than those from wild-type (wt) mice. Although the proliferative response to IL-3 was not significantly different between the wt and xid mast cells, xid and btk null mast cells died by apoptosis more slowly than their wt counterparts upon IL-3 deprivation. Consistent with these findings, the apoptosis-linked c-Jun N-terminal kinase/stress-activated protein kinase (JNK) activity was compromised in these btk-mutated cells upon Fc(epsilon)RI crosslinking or upon stimulation with IL-3 or with stem cell factor. p38 activity was less severely, but significantly, affected by btk mutation, whereas extracellular signal-regulated kinases were not affected by the same mutation. Btk-mediated regulation of apoptosis and JNK activity was confirmed by reconstitution of btk null mutant mast cells with the wt btk cDNA. Furthermore, growth factor withdrawal induced the activation and sustained activity of JNK in wt mast cells, while JNK activity was consistently lower in btk-mutated mast cells. These results support the notion that Btk regulates apoptosis through the JNK activation.

Agammaglobulinaemia Tyrosine Kinase↗
PubMed1997

Current status of photodynamic therapy in dermatology.

The accessibility of skin to light treatment, as well as the expertise developed by dermatologists in laser surgery and phototherapy, creates an exciting opportunity for dermatologic PDT to become part of our standard therapeutic armamentarium. PDT appears to be viable alternative to conventional therapy for superficial BCC and Bowen's disease, although definitive controlled studies are lacking. The introduction of ongoing research developments, new photosensitizers, and better light sources into clinical PDT trials in the coming years will undoubtedly expand the range of indications for this novel form of therapy, particularly for nononcologic conditions.

Humans↗