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Biomedical subjects

C Whitehurst

Publications and source records attributed to C Whitehurst.

At least 19 recordsLinked to original sources
PubMed2005

An open study to determine the efficacy of blue light in the treatment of mild to moderate acne.

BACKGROUND: The effective management of acne remains a challenge; achieving an optimal response whilst minimizing adverse events is often difficult. The rise in antibiotic resistance threatens to reduce the future usefulness of the current mainstay of therapy. The need for alternative therapies remains important. Phototherapy has previously been shown to be effective in acne, with renewed interest as both endogenous and exogenous photodynamic therapies are demonstrated for this condition. OBJECTIVES: To determine the effect of narrowband blue light in the reduction of inflammatory and non-inflammatory lesions in patients with mild to moderate acne and to evaluate patient tolerance of the therapy. METHODS: We performed an open study utilizing a blue LED light source in 30 subjects with mild to moderate facial acne. Two weeks after screening, lesions were counted and recorded by lesion type. Over 4 weeks, patients received eight 10- or 20-minute light treatments, peak wavelength 409-419 nm at 40 mW/cm2. Assessments were taken at weeks 5, 8 and 12 and lesion counts were recorded. Repeated measures-ANOVA and Dunnett's tests, respectively, allowed assessment of the different scores over time and permitted comparison of mean counts. RESULTS: An overall effect on inflammatory counts was observed at week 5, and a statistically significant decrease in inflamed counts was detected at the week 8 assessments, which continued to week 12. There was little effect on non-inflamed lesions. The treatment was well tolerated with adverse events experienced generally rated as being mild and usually self-limiting. CONCLUSIONS: Eight 10- or 20-minute treatments over 4 weeks with a narrowband blue light was found to be effective in reducing the number of inflamed lesions in subjects with mild to moderate acne. The treatment had little effect on the number of comedones. The onset of the effect was observable at the first assessment, at week 5, and maximal between weeks 8 and 12. Blue light phototherapy using a narrowband LED light source appears to be a safe and effective additional therapy for mild to moderate acne.

Acne Vulgaris↗
PubMed2002

Photodynamic therapy for superficial bladder cancer under local anaesthetic.

OBJECTIVES: To evaluate the use of local anaesthesia (LA) in 5-aminolaevulinic acid (ALA) photodynamic therapy (PDT) for superficial transitional cell carcinoma (TCC) of the bladder, and to provide further toxicity and tolerability data on this new method within the context of a phase 1 trial. PATIENTS AND METHODS: ALA PDT was administered to 19 patients with recurrent superficial TCC (stage Ta/carcinoma in situ, grades 1-3) using escalating doses of ALA (3-6%) and 633 nm laser light (25-50 J/cm2) under various LA (lignocaine) protocols. Pain was assessed using a linear analogue scale from 0 to 10. The endpoints of tolerability and toxicity were assessed for the different LA, light and ALA doses, with lignocaine levels. RESULTS: ALA PDT is painful and requires some form of anaesthesia. The discomfort was immediate, associated with bladder spasm, and was a function of the ALA concentration rather than the total light dose given. Simple passive diffusion (PD) of 2% lignocaine instilled for 40 min before PDT gave adequate anaesthesia with 3% ALA (n=8; median pain score 1, range 0-2). With 6% ALA the pain was dramatically increased using PD (n=6; median pain score 8, range 5-10) and therefore the more potent LA technique of electromotive drug administration (EMDA) of 2% lignocaine was used, with excellent results (n=3; median pain score 1, range 0-2). All patients had transient bladder irritability that typically lasted 9-12 days, with no subjective/objective change in long-term bladder function. No other toxicity was reported. Serum lignocaine levels were minimal. CONCLUSION: Bladder ALA PDT is both safe and feasible under LA. At a dose of 3% ALA, the procedure was well-tolerated using PD of lignocaine. At higher doses (6% ALA) more effective anaesthesia is required and this can be obtained satisfactorily with EMDA of lignocaine. With refinement, ALA PDT may be feasible as an outpatient treatment for superficial bladder TCC.

Aged↗
PubMed2002

Comparison of the cellular molecular stress responses after treatments used in bladder cancer.

OBJECTIVE: To investigate the molecular stress responses related to the quality of recovery of normal tissue after various treatments for bladder cancer, i.e. hyperthermia, ionizing radiation, mitomycin-C and 5-aminolaevulinic acid photodynamic therapy (ALA-PDT). MATERIALS AND METHODS: The study focused particularly on intracellular fibroblast levels of heat-shock protein-47 (HSP47) and HSP72, which are associated with collagen metabolism and the development of tolerance to repeated treatment, respectively. Iso-effective treatment doses (50% clonogenic cell survival) of each method were delivered to a 3T6 murine fibroblast model. Intracellular extracts were analysed at 3, 6, 9, 12 and 24 h after treatment, using Western blot analysis to compare the levels of HSP47 and HSP72. Time-matched treatment and control groups were quantified by comparison with actin and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) expression using appropriate software. RESULTS: There were various changes in levels of HSP expression with treatment method; HSP47 levels were significantly higher after hyperthermia and radiation but not with mitomycin-C or ALA-PDT. HSP72 levels were significantly higher with all methods except ALA-PDT. CONCLUSIONS: Hyperthermia and ionizing radiation are associated with early increases in levels of HSP47 (a marker of collagen metabolism), in contrast to ALA-PDT and mitomycin-C. These findings are compatible with clinical findings where fibrosis/scarring is common with the first two but not the last two methods. In addition, all methods except ALA-PDT are associated with an increase in HSP 72 (a protein associated with cellular tolerance) and this may help to explain, at a cellular level, why resistance to repeated ALA-PDT treatments does not seem to occur.

Animals↗
PubMed2001

Photodynamic therapy for superficial bladder cancer.

In photodynamic therapy, a photosensitizing drug is activated by visible light and in the presence of oxygen, results in local cell death. This evolving modality is now being used to treat and palliate a very wide variety of human solid tumors and carcinoma-in-situ lesions. With regard to bladder cancer, advances in drug development and modern light delivery techniques mean that photodynamic therapy shows promise in the treatment of superficial bladder cancer resistant to conventional treatments.

Aminolevulinic Acid↗
PubMed2001

Photodynamic therapy for large or multiple patches of Bowen disease and basal cell carcinoma.

BACKGROUND: Photodynamic therapy (PDT) using topical delta-aminolevulinic acid (delta-ALA) is an effective treatment for Bowen disease and certain basal cell carcinomas (BCCs), but its place in clinical practice remains to be established. Patients with large and/or multiple lesions of Bowen disease or BCC can represent a considerable therapeutic challenge. We suggest that delta-ALA PDT may be of particular benefit in such patients. OBSERVATION: In an open study, 35 (88%) of 40 large patches of Bowen disease, all with a maximum diameter greater than 20 mm, cleared following 1 to 3 treatments of delta-ALA PDT, although 4 patches recurred within 12 months. delta-Aminolevulinic acid PDT was also used to treat 40 large BCCs, with an identical 88% initial clearance (after 1-3 treatments), with 4 recurrences within 34 months (range, 12-60 months). In 10 further patients with multiple (> or =3) patches of Bowen disease, 44 (98%) of 45 patches cleared following delta-ALA PDT, although 4 lesions recurred over 12 months. In 3 patients with multiple BCCs, PDT cleared 52 (90%) of 58 lesions, with 2 recurrences during 41 months (range, 12-52 months). Treatments were well tolerated, with only 5 patients with solitary large lesions requiring local anesthesia. CONCLUSIONS: delta-Aminolevulinic acid PDT is an effective tissue-sparing modality achieving good cosmesis. We propose that delta-ALA PDT be considered as a first-line therapy for large and/or multiple areas of Bowen disease and superficial BCCs.

Adult↗
PubMed2000

Comparison of red and green light in the treatment of Bowen's disease by photodynamic therapy.

BACKGROUND: A variety of protocols exist for the treatment of Bowen's disease by photodynamic therapy (PDT) using topical 5-aminolaevulinic acid (5-ALA). OBJECTIVE: To determine the optimal wavelength (red or green light) for this treatment. METHODS: A randomized comparison study of ALA-PDT using red (630 +/- 15 nm) or green (540 +/- 15 nm) light in the treatment of Bowen's disease. RESULTS: The initial clearance rate for lesions treated by red light was 94% (30 of 32) in comparison with 72% (21 of 29) for those lesions receiving green light (P = 0.002). Over the following 12 months, there were two recurrences in the red light group and seven in the green light group reducing the clearance rates to 88% and 48%, respectively. The frequency and severity of pain experienced were similar between the two treatment groups. No hyperthermia, nor significant difference in lesional temperatures, was observed between the wavelengths studied. CONCLUSION: Green light is less effective than red light, at a theoretically equivalent dose, in the treatment of Bowen's disease by topical ALA-PDT.

Aged↗
PubMed2000

Routine double treatments of superficial basal cell carcinomas using aminolaevulinic acid-based photodynamic therapy.

BACKGROUND: Superficial basal cell carcinomas of the skin (sBCC) often respond poorly to single-treatment aminolaevulinic acid-based photodynamic therapy (ALA-PDT), with a number of reports indicating a relapse rate of 50% or more. OBJECTIVES: To determine whether a second treatment at seven days can improve the response. METHODS: Twenty-six lesions were treated twice with ALA-PDT, with an interval of 7 days between the two treatment sessions. RESULTS: We observed a complete response rate of 100% 1 month after treatment. Only one lesion relapsed (16 months post-PDT), a relapse rate of 4% (median follow up 27 months; range 15-45 months). Cosmetic results were excellent. CONCLUSIONS: We consider routine double treatments with ALA-PDT to be an effective approach to the management of sBCC, particularly those located in anatomically difficult, or cosmetically sensitive, sites.

Administration, Cutaneous↗
PubMed2000

Light penetration in bladder tissue: implications for the intravesical photodynamic therapy of bladder tumours.

OBJECTIVES: To assess (i) the optical properties and depth of penetration of varying wavelengths of light in ex-vivo human bladder tissue, using specimens of normal bladder wall, transitional cell carcinoma (TCC) and bladder tissue after exposure to ionizing radiation; and (ii) to estimate the depth of bladder wall containing cancer that could potentially be treated with intravesical photodynamic therapy (PDT), assuming satisfactory tissue levels of photosensitizer. Materials and methods The study included 11 cystectomy specimens containing invasive TCC (five from patients who had previously received external-beam bladder radiotherapy, but with recurrent TCC) and three 'normal' bladders removed from patients treated by exenteration surgery for extravesical pelvic cancer. Full-thickness bladder wall and tumour samples were taken from these specimens and using an 'intravesical' and a previously validated interstitial model, the optical penetration depths (i.e. the tissue depth at which the light fluence is 37% of incident) were calculated at wavelengths of 633, 673 and 693 nm. RESULTS: There were no significant differences in light penetration between normal and tumour-affected bladder tissue at each wavelength. There were significant differences in light penetration among wavelengths; light at 693 nm penetrated approximately 40% further than light at 633 nm (P < 0.002). The light currently used in bladder PDT (633 nm) has a mean (SEM) optical penetration depth of 4.0 (0.1) mm within TCC. In addition, at this wavelength, there was 29% greater light penetration in previously irradiated than in unirradiated bladder wall (P = 0.001). This did not occur in the tumour-affected bladder. CONCLUSIONS: Bladder tissue is relatively more translucent than other human tissues and there is therefore great potential for PDT in the treatment of bladder cancer. As there is no difference in light penetration between TCC and normal bladder tissue, a tumour-specific response with diffuse illumination of the bladder will depend on drug localization within the tumour. The currently used wavelength of 633 nm can be expected to exert a PDT effect within bladder tumour up to a depth of 20 mm. Increasing the wavelength will allow deeper pathology to be treated.

Humans↗
PubMed1999

An interstitial light assembly for photodynamic therapy in prostatic carcinoma.

OBJECTIVE: To develop an interstitial laser light delivery system using multiple optical fibres for photodynamic therapy (PDT) in the treatment of prostate cancer. PATIENTS AND METHODS: A laser beam was divided equally with a 1 x 4 fibre splitter to deliver PDT simultaneously through four 2-cm long, flexible cylindrical optical diffusers. Biplanar transrectal ultrasonography (TRUS) and a template were used to position the optical fibres percutaneously. In vivo measurements of light penetration depth (1/micro[eff] ) in prostate tissue were made in seven patients, using a sheathed isoprobe to measure light fluence rates at varying radial distances from the diffuser. The prostate was fixed with stabilization needles to minimize displacement during needle placement. RESULTS: The mean (sd, range) micro(eff) in the prostates of the seven patients was 0.35 (0.07, 0.22-0.44) mm-1, which produced closely parallel slopes of light attenuation. However, there was up to a 10-fold variation in absolute light levels at the same diffuser-detector separation distances amongst the seven patients, probably caused by blood pooling around the diffuser light source. A similar problem around the isoprobe detector was overcome by sheathing the probe in clear plastic tubing. By stabilizing the prostate, the optical fibre positioning was precise to within 2 mm. CONCLUSION: Although this light delivery and TRUS assembly were developed for clinical PDT in the prostate, the same instrumentation can be used reliably for in vivo light-penetration studies. Haemorrhage was unpredictable and highlighted one of the main problems which needs to be overcome.

Aged↗
PubMed1997

Interstitial photodynamic therapy in the canine prostate.

OBJECTIVE: To determine the depth of tissue destruction and the minimum light dose required for necrosis in interstitial photodynamic therapy (PDT), as a prerequisite for the investigational therapy of patients. MATERIALS AND METHODS: Seven adult beagle dogs were given 2 mg/kg of the photosensitizer Photofrin intravenously and two controls received none. After 24 h, 450 J/cm of 630 nm wavelength laser light was delivered interstitially to the prostate via a 2 cm long diffuser fibre. Seven single-fibre treatments were performed in five sensitized dogs and two single-fibre treatments in the controls. The two remaining sensitized dogs had two fibres placed 10 mm apart within the prostate to determine the coalescence of PDT lesions. The penetration depth of light was measured in all prostates, and after PDT the extent of necrosis was assessed histologically. RESULTS: The mean (standard deviation, SD) radius of PDT destruction around each diffuser was 5.3 (1.4) mm and PDT lesions overlapped in prostates treated with two fibres placed 10 mm apart. There was no observable tissue damage in the controls. The mean (SD) minimum light dose required for PDT necrosis was 84 (64) J/cm2. Differences among animals in the light penetration depth were small, with a mean of 2.14 (0.2) mm, and did not correlate with the depth of necrosis (P = 0.07). Bleeding around the optical diffuser fibre impeded light penetration. CONCLUSION: Interstitial PDT in the canine prostate using Photofrin produced modest volumes of tissue necrosis. The minimum light dose required to induce necrosis was variable because bleeding was unpredictable in relation to the optical fibre.

Animals↗
PubMed1997

The biology of photodynamic therapy.

The subcellular, cellular and tissue/tumour interactions with non-toxic photosensitizing chemicals plus non-thermal visible light (photodynamic therapy (PDT) are reviewed. The extent to which endothelium/vasculature is the primary target is discussed, and the biochemical opportunities for manipulating outcome highlighted. The nature of tumour destruction by PDT lends itself to imaging outcome by MRI and PET.

Animals↗
PubMed1996

Comparison of photodynamic therapy with cryotherapy in the treatment of Bowen's disease.

The efficacy and suitability of photodynamic therapy (PDT) was compared with that of cryotherapy in the treatment of 40 lesions of Bowen's disease. Lesions were randomized to receive either cryotherapy with liquid nitrogen, or PDT using a portable desktop lamp incorporating a 300 W xenon short arc discharge source. A porphyrin precursor, 5-aminolaevulinic acid (5-ALA), was applied topically 4 h before irradiation in the PDT group. Each lesion received 125 J/cm2 at a fluence rate of 70 mW/cm2. All patients were reviewed at 2-monthly intervals and treatments repeated if required. Cryotherapy produced clearance in 10 of 20 lesions after one treatment, the remaining 10 lesions requiring two or three treatment applications. PDT resulted in clearance of 15 of 20 lesions after one treatment and of the remaining five lesions after a second treatment. The probability that a lesion cleared after one treatment was greater with PDT than cryotherapy (P < 0.01). Cryotherapy was associated with ulceration (five of 20), infection (two of 20) and recurrent disease (two of 20); no such complications occurred following PDT. PDT using a non-laser light source and topical 5-ALA appears to be at least as effective as cryotherapy in the treatment of Bowen's disease with fewer adverse effects.

Aged↗