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Biomedical subjects

M R Stringer

Publications and source records attributed to M R Stringer.

13 recordsLinked to original sources

The analysis of human cortical bone by terahertz time-domain spectroscopy.

Samples of cortical bone, derived from human femur, have been studied using terahertz time-domain transmission spectroscopy. The relationship between the broadband THz parameters and the previously acquired values of Young's modulus and x-ray attenuation (CT number), and the density of each bone sample, is investigated. The only significant correlation is that between THz transmission and sample density, suggesting that the potential use of THz radiation as a non-invasive probe of bone quality is limited. The spectra of absorption coefficient and refractive index are plotted over the frequency range 0.1-1.25 THz. There is evidence that the sample hydration state is a factor in the resultant THz parameters.

Bone Density↗

Topical aminolaevulinic acid-photodynamic therapy for the treatment of acne vulgaris: a study of clinical efficacy and mechanism of action.

BACKGROUND: Acne affects 83-95% of 16-year-olds of both sexes, and many seek help from a clinician. Emerging problems with conventional acne treatments, specifically antibiotic resistance of Propionibacterium acnes and fears over the safety and tolerance of oral isotretinoin, create a demand for novel treatment modalities in acne. OBJECTIVES: To study the efficacy of aminolaevulinic acid-photodynamic therapy (ALA-PDT) in the treatment of acne and to identify the mode of action, looking specifically at the effects on surface numbers of P. acnes and on sebum excretion. METHODS: Ten patients (nine men and one woman, age range 16-40 years) with mild to moderate acne on their backs were recruited. Each patient's back was marked with four 30-cm2 areas of equal acne severity. Each site was then randomly allocated to either ALA-PDT treatment, light alone, ALA alone or an untreated control site. At baseline, numbers of inflammatory and noninflammatory acne lesions were counted, sebum excretion measured by Sebutapes (CuDerm, Dallas, TX, U.S.A.) and surface P. acnes swabs performed. ALA cream (20% in Unguentum Merck) was applied under occlusion to the ALA-PDT and ALA alone sites for 3 h. Red light from a diode laser was then delivered to the ALA-PDT and light alone sites (635 nm, 25 mW cm(-2), 15 J cm(-2)). Each patient was treated weekly for 3 weeks. At each visit acne lesion counts were performed and 3 weeks following the last treatment sebum excretion rates and P. acnes swabs were repeated. RESULTS: There was a statistically significant reduction in inflammatory acne lesion counts from baseline after the second treatment at the ALA-PDT site but not at any of the other sites. No statistically significant reduction in P. acnes numbers or sebum excretion was demonstrated at any sites including the ALA-PDT site. CONCLUSIONS: ALA-PDT is capable of clinically improving acne. An alternative mode of action for ALA-PDT other than direct damage to sebaceous glands or photodynamic killing of P. acnes is suggested from the results of this study.

Acne Vulgaris↗

Effect of photodynamic therapy on recurrent pituitary adenomas: clinical phase I/II trial--an early report.

Pituitary adenomas, although histologically benign, are not always curable by surgery alone, principally because of dural infiltration, as well as their peculiar anatomical location. Radiotherapy has been employed as an adjuvant therapy to address residual disease with favourable results. This approach is, however, not without side effects, and it cannot be repeated. We are therefore investigating the effectiveness of photodynamic therapy (PDT) on recurrent pituitary adenomas in humans. This study details the protocol applied to 12 patients with recurrent pituitary adenomas, which involved systemic administration of photosensitizer (Photofrin) followed, after a period of 24-48 h, by intraoperative illumination of the tumour bed using 630 nm laser light. The primary end points were visual, endocrine and radiological improvement. The incidence of side effects was also monitored. The longest follow-up is 2 years. Most patients suffering from visual acuity or field defects have shown improvement when followed for 12 months or more. Three patients showed complete recovery of their visual fields. All those who presented with functional adenomas have shown reduction in their hormone levels. Tumour volume, relative to the preoperative size, was 122, 87, 66, 60 and 46% at 4 days, and 3, 6, 18 and 24 months, respectively. One patient developed severe skin photosensitization due to early exposure to direct sunlight and three others displayed minor skin reactions. There was no treatment-related mortality or morbidity. One patient (operated transcranially) developed hemiparesis postoperatively, which recovered completely. We think this is unrelated to the treatment. This prospective study demonstrates that PDT may be safely applied to the pituitary fossa by the trans-sphenoidal route and indicates the need for a randomized, controlled trial in order to establish its therapeutic potential.

Adenoma↗

Erythroplasia of Queyrat treated by topical aminolaevulinic acid photodynamic therapy.

Erythroplasia of Queyrat (EQ) is an intraepithelial carcinoma in situ affecting the mucosal surfaces of the penis, with a significant risk of invasion and metastasis. Treatment is often difficult and is associated with significant recurrence rates. Topical 5-aminolaevulinic acid (ALA) photodynamic therapy (PDT) combines a photosensitizer precursor and visible light to produce a photodynamic effect. It has been used successfully to treat benign, premalignant and malignant skin diseases. We present four patients with EQ who have been treated by topical ALA PDT. Of two patients with limited disease one has achieved a long-term complete response (36 months) and the other developed a recurrence at 18 months after a complete response. Two further patients with more extensive disease achieved a significant improvement, allowing easier treatment by laser vaporization. Although topical ALA PDT offers the advantages of tumour specificity, preservation of function and a good cosmetic result, more extensive EQ appears less responsive to this new therapeutic modality using current treatment parameters.

Administration, Topical↗

Improved response of plaque psoriasis after multiple treatments with topical 5-aminolaevulinic acid photodynamic therapy.

We investigated the clinical response of 10 patients with plaque psoriasis to multiple treatments with photodynamic therapy, using topical application of 5-aminolaevulinic acid followed by exposure to broad-band visible radiation. Treatment was performed up to 3 times per week, with a maximum of 12 treatments, using a light dose of 8 Jcm(-2) delivered at a dose-rate of 15 mW cm(-2). Eight patients showed a clinical response. Out of 19 treated sites, 4 cleared, 10 responded but did not clear and 5 showed no improvement. Of the 4 sites that cleared only 1 did so fully, after 7 treatments, 45 days after the start of therapy. Of the 10 sites that responded partially, the greatest reduction in scale, erythema and induration index occurred after a minimum of 3 and a maximum of 8 treatments. The intensity of 5-aminolaevulinic acid-induced protoporphyrin IX fluorescence, recorded prior to the first treatment, varied between sites on the same patient as well as between patients. There was also a variation in fluorescence intensity recorded from the same site immediately prior to subsequent treatments, although the pretreatment levels generally decreased as the study progressed and then increased as psoriasis relapsed. Biopsies confirmed that fluorescence was localized throughout the epidermis and stratum corneum, but the level was not consistent between sections taken within the same biopsy. We also observed fluorescence at sites distant from the ones that received 5-aminolaevulinic acid, which was not present prior to the start of the treatment programme, but found no evidence of elevated levels of plasma porphyrins. The level of discomfort associated with this therapy increased with increasing values of the calculated photodynamic dose, defined as the product of the initial photosensitizer concentration and the percentage reduction in fluorescence following irradiation. Therefore, although clinical efficacy improved with multiple treatments, unpredictable response and patient discomfort make ALA-PDT unsuitable for the treatment of psoriasis.

Administration, Topical↗

Protoporphyrin IX fluorescence photobleaching during ALA-mediated photodynamic therapy of UVB-induced tumors in hairless mouse skin.

Fluorescence photobleaching of protoporphyrin IX (PpIX) during superficial photodynamic therapy (PDT), using 514 nm excitation, was studied in UVB-induced tumor tissue in the SKH-HR1 hairless mouse. The effects of different irradiance and light fractionation regimes upon the kinetics of photobleaching and the PDT-induced damage were examined. Results show that the rate of PpIX photobleaching (i.e., fluorescence intensity vs fluence) and the PDT damage both increase with decreasing irradiance. We have also detected the formation of fluorescent PpIX photoproducts in the tumor during PDT, although the quantity recorded is not significantly greater than generated in normal mouse skin, using the same light regime. The subsequent photobleaching of the photoproducts also occurs at a rate (vs fluence) that increases with decreasing irradiance. In the case of light fractionation, the rate of photobleaching increases upon renewed exposure after the dark period, and there is a corresponding increase in PDT damage although this increase is smaller than that observed with decreasing irradiance. The effect of fractionation is greater in UVB-induced tumor tissue than in normal tissue and the damage is enhanced when fractionation occurs at earlier time points. We observed a variation in the distribution of PDT damage over the irradiated area of the tumor: at high irradiance a ring of damage was observed around the periphery. The distribution of PDT damage became more homogeneous with both lower irradiance and the use of light fractionation. The therapeutic dose delivered during PDT, calculated from an analysis of the fluorescence photobleaching rate, shows a strong correlation with the damage induced in normal skin, with and without fractionation. The same correlation could be made with the data obtained from UVB-induced tumor tissue using a single light exposure. However, there was no such correlation when fractionation schemes were employed upon the tumor tissue.

Aminolevulinic Acid↗

Fluorescence photobleaching of ALA-induced protoporphyrin IX during photodynamic therapy of normal hairless mouse skin: the effect of light dose and irradiance and the resulting biological effect.

The photobleaching of 5-aminolaevulinic acid (ALA)-induced protoporphyrin IX (PpIX) was investigated during superficial photodynamic therapy (PDT) in normal skin of the SKH HR1 hairless mouse. The effects of light dose and fluence rate on the dynamics and magnitude of photobleaching and on the corresponding PDT-induced damage were examined. The results show that the PDT damage cannot be predicted by the total light dose. Photobleaching was monitored over a wide range of initial PpIX fluorescence intensities. The rate of PpIX photobleaching is not a simple function of fluence rate but is dependent on the initial concentration of sensitizer. Also, at high fluence rates (50-150 mW/cm2, 514 nm) oxygen depletion is shown to have a significant effect. The rate of photobleaching with respect to light dose and the corresponding PDT damage both increase with decreasing fluence rate. We therefore suggest that the definition of a bleaching dose as the light dose that causes a 1/e reduction in fluorescence signal is insufficient to describe the dynamics of photobleaching and PDT-induced damage. We have detected the formation of PpIX photoproducts during the initial period of irradiation that were themselves subsequently photobleached. In the absence of oxygen, PpIX and its photoproducts are not photobleached. We present a method of calculating a therapeutic dose delivered during superficial PDT that demonstrates a strong correlation with PDT damage.

Aminolevulinic Acid↗

Large patches of Bowen's disease treated by topical aminolaevulinic acid photodynamic therapy.

Large patches of Bowen's disease (intraepidermal carcinoma in situ) can be difficult to treat by conventional methods. Photodynamic therapy (PDT) uses the combination of a photosensitizer, which preferentially accumulates in malignant cells, and photoactivation by visible light to kill the malignant cells. 5-aminolaevulinic acid (ALA) PDT uses excess exogenous ALA, which produces, via the haem synthesis pathway, a build up of the photosensitizer protoporphyrin IX. We describe the use of topical ALA PDT to treat three patients with three especially large patches of Bowen's disease. Following two treatments all three lesions achieved a complete clinical and histological response with a good cosmetic result. ALA PDT is a simple, effective and well tolerated treatment for large patches of Bowen's disease.

Aged↗

The variable response of plaque psoriasis after a single treatment with topical 5-aminolaevulinic acid photodynamic therapy.

We have investigated the clinical response of 22 patients with plaque psoriasis to photodynamic therapy using topical application of 5-aminolaevulinic acid followed by a single exposure to broad-band visible radiation. Light doses in the range 2-16 J/cm2 delivered at dose of 10-40 mW/ cm2 resulted in a variable clinical response. Seven (35%) patients showed clearing of psoriasis at some treated sites. The intensity of protoporphyrin IX fluorescence was recorded before, during and after treatment. Pre-illumination fluorescence intensity varied considerably between sites on the same patient and between patients. Protoporphyrin IX fluorescence recovered and persisted after treatment for up to 14 days and became higher than preillumination levels at 25% of sites. The rate of protoporphyrin IX photo-oxidation during treatment was proportional to both initial fluorescence intensity and incident light dose rate and was almost complete after 16 J/cm2. We have defined the photodynamic dose as the product of time-dependent protoporphyrin IX concentration and light dose and demonstrated that only in those patients who showed clearance of psoriasis was there a relationship between photodynamic dose and clinical response. Discomfort ranged from stinging through to burning, was significant in some patients and tended to be more severe with increasing photodynamic dose but was not predictable. Efficacy may improve by achieving consistent protoporphyrin IX levels or by using multiple treatments.

Aminolevulinic Acid↗

The accumulation of protoporphyrin IX in plaque psoriasis after topical application of 5-aminolevulinic acid indicates a potential for superficial photodynamic therapy.

The success reported for the treatment of superficial skin carcinomas by photodynamic therapy with topical application of the photosensitizer precursor 5-aminolevulinic acid has therapeutic implications for the treatment of other skin disorders. This paper describes the accumulation of the photosensitizing agent protoporphyrin IX in areas of plaque psoriasis by monitoring of the fluorescence emission induced by low-intensity laser excitation at 488 nm. We present results from 15 patients with a total of 42 plaques and show that the characteristic fluorescence emission of protoporphyrin IX increases in intensity within the 6-h period following application of 5-ami-nolevulinic acid, suggesting that there is a potential for superficial photodynamic therapy. The rate of increase and maximum intensity of fluorescence emission was not directly related to the applied quantity of the precursor. The variability of the fluorescence intensity was as great between plaques at different sites on the same patient as between different patients. Also, the effect of plaque occlusion following application appeared insignificant. Although there was only limited enhancement of emission from areas of skin surrounding the plaque, a significant buildup of sensitizer was detected after several days in some areas of psoriasis that received no application.

Administration, Topical↗

Superficial photodynamic therapy with topical 5-aminolaevulinic acid for superficial primary and secondary skin cancer.

Between January 1991 and December 1992 a phase I trial of superficial photodynamic therapy (PDT) using topical application of 5-aminolaevulinic acid (ALA) was undertaken to treat Bowen's disease, superficial basal cell carcinomas (BCCs) and metastatic skin secondaries from breast (adenocarcinoma) or pinna (squamous cell carcinoma). Promising results were obtained with 36 areas of Bowen's disease, with a complete response rate of 89% at a median follow-up of 18 months. The treatment of BCCs was less successful, with 50% complete responses in 16 lesions at a median follow-up of 17 months. Metastatic nodules responded poorly. The treatment was well tolerated and discomfort during light irradiation could be reduced by prior application of 'Emla' cream. Lesions wept for 1-2 weeks following treatment and healed over a period of approximately 2 months. For large areas of Bowen's disease, particularly in anatomically difficult areas and in elderly patients, PDT using ALA may constitute a single simple alternative outpatient treatment to existing therapies. Further work is required to improve the results with BCCs.

Adenocarcinoma↗

Chorionic villi sampling: a nursing perspective.

A relatively new procedure, chorionic villi sampling is now available as an alternative method for prenatal diagnoses of genetic disorders during pregnancy. Indications, procedures, risks, advantages, and nursing implications of this procedure are defined and described. Readers are thereby provided with current information concerning prenatal genetic diagnosis that may be passed on to patients in need of this information.

Biopsy, Needle↗