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C Whitehurst

Publications and source records attributed to C Whitehurst.

26 records · Page 2Linked to original sources

In situ comparison of 665 nm and 633 nm wavelength light penetration in the human prostate gland.

The depth of treatment in photodynamic therapy (PDT) of tumors varies with the wavelength of light activating the photosensitizer. New generation photosensitizers that are excited at longer wavelengths have the potential for increasing treatment depths. Tin ethyl etiopurpurin (SnET2), a promising second-generation photosensitizer is maximally activated at 665 nm, which may be significantly more penetrating than 633 nm light currently used with porphyrins in PDT. The penetration of 665 nm and 633 nm wavelength red light in the prostate gland was compared in 11 patients undergoing prostatic biopsies for suspected prostatic cancer. Interstitial optical fibers determined the light attenuation within the prostate gland. Of the 11 patients, 7 had dual wavelength and 4 had single wavelength studies. The mean attenuation coefficients, mueff, for 665 nm and 633 nm wavelength light were 0.32 +/- 0.05 mm-1 and 0.39 +/- 0.05 mm-1, respectively, showing a statistically significant difference (P = 0.0003). This represented a 22% increase in the mean penetration depth and at 10 mm from the delivery fiber there was 1.8 times as much 665 nm light fluence than 633 nm. The mean mueff at 665 nm for benign and malignant prostate tissue were similar (P = 0.42), however, there was significant interpatient variation (mueff ranging from 0.24 to 0.42 mm-1) reflecting biological differences of therapeutic importance. The enhanced light fluence and penetration depth with 665 nm light should allow significantly larger volumes of prostatic tissue to be treated with SnET2-mediated PDT.

Humans↗

In vivo laser light distribution in human prostatic carcinoma.

The extent of laser light diffusion within prostatic tumor is of major importance in the treatment of localized prostatic cancer with photodynamic therapy (PDT). The penetration of 633 nm. wavelength red light was studied in eleven patients with suspected prostatic cancer using a novel method suitable for in situ measurements. Light delivery and detector fiber, placed interstitially within the gland, determined light attenuation at different interfiber separations. Of 11 patients, 10 had bilateral and 1 had single lobe studies. The mean +/- the standard error of the mean attenuation coefficients (sigma eff) for benign and malignant prostate tissue were 0.35 +/- 0.02 mm-1 and 0.36 +/- 0.02 mm-1, respectively, indicating similar optical densities (p = .58). Patients with bilateral lobe involvement showed little intraglandular variation in sigma eff (p = 0.23). However, there was interpatient variation (sigma eff = 0.28 to 0.48 mm-1) reflecting biological differences which, though therapeutically important, were not statistically significant (p = 0.057). This study showed that treatment requires individualization and predicted that 4 cylindrical diffusers are expected to destroy 25 ml. of prostatic tumor with PDT.

Humans↗

Optimization of multifiber light delivery for the photodynamic therapy of localized prostate cancer.

The understanding of light distribution within the target organ is essential in ensuring efficacy and safety in photodynamic therapy (PDT). A computer simulator of light distribution in prostatic tissue was employed for optimizing dosimetry for PDT in localized prostatic cancer. The program was based on empirically determined light distributions and optical constants and an assumed fluence rate differential from fiber source to necrosis periphery. The diffusion theory approximation to the Boltzmann transport equation was the applicable formulation relevant to prostatic tissue, which has a high albedo with forward-scattering characteristics. Solving this equation of diffusive transfer for the appropriate fiber geometry yielded the energy fluence distributions for cleaved fiber and cylindrical diffuser light delivery. These distributions, confirmed by our measurements, show a 1/r and 1/square root of r dependency (r = distance from light source) of the fluence phi (r) for the cleaved fiber and diffuser, respectively. This manifests itself by the tighter spacing of energy fluence isodoses in the case of the cleaved fiber. It was predicted that for a typical PDT regime a single interstitially placed cleaved fiber would treat 0.05-0.72 cm3. Four parallel fibers improved the uniformity of light distribution and treatment volume, and an interfiber separation of 12 mm would be necessary to provide optimal overlap of PDT necrosis, treating 0.26-3.6 cm3. The cylindrical diffuser, however, could treat larger volumes, and it was predicted that four 3 cm long diffusers at an optimal separation of 25 mm would treat 25-88 cm3 of prostatic tissue.

Computer Simulation↗

Identification of clusters of biallelic polymorphic sequence-tagged sites (pSTSs) that generate highly informative and automatable markers for genetic linkage mapping.

Using a combination of denaturing gradient gel electrophoresis and direct DNA sequencing, we have found that multiple (4 to 7) biallelic sequence polymorphisms can be located within short DNA segments, 300 to 2400 bp. Here, we report on the identification of three clusters of DNA polymorphisms, one in each of the constant regions of the human T cell receptor alpha and beta gene complexes on human chromosomes 14 and 7, respectively, and a third among the human t-RNA genes on human chromosome 14. The frequency of these polymorphisms and the extent of linkage disequilibrium between individual polymorphisms have been determined using a semiautomated DNA typing system combining DNA target amplification by the polymerase chain reaction with the analysis of internal sequence polymorphisms by a colorimetric oligonucleotide ligation assay. We have found that individual biallelic polymorphisms in each cluster are often in partial linkage disequilibrium with one another. This partial linkage disequilibrium permits the combined use of three to four markers in a cluster to generate a haplotype with high levels of heterozygosity, 71 to 88%. Therefore, clusters of physically linked biallelic polymorphisms provide an automatable and highly informative type of genetic marker for general linkage analysis as well as an attractive alternative marker system for fine-point mapping of disease-causing genes and phenotypic traits relative to their framework locations in the genome.

Alleles↗

Photodynamic therapy for localised prostatic cancer: light penetration in the human prostate gland.

We are investigating the feasibility of photodynamic therapy in the treatment of localised prostatic cancer. Of major importance in this form of treatment is the extent to which light penetrates the target organ; hence, our interest in the optical properties of the human prostate gland. We obtained three whole prostates from autopsies of patients who died of non-urological causes. Red light was launched interstitially and detector fibres measured light intensity as a function of distance from the delivery fibre end. The optical constants derived from the three prostates were almost identical and indicated that light was predominantly scattered rather than absorbed (mean absorption and scattering coefficients 0.07 +/- 0.02 mm.-1 and 0.86 +/- 0.05 mm.-1 respectively). In a comparison of the tissue penetration by four different wavelengths, 633 nm red light was found to be transmitted best. Light propagation in the heavily absorbing tissue of the human liver was 4.3 times poorer than in the prostate. Such a combination of low absorption and high scattering characteristics in prostatic tissue would enhance the effectiveness of PDT. The optical constants derived will enable "light treatment planning" in patients with prostatic cancer.

Aged↗

Identification of urinary stone composition by pulsed dye laser.

Stones were recovered from the urinary tract and their composition determined by X-ray diffraction before exposure to a pulsed dye laser beam. The resultant fluorescent emissions were recorded using a scanning reticon and they appeared to be specifically related to the composition of each stone. This technique has a practical application as it may allow identification of the composition of urinary tract stones in vivo, and so indicate the best mode of lithotripsy.

Humans↗

Photodynamic therapy for superficial basal cell carcinoma and Bowen's disease.

Photodynamic therapy (PDT) is an effective treatment for superficial basal cell carcinoma (BCCs) and Bowen's disease. Several studies have reported complete response rates of 80-95% and an excellent cosmetic outcome. Bowen's disease and superficial basal cell carcinomas characteristically affect older patients who may also have associated difficulties with mobility. Using a portable PDT light source we were able to deliver PDT in a community setting with the aim of providing a more convenient service for patients. This randomised study confirmed that community delivered PDT is a viable treatment option and can be administered safely in the community by a trained dermatology nurse. The results from patient questionnaires suggest that community delivered PDT is more convenient to the patient, and also cost effective.

Adult↗