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Biomedical subjects

B C Wilson

Publications and source records attributed to B C Wilson.

At least 91 records · Page 5Linked to original sources

Resistance to photodynamic therapy in radiation induced fibrosarcoma-1 and Chinese hamster ovary-multi-drug resistant. Cells in vitro.

A degree of resistance to photodynamic therapy (PDT) has been induced in radiation-induced fibrosarcoma-1 (RIF-1) tumor cells by repeated photodynamic treatment with Photofrin (4 or 18 h incubation) in vitro to the 0.1-1% survival level, followed by regrowth from single surviving colonies. The resistance is shown as increased cell survival in the strain designated RIF-8A, compared to the wild-type RIF-1 cells, when exposed to increasing Photofrin concentration for 18 h incubation and fixed light exposure. No difference was found between RIF-1 and RIF-8A in the uptake of Photofrin per unit cell volume at 18 h incubation. Resistance to PDT was also observed in Chinese hamster ovary-multi-drug resistant (CHO-MDR) cells compared to the wild-type CHO cells, possibly associated with decreased cellular concentration of Photofrin in the former. By contrast, the PDT-resistant RIF-8A cells did not show any cross-resistance to Adriamycin, nor was there any significant drug concentration difference between RIF-1 and RIF-8A. These findings suggest that different mechanisms are responsible for PDT-induced resistance and multi-drug resistance.

Animals↗

Current and future trends in laser medicine.

In this overview, a number of the major current, and possible future developments in laser medicine are explored. In therapeutic applications, particular emphasis is given to obtaining selectivity in tissue targets and interaction mechanisms in order to achieve specific biological effects. This includes spatial confinement of thermal damage by pulsed laser irradiation and targetting by exogenous photothermal or photochemical chromophores. The potential for diagnostic applications of lasers in medicine is illustrated primarily by various in vivo spectroscopic techniques. Both therapeutic and diagnostic applications will rely increasingly on the development of total systems in which lasers will form only one, albeit an essential, part. Numerous scientific and technical problems need to be solved in order to realize the full clinical potential of the many new concepts in laser medicine. The impetus for such progress will come from integrated, multidisciplinary collaborations between medical, scientific and industrial groups.

Cornea↗

Experimental tests of the feasibility of singlet oxygen luminescence monitoring in vivo during photodynamic therapy.

Singlet oxygen (1O2) is thought to be the cytotoxic agent in photodynamic therapy (PDT) with current photosensitizers. Direct monitoring of 1O2 concentration in vivo would be a valuable tool in studying biological response. Attempts were made to measure 1O2 IR luminescence during PDT of cell suspensions and two murine tumour models using the photosensitizers Photofrin II and aluminium chlorosulphonated phthalocyanine. Instrumentation was virtually identical to that devised by Parker in the one positive report of in vivo luminescence detection in the literature. Despite the fact that our treatments caused cell killing and tissue necrosis, we were unable to observe 1O2 emission under any conditions. We attribute this negative result to a reduction in 1O2 lifetime in the cellular environment. Quantitative calibration of our system allowed us to estimate that the singlet oxygen lifetime in tissue is less than 0.5 microsecond. Some technical improvements are suggested which would improve detector performance and perhaps make such measurements feasible.

Humans↗

Photodynamic therapy of malignant brain tumours.

Fifty patients with malignant supratentorial tumours were treated with intra-operative photodynamic therapy (PDT); in 33 cases the tumour was recurrent. In 45 patients the tumour was a cerebral glioma and in 5 cases a solitary cerebral metastasis. All patients received a porphyrin photosensitizer 18-24 hours pre-operatively. Photoillumination was carried out at 630 nm to a tumour cavity created by radical tumour resection and/or tumour cyst drainage. The light energy density ranged from 8 to 175 J/cm2. In 8 patients additional interstitial light was administered. The operative mortality was 4%. Follow up has ranged from 1 to 30 months. The median survival for the 45 primary malignant tumours was 8.6 months with a 1 and 2 year actuarial survival rate of 32% and 18%, respectively. In 12 patients a complete or near complete CT scan response was identified post PDT. These patients tended to have a tumour geometry (eg. cystic) that allowed complete or near complete light distribution to the tumour. The median survival for this group was 17.1 months with a 1 and 2 year actuarial survival of 62% and 38%, respectively. In the 33 cases who did not have a complete response the median survival was 6.5 months with a 1 and 2 year actuarial survival of 22% and 11%, respectively. Photodynamic therapy of malignant brain tumours can be carried out with acceptable risk. Good responses appear to be related to adequate light delivery to the tumour.

Adolescent↗

In vivo tests of the concept of photodynamic threshold dose in normal rat liver photosensitized by aluminum chlorosulphonated phthalocyanine.

In its simplest form, the photodynamic therapy (PDT) threshold dose model states that tissue necrosis due to PDT will occur if the number of photons absorbed by the photosensitizer per unit volume of tissue exceeds a critical value. This threshold is given by the product of photon fluence, photosensitizer concentration and specific absorption coefficient. To test the validity of this concept for PDT of normal rat liver sensitized with aluminum chlorosulphonated phthalocyanine (AISPC), all three of these parameters were varied by changing the injected AISPC dose, the wavelength of excitation and the irradiation geometry. The extent of necrosis caused by the treatment was consistent with the threshold model, except when the concentration of AISPC in the liver exceeded 20 micrograms g-1. For this animal model, we estimate the threshold to be (3.8 +/- 0.2) x 10(19) photons cm-3.

Animals↗

Photodynamic therapy: light delivery and dosage for second-generation photosensitizers.

With the development of new photosensitizers that have enhanced photoactivation at longer wavelengths than haematoporphyrin derivative, new considerations arise in the light source and delivery systems and in the techniques for physical dosimetry and in vivo optical measurements in photodynamic therapy. The limitations and future potential of solid-state laser sources are presented. The relationships between photosensitizer photoactivation characteristics and the effective photodynamic treatment volume are developed and discussed quantitatively. The problems in defining and measuring the photodynamic dose are examined, and potential techniques for measuring the factors involved in this are evaluated with emphasis on noninvasive approaches which may be used clinically.

Humans↗

Monte Carlo modeling of light propagation in highly scattering tissues--II: Comparison with measurements in phantoms.

Measurements of the fluence-depth distributions and of the diffuse reflectance of 633 nm light have been made in liquid media with optical properties similar to soft tissues. The results are compared with predictions of Monte Carlo computer calculations in order to test the adequacy of Monte Carlo modeling of light transport in tissue. Except at extremely high albedo, the experimental data and the Monte Carlo results agree well for the depth dependence of the fluence as a function of incident light beam diameter and optical absorption and scattering, and for the dependence of the diffuse reflectance on the albedo. The absolute experimental values for the fluence must be renormalized by a factor which varies with the albedo in order to match the model values, and the possible sources of this discrepancy are discussed.

Connective Tissue↗

Monte Carlo modeling of light propagation in highly scattering tissue--I: Model predictions and comparison with diffusion theory.

Using optical interaction coefficients typical of mammalian soft tissues in the red and near infrared regions of the spectrum, calculations of fluence-depth distributions, effective penetration depths and diffuse reflectance from two models of radiative transfer, diffusion theory, and Monte Carlo simulation are compared for a semi-infinite medium. The predictions from diffusion theory are shown to be increasingly inaccurate as the albedo tends to zero and/or the average cosine of scatter tends to unity.

Light↗

Comparison of serum beta-2-microglobulin levels in patients with symptoms of allergic rhinitis and elevated modified RAST scores vs. a control population.

Forty-four subjects, having clinical histories consistent with allergic rhinitis with modified RAST score(s) of two or more for at least one of five locally prevalent aeroantigens, were compared with 48 control subjects with modified RAST scores of zero for all given aeroallergens. There was no significant difference between these two groups in mean levels of serum beta-2-microglobulin (Student's t, p greater than 0.05).

Adult↗

Hemodynamic, renal, and neurohumoral effects of a selective oral DA1 receptor agonist (fenoldopam) in patients with congestive heart failure.

Fenoldopam mesylate (SK&F 82526-J) is a novel benzazepine derivative. It has selective agonist activity at post-junctional (DA1) vascular dopaminergic receptors, which normally subserve renal artery vasodilation. Previous studies in normal subjects and in patients with hypertension indicate that fenoldopam increases renal blood flow and promotes a sodium diuresis. Drug efficacy was clinically evaluated in eight patients with chronic congestive heart failure (CHF) after a single oral dose of 100 mg of fenoldopam and following 3 days of therapy (100 mg four times daily). Stroke volume index acutely increased from 26 +/- 7 (mean +/- SD) to 30 +/- 4 ml/beat/m2 (p less than 0.05) and left ventricular filling pressure decreased from 26 +/- 13 to 23 +/- 11 mm Hg (p less than 0.05). Systemic vascular resistance decreased from 1513 +/- 159 to 1128 +/- 319 (p less than 0.05). Hemodynamic changes were seen as early as 30 minutes following fenoldopam and returned to control levels by 4 hours. Forearm blood flow, hepatic blood flow, and venous capacitance did not significantly change acutely, but renal blood flow index was significantly reduced (34 +/- 4 to 30 +/- 3 min-1 X 1000, p less than 0.01). Plasma norepinephrine, plasma renin activity, plasma arginine vasopressin, and plasma aldosterone did not significantly change acutely. After 3 days of treatment, 100 mg of fenoldopam again reduced the renal blood flow index (35 +/- 7 to 26 +/- 7 min-1 X 1000, p less than 0.01) and tended to increase plasma renin activity (11.7 +/- 8 to 21.2 +/- 19.4 ng/ml/hr, p = NS).(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗

Some probability models for diagnosing neurogenic disorders.

Healthy human skeletal muscles are composed of two distinguishable types of fibre, apparently randomly arranged within fascicles (bundles of fibres surrounded by connective tissue). Large groups of fibres of the same type indicate a neurogenic muscle disorder. An objective method for detecting nonrandom arrangements of fibres could improve the diagnosis of such disorders, particularly at an early stage. The number of enclosed fibres (NEF)--fibres surrounded by others of the same type--is considered here as a measure of nonrandomness. The distribution of NEF is shown to be approximately negative binomial for a non-free-sampling model, which is then compared with a free-sampling model studied previously. A modification for a known boundary effect is also investigated. The models are applied to data from m. vastus lateralis obtained post mortem from 24 previously healthy men. Finally, the relationship between size of biopsy and the accuracy of predictions is discussed.

Humans↗

Comparison of complications following frontal sinus fractures managed with exploration with or without obliteration over 10 years.

Two hundred twelve patients were treated for facial or skull trauma at the West Virginia University Hospital between the years 1977 and 1987. Sixty-six of these patients had frontal sinus or nasofrontal duct trauma. Follow-up information was obtained on 64 of these patients through clinic visits, chart review, questionnaires to patients and physicians, and telephone calls to the patients. Follow-up greater than 1 year was obtained on 52 patients. Sixty-four patients were managed either with a frontal sinus obliteration or with an open exploratory procedure. The incidence of complications occurring in the past 10 years after each of these procedures is compared. Because the indications for each procedure vary somewhat, data is presented on fracture etiology, associated injuries, specific fracture location, fracture displacement, severity of injury, and associated cerebrospinal fluid leaks.

Adolescent↗

Distribution of different fibre types in human skeletal muscles: a method for the detection of neurogenic disorders.

Human skeletal muscles are composed of two distinguishable types of fibres, which in healthy muscles appear to be randomly arranged. Large groups of one fibre type are commonly regarded as evidence of a neuropathological process affecting the peripheral nerves or the nerve cells in the spinal cord. An objective method that detects non-random arrangements as a sign of a neurogenic disorder, particularly in its early stages, could improve diagnosis. The randomness, or otherwise, of the fibre type arrangement is here considered in terms of the numbers of fibres surrounded entirely by others of the same type (enclosed fibres). The distribution of the number of enclosed fibres is studied for a free-sampling model using Monte Carlo methods. The negative binomial distribution is shown to fit closely, where the parameters can be expressed in terms of the number of fibres and the fibre type proportion in a sample area. This result permits the calculation of significance levels for a sample area and the combination of information in several sample areas. Finally, the method is applied to whole cross-sections of 24 male human autopsied muscles.

Humans↗