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S G Bown

Publications and source records attributed to S G Bown.

At least 19 recordsLinked to original sources
PubMed2002

The role of reperfusion injury in photodynamic therapy with 5-aminolaevulinic acid--a study on normal rat colon.

Reperfusion injury can occur when blood flow is restored after a transient period of ischaemia. The resulting cascade of reactive oxygen species damages tissue. This mechanism may contribute to the tissue damage produced by 5-aminolaevulinic acid-induced photodynamic therapy, if this treatment temporarily depletes oxygen in an area that is subsequently reoxygenated. This was investigated in the normal colon of female Wistar rats. All animals received 200 mg kg(-1) 5-aminolaevulinic acid intravenously 2 h prior to 25 J (100 mW) of 628 nm light, which was delivered continuously or fractionated (5 J/150 second dark interval/20 J). Animals were recovered following surgery, killed 3 days later and the photodynamic therapy lesion measured macroscopically. The effects of reperfusion injury were removed from the experiments either through the administration of free radical scavengers (superoxide dismutase (10 mg kg(-1)) and catalase (7.5 mg kg(-1)) in combination) or allopurinol (an inhibitor of xanthine oxidase (50 mg kg(-1))). Prior administration of the free radical scavengers and allopurinol abolished the macroscopic damage produced by 5-aminolaevulinic acid photodynamic therapy in this model, regardless of the light regime employed. As the specific inhibitor of xanthine oxidase (allopurinol) protected against photodynamic therapy damage, it is concluded that reperfusion injury is involved in the mechanism of photodynamic therapy in the rat colon.

Allopurinol↗
PubMed2002

Optimisation of illumination for photodynamic therapy with mTHPC on normal colon and a transplantable tumour in rats.

Recent reports suggest that the effect of photodynamic therapy (PDT) can be enhanced by fractionating the light dose or reducing the light fluence rate. We assessed these options on two tissues in rats (normal colon and a transplanted fibrosarcoma) using the photosensitiser meta-tetrahydroxyphenylchlorin (mTHPC). Animals were sensitised with 0.3 mg/kg mTHPC, 3 days prior to illumination with red light (652 nm) using a single fibre touching the target tissue and killed 1-3 days later for quantitative measurement of the extent of PDT necrosis. Results were similar for both tissues, although the differences between illumination regimens were less marked in tumour tissue. Using continuous illumination and a fixed low energy in colon, the extent of necrosis was up to almost three times larger with 5 mW than with 100 mW, although the maximum attainable necrosis was independent of power. The long treatment time using 5 mW could be halved without loss of effect by increasing the power during treatment. Dividing the light into two equal fractions at 100 mW increased the lesion size by up to 20% in colon (independent of the timing of the dark interval), but by only 10% in tumour and had no effect at 20 mW. Previous studies using 5-aminolaevulinic acid (ALA) showed a much larger effect of fractionation that was critically dependent on the timing of the dark interval. We postulate that enhancement of PDT by fractionation is due to improved oxygen supply to the treated area which may be due to reversal of temporary vascular occlusion (more likely with ALA) or less rapid photochemical consumption of oxygen (more likely with mTHPC). At lower fluence rates, the oxygen consumption rate is not fast enough to be improved by fractionation. We conclude that fractionated or low power light delivery can enhance PDT with mTHPC. Although the effects are not large, this may be of value for interstitial treatment of solid tumours when multiple sites are treated simultaneously.

Animals↗
PubMed2002

Laser augmented by brachytherapy versus laser alone in the palliation of adenocarcinoma of the oesophagus and cardia: a randomised study.

BACKGROUND: Many patients with advanced malignant dysphagia are not suitable for definitive treatment. The best option for palliation of dysphagia varies between patients. This paper looks at a simple technique for enhancing laser recanalisation. AIM: To assess the value of adjunctive brachytherapy in prolonging palliation of malignant dysphagia by endoscopic laser therapy. PATIENTS: Twenty two patients with advanced malignant dysphagia due to adenocarcinoma of the oesophagus or gastric cardia, unsuitable for surgery or radical chemoradiotherapy. METHODS: Patients able to eat a soft diet after laser recanalisation were randomised to no further therapy or a single treatment with brachytherapy (10 Gy). Results were judged on the quality and duration of dysphagia palliation, need for subsequent intervention, complications, and survival. RESULTS: The median dysphagia score for all patients two weeks after initial treatment was 1 (some solids). The median dysphagia palliated interval from the end of initial treatment to recurrent dysphagia or death increased from five weeks (control group) to 19 weeks (brachytherapy group). Three patients had some odynophagia for up to six weeks after brachytherapy. There was no other treatment related morbidity or mortality. Further intervention was required in 10 of 11 control patients (median five further procedures) compared with 7/11 brachytherapy patients (median two further procedures). There was no difference in survival (median 20 weeks (control), 26 weeks (brachytherapy)). CONCLUSIONS: Laser therapy followed by brachytherapy is a safe, straightforward, and effective option for palliating advanced malignant dysphagia, which is complementary to stent insertion.

Adenocarcinoma↗
PubMed2002

Photodynamic therapy for cancer of the pancreas.

BACKGROUND: Few pancreatic cancers are suitable for surgery and few respond to chemoradiation. Photodynamic therapy produces local necrosis of tissue with light after prior administration of a photosensitising agent, and in experimental studies can be tolerated by the pancreas and surrounding normal tissue. AIMS: To undertake a phase I study of photodynamic therapy for cancer of the pancreas. PATIENTS: Sixteen patients with inoperable adenocarcinomas (2.5-6 cm in diameter) localised to the region of the head of the pancreas were studied. All presented with obstructive jaundice which was relieved by biliary stenting prior to further treatment. METHODS: Patients were photosensitised with 0.15 mg/kg meso-tetrahydroxyphenyl chlorin intravenously. Three days later, light was delivered to the cancer percutaneously using fibres positioned under computerised tomographic guidance. Three had subsequent chemotherapy. RESULTS: All patients had substantial tumour necrosis on scans after treatment. Fourteen of 16 left hospital within 10 days. Eleven had a Karnofsky performance status of 100 prior to treatment. In 10 it returned to 100 at one month. Two patients with tumour involving the gastroduodenal artery had significant gastrointestinal bleeds (controlled without surgery). Three patients developed duodenal obstruction during follow up that may have been related to treatment. There was no treatment related mortality. The median survival time after photodynamic therapy was 9.5 months (range 4-30). Seven of 16 patients (44%) were alive one year after photodynamic therapy. CONCLUSIONS: Photodynamic therapy can produce necrosis in pancreatic cancers with an acceptable morbidity although care is required for tumours invading the duodenal wall or involving the gastroduodenal artery. Further studies are indicated to assess its influence on the course of the disease, alone or in combination with chemoradiation.

Adenocarcinoma↗
PubMed2001

Interstitial laser photocoagulation and interstitial photodynamic therapy of normal lung parenchyma in the pig.

Interstitial laser photocoagulation (ILP) and interstitial photodynamic therapy (PDT) involve delivery of light to lesions in solid organs using thin fibres passed through needles inserted percutaneously under image guidance. In ILP, the laser energy heats the tissue, whereas in PDT it activates a previously administered photosensitising agent. This study looks at their potential for treating localised, small, peripheral lung cancers in patients unsuitable for surgery. Experiments were undertaken on nine normal pigs, up to four fibres being inserted into the lung parenchyma percutaneously under X-ray guidance (ILP: 2-3 W, 1000 q/fibre, from 805 nm diode laser, PDT, 100-200 J/fibre from 652 nm diode laser at 50-100 W, 3 days after 0.15 mg/kg mTHPC). Animals were killed from 3 days to 3 months later and the treated areas examined macroscopically and microscopically. Both techniques were well tolerated, producing well-defined, localised lesions, typically 3.5 x 2 x 2 cm using four fibres. Histology showed thermal coagulative necrosis after ILP and haemorrhagic necrosis after PDT. Early small haematomas and late cavitation were sometimes seen after ILP, but not after PDT. PDT lesions healed with preservation of larger arteries and bronchi in the treated area. A few small pneumothoraces were seen which resolved spontaneously, probably related to the chest wall puncture. It was concluded that ILP and PDT lesions of a size large enough to cover a small tumour can be made safely in the lung parenchyma, although healing was better after PDT. Pilot clinical studies with both techniques are now justified on carefully selected patients.

Animals↗
PubMed2000

Reduction in the response to coronary and iliac artery injury with photodynamic therapy using 5-aminolaevulinic acid.

OBJECTIVE: Photodynamic therapy (PDT) uses red light (non-thermal, non-ionising) to activate a previously administered photosensitizing drug. This inhibits neointimal hyperplasia in injured arteries in small animals where it appears safe and well tolerated. Our aim was to develop a method for percutaneous application of PDT to iliac and coronary arteries in a large animal model and investigate its influence on the remodeling and intimal hyperplastic response to balloon injury. METHODS: Studies were undertaken on 13 juvenile Large White-Landrace crossbred pigs (15-20 kg). After intravenous administration of the photosensitizing agent 5-amino laevulinic acid (ALA), the arterial tree was accessed via the left common carotid artery and balloon injuries made by over-distension in both common iliacs (thirteen animals) and one or two main coronary arteries (eight animals). Half the injured sites were then illuminated with red laser light transmitted via the catheter. Animals were culled 28 days later and tissue harvested for histomorphometry. RESULTS: Compared with control injured vessels, PDT treated, balloon injured coronary arteries had a larger lumen (1.4 vs. 0.8 mm2, P = 0.002), larger area within the external elastic lamina (2.8 vs. 2.2 mm2, P = 0.006) and smaller area of neointimal hyperplasia (0.4 vs. 0.7 mm2, P = 0.06), 28 days after intervention. Less neointimal hyperplasia and the absence of negative remodeling resulted in the lumen of PDT-treated, injured segments being the same as that of adjacent reference segments (1.5 vs. 1.6 mm2). Similar trends, but with smaller differences, were seen in the iliac vessels. CONCLUSIONS: Intra-arterial, trans-catheter PDT favourably influences the arterial response to balloon injury in both the coronary and peripheral circulations. This technique offers a promising new approach to restenosis after endovascular procedures.

Aminolevulinic Acid↗
PubMed2000

Oxygen monitoring during 5-aminolaevulinic acid induced photodynamic therapy in normal rat colon. Comparison of continuous and fractionated light regimes.

Currently, the clinical use of 5-aminolaevulinic acid (ALA) induced protoporphyrin IX (PPIX) for photodynamic therapy (PDT) is limited by the maximum tolerated oral ALA dose (60 mg/kg). Attempts have been made to enhance this treatment modality without increasing the administered dose of ALA. One way to do this is through light dose fractionation, where the irradiation is interrupted at a particular point for a short period of time. This can produce up to three times more necrosis than with the same light dose delivered without a break. An oxygen microelectrode was employed to study the effect of continuous and fractionated light regimes on the level of oxygen in the colon of normal Wistar rats during ALA PDT. A rapid decline in pO2 occurred close to the irradiation fibre as soon as the light dose commenced. With the fractionated regime, a partial recovery in pO2 was observed during the dark interval which was reversed soon after the second light fraction commenced. We have shown that the level of tissue oxygen at the treatment site is affected differently when the light dose is fractionated, than when continuous illumination is employed. This factor may at least partially explain the difference in outcome of these two treatment regimes. Further, oxygen measurements might prove to be a useful way of monitoring PDT treatments if they can predict whether tissue is likely to be viable following treatment.

Aminolevulinic Acid↗
PubMed2000

Photodynamic therapy of rat bladder and urethra: evaluation of urinary and reproductive function after inducing protoporphyrin IX with 5-aminolaevulinic acid.

OBJECTIVE: To assess the urinary and reproductive function of rats after inducing protoporphyrin IX with 5-aminolaevulinic acid (ALA) and subsequent intraurethral photodynamic therapy (PDT). Materials and methods Twelve female Wistar rats were given ALA orally or intravesically (four each), followed by intraurethral PDT through a 10-mm cylindrical fibre at 100 mW for 500 s (argon laser, 632 nm). Urinary frequency, the number of gestations and histological changes were then evaluated and compared with a group of eight control rats. RESULTS: There was only a slight increase in urinary frequency during the first 2 weeks after PDT in the group given oral ALA, while the same degree of urinary frequency was evident for up to 4 weeks in those given intravesical ALA. Despite the occurrence of urinary incontinence from undefined causes in two rats, reproductive function remained unchanged. There was no histological evidence of damage to the reproductive system adjacent to the bladder. CONCLUSIONS: PDT of the urethra with ALA is relatively safe and carries few risks of inducing permanent urological complications.

Administration, Intravesical↗
PubMed2000

Diagnosis of breast cancer using elastic-scattering spectroscopy: preliminary clinical results.

We report on the first stages of a clinical study designed to test elastic-scattering spectroscopy, mediated by fiberoptic probes, for three specific clinical applications in breast-tissue diagnosis: (1) a transdermal-needle (interstitial) measurement for instant diagnosis with minimal invasiveness similar to fine-needle aspiration but with sensitivity to a larger tissue volume, (2) a hand-held diagnostic probe for use in assessing tumor/resection margins during open surgery, and (3) use of the same probe for real-time assessment of the "sentinel" node during surgery to determine the presence or absence of tumor (metastatic). Preliminary results from in vivo measurements on 31 women are encouraging. Optical spectra were measured on 72 histology sites in breast tissue, and 54 histology sites in sentinel nodes. Two different artificial intelligence methods of spectral classification were studied. Artificial neural networks yielded sensitivities of 69% and 58%, and specificities of 85% and 93%, for breast tissue and sentinel nodes, respectively. Hierarchical cluster analysis yielded sensitivities of 67% and 91%, and specificities of 79% and 77%, for breast tissue and sentinel nodes, respectively. These values are expected to improve as the data sets continue to grow and more sophisticated data preprocessing is employed. The study will enroll up to 400 patients over the next two years.

Adenocarcinoma↗
PubMed2000

Interstitial laser photocoagulation for the treatment of osteoid osteoma.

We report the results of a prospective study of 23 patients in which interstitial laser photocoagulation (ILP) was used to treat an osteoid osteoma. ILP is a technique in which tumour tissue is destroyed by direct heating using low-power laser light energy delivered by thin (400 microm) optical fibres which are introduced percutaneously into the tumour under image guidance. Pain was evaluated before operation and at the latest follow-up using a visual analogue scale with 0 denoting no pain and 10 the worst pain imaginable. The mean follow-up was for 15 months. The results showed that the mean pain score decreased from 7.5 before operation to 0.95 at the latest follow-up. Fourteen patients had no pain and eight had minor discomfort, not requiring analgesia. One patient required a second procedure because placement of the fibre had not been accurate enough and one developed recurrent symptoms eight months after treatment. All patients were satisfied with the operation because of the rapid resolution of pain, the minimally invasive nature of the procedure, and the fact that there was no postoperative restriction of activity.

Adolescent↗
PubMed2000

The biology of photodynamic therapy in the gastrointestinal tract.

This article reviews current knowledge on the biology of photodynamic therapy on normal and diseased tissues in the gastrointestinal tract. There is little effect on connective tissue, so the mechanical integrity of the luminal gut is well preserved, even with full thickness damage. This makes photodynamic therapy suitable for treating small tumors, but strictures may occur after circumferential treatment of conditions like Barrett's esophagus unless a muscle-sparing photosensitizing agent is used. Animal studies show that the pancreas and surrounding tissues can tolerate photodynamic therapy, justifying pilot clinical trials on percutaneous, interstitial photodynamic therapy for localized, inoperable pancreatic cancers.

Animals↗
PubMed2000

Optical biopsy systems for the diagnosis and monitoring of superficial cancer and precancer.

Histopathology is the gold standard in the diagnosis of cancer and dysplasia. Screening for the disease in high-risk populations(6,15) and choosing the correct site for biopsy have implications for the choice of follow-up intervals and therapy. Sully & Field(12) suggest that molecular genetic analysis, such as the polymerase chain reaction, for detecting progressive loss of heterozygosity, may be a more accurate predictor of the clinical course of oral cancer. This technique is now semi-automated and compares favourably with the time taken for histopathology (commonly 1-2 weeks). Recent developments suggest that the fluorescent and spectroscopic features may distinguish diseased from healthy tissue, and below follows an introduction for the clinician to this fascinating and complex field. It is possible to obtain a diagnosis in real-time and, with the appropriate use of photochemicals and image enhancement, it may be possible to treat and monitor the effects of treatment in real-time.

Biopsy↗
PubMed1999

Clinical study of adjuvant photodynamic therapy to reduce restenosis following femoral angioplasty.

BACKGROUND: Photodynamic therapy (PDT) reduces neointimal hyperplasia and negative remodelling following balloon injury in small and large animal models. This clinical study investigated the role of adjuvant PDT following femoral percutaneous transluminal angioplasty (PTA). METHODS: Eight PTAs in seven patients (two women) with a median age of 70 (range 59-86) years were performed with adjuvant PDT. All patients had previously undergone conventional angioplasty at the same site which resulted in symptomatic restenosis or occlusion between 2 and 6 months. Each was sensitized with oral 5-aminolaevulinic acid 60 mg/kg, 5-7 h before the procedure. Following a second femoral angioplasty, up to 50 J/cm2 red light (635 nm) was delivered to the angioplasty site via a laser fibre within the angioplasty balloon. Patients were kept in subdued light overnight and discharged the following day. Outcome was assessed by duplex imaging at 24 h, 1, 3 and 6 months and by intravenous digital subtraction angiography at 6 months. A peak systolic velocity ratio (PSVR) of more than 2.0 at the angioplasty site was taken to represent restenosis. RESULTS: All patients tolerated the procedure well without adverse complications or death. All were rendered asymptomatic which was sustained throughout the study interval. All vessels remained patent and no lesion attained the duplex definition of restenosis. Median (interquartile range) PSVR across stenotic segments was 4.7 (3.7-5.7) before angioplasty, 1.1 (0.9-1.3) at 24 h and 1.4 (1.0-1.8) at 6 months after intervention (P = 0.04 compared with preoperative value). CONCLUSION: This pilot study suggests that endovascular PDT is safe and may reduce restenosis follow- ing angioplasty. The data justify a randomized controlled trial.

Aged↗
PubMed1999

Near-infrared optical properties of ex vivo human uterus determined by the Monte Carlo inversion technique.

The optical properties, absorption (mua) and reduced scattering coefficient (mu's), of ex vivo human myometrium and leiomyoma (fibroid) have been determined by the Monte Carlo inversion technique over the wavelength range 600-1000 nm. This region is currently of interest for new, minimal-access, surgical laser procedures such as photodynamic therapy (PDT) for abnormalities of the uterus, and interstitial laser photocoagulation (ILP) for the thermal ablation of fibroids. In the region 630-675 nm (corresponding to PDT), the optical coefficients of myometrium are mua = 0.041+/-0.012 mm(-1) and mu's = 1.37+/-0.19 mm(-1). For the wavelength range 800-1000 nm (associated with infrared lasers for ILP), the optical coefficients of fibroid were found to be mua = 0.020+/-0.003 mm(-1) and mu's = 0.56+/-0.03 mm(-1). Overall, the optical properties of fibroid were found to be lower than myometrium, and this was attributed to the differences in both anatomy and vascularity. The results show that PDT for ablation of the uterine endometrium is most unlikely to affect any tissues beyond the myometrium, and that the region around 800 nm is the most effective for ablation of fibroids using ILP as the penetration depth of light is greatest at this wavelength.

Adult↗
PubMed1999

New photosensitizers for photodynamic therapy in gastroenterology.

Most applications of photodynamic therapy (PDT) in gastroenterology to date have used porfimer sodium as the photosensitizing agent. For destroying small lesions in the wall of the gastrointestinal tract in inoperable patients, it has proved to be most effective, but attempts to achieve circumferential mucosal ablation, as in the treatment of Barrett's esophagus, have led to a high incidence of strictures, and all patients have cutaneous photosensitivity, which can last up to three months. Two new photosensitizers are of particular interest to gastroenterologists. PDT with metatetrahydroxyphenyl chlorin produces a similar biological effect as PDT with porfimer sodium, but the light doses required are much smaller, and cutaneous photosensitivity lasts only two to three weeks. Further, it can be used with percutaneous light delivery to destroy localized pancreatic cancers. The photosensitizing agent 5-amino levulinic acid, converted in vivo into the photoactive derivative protoporphyrin IX, sensitizes the mucosa much more than the underlying layers. This makes it feasible to destroy areas of abnormal mucosa without damaging the underlying muscle and is, therefore, better for treating Barrett's esophagus. Detailed clinical studies are required to establish the real role of PDT with the use of these and other new photosensitizers.

Aminolevulinic Acid↗