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H Barr

Publications and source records attributed to H Barr.

At least 55 records · Page 3Linked to original sources

Limitations to the widespread usage of low-dose intra-arterial thrombolysis.

Despite encouraging results, intra-arterial thrombolysis (IAT) has not been readily accepted by British surgeons. In an attempt to clarify the reasons for this we sent a postal questionnaire to surgeons with a vascular interest, asking them to define their present attitude towards IAT. Subsequently, we re-analysed our own clinical data in the light of the answers received. In all 134 surgeons (58%) replied to the questionnaire; 48 (38%) never used IAT and 56 (45%) used it only occasionally. When stated, the main reasons for this limited use were the doubts about efficacy (45%) and lack of radiological support (47%). From November 1988 to August 1990 we used IAT for 82 occlusions (streptokinase 74, rt-PA8). Lysis was achieved in 82% of cases when treatment was started within 1 week of symptoms starting, and 62% with symptoms of longer duration. Following successful IAT no further treatment was required in 44% of cases, reconstruction was needed in 26% and angioplasty in 23%, one major amputation was performed. Unsuccessful lysis resulted in reconstruction in 40% of cases. Overall, the limb salvage rate was 89%. Major complications occurred in six cases. One patient sustained a fatal CVA and five bled from the catheter insertion site. Two of these patients required an emergency operation and one other, who had an angioplasty immediately following lysis, died. Minor complications included local haematoma formation (16), catheter problems (6), and allergic reactions (2). After insertion of the perfusing catheter, angiograms (median 4, maximum 10) were performed at intervals, with repositioning of the catheter if necessary, until lysis was complete.(ABSTRACT TRUNCATED AT 250 WORDS)

Angioplasty, Balloon↗

Comparison of distribution and photodynamic effects of di- and tetra-sulphonated aluminium phthalocyanines in normal rat colon.

We have previously reported photodynamic therapy of normal rat colon using aluminium sulphonated phthalocyanine (AISPc). In that study, the AISPc used was a mixture of phthalocyanines of different degrees of sulphonation. Phthalocyanines of defined degrees of sulphonation have recently become available and we compared the distribution of the di- and tetra-sulphonates (AIS2Pc and AIS4Pc) in rat colon and colon wall structures employing both chemical extraction and fluorescence photometry using a charge coupled device imaging system. Also, the photodynamic effects produced by these components in rat colon were compared at various times after photosensitization. After intravenous photosensitizer administration using equimolar doses, the concentration of AIS2Pc in colon fell off more rapidly with time than AIS4Pc. Differences were noted in the microscopic distribution of these compounds, with the di-sulphonate exhibiting peak fluorescence in colon wall structures by 1 h after photosensitization, while mucosal fluorescence with the tetra-sulphonate peaked at 5 h. Fluorescence was also lost from the colon wall much more slowly with the tetra-sulphonate, which tended to be retained in the submucosa. Maximum photosensitizing capability was seen at 1 h with AIS2Pc and no lesions could be produced with photodynamic therapy at 1 week, with up to 5.65 mumol/kg. With AIS4Pc (5.65 mumol/kg), while no lesions could be produced with light treatment at 1 h, photodynamic therapy at 1 week produced lesions only slightly smaller than those produced with treatment at 48 h (the time of maximum effect), and significant photosensitization was present at 2 weeks.(ABSTRACT TRUNCATED AT 250 WORDS)

Aluminum↗

Enhanced tumour selectivity of photodynamic therapy in the rat colon using a radioprotective agent.

Radioprotective agents have been found to protect normal tissues during photodynamic therapy (PDT). We have investigated a phosphorylated thiol protectant WR-77913 (W7) with the photosensitizer aluminium sulphonated phthalocyanine (AISPc). We compared the effects of PDT on normal and tumour tissue in the rat colon, with and without this protectant. In normal colon no necrosis was seen in sites treated after administration of the W7. Necrosis of mean diameter 4.2 mm was seen in those given the protectant after light exposure. At tumour sites the area of necrosis was similar after light exposure before and after the administration of the protective agent. These results suggest a possible role for W7 in enhancement of selectivity of PDT action. Several mechanisms of protection against porphyrin phototoxicity by these drugs have been proposed, including acceleration of photobleaching. We used fluorescence to detect AISPc in strips of rat colon before and after laser treatment, with and without W7. However, a primary role for the photobleaching of AISPc as the mechanism for the protection shown is not supported by these observations.

Aluminum↗

Local eradication of rat colon cancer with photodynamic therapy: correlation of distribution of photosensitiser with biological effects in normal and tumour tissue.

Photodynamic therapy is a photochemical technique for the local destruction of tumours, entailing the interaction of light with an administered photosensitiser to produce a cytotoxic effect. We investigated the tissue distribution of the photosensitiser aluminium sulphonated phthalocyanine (AlSPc) in dimethylhydrazine induced colonic tumours and adjacent normal colon in rats. Forty eight hours after intravenous injection, most tumours contained twice as much AlSPc as normal colon. Tumour size and position in the colon did not affect AlSPc concentration. Microscopic fluorescence localisation of AlSPc showed significant photosensitiser accumulation in tumour stroma, whereas tumour and normal mucosa contained similar amounts. Thus, some normal tissue damage, where malignant cells invade normal areas, would inevitably accompany eradication of tumours. Tumour destruction and healing of colon after tumour eradication were examined histologically. There was sharp demarcation between necrotic areas (tumour or normal) and adjacent tissue and, whether the treated area was tumour or normal, healing occurred by regeneration of normal tissue. Some incompletely eradicated large tumours showed evidence of delayed bleeding. The possibility of selective uptake or preferential retention of the photosensitiser in tumours formed the initial basis for investigation of photodynamic therapy, but it is now clear that this is seldom the most important factor for tumour eradication. Of far greater importance is the nature of the biological effect of photodynamic therapy as necrosis of small tumours involving the full thickness of the bowel wall can be achieved with safe healing by regeneration of normal colon. The maximum depth of necrosis produced was only a few millimetres, so this technique is unlikely to be of value as the primary treatment for large colonic tumours but may prove of value for eradicating small lesions or as adjunctive therapy for eradication of small nests of tumour remaining or recurring in the tumour bed after conventional surgery.

Aluminum↗

An outbreak of tuberculosis in a shelter for homeless men. A description of its evolution and control.

An outbreak of tuberculosis at a shelter for homeless men was studied in detail to further the understanding of the epidemiology of tuberculosis in this setting. The shelter provides evening accommodations for men aged 50 yr and older. The capacity is approximately 200 clients, and the client pool is approximately 1,000 men/yr. During a 6-wk period in December 1986 and January 1987, seven cases of tuberculosis were diagnosed in shelter clients. Nine cases were reported in clients during the preceding 12 months, and four cases in the year previous to that. The majority of outbreak cases were pulmonary tuberculosis, sputum smear positive. Drug resistance was rare. Phage typing of 15 Mycobacterium tuberculosis isolates revealed one predominant type and four other types. The goals of the control plan (and the steps taken to achieve them) were to render known infectious cases noninfectious (directly observed therapy); to find undiagnosed infectious cases (repetitive mass screenings); to protect exposed clients (repetitive tuberculin skin testing and isoniazid preventive therapy); and to make the shelter environment safe (exclude infectious, noncompliant clients and improve the shelter's ventilation system). Implementation of this plan rapidly terminated the outbreak; following the first mass screening in January 1987, at which six asymptomatic cases were detected, only five additional cases occurred in shelter clients during a 2-yr period of follow-up. The investigation suggested that the outbreak evolved during 1986 as a result of the presence at the shelter of an increasing number of men with undiagnosed infectious pulmonary tuberculosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Air↗

Photodynamic therapy for colorectal cancer: a quantitative pilot study.

Ten patients with colorectal cancers unsuitable for operation were treated with endoscopic photodynamic therapy (PDT). The patients were assessed before treatment, and at 1 week and 1 month after treatment by colonoscopy with biopsy and endoluminal ultrasound examination. The depth of tumour was measured and the effect of PDT was quantified by measuring the reduction in tumour depth. All patients were sensitized with 2.5 mg kg-1 of haematoporphyrin derivative, 48 h before phototherapy. A standard treatment protocol of light exposure was used. Up to four parts of the tumour were treated with 50J of red light (630 nm) from a tuneable dye laser, through a flexible optical fibre passed through the colonoscope and inserted into the tumour. Two patients with small lesions are tumour-free 20 and 28 months after PDT. One treatment of an advanced tumour was complicated by a haemodynamically significant secondary haemorrhage. PDT may be most suitable for the treatment of small tumours or for small areas of persistent tumour where the bulk has been removed by alternative techniques.

Adenocarcinoma↗

Selective necrosis in dimethylhydrazine-induced rat colon tumors using phthalocyanine photodynamic therapy.

Photodynamic therapy is a relatively new method for the local destruction of tumors based on the administration of a photosensitizing agent that is retained in tumors and then activated to produce cytotoxic agents following irradiation with light. The selective retention of photosensitizers by dimethylhydrazine-induced colonic tumors over adjacent normal tissue is small (2:1, tumor to normal), making the possibility of producing selective tumor necrosis with total sparing of normal tissue difficult. Colonic cancers and adjacent normal colon were treated with the same light doses from an argon-pumped dye laser 48 h after intravenous injection of 0.5 or 5 mg/kg of the photosensitizer, aluminum-sulfonated phthalocyanine. There was little difference between the amount of necrosis in the tumor and the adjacent normal colon if the injected dose of photosensitizer was 5 mg/kg. However, at the lower dose of 0.5 mg/g, up to 2 mm of necrosis could be produced in the tumor without damaging the normal colon. In vivo fluorescence measurements showed that the photosensitizer was photodegraded during irradiation. This was confirmed by in vitro fluorescence scans of the normal colon after irradiation; the fluorescence from the photosensitizer was lowest at the point of irradiation. It is postulated that at low dosage, selective necrosis can occur because the photosensitizer is photodegraded in the normal colon before a threshold photodynamic dose is reached, whereas in tumor containing twice as much photosensitizer, a photodynamic threshold dose can be achieved and necrosis produced.

1,2-Dimethylhydrazine↗

The significance of the nature of the photosensitizer for photodynamic therapy: quantitative and biological studies in the colon.

Photodynamic therapy (PDT) depends on the interaction of light with an administered photosensitiser to produce a local cytotoxic effect. The most widely used photosensitiser is haematoporphyrin derivative (HpD), but newer photosensitisers such as aluminium sulphonated phthalocyanine (A1SPc) are promising. HpD and A1SPc have been compared as photosensitisers for colonic PDT in the rat. Quantitative analysis showed that following injection of a standard photosensitiser dose, A1SPc produced more damage than HpD with increasing energy (fluence). Alteration of the injected dose of photosensitiser did not produce a clear difference. There was a loss of reciprocity for photosensitiser/light combinations at low injected dose (0.5 mg kg-1), both HpD and A1SPc producing no damage. Similarly at high photosensitiser dosage (25 mg kg-1) there was no quantitative difference between A1SPc and HpD. Photosensitiser photodegradation at low photosensitiser doses, and light attenuation by high tissue concentrations of A1SPc account for these findings. PDT with either agent produced the same histological damage and full thickness necrosis produced no mechanical weakening of the colon measured by the bursting pressure. The submucosal collagen was preserved and healing was by regeneration.

Animals↗

Prospective randomised trial of laser therapy only and laser therapy followed by endoscopic intubation for the palliation of malignant dysphagia.

Forty six consecutive patients admitted for the relief of malignant dysphagia were prospectively randomised to receive laser therapy only or initial laser therapy followed by endoscopic intubation. Twenty patients were treated in each group with six exclusions. The patients' swallowing ability was assessed before and during the remainder of their life on a 0-4 scale with 0 being normal swallowing and 4 total dysphagia. The patient's quality of life was measured at the same times, using a physician's assessment (QL index) and the patient's own assessment using a linear analogue self assessment (LASA). There was a significant correlation between all the QL index and the LASA scores collected (n = 126; rs = 0.594, p less than 0.001). The mean monthly dysphagia grade correlated with the QL index (rs = 0.433, p less than 0.001) and the LASA (rs = 0.272, p less than 0.002). There was no significant difference in the dysphagia grade before or after treatment in either group. Dysphagia fluctuated more in those treated with the laser only, however, than in those with a tube inserted. There was also no significant difference in the quality of life measured between the two groups of patients. The complication rate (laser only 10%, laser/intubation 40%, p less than 0.05) was significantly higher in intubated patients. The recurrent dysphagia rate (laser only 25%, laser/intubation 45%, NS) was higher in patients treated with intubation, but they required fewer endoscopic procedures. Overall both procedures were effective in relieving dysphagia and in maintaining quality of life. There was no procedure related mortality in either group.

Adenocarcinoma↗

Palliative laser therapy for inoperable rectal cancer--does it work? A prospective study of quality of life.

Endoscopic neodymium yttrium aluminium garnet (Nd YAG) laser therapy, is a new and simple method for the palliative treatment of inoperable colorectal cancer. To date the authors have treated 70 patients and the value of this method was assessed prospectively in 14 patients. Quality of life was measured before, during, and after treatment. The quality of life (QL) index, a physician's assessment and a linear analogue self-assessment (LASA) were used. A close correlation was found between the two assessment methods (r = 0.79). Overall there was a significant improvement from the mean pretreatment score and the best score achieved posttreatment (QL: P = 0.002; LASA: P = 0.002). Patients with diarrhea, rectal bleeding, mucus discharge, or pain secondary to tumor bulk, will benefit most from this treatment. Malignant cachexia, pain secondary to sacral plexus involvement, tumor encroachment on the anal canal and/or sphincter dysfunction resulting from tumor invasion should be viewed as relative contraindications to laser therapy. The authors conclude that in selected patients endoscopic laser therapy can provide effective palliation in patients with malignant tumors of the rectum and descending colon.

Aged↗

Low power interstitial Nd YAG laser photocoagulation: studies in a transplantable fibrosarcoma.

The effects of interstitial delivery of low power (1.2-2 W), long exposure (600-1200 s) Nd YAG laser light on a transplantable fibrosarcoma in rats have been studied. Three cohorts of ten animals were treated either by 1.2 W for 600 s, 1.2 W for 1200 s or 2 W for 600 s to each tumour nodule. An additional untreated cohort served as controls and a further cohort was treated by radical surgical resection. A partial response as evidenced by ulceration was seen in all laser-treated tumours. In the cohort treated by 2 W for 600 s there was complete loss of palpable tumour, and in five out of the ten animals there was no evidence of local recurrence following a prolonged period of observation. Three of these eventually died from metastatic disease and two were cured. There was a significant prolongation of survival in this cohort compared with the controls (median 70 days versus 30 days, P less than 0.05), but not in any of the other cohorts. Histological assessment of tumours 2 days after laser treatment showed a central area of degeneration with shrunken and densely staining nuclei and disorganized cytoplasm, the boundary between the degenerate zone and surrounding viable tumour being well defined. The technique might be used to induce necrosis of intrahepatic and other solid organ tumours.

Animals↗

Photodynamic therapy for colorectal disease.

Photodynamic therapy (PDT) involves the parenteral administration of a photosensitising agent with some selectivity for malignant tissue. When activated by light, usually from a laser, local tissue destruction occurs. The amount of tissue destruction is dependent on the concentration of the photosensitising agent in the tissue and the light energy delivered. By careful manipulation of laser energy and photosensitiser dosage true selective destruction of malignant tissue can be produced in experimental colon cancers with total sparing of normal colon although under these conditions, the extent of necrosis in the tumour is only 2-3 mm from the light source. In addition, PDT has been shown not to reduce the mechanical strength of the colon even if full thickness necrosis is produced in normal areas. In contrast, thermal full thickness laser damage of the colon considerably weakens the colonic wall and may cause perforation. Light microscopy with specific collagen stains and electron microscopy have shown that the submucosal collagen layer is preserved following PDT, but is destroyed by thermal laser therapy. An initial clinical trial of PDT has been performed in ten patients with inoperable tumours because of advanced metastatic disease or severe medical problems. PDT has been shown to be safe and some small colorectal cancers can be totally eradicated.

Animals↗

Local control of rectal cancer with the Nd-YAG laser.

Three patients with locally recurrent rectal cancer were treated using the Neodymium YAG laser to palliate the symptoms of tenesmus, discharge and bleeding. All were considered unfit for further surgical excision. The local tumour was completely removed following repeated laser therapy over a period of 4, 6 and 11 months, respectively. These patients remain well without evidence of local or systemic disease 26, 33 and 42 months after laser treatment. Laser therapy for palliation of local disease may be rewarded by prolonged local control and possible cure.

Aged↗

Massive pneumoperitoneum following laser therapy of inoperable oesophageal carcinoma.

Two cases of large pneumoperitoneum are described following palliative laser therapy for inoperable oesophageal carcinoma. In both cases there was no constitutional upset and no perforation demonstrated on contrast examination of the oesophagus. The pneumoperitoneum is considered to be due to high pressure CO2, used to keep the tip of the laser clean, passing through the tumour and tracking into the peritoneum. The condition requires only conservative treatment.

Adenocarcinoma↗

Use of lectin histochemistry in pancreatic cancer.

Lectin peroxidase histochemical analysis was carried out on pancreatic tissue from patients with pancreatic carcinoma and chronic pancreatitis and from subjects with normal pancreas to find a tumour specific pattern of lectin binding that would aid histological and cytological diagnosis. There were striking differences between the lectin binding characteristics of the different cell types in the normal pancreas. Acinar cells were uniformly positive for binding with wheat germ agglutinin and soy bean agglutinin while islet cells were usually negative for these lectins. Ulex europaeus I lectin however, was found not to be specific for endothelium, showing positivity also for acinar and ductal tissue. Griffonia simplicifolia II lectin was found to be highly specific for ductal epithelium, and because of this was tested in a hamster pancreatic cancer model where it was not specific for ductal epithelium, reflecting differing carbohydrate expression in the hamster pancreas. Pancreatic carcinomas and chronic pancreatitis bound all five lectins without any qualitative distinction from each other or from normal pancreatic tissue, but there was increased intensity of peanut agglutinin binding to secreted mucins in pancreatic carcinoma, which may be of potential use in radiolabelled lectin scanning.

Animals↗

Photodynamic therapy in the normal rat colon with phthalocyanine sensitisation.

Photodynamic therapy (PDT) involves the interaction of light with an administered photosensitising agent to produce cellular destruction. It has promising potential for the local and endoscopic treatment of gastrointestinal cancer. There is however little data on the response of normal intestine to PDT. We have investigated the use of a new photosensitiser chloro aluminum sulphonated phthalocyanine (AlSPc) for colonic PDT. The peak concentration of AlSPc in the colon measured by alkali extraction occurred 1 h after i.v. injection. The cellular uptake demonstrated by laser fluorescence microscopy was greater in the mucosa than in the muscle. AlSPc was activated in the tissues by light from an argon ion pumped dye laser at 675 nm. The laser power was set at 100 mW and the fibre placed touching the mucosa. In control animals no macroscopic damage was seen. Temperature measurement using a microthermocouple array showed no temperature rise during light exposure. The energy (fluence), dose of sensitiser and time from sensitisation to phototherapy were altered and the area of necrosis measured. The geometry of the colon made theoretical analysis of the correlation between laser energy and size of lesion difficult. However, following direct measurement of the relative light intensity (fluence rate) in the colon we were able to confirm that there was a threshold fluence for colonic necrosis. The area of photodynamic damage seen 72 h after phototherapy fell with the fall in tissue concentration of AlSPc from 1 h to 1 month after i.v. injection. However, maximum tissue necrosis occurred when treatment was performed immediately after i.v. injection. In this situation, intense vascular spasm was seen and any light transmitted through the colon which fell on the small bowel mesentery caused a lethal ischaemic necrosis. The initial histological changes after PDT were vascular, followed by full thickness necrosis at 72 h. Healing by regeneration was complete by 2-3 weeks. Despite full thickness necrosis there was no reduction in the colonic bursting pressure at any time. Colon treated by hyperthermia had a reduced bursting pressure. Specific collagen stains showed that PDT did not alter the submucosal collagen architecture whereas hyperthermia did.

Animals↗