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N Krasner

Publications and source records attributed to N Krasner.

At least 37 records · Page 2Linked to original sources

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↗

Enteral feeding as sole treatment for Crohn's disease: controlled trial of whole protein v amino acid based feed and a case study of dietary challenge.

A controlled trial was performed to compare enteral feeding with either an amino acid based feed or a whole protein feed as sole treatment for active Crohn's disease. Twenty four patients were studied (nine with ileal, 11 with ileocolonic, and four with colonic disease). Both feeds proved effective; nine of 13 patients randomised to receive the amino acid based feed were in clinical remission within three weeks as defined by a simple activity index compared with eight of 11 treated with the whole protein feed. Patients in clinical remission were then crossed over onto the other feed. None of the six patients who were changed to the whole protein feed relapsed over the subsequent three week period compared with three of seven patients who were changed to the amino acid based feed. In responders the median serum C reactive protein concentration fell from 21 mg/l (range 9-82) on entry to 6 mg/l (range 3-19) at six weeks. Seven patients relapsed within eight months of starting solid food (mean 3.7 months), while nine were still in remission (follow up period 3-9 months, median six months). Detailed studies of staged reintroduction of food and permitted food additives were carried out over a four year period in a patient with extensive stricturing small bowel Crohn's disease who had been brought into remission by open treatment with enteral feeding. Carrageenan, other permitted emulsifiers, bread, meat, potatoes, oranges, refined sugar, dairy produce, flour, and rice were all reintroduced without any objective ill effect, but green vegetables provoked a clinical and biochemical relapse within one week of introduction. Remission was rapidly achieved by switching back to the enteral feed but reintroduction of the low residue diet that had been previously tolerated produced a brisk relapse. Clinical and biochemical remission was again achieved by a return to the enteral feed but relapse again occurred with reintroduction of the low residue diet. These studies confirm the therapeutic effect of enteral feeding in Crohn's disease. This effect does not seem to be due to avoidance of whole protein, but the very low residue of chemically defined enteral feeds may be important, particularly in patients with intestinal strictures.

Adult↗

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↗

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↗

Laser therapy in the management of benign and malignant tumours in the colon and rectum.

Since 1983 the Neodymium-YAG laser has been used endoscopically to treat 93 patients with inoperable colorectal carcinoma and 18 patients with benign sessile adenomas. In an additional 11 patients with colorectal cancer, photodynamic therapy (PDT) has been applied using an argon-pumped dye laser. Objective and subjective measurements of quality of life have shown the beneficial effects of the Nd-YAG laser in the relief of symptoms, and four patients have apparently been rendered disease free. Benign tumours also respond to Nd-YAG ablation but close histological supervision is necessary to detect malignant transformation at an early stage. Although PDT may offer a potential for cure in small inoperable tumours, it seems likely that Nd-YAG laser treatment will remain the laser option of choice for advanced bulky tumours.

Adenoma↗

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↗

A prospective randomised controlled trial of tamoxifen and cyproterone acetate in pancreatic carcinoma.

In a prospective controlled clinical trial, 108 patients with pancreatic adenocarcinoma were randomly allocated to receive tamoxifen 20 mg b.d., cyproteron acetate 100 mg t.d.s. or no active treatment. The median survival of those receiving tamoxifen was longer than either of the other two groups (5.25 compared to 4.25 and 3 months, respectively) but this difference did not achieve statistical significance. Cox regression analysis of 12 clinical and biochemical features showed that, for the entire group of patients, survival was significantly longer in younger patients, those undergoing surgical bypass and those with better initial performance status. However, even when adjustment was made to allow for the distribution of these prognostic variables within the three groups, the difference in survival still did not achieve statistical significance. No side-effects attributable to treatment was observed.

Adenocarcinoma↗

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↗

Endoscopic application of lasers in gastrointestinal disease.

Laser therapy in gastrointestinal disease offers ever-increasing possibilities for therapeutic endoscopy with the prospect of reducing hospitalization, morbidity and mortality in many conditions traditionally treated by conventional surgery, as well as the opportunity to provide worthwhile palliation for previously inoperable disorders.

Gastrointestinal Diseases↗

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↗

Palliative laser therapy for malignant dysphagia.

Seventy six patients with dysphagia caused by malignant tumours of the oesophagus or gastric cardia have been treated using the Neodymium Yttrium Aluminium Garnet (NdYag) laser. The laser was set to deliver 80-100 watts of power for 0.5-1 second pulses. To obtain improvement, patients on average needed four treatment sessions with a mean energy per treatment of 3586 joules. Follow up endoscopy and laser treatment was at four week intervals, unless the clinical or endoscopic results indicated otherwise. The immediate result was to allow 32% of patients to swallow anything they liked, a further 54% were able to take most solids and 9% were improved, or maintained on liquids only. The mortality of laser recanalisation and associated treatment was 5%. The improvement in swallowing was maintained until death in all but 15% of these patients, some of the 15% needed intubation to allow adequate swallowing. Endoscopic, or surgical intubation was required immediately in five patients after an initial laser course failed to provide improvement. The mean survival of the whole group was 19 weeks (range one to 112 weeks).

Adult↗

Oesophagogastric tumour in old age: palliative treatment by endoscopic laser photocoagulation.

The results of palliative treatment, with laser photocoagulation used alone, of oesophagogastric tumours in 23 patients mean age 81.9 (range 75-93) years are reviewed. Most were frail including five with metastatic disease, seven with cardiovascular disease and five with cerebrovascular disease. Dysphagia was the presenting symptom in 21 patients, two presented with an acute haematemesis. Improvement in swallowing was achieved in 19 (90.5%). Hospital stay was minimal, and 93.3% deaths were in the community. The only complication was perforated oesophagus in 1 patient, treated successfully by conservative management. We suggest laser photocoagulation as the palliative treatment of choice for dysphagia due to oesophagogastric tumour in the frail elderly patient even when the malignancy is at an advanced stage. The major benefit of the technique is the ability to maintain patients comfortably in the community rather than committing them to terminal care in a hospital environment.

Aged↗

Alcohol enhances vitamin C excretion in the urine.

Urinary ascorbic acid excretion was measured on four consecutive days in 9 normal male volunteers for 4 hr before and after drinking nothing (control), 0.58 g alcohol/kg body wt as whisky or lager or water (11./70 kg body wt). The normal reduction in ascorbic acid excretion under control conditions was abolished by drinking water. Alcohol in either form produced a 47% increase in urinary ascorbic acid excretion. A similar ascorbiuresis in chronic alcoholics would be an additional factor in the causation of vitamin C deficiency in these patients.

Adult↗