Photodynamic therapy: successful destruction of gastrointestinal cancer after oral administration of aminolevulinic acid.
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Biomedical subjects
Publications and source records attributed to E G Hahn.
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AIM: With the introduction, in 1994, of Ultrasound Angio (UA), a technical innovation in sonographic colour coded blood-flow detection has become available using angle-independent amplitude signal plotting leading to an enhanced sensitivity in blood flow detection. METHOD: In a first application study we attempted to verify an improved blood-flow detection in hepatocellular carcinomas (HCC) compared to conventional colour coded duplex sonography. RESULTS AND CONCLUSION: In all patients with HCC we found a highly improved detection of internal vascularity. In one patient, we could even detect blood flow in the tumour which was not visible with several other conventional highly sensitive colour duplex equipment.
BACKGROUND AND STUDY AIMS: To date there is no information available on whether drugs that are commonly used in premedication for colonoscopy procedures, such as diazepam and pethidine, may activate intestinal mast cells and thereby give rise to adverse effects. Since opioids such as pethidine are well-known for their ability to induce histamine release from several mast cell subtypes, the present study investigated the effect of diazepam and pethidine, intravenously administered as premedication for colonoscopy, on mast cell mediator secretion from colonic and rectal mucosa. PATIENTS AND METHODS: The secretion of the mast cell mediators histamine and tryptase was followed from biopsies of patients with and without premedication for 30 minutes in an air-bubbled incubation medium (mucosa oxygenation). The mediator release and tissue histamine content were studied prospectively in 17 control persons (histologically normal mucosa) as well as in 71 patients with inflammatory bowel disease (IBD) (histologically uninvolved and involved tissue). RESULTS: Although a significant accumulation of histamine was found in inflamed IBD-tissue, the results indicate, however, that this premedication does not enhance the release of histamine or tryptase from gut mucosal samples, neither in the histologically normal mucosa of control persons nor in tissue unaffected or affected by inflammatory bowel disease. CONCLUSION: This study demonstrates that colonoscopy premedication with diazepam and pethidine is safe in terms of gut mucosal mast cell activation.
BACKGROUND AND STUDY AIMS: The palliative endoscopic treatment of malignant obstruction of the upper gastrointestinal tract, including esophagorespiratory fistulas, is often difficult. The efficacy of polyethylene-coated [corrected] Gianturco-Z stents in these sometimes complicated tumor stenoses was investigated. PATIENTS AND METHODS: Twenty patients with malignant obstruction of the esophagus and the cardia, including six patients with esophagotracheal fistulas, were treated with Gianturco-Z stents. Five patients had previously been provided with another type of self-expanding metal endoprosthesis (two with Wallstents and three with Ultra-flex memory metal stents), and needed retreatment because of tumor ingrowth or overgrowth, esophagotracheal fistulas, or insufficient stent expansion. All data acquired prior to and during stent implantation, as well as during the follow-up period, were recorded prospectively. RESULTS: No technical problems occurred during the implantation of the stents. Nineteen of 20 Gianturco-Z stents (95%) spontaneously showed sufficient expansion at the endoscopic control, which was conducted within the following 48 hours. All patients, with the exception of one, reported immediate improvement of their dysphagia. The sealing of the six fistulas was also achieved. Severe early complications, such as bleeding or perforation, did not occur, but one stent migration was encountered. Two types of minor problems were observed: short-term retrosternal and epigastric pain (11 patients) and formation of a pouch at the upper rim of the stent (one patient). In the follow-up, tumor overgrowth of the stent ends was found in one patient, who was retreated with electrocoagulation. Tumor infiltration of the wire mesh has not been observed so far. In one patient, dislocation of a stent into the stomach occurred (probably as a result of endoscopic measures being performed to control tumor bleeding). CONCLUSIONS: We conclude that the treatment of malignant esophageal obstructions, including esophagorespiratory fistulas, with Gianturco-Z stents is effective, and that implantation is safe, especially in the case of tumor stenoses in the proximal esophagus. The expansile force of the stent is sufficient even for very firm strictures; and the polyethylene [corrected] covering of the stent seems to prevent tumor ingrowth.
Thirty patients with incurable malignant obstruction of the oesophagus and cardia were treated with self expanding oesophageal memory metal stents (Ultraflex) in a prospective study. The endoprostheses were successfully placed in all patients. Within one week after implantation dysphagia had improved in 25 of 30 patients (83%). Stent expansion was incomplete within one week after implantation in 12 of 30 patients (40%). After an average of two dilatation sessions eight of 12 stents had expanded completely. Five patients complained of retrosternal pain and three of them suffered from heartburn over several days despite acid inhibition. Major problems in the follow up period occurred in 10 of 30 patients (30%) and included late perforation (one) and tumour ingrowth/overgrowth (nine). All of these complications were treated endoscopically. Improvement of the dysphagia of the patients with tumour ingrowth/overgrowth lasted for about eight weeks (median; range: 2-38 weeks). Until November 1994 six of 30 patients were still alive with a survival time of 309 days (median; range: 103-368 days). It is concluded that oesophageal memory metal stents are easy to implant, prove effective in the palliation of malignant oesophageal obstructions, and have a low risk of severe complications. The only disadvantages are that incomplete initial stent expansion as well as tumour ingrowth/overgrowth occurred in nearly one third of the patients.
Gastric adaptation to injury during repeated doses of acetyl salicylic acid (ASA) is a well documented finding but it is not known whether this adaptation affects the tolerance of the mucosa to other strong irritants. Gastric adaptation was induced by repeated daily doses of acidified ASA (100 mg/kg in 1.5 ml of 0.2 N HCl) given intragastrically (series A rats). Control rats with an intact stomach were given daily intragastric vehicle only (1.5 ml of 0.2 N HCl) (series B). After full adaptation to ASA (5 days), rats were challenged again with acidified ASA or, for comparison, with strong irritants such as 100% ethanol, 200 mM acidified taurocholate, or 25% NaCl for 1 hour or with water immersion and restraint for 3.5 hours. The first dose of ASA produced numerous gastric lesions and deep histological necrosis accompanied by a fall in the gastric blood flow, negligible expression of epidermal growth factor (EGF) and transforming growth factor alpha (TGF alpha) or their receptors, and no evidence of mucosal proliferation. As adaptation to ASA developed, however, the areas of gastric lesions were reduced by more than 80% and there was a noticeable decrease in deep necrosis, a partial restoration of gastric blood flow, an approximately four-fold increase in EGF expression (but not in TGF alpha) and its receptors, and an appreciable increase in mucosal cell proliferation compared with vehicle treated rats. Increases in the mucosal expression of EGF receptors and the luminal content of EGF were also found in ASA adapted animals. In ASA adapted rats subsequently challenged with 100% ethanol, 200 mM TC, 25% NaCl, or stress, the area of the gastric lesions and deep histological necrosis were appreciably reduced compared with values in vehicle treated rats. This increased mucosal tolerance to strong irritants was also accompanied by the return of the gastric blood flow towards control levels and further significant increases in the mucosal expression of EGF receptors and mucosal cell proliferation. Gastric adaptation to ASA enhances the mucosal resistance to injury by strong irritants probably as a result of the restoration of the gastric blood flow and increased cell proliferation that may result from increased mucosal expression of EGF and its receptors.
Histamine exhibits various biological effects in inflammatory and immunological reactions. To further define its potential role in allergic enteropathy and inflammatory bowel disease, both gut mucosal histamine levels and histamine release from endoscopic biopsy samples were measured. Tissue histamine content resulted from addition of the released amount of histamine and the remaining part of tissue histamine. The results demonstrate highly elevated mucosal histamine levels of the large intestine in allergic enteropathy. In inflammatory bowel disease histamine content and secretion were found to be significantly increased particularly in affected mucosa of Crohn's disease and ulcerative colitis than in unaffected tissue or in healthy controls. These findings give strong evidence that mast cell mediators like histamine play a role in the pathogenesis of these diseases. Mucosal histamine is thus concluded to contribute to the immuno-inflammatory reactions of the intestine found in these disease states and to reflect the degree of colonic inflammation in Crohn's disease and ulcerative colitis.
INTRODUCTION: We investigated the distribution of extracellular matrix (ECM) proteins in indomethacin-induced lesions of the rat stomach. METHOD: Twenty rats received indomethacin orally at a dose of 8 mg/kg/body weight. The animals were killed at 3, 6, 12, 24, and 48 h after administration of the drug. The stomachs were removed and frozen in liquid nitrogen. Cryostat serial sections of the lesions were immunostained with antibodies to collagen III, IV, and VI, laminin, and fibronectin. RESULTS: Fibronectin was the dominant extracellular protein of the provisional ECM in deep gastric lesions and gastric ulcers. Collagen III was strongly positive in stromal cells under the necrotic material in gastric erosions. Basal membrane proteins (collagen IV and laminin) were found to originate from the muscularis mucosae at the ulcer edge. CONCLUSION: There is a typical distribution of ECM proteins in erosions and ulcers of the rat stomach. Fibronectin was most prominent in the provisional matrix of gastric erosions and ulcers.
OBJECTIVE: To investigate the presence of extracellular matrix (ECM) proteins in human bile and gallstones and to determine whether they play a role in gallstone formation. METHODS: ECM components [procollagen-III-peptide (P-III-P), laminin, and hyaluronic acid] in bile from patients with (n = 22) and without (n = 6) gallstone disease were investigated by immunoassay. Bile, gallstones, and serum were assayed for extracellular matrix components in an additional 19 patients with gallstone disease and gallstones were analysed in a third set of 26 patients. The expression of hyaluronic acid synthetase in bile duct and gall bladder epithelia was investigated by immunocytochemistry. RESULTS: Hyaluronic acid levels were significantly elevated in hepatic and gall bladder bile, but not in the serum of patients with compared with those without gallstone disease (137 versus 81 micrograms/l, respectively; P < 0.05). No differences were found between hepatic and gall bladder bile. Procollagen-III-peptide and laminin were detected in the hepatic bile of patients in both groups. Laminin levels were higher in gall bladder bile than in serum in all patients and measurable amounts of hyaluronic acid were found in gallstones. The amount of hyaluronic acid was inversely correlated to the volume of the gallstone, i.e., the smallest gallstones contained the highest levels of hyaluronic acid. No procollagen-III-peptide or laminin was found in the gallstones. Immunocytochemistry of the epithelial cells of bile duct and gall bladder mucosa stained strongly for hyaluronic acid synthetase. CONCLUSIONS: Hyaluronic acid as a progenitor of ECM can be detected in bile and is significantly elevated in patients with gallstone disease. Small gallstones contain more hyaluronic acid than large stones, suggesting that hyaluronic acid may play a role in gallstone formation, particularly since it is produced by the epithelial lining of bile ducts and is found in gall bladder mucosa.
This study investigated the relationship between urinary sodium excretion and liver function, as assessed by the aminopyrine breath test (ABT) and conventional parameters, in 62 patients with cirrhosis kept on a constant salt diet. Urinary sodium excretion was related non-linearly to the ABT (r = 0.76). Less significant correlations were observed to the Child-Pugh score (r = -0.65), cholinesterase (r = 0.58), bilirubin (r = -0.56), albumin (r = 0.51) and prothrombin time (r = 0.49). When patients were arbitrarily divided into 6 groups according to the ABT, sodium excretion balanced the sodium intake up to a 50% reduction in ABT. In groups with more than a 50% reduction sodium retention occurred. When patients were grouped according to the Child-Pugh score, urinary salt output was balanced in patients with scores of 5 and 6 and decreased in patients with scores greater six. However, the change in sodium output from normal salt excretion to sodium retention was less pronounced in patients grouped according to the Child-Pugh score than in patients grouped according to the ABT. The results suggest a non-linear relationship between the impairment in hepatic and renal function in cirrhosis. They are compatible with the concept of a threshold of hepatic function necessary to maintain normal renal function.
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Urease and ammonia (NH4OH) have been proposed to be play a major role in the pathogenesis of the the Helicobacter pylori (Hp)-associated gastric damage but the mechanism of this damage has not been fully explained. This study was designed the determine whether topical application with NH4OH at low concentration or the generation of the NH4OH in gastric lumen by the hydrolysis of urea in the presence of urease can induce adaptive cytoprotection. Single insult of NH4OH alone in various concentrations (15-500 mM) caused the mucosal damage starting at 30 mM and reaching at 250 mM the value similar to that obtained with 100% ethanol and being accompanied by the fall in gastric blood flow to about 30% of the normal value. When the mucosa was first exposed to the low concentration (15 mM) of NH4OH, causing by itself only small microscopic damage of surface epithelium, but then insulted by a high concentration (250 mM) of NH4OH, the extent of mucosal damage was greatly attenuated as compared to that caused by NH4OH alone. This "adaptive" cytoprotection, accompanied by the rise in the GBF, was reversed in part, after the pretreatment with indomethacin to inhibit PG-cyclooxygenase, with L-NAME to suppress NO-synthase or with capsaicin to induce deactivation of sensory nerves. The combined topical pretreatment with urea (2%) and urease (100 U) to generate NH4OH in the stomach, also significantly reduced the severity of gastric lesions induced by 100% ethanol and this was also accompanied by a significant rise in the gastric blood flow. The protective and hyperemic effects of urea and urease were significantly attenuated by the pretreatment with indomethacin or suppression of NO-synthase by L-NAME. The functional ablation of sensory nerves by the pretreatment with capsaicin also reversed, in part, the protective effect of the combination of urea plus urease and abolished completely the mucosal hyperemia accompanying this protection. We conclude that 1) NH4OH alone at higher concentrations damages the gastric mucosa but when applied at lower concentration corresponding to that in the stomach of Hp-infected patients, or generated by the urea in the presence of urease, NH4OH acts like "mild irritant" to induce adaptive cytoprotection, 2) this adaptive cytoprotection is mediated, in part, by endogenous PG, sensory nerves and arginine-NO-dependent pathway.
A 24-year-old patient presented with severe back pain in the lumbar and sacral regions and septic temperatures up to 40 degrees C. Lasègue's sign was bilaterally positive. An enhanced cell count was seen in the CSF (1877 cells/microliters, erythrocytes 1024/microliters). Total protein concentration was 4440 mg/dl. The patient also suffered from granulocytic pleocytosis. X-ray as well as scintigrams revealed inflammation of the presacral soft parts involving the os sacrum and bone marrow. Treatment with doxycycline (200 mg/d), fosfomycin (5 g/d), netilmicin (400 mg/d) and ofloxacin (200 mg/d) succeeded in curing the meningitis, whereas the presacral phlegmon persisted. Endoscopic examination showed a rod-shaped foreign body in the rectum that had penetrated deeply into the mucosa and required deformation and removal by laser. The plastic rod of 10 cm length was probably a liquorice stick. The patient denied introducing it per anum; he suspected having swallowed it while drunk. The inflammation subsided rapidly after removal of the foreign body.
Photodynamic treatment (PDT) of malignant tumours rests on the intravenous administration of a photosensitizer, which is predominantly in tumour tissue, and subsequent activation of this substance with light of a specific wavelength. The method was used in a 76-year-old man who had undergone a 2/3 gastric resection for ulcer in 1948 and was now found to have a carcinoma of the stump at the anastomosis. He refused surgical resection, but accepted PDT. 48 hours after intravenous administration of the photosensitizer dihematoporphyrin ether-ester (2 mg/kg) the 1.5 x 1.0 cm tumour was irradiated with an argon ion laser pumped colour laser system at a wavelength of 630 nm and energy density of 150 J/cm3. The irradiation was performed under endoscopic control via a specially developed applicator which had first been introduced through the biopsy channel of the endoscope. Four weeks after the first treatment biopsies from a 5 mm ulceration in the area of the tumour revealed malignant cell groups, so that a second treatment was undertaken. Two, three and six months later the ulcer was shown to have healed and biopsies were free of tumour. But nine months later tumour cells were again demonstrated and a third PDT was performed. Although biopsies were again free of tumour at the next control, it can not yet be assumed that the tumour has been cured.
In a prospective study the reliability of colour-coded duplex-sonography (CCDS) and phlebography in the diagnosis of deep leg and pelvic vein thrombosis was compared. In 82 consecutive in- or out-patients (42 men, 40 women; mean age 53 [19-86] years) with clinically suspected leg or pelvic vein thrombosis the results of 275 phlebographies (reference method) and 275 CCDS were compared on admission and during follow-up. The two methods were performed less than 6 hours apart. In the diagnosis of thrombosis the sensitivity of CCDS was 99%, specificity 80%. In 88% of all tests, the different thrombosis levels, as diagnosed by phlebography, were also demonstrated by CCDS. These data indicate that, if the clinical picture of suspected deep leg or pelvic vein thrombosis is unclear, CCDS should be done first. Phlebography should be performed only if the results of the former are inconclusive.
The dynamics of cognitive brain functions of 104 patients with both chronic non-cirrhotic (NC) and cirrhotic liver disease (C: C1, non-encephalopathic; C2, encephalopathic) were investigated by means of visual P300 potentials elicited in both the paradigms of transient (PI) and selective attention (PII). Conventional PVEPs, psychometric tests and quantitative liver function tests were also performed. As compared to both an age-matched control group (N) and the non-cirrhotic patients (NC), the N250 and P300 latencies of the cirrhotics (C) were equally prolonged in both P300 paradigms (P = 0.0001). By contrast, the P300 amplitudes were not different between the patient groups in either P300 paradigm. In the cirrhotics, however, the P300 amplitude differences between PII and PI (+ 3.7 +/- 2.8 muV, mean +/- 1 S.D.) were significantly (P < 0.01) smaller than in the non-cirrhotics (+ 7.5 +/- 5.2 muV) reflecting disturbances in the dynamics of visual attention. Interestingly, these P300 amplitude differences between both paradigms were positively correlated (r = 0.35; P = 0.005) with hepatic metabolic capacity, but not with liver blood flow (r = 0.23; P > 0.05). The diagnostic efficacy of the visual P300 in PI (sensitivity, 48%; specificity, 100%) was lower than that of the visual P300 in PII (79%; 100%) and that of the psychometric tests (63%; 94%), but it remained superior to that of the PVEPs (29%; 97%). It is concluded that in patients with cirrhotic liver disease visual P300 potentials can even reveal the dynamics of minor cognitive brain dysfunction and may also provide interesting pathophysiological information.
OBJECTIVES: The clinical feasibility of self-expanding metal stents with respect to the technical success, complications, and reintervention rate should be tested. METHODS: Five coated and 26 uncoated prototype Wallstents, especially designed for stenosis of the upper GI tract, were implanted in 23 patients. All patients with dysphagia suffered from inoperable tumor stenosis of the esophagus or the cardia. Stent implantation was performed under slight i.v. sedoanalgesia. RESULTS: Technical success was achieved in all 31 implanted stents. Forty-eight hr after implantation, dysphagia was improved in 21/23 patients. Acute problems observed within 1 wk were stent migration (1 patient, uncoated stent), oblique position of the stent (3 patients), epigastric or retrosternal pain (9 patients), insufficient stent expansion (4 patients), and pouch formation at the upper rim of the stent (4 patients). An uncomplicated follow-up (median 66 days, range 10-139 days) was seen in 12 patients (52%). Major problems in the follow-up period were stent migration in three patients (three coated stents, two stent migrations in one patient) and stent obstruction by tumor ingrowth/overgrowth and/or food impaction in eight patients (35%). Most of these problems could be successfully resolved by implantation of a second stent or electrocoagulation of overgrowing tumor tissue. By the 1st of March, 1994, three patients were still alive with a follow-up period of 530 days (median range, 336-880 days); 20 patients were decreased with a follow-up period of 70 days (median range, 3-374 days). CONCLUSIONS: Implantation of esophageal Wallstents is safe and has a low risk of acute complications and mortality for the patient. Early complications such as perforation and bleeding did not occur. Tumor ingrowth/overgrowth are the major reasons for the high reintervention rate in the follow-up period. Coated stents can resolve this problem, provided that stent migration can be avoided by improvement of the coating technology.