PubMed Health⌕ Search

Biomedical subjects

H Messmann

Publications and source records attributed to H Messmann.

72 records · Page 4Linked to original sources
PubMed1997

Influence of a haematoporphyrin derivative on the protoporphyrin IX synthesis and photodynamic effect after 5-aminolaevulinic acid sensitization in human colon carcinoma cells.

Haematoporphyrin derivatives (HPDs) are potent sensitizers in photodynamic therapy (PDT), associated with prolonged skin photosensitivity. 5-Aminolaevulinic acid (5-ALA), a natural precusor of haem, is converted intracellularly into the photosensitive agent protoporphyrin IX (PPIX), causing direct cytotoxicity after laser light irradiation but limited skin photosensitivity over 1-2 days and higher tumour selectivity. Unfortunately, the use of 5-ALA in PDT has been shown to cause only superficial tissue necrosis. Therefore, a combination of HPD and 5-ALA could be of great clinical value in the treatment of tumours if a synergistic effect of both sensitizers on tumour cell necrosis with less skin photosensitivity could be demonstrated. Human colon adenocarcinoma cells (HT-29) were cultured with either HPD or 5-ALA alone, simultaneously for 24 h with 5-ALA and HPD or in succession with 5-ALA (18 h) followed by HPD (6 h at different concentrations. Intracellular PPIX concentrations were determined by high-performance thin-layer chromatography. Furthermore, PDT was performed with an incoherent light source (lambda = 580-740 nm) using a light dose of 30 J cm(-2) and an output power of 40 mW cm(-2). The intracellular PPIX concentration correlated well with 5-ALA drug dose and incubation time and was highest after single 5-ALA sensitization. In the presence of HPD, either simultaneously or sequentially, PPIX decreased significantly. The PDT effect after simultaneous incubation with both sensitizers for 24 h was not superior to incubation with HPD alone. If 5-ALA incubation (18 h) was followed by HPD (6 h) cytotoxicity after PDT was higher than with either single drug. 5-ALA (80 microg ml(-1)) led to a decrease in tumour cell viability by 40%. A similar effect could be observed when 5-ALA and HPD were sequentially combined allowing for a reduction of the 5-ALA dose from 80 microg ml(-1) in the absence of HPD to 60 microg ml(-1) and 5 microg ml(-1) together with 0.5 microg ml(-1) and 2 microg ml(-1) HPD respectively. We speculate that the enhanced PDT effect after the combined administration of 5-ALA and HPD to cultures of colon carcinoma cells should be even more impressive in the tumour in vivo, since HPD primarily targets the tumour microvasculature and secondarily tumour cells.

Aminolevulinic Acid↗
PubMed1997

Enhanced effectiveness of photodynamic therapy with laser light fractionation in patients with esophageal cancer.

BACKGROUND AND STUDY AIMS: The fractionated application of laser light has been shown to enhance the effect of photodynamic therapy (PDT) on normal rat colon after photosensitization with 5-aminolevulinic acid. In a pilot study, we examined whether this modified laser treatment can also enhance the effect of PDT in patients with esophageal cancer after sensitization with hematoporphyrins. PATIENTS AND METHODS: Six patients (four cases of early esophageal carcinoma and two cases of advanced esophageal carcinoma, one of the latter patients having tumor overgrowth on a metal stent) were treated in nine sessions. In four sessions, laser energy was fractionated to enhance the PDT effect using a hematoporphyrin polyester. Irradiation was carried out 48 hours after sensitization. The total laser energy of 150 J/cm2 was applied either continuously or in fractions, with a single break of five minutes after 75 J/cm2. RESULTS: Among the three patients who underwent continuous laser light irradiation, one patient experienced a complete remission of two of three superficial esophageal cancers. The patient with tumor overgrowth on an implanted metal stent showed a partial response, with improvement of dysphagia without destruction of the stent, while in another patient with advanced esophageal cancer, the dysphagia did not improve after continuous laser treatment. Fractionated laser therapy led to complete remission in all three patients with early cancers, one of whom had failed to respond to previous treatment with continuous PDT. A partial remission was obtained in a fourth patient with a uT2 cancer who had also shown no remission after continuous PDT treatment. However, after fractionated laser therapy, three mild esophageal stenoses occurred, in comparison with none after continuous PDT. CONCLUSIONS: Light fractionation during PDT improved the effectiveness of the treatment in a small number of patients, and increased side effects such as the occurrence of mild esophageal stenosis. This modified treatment can be a promising approach in the effort to reduce the dose of hematoporphyrins or other sensitizers required, and to avoid prolonged skin sensitization or local stenosis.

Aged↗
PubMed1997

Post-ERP pancreatitis as a model for cytokine induced acute phase response in acute pancreatitis.

BACKGROUND/AIMS: By contrast with animal models, in most cases it is not possible to examine the systemic response in patients in the first hours after onset of acute pancreatitis. The aim was to determine whether endoscopic retrograde cholangiopancreaticography (ERP)-induced pancreatitis can be used as a human model for the study of cytokine release and acute phase response in the first hours of the disease. PATIENTS AND METHODS: Seventy consecutive patients undergoing ERP for different reasons were prospectively evaluated by sampling blood before and 0, 1, 4, 12, 24, and 48 hours after ERP and, in patients who developed an acute post-ERP pancreatitis, daily until C reactive protein (CRP) was within normal range. A post-ERP pancreatitis was defined as a three-fold increase of amylase or lipase and at least two of the clinical symptoms: abdominal pain, nausea, vomiting, and peritonism during 24 hours after ERP. RESULTS: Nine out of 70 patients developed an acute pancreatitis. Cytokines and other biochemical variables were measured in those nine and in 34 patients out of the 61 not developing pancreatitis. In the nine patients amylase and lipase increased within the first hour after ERP with maximum values between four and 12 hours. Interleukin-6 increased to maximal concentrations after 24-48 hours and the highest CRP concentrations were found 72 hours after ERP. Tumour necrosis factor did not change. CONCLUSION: Post-ERP pancreatitis is an ideal model in which to examine the initial cytokine and acute phase response in the first hours after the initiation of the disease.

Acute Disease↗
PubMed1996

[CT-guided percutaneous endoscopic gastrostomy: a successful method if transillumination is not possible].

BACKGROUND AND OBJECTIVE: If transillumination is not possible, percutaneous endoscopic gastrostomy (PEG) is contraindicated. In these cases the stomach had so far to be punctured directly during radiological monitoring. A new method is described which combines endoscopy and computed tomography (CT) for performing a percutaneous endoscopic gastrostomy. PATIENTS AND METHODS: Among 189 patients who were to have the procedure there were eleven (nine men, two women) in whom transillumination was not possible. After endoscopic insufflation of air PEG was done under CT guidance, using the common pull-through technique. RESULTS: The combined method was successful in ten of the eleven patients without complication. In one patient with hepatomegaly and interposition of the transverse colon PEG was not possible even with CT guidance. CONCLUSIONS: The combined endoscopic-radiological method is practicable and safe in cases in which transillumination is not possible. There are several advantages compared with direct puncturing: The common pull-through technique can be used; radiological exposure is low and other clinically relevant findings may be revealed by the endoscopy.

Adult↗
PubMed1996

9-Acetoxy-2,7,12,17-tetrakis-(beta-methoxyethyl)-porphycene (ATMPn), a novel photosensitizer for photodynamic therapy: uptake kinetics and intracellular localization.

The optimal photosensitizer for topical or systemic photodynamic therapy (PDT) has not yet been found. A promising new second-generation sensitizer is 9-acetoxy-2,7,12,17-tetrakis-(beta-methoxyethyl)-porphycene (ATMPn) whose time- and temperature-dependent uptake and intracellular localization were investigated in two human-skin-derived cell lines (HaCaT keratinocytes and dermal fibroblasts). Flow cytometry analysis (0-800 s) revealed an immediate increase in fluorescence in the cells after start of incubation with 100 ng ml-1 ATMPn (in cell culture medium). At longer incubation periods (0-24 h) a constant increase in fluorescence up to 12 h, with a steady state up to 24 h, was observed. Keratinocyte showed a faster rate of ATMPn uptake than fibroblasts within the first 12 h. Temperature-dependent ATMPn uptake was measured at 4 and 37 degrees C. An increase in fluorescence was observed even at 4 degrees C, suggesting that cellular uptake of ATMPn is partially based on passive diffusion. Confocal laser scan miscroscopy showed spotty, granular fluorescence inside the cytoplasm after incubation with ATMPn, similar to the pattern of rhodamine 123 which stains mitochondria. These results demonstrated an unusually fast intracellular, probably intramitochondrial, uptake of ATMPn in vitro. Therefore the use of ATMPn in photodynamic therapy might allow a reduction of the time span between administration of drug and irradiation.

Cell Line↗
PubMed1996

Distribution and photodynamic effects of meso-tetrahydroxyphenylchlorin (mTHPC) in the pancreas and adjacent tissues in the Syrian golden hamster.

Photodynamic therapy (PDT) has the potential to destroy small tumours with safe healing of adjacent normal tissue. This study looks at the effects of PDT on the normal pancreas and adjacent tissues in hamsters using the photosensitiser meso-tetrahydroxyphenylchlorin (mTHPC). Pharmacokinetic studies used fluorescence microscopy on sections of pancreas, stomach and duodenum 1 h to 6 days after mTHPC. Highest levels of sensitiser were seen in the gastric and duodenal mucosa and in the acinar pancreas after 2-4 days. For PDT, light at 652 nm was delivered by placing a 0.2 mm diameter bare-ended fibre against the tissue. An energy of 50 J was used 2 or 4 days after 0.1 or 0.3 mg kg-1 mTHPC and animals killed 1 to 7 days later. Maximum necrosis was seen 3 days after PDT with lesions up to 4 mm in pancreas, 4.5 mm in duodenum and 2.5 mm in stomach. By fractionating the light dose, the lesion size could be increased by 30%. The main complication was free or sealed duodenal perforation (avoided by shielding the duodenum). Partial, reversible bile duct obstruction was seen occasionally. There was no macroscopic damage to the bile ducts or major blood vessels. Apart from the duodenum, all lesions healed safely. In this animal model, only the duodenum was at risk of serious, irreversible damage. Treatment is likely to be safer in the much thicker human duodenum. mTHPC is a powerful photosensitiser and suitable for further study for tumours in the region of the pancreas although care is required near the duodenum.

Animals↗
PubMed1995

Enhancement of photodynamic therapy with 5-aminolaevulinic acid-induced porphyrin photosensitisation in normal rat colon by threshold and light fractionation studies.

5-Aminolaevulinic acid (ALA)-induced prophyrin photosensitisation is an attractive option for photodynamic therapy (PDT) since skin photosensitivity is limited to 1-2 days. However, early clinical results on colon tumours using the maximum tolerated oral dose of 60 mg kg-1 showed only superficial necrosis, presumably owing to insufficient intratumoral porphyrin levels, although inadequate light dosimetry may also be a factor. We undertook experiments using ALA, 25-400 mg kg-1 intravenously, to establish the threshold doses required for a PDT effect. Laser light at 630 nm (100 mW, 10-200 J) was delivered to a single site in the colon of photosensitised normal Wistar rats at laparotomy. The animals were killed 3 days later and the area of PDT-induced necrosis measured. No lesion was seen with 25 mg kg-1. The lesion size increased with larger ALA doses and with the light dose but little benefit was seen from increasing the ALA dose above 200 mg kg-1 or the light dose above 100 J. Thus there is a fairly narrow window for optimum doses of drug and light. Further experiments showed that the PDT effect can be markedly enhanced by fractionating the light dose. A series of animals was sensitized with 200 mg kg-1 ALA and then treated with 25 J. With continuous irradiation, the lesion area was 13 mm2, but with a single interruption of 150 s the area rose to 94 mm2 with the same total energy. Results were basically similar for different intervals between fractions (10-900 s) and different numbers of fractions (2-25). This suggests that a single short interruption in the light irradiation may dramatically reduce the net light dose required to achieve extensive necrosis.

Aminolevulinic Acid↗
PubMed1995

Sensitization and photodynamic therapy (PDT) of gastrointestinal tumors with 5-aminolaevulinic acid (ALA) induced protoporphyrin IX (PPIX). A pilot study.

5-Aminolaevulinic acid (ALA) is a promising agent for photodynamic therapy (PDT) sensitization as it can be given orally and only causes skin photosensitivity for 1-2 days. In fluorescence and photodynamic studies 26 patients with benign and malignant gastrointestinal tumors were given 30-60 mg ALA orally (single or divided doses) and biopsies were taken of tumor and normal tissue at 1-24 hours for fluorescence microscopy. With 30 mg/kg, highest protoporphyrin IX (PPIX) levels were seen in esophagus, duodenum and less in colon, but without tumor selectivity. Better tumor selectivity was seen in colon after 60 mg/kg (5:1). Six patients had transient rises in transaminases and five mild nausea. Sixteen patients were later treated (after further ALA) with red light (628 nm, bare or diffuser fibre, 50-100 J at 50 mW at each site). All but two showed subsequent necrosis, but only 0.5-1.5 mm of depth. PDT with ALA is simple, safe and promising for tumors in the gastrointestinal tract. Modification of treatment parameters may make it suitable for larger lesions.

Administration, Oral↗
PubMed1995

[Multiple gastric wall abscesses--a rare differential endosonographic diagnosis of submucous stomach tumors].

We report a rare case of a 52 year old patient with multiple gastric wall abscesses. In 1987 a selective proximal vagotomy was performed. Because of non-specific gastric symptoms in 1993 an endoscopy and an endoscopic ultrasound was performed at another hospital which resulted in the likely diagnosis of multiple leiomyomas. Three months later a control endosonography showed three well demarcated submucosal tumors, partly echo-genic, but with an inhomogeneous echo-pattern. A laparotomy and histological examination of the submucosal gastric tumors revealed multiple gastric abscesses with granulomas after selective proximal vagotomy. Difficulties in the differential diagnosis of submucosal gastric tumors arising from this case are demonstrated and discussed.

Abscess↗
PubMed1994

Delayed spontaneous opening of a self-expanding metal stent bridging a malignant esophageal stenosis.

We report on a case of an 85-year-old man with dysphagia who suffered from a stenosing esophageal adenocarcinoma that could not be treated by surgery. The tumor demonstrated circumferential growth and extended from 14 to 22 cm from the incisors. There were no esophago-tracheal fistulas. The stenosis could be negotiated with the endoscope. Under fluoroscopic guidance, a self-expanding Strecker stent was placed in the stenosed area with no prior dilatation. After releasing the stent an x-ray revealed a twisted and wrinkled stent which had expanded to only half of its maximum diameter. The patient's symptoms had not improved. Four days later dysphagia resolved when the stent spontaneously corrected its position and was found to be maximally expanded. On the basis of this observation it may be concluded that, at least in some cases, self-correction of an initially unsatisfactory positioning of a Strecker stent may be expected, even after four days.

Adenocarcinoma↗
PubMedDate not supplied

Photodynamic therapy for polyps in familial adenomatous polyposis--a pilot study.

Photodynamic therapy (PDT) produces localised necrosis with light after prior administration of a photosensitising drug. As PDT lesions in the gastrointestinal tract heal so well, the technique is suitable for repeated endoscopic use. In this study, PDT was used to treat large polyps (four duodenal and two colorectal) unsuitable for surgery in 6 patients with familial adenomatous polyposis (FAP). Patients were sensitised with 60 mg/kg 5-aminolaevulinic acid (ALA) orally or intravenous (i.v.) 2.0 mg/kg Photofrin. Laser treatment was performed 6 h after ALA or 48 h after Photofrin using a gold vapour laser. Necrosis was only superficial (up to 1.8 mm) using ALA but much deeper using Photofrin. The one malignant polyp (8 mm diameter in the colon) showed a complete response using Photofrin. All healed safely with no complications. Photofrin worked better, but caused cutaneous photosensitivity lasting up to 3 months. ALA cleared within 2 days, but its use is limited by the superficial effect. Better results with ALA may be obtained using higher drug doses or modified light dosimetry. Fluorescence microscopy showed no evidence of selectivity of photosensitisation between neoplastic and normal tissue. PDT is a promising treatment for inoperable polyps in patients with FAP, but further work is required to optimise the treatment conditions.

Adenoma↗
PubMedDate not supplied

Long-term follow-up of patients with necrotizing pancreatitis treated by percutaneous necrosectomy.

BACKGROUND/AIMS: The objective of this follow-up study was to assess the long-term outcome of patients with infected necrotizing pancreatitis treated with percutaneous catheter drainage and necrosectomy. METHODOLOGY: Nine patients (median age 44 years, range 19-69) with infected pancreatic necrosis and catheter drainage for initial treatment were evaluated after a median follow-up of 30 months (range 15-52) with respect to quality of life (pain, diarrhea, fat intolerance), morphology and endocrine and exocrine pancreatic function. RESULTS: At follow-up all 9 patients (100%) were in good general condition with respect to quality of life. Only 2/9 (22%) patients had moderate to marked changes in computed tomography. There was mild to moderate exocrine dysfunction in 5/8 (63%) patients, 2/8 (25%) patients had a severe restriction of the exocrine pancreatic function; in one patient the serum pancreoaryl test was normal. An oral glucose tolerance test was performed in 6/9 patients, with a normal result in 3/6 (50%) patients. 2/6 (33%) patients had an impaired oral glucose tolerance test with metabolic pathogenesis. One patient with diabetes in the oral glucose tolerance test had a preexisting type II diabetes requiring insulin therapy since the onset of acute pancreatitis. In 3/9 (33%) patients an oral glucose tolerance test was not performed due to known preexisting diabetes. CONCLUSIONS: Percutaneous drainage of infected necrotizing pancreatitis has given good long-term results with regard to quality of life, endocrine and exocrine pancreatic function and may be an alternative to surgical treatment.

Adult↗
PubMedDate not supplied

Modified serum pancreolauryl test in chronic pancreatitis: evaluation in comparison to endoscopic retrograde pancreatography.

BACKGROUND/AIMS: The aim of this study was to assess the applicability and accuracy of the modified serum pancreolauryl test (sPLT) in patients with chronic pancreatitis (cP). METHODOLOGY: We compared the results of a modified serum pancreolauryl test to morphological changes as detected by endoscopic retrograde pancreatography (ERP) in 60 patients with a history suggesting chronic pancreatitis were compared. Serum fluorescein was measured 30, 60, 120, 150, 180 and 240 minutes after the ingestion of fluoresceindilaureat, a standardized breakfast, and i.v. administration of secretin (1 U/kg) and metoclopramide (10 mg). Furthermore, the results of sPLT and ERP were compared to the findings on abdominal ultrasonography. RESULTS: Forty of 60 patients suffered from cP according to ERP criteria. With a fluorescein cut-off point of 4.5 micrograms/ml, sPLT reached a sensitivity of 68% and a specificity of 50%. According to the ROC curve, the optimal cut-off point was at a fluorescein level of 4.1 micrograms/ml; however, predictive accuracy was only slightly improved at this point. In the subgroup of patients with advanced pancreatic duct changes (n = 23), however, sPLT reached a sensitivity of 87% with 16 patients showing a peak fluorescein concentration below 2.5 micrograms/ml. CONCLUSION: Like other indirect pancreatic function tests, modified sPLT provides good recognition of patients with advanced cP but poor identification of patients with mild or moderate cP, leading to an unsatisfying overall performance of the test.

Adult↗