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Biomedical subjects

A E Goetz

Publications and source records attributed to A E Goetz.

At least 73 records · Page 4Linked to original sources
PubMed1996

Photodynamic eradication of amelanotic melanoma of the hamster with fast acting photosensitizers.

Three porphycenes with fast pharmacokinetics were tested for their ability to photosensitize amelanotic hamster melanoma A-Mel-3 at short time intervals after injection. Laser light irradiation was performed at the time of maximal photosensitizer level in tumor tissue. Photodynamic therapy as short as 5 min after injection led to complete local tumor remission at a dosage of 1.4 mumol/kg for the porphycene CBPn. In comparison, Photofrin required 8.4 mumol/kg for local tumor remission in 5 of 6 animals with 24 hr accumulation time after injection. We propose a swift photodynamic protocol which can compete favorably with conventional techniques of tumor treatment.

Animals↗
PubMed1996

Strong and prolonged induction of c-jun and c-fos proto-oncogenes by photodynamic therapy.

Photodynamic therapy (PDT) is currently under investigation in phase II and III clinical studies for the treatment of tumours in superficial localisations. Thus far, the underlying mechanisms of PDT regarding cellular responses and gene regulation are poorly understood. Photochemically generated singlet oxygen (1O2) is mainly responsible for cytotoxicity induced by PDT. If targeted cells are not disintegrated, photo-oxidative stress leads to transcription and translation of various stress response and cytokine genes. Tumour necrosis factor (TNF) alpha, interleukin (IL) 1 and IL-6 are strongly induced by photodynamic treatment, supporting inflammatory action and immunological anti-tumour responses. To investigate the first steps of gene activation, this study focused on the proto-oncogenes c-jun and c-fos, both coding for the transcription factor activator protein 1 (AP-1), which was found to mediate IL-6 gene expression. We here determine the effects of photodynamic treatment on transcriptional regulation and DNA binding of transcription factor AP-1 in order to understand the modulation of subsequent regulatory steps. Photodynamic treatment of epithelial HeLa cells was performed by incubation with Photofrin and illumination with 630 nm laser light in vitro. Expression of the c-jun and c-fos genes was determined by way of Northern blot analysis, and DNA-binding activity of the transcription factor AP-1 was evaluated by electrophoretic mobility shift assay (EMSA). Photofrin-mediated photosensitisation of HeLa cells resulted in a rapid and dose-dependent induction of both genes but preferential expression of c-jun. Compared with the transient expression of c-jun and c-fos by phorbol ester stimulation, photodynamic treatment led to a prolonged activation pattern of both immediate early genes. Furthermore, mRNA stability studies revealed an increased half-life of c-jun and c-fos transcripts resulting from photosensitisation. Although mRNA accumulation after PDT was stronger and more prolonged compared with phorbol ester stimulation, with regard to AP-1 DNA-binding activity, phorbol ester was more efficient. Surprisingly, in addition to the activation of AP-1 DNA-binding via PDT, photodynamic treatment can decrease AP-1 DNA-binding of other strong inducers, such as the protein kinase C-mediated pathway of phorbol esters and the antioxidant pyrrolidine dithiocarbamate (PDTC). This study demonstrates a strong induction of c-jun and c-fos expression by PDT, with prolonged kinetics and mRNA stabilisation as compared with activation by phorbol esters. Interestingly, this observation is not coincident with an overinduction of AP-1 DNA-binding, hence suggesting that post-translational modifications are dominant regulatory mechanisms after PDT that tightly control AP-1 activity in the nucleus thus limiting the risk of deregulated oncogene expression.

Antioxidants↗
PubMed1996

Local photodynamic therapy reduces tissue hyperplasia in an experimental restenosis model.

Local photodynamic therapy may have potential in preventing myointimal hyperplasia after angioplasty. In this study, the effect of photodynamic therapy was evaluated in an experimental model of restenosis. Standardized unidirectional arterial injury with a directional atherectomy catheter was performed in porcine arteries. Animals were randomly allocated to four groups: group 1, unidirectional injury only; group 2, injury followed by local delivery of photosensitizer; group 3, injury followed by local exposure to monochromatic light; and group 4, where injury was followed by local drug delivery of photosensitizer and subsequent exposure to light (photodynamic therapy). Seven, 14 or 21 days after treatment, all experimental vessels were excised, fixed and processed for histology. An inflammatory and myoproliferative response was observed after injury in vessels from groups 1, 2 and 3. In group 4, after injury followed by photodynamic therapy, the myoproliferative response was significantly reduced. Thus, in this study, tissue hyperplasia after unidirectional injury was effectively suppressed by photodynamic therapy.

Animals↗
PubMed1995

[The effect of mechanical ventilation, thoracotomy, and one-lung respiration on intrapulmonary perfusion distribution. An animal experimental study].

The physiological pattern of regional pulmonary blood flow is mainly determined by the relationship of pulmonary arterial, venous, and alveolar pressures. Changes in alveolar pressure and pulmonary geometry may therefore be expected to influence regional perfusion, which is a key determinant of pulmonary gas exchange. Unilateral thoracotomy is usually performed with the patient in the lateral decubitus position. The present study examined the influence of mechanical factors on regional pulmonary blood flow distribution in rabbits in the lateral decubitus position during normoxia and unilateral hypoxia. METHODS. Anaesthetised white New Zealand rabbits (n = 8) weighing 2200-3900 g (mean = 2860 g) received central venous injections of radioactive microspheres while in the left lateral decubitus position during spontaneous breathing (SB) and during mechanical ventilation (two-lung ventilation, 2LV), under closed (2LVC) and open chest (2LVT) conditions, as well as during unilateral hypoxia of the nondependent lung induced by nitrogen inflation (1LVN) or atelectasis (1LVA). The method used for one-lung ventilation (1LV) has been previously described in detail. Arterial, central venous, and pulmonary arterial pressures were recorded continuously. Lungs were excised, dried in the inflated state, and cut into 16 sagittal slices, which were further divided into lobar components, the lower lobes into center and periphery. The radioactivity of each specimen was measured in a gamma-counter; perfusion of the individual tissue specimens was quantified using the software program MIC III. The Friedman test followed by paired comparisons according to Conover was used for statistical analysis of differences between the experimental phases. Perfusion of central and peripheral parts of isogravitational slices was compared by use of the Wilcoxon matched pairs test. Values are given as means +/- SE; the level of significance was P < 0.05 unless otherwise indicated. RESULTS AND DISCUSSION. Haemodynamic parameters did not differ significantly between the experimental phases (Table 1). Compared to 2LV, a significant increase in venous admixture (P < 0.05) and a corresponding decrease in PaO2 (P < 0.01) were observed during 1LV. This effect was significantly more pronounced during 1LVA as compared to 1LVN (P < 0.01). Since inspiratory pressure was kept constant throughout the experiments, moderate respiratory acidosis developed during both phases of 1LV. Regional perfusion (Qr) of the nondependent lung was slightly reduced during 2LVC compared to SB and 2LVT. One-lung ventilation induced a significant decrease in perfusion of the hypoxic lung (P < 0.001 1LVN, 1LVA vs. SB,2LVC,2LVT). In accordance with the data obtained from blood gas analysis and oximetry, this effect was more pronounced during N2 insufflation than during atelectasis (P < 0.01 1LVN vs. 1LVA). Among the factors that may account for this effect, PaCO2 did not differ significantly between both phases of 1LV. During N2 insufflation PO2 at the hypoxia-sensitive site is lower than during atelectasis, where it equals mixed-versus PO2 (PvO2). The difference in local PO2 is unlikely, however, to have caused the changes in regional perfusion between 1LVN and 1LVA, since PvO2 was as low as 40 mmHg during 1LVA and the pulmonary vascular response to hypoxia has been found to reach its maximum in this PO2 range [2, 11]. Enhanced redistribution of regional perfusion during 1LVN as compared to 1LVA is therefore most likely attributed to differences in alveolar pressure and pulmonary geometry. Apart from a radial perfusion gradient in the right lower lobe during 2LVC and 2LVT, no isogravitational Qr gradients were observed. CONCLUSION. We conclude that controlled mechanical ventilation in the lateral decubitus position causes only minor changes in vertical blood flow distribution.

Animals↗
PubMed1995

Comparison of local intravascular drug-delivery catheter systems.

Systemic and local delivery of the photosensitive drug Photofrin polyporphyrin was investigated in normal porcine arteries (n = 192). A macroporous balloon and a novel needle injection catheter were used for local drug delivery and compared with systemic delivery. Fluorescence microscopy combined with digital image analysis was used to quantify the drug-related fluorescence. Systemic delivery showed a maximum in the intima at 4 hours. Application with the porous balloon revealed maximum indicator-related fluorescence intensity in the intima after 5 minutes; delivery with the needle injection catheter resulted in a several-fold enhanced maximum in adventitia after 30 minutes compared with the maximum achieved with either systemic injection or porous balloon application. After 21 days fluorescence was detectable in arteries treated with the new needle injection catheter. Local drug delivery is feasible with either system, but prolonged delivery was achieved only with the needle injection catheter.

Animals↗
PubMed1995

Effects of photodynamic therapy on leucocyte-endothelium interaction: differences between normal and tumour tissue.

An inflammatory reaction is regularly noticed in irradiated tissues following photodynamic therapy (PDT). This observation is potentially associated with leucocyte-mediated tissue damage, which might further contribute to the tumoricidal effect of this therapy. The objective of our study was to investigate the effects of PDT on leucocyte-endothelium interaction in the microvasculature of tumours and normal tissue. Experiments were performed in the dorsal skinfold chamber preparation of Syrian golden hamsters bearing amelanotic melanoma A-Mel-3. The photosensitiser. Photofrin (5 mg kg-1 i.v.) was injected 24 h before laser irradiation (630 nm, 100 mW cm-2, 10 J cm-2 or 100 J cm-2). Post-capillary confluent venules (diameter 15-40 microns) of subcutaneous (s.c.) tissue or the amelanotic melanoma A-Mel-3 were observed by intravital microscopy before, 5, 30, 60 and 180 min after laser irradiation and recorded for off-line analysis. Before treatment, the number of adherent leucocytes in tumour vessels was only 22% of the number observed in vessels of s.c. tissue (P < 0.01). The maximum increase in adhering leucocytes was observed in post-capillary venules of s.c. tissue 1 h after PDT (P < 0.01). In contrast, enhanced leucocyte-endothelium interaction was missing in tumour vessels and in control groups. These results indicate that the tumour destruction observed after PDT is not mediated by leucocyte-endothelium interaction in the tumour. Induction of leucocyte adhesion in the PDT-treated normal tissue suggests a contribution to the peritumoral inflammatory response. Different maturational status or biochemical properties of tumour microvascular endothelium may explain the lack of leucocyte adherence upon PDT.

Animals↗
PubMed1995

Effects of isoflurane on regional pulmonary blood flow during one-lung ventilation.

Isoflurane has been reported to inhibit hypoxic pulmonary vasoconstriction. However, the effects of one-lung ventilation and isoflurane on regional pulmonary blood flow (Qr) have not been investigated in detail. Therefore, using radionuclide labelled microspheres we measured Qr in rabbits (n = 8) in the left lateral decubitus position during two- and one-lung ventilation under i.v. baseline anaesthesia and during additional administration of 1.5% isoflurane. Macrohaemodynamic variables were recorded continuously. Isoflurane increased non-dependent lung blood flow during two-lung ventilation. One-lung ventilation caused a homogeneous decrease in Qr throughout the hypoxic lung, irrespective of isoflurane administration (P < 0.001). However, isoflurane significantly augmented Qr of the hypoxic lung during one-lung ventilation (P < 0.05). During all phases, Qr of the upper lobe was higher compared with that in the lower lobe in isogravitational slices of both lungs; a ventrodorsal perfusion gradient was found in the left upper lobe. We conclude that 1.5% isoflurane increased perfusion of the non-dependent lung, inhibited hypoxic pulmonary vasoconstriction-induced redistribution of pulmonary blood flow and did not influence isogravitational perfusion gradients.

Anesthesia, Intravenous↗
PubMed1995

A new catheter for prolonged local drug application.

BACKGROUND: Local drug delivery using a new 5F catheter with six small needles is described. The needles can be extended laterally into vascular tissue for drug deposition. METHODS: A fluorescent indicator (Photofrin) was injected with a new local drug delivery device into porcine carotid arteries. The vessels were explanted 15, 30, 60 min and 14 days after local drug delivery. Vascular segments were analyzed using semi-quantitative measurement of fluorescence (calculated in relation to a standard, 100% representing the maximum fluorescence achieved by systemic intravenous application of Photofrin). RESULTS: Maximum fluorescence was found in adventitia (15 min: 374%; 30 min: 388%; 60 min: 251%). In intimal tissue, the detected fluorescence was 107% after 15 min, 294% after 30 min, and 25% after 60 min. Media fluorescence was lower (15 min: 151%, 30 min: 102%, 60 min: 55%). No systemic drug content was measured. Fourteen days after local drug delivery, 15% of maximal fluorescence was still found in media but no adverse tissue hyperplasia was observed. CONCLUSIONS: These experiments demonstrate that high-dose perivascular local drug delivery is feasible and allows prolonged and selective application of drugs in a vessel segment without side effects.

Angioplasty, Balloon↗
PubMed1995

Wavelength dependency of photodynamic effects after sensitization with 5-aminolevulinic acid in vitro and in vivo.

A promising new therapeutic modality for skin cancer, administration of the heme precursor 5-aminolevulinic acid followed by light irradiation, is known as photodynamic therapy. Photofrin, the only clinically approved sensitizer, has an absorption maximum at 630 nm, the wavelength used in most experimental and clinical trials with 5-aminolevulinic acid. We investigated photodynamic efficacy of irradiation with coherent light at wavelengths ranging from 622 to 649 nm in vitro and in vivo as well as the content and distribution of intracellular porphyrin after administration of 5-aminolevulinic acid. HaCaT immortalized human keratinocytes were sensitized with 30 micrograms/ml 5-aminolevulinic acid for 24 h in vitro. By cell viability determined with the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay, the best cell-killing effects were observed after irradiation at 635 nm. Using an amelanotic melanoma (A-Mel-3) grown subcutaneously in Syrian Golden hamsters, we confirmed these results in vivo: tumor growth was markedly delayed in animals treated with 100 mg/kg 5-aminolevulinic acid intravenously and irradiated with coherent light at 635 nm as compared to animals irradiated at 630 nm. This photodynamic effect is probably mediated by large amounts of the photosensitizing porphyrin, protoporphyrin IX, localized in cell membranes as visualized by confocal laser scan microscopy and as determined by high pressure liquid chromatography in vitro. The results suggest that irradiation at 635 nm with a coherent light source is more effective than irradiation at 630 nm for photodynamic therapy with 5-aminolevulinic acid.

Aminolevulinic Acid↗
PubMed1995

[Use of photodynamic laser therapy in gynecology].

OBJECTIVE: Dysplasia of the vulva and uterine cervix are often multicentric, tend to recur and have mostly to be treated by surgical procedures. The photodynamic laser therapy (PDT) may be an alternative, which selectively destroys neoplastic tissue after topical delta-aminolevulinic acid (ALA) used as a photosensitizer. METHODS: We measured the distribution of fluorescence in dysplastic and nondysplastic tissue after topical application of ALA in 27 patients with dysplasia. In 3 vulvar and 2 cervical dysplasias, PDT was performed. RESULTS: We could show a selective enrichment of endogenous porphyrins in dysplastic tissues, whereas benign tissue showed no fluorescence. The fluorescence was limited to the mucosa. The heterogeneous fluorescence pattern was influenced by the duration of ALA application. In the treated patients, cytological and clinical parameters showed improvement after use of PDT. The longest recurrence-free interval from treatment up to date is 15 months (range 3-15 months). CONCLUSIONS: After first results of penetration studies and clinical follow-up, PDT after topical ALA application seems to be a good alternative to surgical procedures in dysplastic changes of the genital tract.

Adult↗
PubMed1995

Effect of blood flow on the leukocyte-endothelium interaction in pulmonary microvessels.

Circulating leukocytes are retained in the microcirculation of the lung. The site of leukocyte retention, however, is still a subject of controversy, and the effects of microvascular blood flow on the leukocyte-endothelium interaction in pulmonary microvessels are unknown. We used in vivo fluorescence microscopy to analyze microhemodynamics and the flow behavior of in vivo-labeled leukocytes in pulmonary arterioles, venules, and alveolar capillaries. Microvascular blood flow was altered by variation of cardiac output. Leukocytes were found to roll and to stick on arteriolar and more pronouncedly on venular endothelium. During their passage through alveolar capillaries, a fraction of passing leukocytes became static for 0.1 to > 5 s. Under control conditions, leukocytes were concentrated approximately 8-fold more in arterioles and 24-fold more in venules than in the blood passing through these vessels. The concentration in capillaries was 1.5 times greater than in venules. The velocity of rolling leukocytes in arterioles and venules correlated significantly with the shear rate in these vessels, whereas the density of sticking cells was negatively correlated with the shear rate. The differences between leukocyte rolling and sticking in arterioles and in venules cannot be explained by respective hemodynamic conditions. In alveolar capillaries, the percentage of temporarily static leukocytes and the time of their stasis were inversely correlated with red-blood-cell (RBC) velocity. We conclude that leukocytes are retained in pulmonary arterioles, venules, and alveolar capillaries according to microvascular blood flow and endothelial factors.

Animals↗
PubMed1994

Photodynamic antitumor agents: beta-methoxyethyl groups give access to functionalized porphycenes and enhance cellular uptake and activity.

Porphycene photosensitizers bearing two or four methoxyethyl side chains were synthesized in nine steps from commercially available starting materials. Ether cleavage led to (hydroxyethyl)- and (bromoethyl)porphycenes that were converted to vinyl and benzo derivatives. Five of the side chain-functionalized porphycenes were biologically studied in comparison with two tetra-n-propylporphycenes. Porphycenes were incorporated in small unilamellar liposomes and incubated with cultivated SSK2 murine fibrosarcoma cells. Cellular uptake and phototoxicity 24 h after 5 J/cm2 laser light treatment were determined. The porphycenes tested were between 17 and 220 times more photodynamically active than the currently clinically used sensitizer Photofrin, although extinction coefficients of the porphycenes' irradiated bands are only approximately 10-fold higher. The LD50 concentration for SSK2 cells in the incubation medium was as low as (8.5 +/- 2.8) x 10(-9) M for tetrakis(methoxyethyl)porphycene. Two methoxy or hydroxy groups enhanced cellular uptake, three or four methoxy groups both enhanced and accelerated cellular uptake of tetraalkylporphycenes. Half-life times of the uptake processes varied between (0.14 +/- 0.04) and (14 +/- 4) h and cellular saturation levels between (1.2 +/- 0.2) and (26 +/- 3) pmol/10(5) cells. When individual uptake rates were accounted for, all porphycenes had a similar "cellular" phototoxicity, pointing toward a common mechanism of action. Evidence is presented for the assumption that cell membranes are the primary targets of the tested porphycenes and that membrane solubility may play a critical role in their photodynamic efficiency. The results show that nonionic polar side chain functionalities can strongly enhance cellular uptake and antitumor activity of lipophilic porphyrinoids and thus that the known lipophilicity/activity relationship can be reversed for very hydrophobic sensitizers.

Animals↗
PubMed1994

High-energy shock waves enhance hyperthermic response of tumors: effects on blood flow, energy metabolism, and tumor growth.

BACKGROUND: The ability to kill cancerous tissue by heating is often limited by heat lost to flowing blood. Recent studies demonstrate that high-energy shock waves (HESWs), when applied to solid tumors, destroy the tumor microvasculature and rapidly decrease blood flow. We hypothesized that impairment of tumor blood flow by HESWs might result in increased effectiveness of hyperthermia treatment. PURPOSE: The purpose of our work was to determine whether HESWs enhance the response of tumors to hyperthermia. METHODS: Seventy A-Mel-3 amelanotic hamster melanomas were exposed to either 700 HESWs (20 kV, 80 nanofarads), local hyperthermia (43.3 degrees C for 30 minutes), or a combination of both. Three, 12, or 24 hours later, tumor blood flow and adenosine triphosphate (ATP) concentrations were measured by [4-N-methyl-14C]iodoantipyrine autoradiography and quantitative ATP imaging bioluminescence, respectively. In separate experiments, the effects of the separate and combined treatments on tumor growth were studied in 52 animals. RESULTS: Combining HESWs and hyperthermia produced a significantly longer and more pronounced reduction of tumor and adjacent tissue perfusion than either HESWs or hyperthermia alone (P < .05). ATP concentrations were markedly reduced following HESW treatment alone and following the combined therapy compared with untreated controls (P < .05). Three hours after combined therapy, ATP concentrations were significantly below values measured after hyperthermia alone (P < .01). Tumor growth was delayed much more effectively by the combination of HESWs and hyperthermia than by either treatment alone (P < .001). Fifty-four percent of the animals receiving combined treatment showed complete local tumor cure over 52 days of observation, and 46% showed partial remission. CONCLUSION: The combination of HESWs and hyperthermia might be an effective new way of treating cancer, especially in patients who are not candidates for surgery. IMPLICATIONS: These results must be viewed cautiously, as the vasculature of human tumors seems to be less sensitive to hyperthermia than has been observed in experimental tumors.

Adenosine Triphosphate↗
PubMed1994

Relation of early Photofrin uptake to photodynamically induced phototoxicity and changes of cell volume in different cell lines.

For efficacy of photodynamic therapy, selective uptake and retention of photoactive substances has been postulated. Therefore, measurements were performed to find out whether the photosensitiser Photofrin is taken up differently in malignant and non-malignant cells in vitro. In addition, the sensitivity of malignant cells and non-malignant cells to photodynamic exposure was investigated, by quantifying viability and volume alterations of the cells. Bovine aortic endothelial cells, mouse fibroblasts and amelanotic hamster melanoma cells were suspended in a specially designed incubation chamber under controlled conditions (e.g. pH, pO2, pCO2 and temperature). After establishing constant baseline conditions, the cellular fluorescence intensity per cell volume, indicative of the uptake of Photofrin, and cell volume were assessed by flow cytometry, and cell viability was quantified by the trypan blue exclusion test. Photodynamic exposure of cells was performed using an argon-pumped dye laser system via a 600 microns optical fibre at energy density of 4 Joules at the cell surface (40 mW/cm2, 100 s). In comparison to endothelial and fibroblast cells, the melanoma cells exhibited no increased uptake of Photofrin, and no enhanced sensitivity to photodynamic therapy (PDT). However, the fluorescence intensity/volume of endothelial cells was two to three times higher at each concentration of the photosensitiser. Following PDT, reduction in cell viability was dependent on the concentration of Photofrin, and directly correlated with fluorescence intensity per cell volume. In addition, the cells of all three lines, treated by PDT, revealed dose-dependent changes in cell volume. Melanoma cells exhibited the most excessive increase. It is suggested that selective uptake of photosensitiser in vitro is not characteristic for tumour cells. The high uptake of Photofrin by endothelial cells may indicate that the vascular endothelium is a major target for PDT, leading to cessation of tumour blood flow and subsequent destruction of tumour tissue. In addition, PDT-induced swelling of tumour cells might represent and effect synergistically impairing tumour perfusion, and thereby promoting tumour death.

Animals↗
PubMed1994

Photodynamic therapy-induced alterations in interstitial fluid pressure, volume and water content of an amelanotic melanoma in the hamster.

The effect of photodynamic therapy (PDT) on interstitial fluid pressure (IFP), tumour volume and water content was measured in melanomas grown in hamsters. Unlike control tumours, treated tumours exhibited a 40-60% increase in volume at 1, 3 and 6 h post PDT. IFP also increased at 1 and 3 h after PDT, but decreased to 50% of control value after 24 h, presumably as a result of PDT-induced microcirculatory impairment.

Animals↗
PubMed1994

In vivo kinetics and spectra of 5-aminolaevulinic acid-induced fluorescence in an amelanotic melanoma of the hamster.

For successful photodynamic diagnosis (PDD) and effective photodynamic therapy (PDT) with the clinically used 'photosensitiser' 5-aminolaevulinic acid (ALA), knowledge of the maximal fluorescence intensity and of the maximal tumour-host tissue fluorescence ratio following systemic or local application is required. Therefore, time course and type of porphyrin accumulation were investigated in neoplastic and surrounding host tissue by measuring the kinetics and spectra of ALA-induced fluorescence in vivo. Experiments were performed in the amelanotic melanoma A-Mel-3 grown in the dorsal skinfold chamber preparation of Syrian golden hamsters. The kinetics of fluorescent porphyrins was quantified up to 24 h after i.v. injection of 100 mg kg-1, 500 mg kg-1 or 1,000 mg kg-1 body weight ALA by intravital fluorescence microscopy and digital image analysis (n = 18). In separate experiments fluorescence spectra were obtained for each dose by a simultaneous optical multichannel analysing device (n = 3). A three-compartment model was developed to simulate fluorescence kinetics in tumours. Maximal fluorescence intensity (per cent of reference standard; mean +/- s.e.) in the tumour arose 150 min post injection (p.i.) (1,000 mg kg-1, 109 +/- 34%; 500 mg kg-1, 148 +/- 36%) and 120 min p.i. (100 mg kg-1, 16 +/- 8%). The fluorescence in the surrounding host tissue was far less and reached its maximum at 240 min (100 mg kg-1, 6 +/- 3%) and 360 min p.i. (500 mg kg-1, 50 +/- 8%) and (1,000 mg kg-1, 6 +/- 19%). Maximal tumour-host tissue ratio (90:1) was encountered at 90 min after injection of 500 mg kg-1. The spectra of tissue fluorescence showed maxima at 637 nm and 704 nm respectively. After 300 min (host tissue) and 360 min (tumour tissue) additional emission bands at 618 nm and 678 nm were detected. These bands indicate the presence of protoporphyrin IX (PPIX) and of another porphyrin species in the tumour not identified yet. Tumour selectivity of ALA-induced PPIX accumulation occurs only during a distinct interval depending on the administered dose. Based on the presented data the optimal time for PDD and PDT in this model following intravenous administration of 500 mg kg-1 ALA would be around 90 min and 150 min respectively. The transient selectivity is probably caused by an earlier and higher uptake of ALA in the neoplastic tissue most likely as a result of increased vascular permeability of tumours as supported by the mathematical model.

Aminolevulinic Acid↗
PubMed1994

[Endoscopic, 3-dimensional measurement of neoplasms and stenoses of the larynx and trachea].

Calculating the exact measures of laryngeal tumours will be crucial for the next generation of the TNM System. Furthermore, cross-sectional area and length of a laryngotracheal stenosis are of major interest for clinical management. It is the aim of this study to assess these parameters endoscopically in a more detailed and exact manner. For this purpose a Hopkins Endoscope (Karl Storz, Tuttlingen, Germany) and a slide caliper are combined. This new instrument is called laryngometer (Fig. 1a u. b). It helps to measure the lengths of a stenosis or neoplasm. In addition it defines the level of a given object and provides a standard in a two-dimensional video sequence. Thus the laryngometer allows to digitally analyse cross-sectional areas and distances as well as to evaluate craniocaudal parameters.

Child↗