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Biomedical subjects

A Leunig

Publications and source records attributed to A Leunig.

52 records · Page 3Linked to original sources

[Photodynamic diagnosis of neoplasms of the mouth cavity after local administration of 5-aminolevulinic acid].

BACKGROUND: The aim of photodynamic diagnosis (PDD) is the complete visualization of all neoplastic lesions in a tumorous organ after topical or systemic application of a tumor selective photosensitizer. In this investigation we performed semiquantitative fluorescence measurements following topical application of 5-aminolevulinic acid (5-ALA) in 11 patients with neoplastic lesions of the oral cavity. METHODS: Time course and type of porphyrin accumulation were analyzed in neoplastic and surrounding normal tissue by measuring emission spectra of 5-ALA-induced protoporphyrin IX (PpIX) fluorescence at regular intervals for up to three hours following 15 min continuous rinsing of a 0.4% 5-ALA solution. After excitation with violet light of a high pressure xenon arc lamp (375-440 nm), fluorescence images in the red spectral range from the tumor tissue and the corresponding macroscopic visible tumor were recorded with a CCD camera. A quantitative analysis of the fluorescence contrast in neoplastic and surrounding tissue was performed using an optical multichannel analyzer. RESULTS: PpIX fluorescence was detected in the oral mucosa of all patients after local application of 5-ALA. PpIX in neoplastic tissue accumulated earlier in comparison to the surrounding normal tissue. The fluorescence contrast between tumor and host tissue was 10:1 and the maximum fluorescence was measured 1-2 hours following 5-ALA application. CONCLUSION: Labeling of mucosal lesions of the oral cavity with PpIX fluorescence induced by the local application of 5-ALA seems to be a promising diagnostic procedure for neoplastic lesions. Further investigations are required to assess the value of this new diagnostic procedure as a non-invasive and sensitive method for patients with head and neck cancer not only in pre- and postoperative diagnostic studies but also for a fluorescence-guided resection of tumors.

Administration, Topical↗

[Central (reparative) giant cell granuloma of the paranasal sinus].

BACKGROUND: The central giant-cell (reprative) granuloma is an uncommon bone lesion usually located in the mandible and maxilla. In contrast to giant cell tumors of the extra-craniofacial skeleton, the origin of this lesion is considered to be non-neoplastic, reactive, and triggered by trauma or inflammation. The tumor occurs mainly in young people; they complain of regional indolent swelling of the jaw eventually leading to loosening of the teeth. CASE REPORT: In the paper, the authors describe the unusual case of a central giant-cell granuloma in a young male. Diagnostic procedures, adequate therapeutic approach, and an overview of differential diagnostic considerations are provided. RESULTS: The pedunculate tumor was removed surgically. In endoscopic controls no recurrent growth has been seen up to one year after removal. CONCLUSIONS: Even though the giant-cell reparative granuloma is rare, it may also occur in the nasal cavity. Diagnosis is established by histologic findings and the typical clinical appearance. Surgical removal is the treatment of choice.

Biopsy↗

MRI-guided laser interstitial thermal therapy (LITT) of head and neck tumors: progress with a new method.

A less invasive method for treatment of tumors is being tested based on interstitial photothermal ablation via infrared Nd:YAG laser fiber optics. The technique can be applied safely and effectively for therapy of common tumors in humans. In the current study five patients were treated by interstitial laser palliation with the Nd:YAG laser using special fiberoptic applicator tips, which distribute laser energy efficiently throughout the tumor volume. Magnetic resonance imaging (MRI) scanning was employed to locate the tumor, position the fibers correctly, and monitor the development of thermal necrosis in the tumors. Two patients were diagnosed with adenoid cystic carcinoma of the paranasal sinuses, one with a recurrent carcinoma of the tongue and oropharynx, one with a recurrent carcinoma limited to the oropharynx, and one patient with a carcinoma of the epi- and oropharynx. The maximum follow-up without recurrence was 2 years in a patient with an adenoid cystic carcinoma tumor of the paranasal sinuses. There were no immediate or delayed complications. Anatomical structures including eyes, brain, and important vessels were recognized by MRI during laser therapy. MRI-guided interstitial laser photothermal ablation appears to be a safe and effective method for treatment of selected tumors of the head and neck region with particular applications in palliation of inoperable tumor recurrences.

Aged↗

[Photodynamic diagnosis and therapy of neoplasms of the facial skin after topical administration of 5-aminolevulinic acid].

Topical application of 5-aminolevulinic acid (5-ALA) is a useful instrument for photodynamic diagnosis and therapy of skin tumours. Diagnostic fluorescence imaging after laser light irradiation (410 nm) revealed a high, tumour-specific fluorescence even in tumour areas not apparent prior to this examination technique. This demonstrates the possibility of photodynamic diagnosis to detect skin tumours. In the therapeutic group 8 patients with 6 solar keratoses and 12 basal cell carcinomas underwent laser light irradiation using a wavelength of 635 nm (dosage 100 J/cm2) 6 hours after topical application of 5-ALA in W/O emulsion. 2-12 hours after laser application we observed reddened tumour tissue with mild oedema, subsequently followed by a crust and epithelised within 4-6 weeks. 2 months after PDT a complete response was observed for all solar keratoses and for 10 of 12 basal cell carcinomas. Photodynamic therapy following topical application of 5-ALA may be an alternative treatment modality for skin tumours.

Administration, Topical↗

[Sarcoma of the nose and paranasal sinuses].

Sarcomas of the head and neck are rare tumours accounting for less than 1% of all malignant neoplasms in this region. The prognosis of these tumours and the survival in adults (< 50% at 5 years) is directly related to histological tumour type, tumour size and the possibility of adequate tumour resection. In the present paper, the authors present the course of sarcomas with special reference to rhabdomyosarcoma and osteosarcoma in the nose and paranasal sinuses. Surgical resection with pathologically free margins represents the best modality of initial therapy. Additional adjuvant radiotherapy and/or chemotherapy have shown better survival rates in pediatric patients and, to some degree, also in adults. The purpose of future studies should be the development of new therapy protocols which could further elucidate the beneficial effects of adjuvant therapy in the treatment of sarcomas of the head and neck.

Adolescent↗

[Clinical and electron microscopy study of sudden deafness treatment with the 10% HES 200/0.5 and pentoxifylline combination].

The incidence of sudden hearing loss has increased. The pathogenetic mechanisms are still unknown, but viral infections and vascular phenomena with acute impairment of microvascular perfusion are thought to play a major role. Infusion of hydroxyethyl starch (HES) is used as a regimen to treat sudden hearing loss. In our clinic, anaphylactic reactions due to HES have not been observed so far. However, the use of HES is still discussed controversially due to long-term storage of HES molecules in tissue and due to high incidence of long-lasting pruritus. In a retrospective analysis of 118 patients treated with HES for sudden hearing loss, we observed pruritus starting in 64% of patients one to three weeks after therapy. This symptom with a duration between two weeks and four months was refractory to medical interventions. During therapy with HES improvement of hearing was observed in 75% of patients, in 62% improvement of hearing persisted still at the end of the observation period (7 months post infusionem). Light and electron microscopic assessment of human skin biopsies of one patient after treatment with HES showed storage of HES especially within dermal macrophages. Pathogenetically a pathway independent of histamin seems responsible for the induction of pruritus. Accordingly, classic antihistaminic drugs had no therapeutic effect in our patients. Dextran is used as an alternative to hydroxyethyl starch. In contrast to HES, the often mentioned higher incidence of severe anaphylactic reactions due to dextran has dramatically decreased with hapten inhibition (after preinjection of monovalent haptendextran Promit).(ABSTRACT TRUNCATED AT 250 WORDS)

Auditory Threshold↗

[Endoscopic and extracorporeal shock wave lithotripsy of salivary calculi].

Shock wave lithotripsy of salivary gland stones has become more and more efficient in the treatment of sialolithiasis during the last years. We use two different methods in our hospital: Extracorporeal shock wave lithotripsy (ESWL) and endoscopically intracorporeal lithotripsy (EISL). The results of both therapies are compatible; 60-70% could be successfully treated. The indication is different due to the localisation of the salivary gland stone. Stones that are located in the glandula or very proximal in the duct should be fragmented by extracorporeal lithotripsy. Stones located in the duct and multiple intraductal stones should be treated by the intracorporeal method. Clinical experiments showed that some salivary stones do not fragment easily. The reason is still unknown. We examined the ability of fragmentation in relation to the physicochemical analysis of the stone. The stones were examined by infrared spectroscopy. This study revealed that pure carbonate apatite stones are more difficult to destroy than stones containing some protein.

Combined Modality Therapy↗

[Middle ear ventilation with the Otovent latex membrane system].

Epidemiological studies have shown that up to 80% of all pre-school children develop Eustachian tube dysfunction with middle ear effusion and corresponding conductive hearing loss. The therapy of choice for hyperplastic adenoids is adenoidectomy, often in combination with paracentesis. The objective of this study was to determine whether regular middle ear aeration (Otovent-system) could obviate the need for paracentesis. To this end treatment of 146 children from four to ten years old was conducted within the guidelines of a study protocol. In one group of children, Otovent-supported middle ear aeration was carried out before and after adenoidectomy. In the control group, adenoidectomy was followed by paracentesis. Parents and children were then assigned to follow-up treatment. As additional supportive therapy, children in both groups received decongestant nose drops and a mucolytic agent for a period of 2 weeks. The success of the treatment was evaluated by tympanometry, tone-wave audiometry and ear microscopy. The patients were followed-up at intervals of two and four weeks after the initiation of treatment. The results show that within the study time frame, Otovent treatment compares well to paracentesis. In summary, regular Otovent-supported aeration of the middle ear in many cases can be an alternative to paracentesis.

Child↗

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↗

[Damage to tumor cells by photodynamic therapy].

Photodynamic therapy (PDT) is a new, promising method in the treatment of cancer. To gain insights into PDT-mediated tumour destruction we studied the influence of treatment with Photofrin and laser light on changes in cell volume and cell viability. A-Mel-3 tumour cells were subjected to Photofrin or illumination with laser light, or a combination of both (PDT). Cell volume was measured by flow cytometry and cell viability by the trypan blue exclusion test for up to 60 min after PDT and the respective controls. In addition, scanning and transmission electron microscopy were performed. Tumour cells incubated in concentrations of 0.75, 1.5 and 3.0 micrograms Photofrin/ml revealed a rapid increase in cell volume to 117%, 207% and 235% 30 min after PDT and to 147%, 210% and 199% 60 min after PDT. Cell viability with 1.5 and 3.0 micrograms Photofrin/ml and laser light was reduced to 83% and 44% at 30 min after PDT and to 38% and 17% 60 min after PDT. At Photofrin concentrations of 1.5 micrograms/ml and exposure to laser light scanning electron microscopy revealed extreme loss of microvilli and formation of blebs on the cellular surface. Transmission electron microscopy showed swollen mitochondria and ruptures of the cell membrane. This study demonstrates that PDT induces a significant time-dependent and dose-related increase in tumour cell volume. We suggest that the PDT-induced swelling of tumour cells contributes to the increase of interstitial fluid pressure and to impairment of microvascular perfusion of tumours.

Cell Division↗

[Pleomorphic adenoma of the maxillary sinus].

Pleomorphic adenoma is the most common benign tumour of the salivary glands, especially the parotid gland. In the present paper we introduce the rare case of a pleomorphic adenoma of the maxillary sinus in a 82-year-old man who was referred to our outpatient clinic with nasal obstruction and occasional events of nose bleeding. Thorough investigation, using endoscopy and computed tomography, revealed a mass extending from the left maxillary sinus to the nasal cavity; the tumour was removed surgically; pathological examination showed a pleomorphic adenoma with no signs of malignancy.

Adenoma, Pleomorphic↗

An in vitro model to study cellular photosensitizer uptake and photodynamic dose-response relationships of tumor cells.

Cellular fluorescence intensity (CFI) after incubation with varying concentrations of the photosensitizer Photofrin and the photodynamically induced dose-response relationships of hamster melanoma cells (A-MEL-3) were studied in a recently developed in vitro model. After administration of Photofrin to the extracellular serum-free medium, CFI was evaluated by flow cytometry together with constantly fluorescing latex particles used as a reference. After 5 min, 50% of maximal CFI was found, and after 60 min CFI was maximal. No further increase was obtained during the exposure to Photofrin over the incubation period of 4 h. During this plateau phase, CFI was significantly related to the concentration of Photofrin in the extracellular medium (r = 0.94; P < 0.001). Subsequent to increasing intervals of Photofrin exposure, cells were irradiated with laser light at 630 nm (40 mW/cm2, 4J). Cell viability as evaluated by trypan blue exclusion was significantly decreased with increasing concentrations of Photofrin in the medium, and significantly correlated with CFI during the plateau phase. After photodynamic treatment (PDT) cell fluorescence was reduced by about 15%. This was neither dose- nor time-dependent. On the basis of these findings we propose that CFI indicates photosensitizer uptake. This is also supported by the relation between CFI and phototoxicity. The latter also suggests that CFI might be useful to predict the PDT in vivo efficacy by this in vitro model. Besides measurements of photosensitizer uptake and cell photoxicity, the model demonstrates an excellent opportunity to study the molecular mechanisms of action associated with PDT.

Animals↗

[Photodynamic laser therapy in the field of otorhinolaryngology].

A clinical study was conducted on the application of photodynamic therapy on tumours in the head and neck region to assess the value of this new modality for superficial cancer (Tis-T2). Patients with recurrent laryngeal papillomatosis were included in a photodynamic treatment pilot study. 2 mg/kg body weight of haematoporphyrin-derivative (Photosan-3) was administered 48 hours prior to laser irradiation intravenously. The patients rooms were advised to avoid daylight for two to three weeks. Tumours of the facial skin were irradiated homogeneously by means of an optical bench. Directly after laser application we observed an extensive extravasation of the tumour tissue, whereas the surrounding normal tissue showed mild erythema. A dry crust formed subsequently, which disappeared within two weeks associated with re-epithelisation. Mucous membrane tumours showed fibrin layers in the tumour area 24 hours after laser application with selective tumour necrosis. These lesions also epithelised completely within three weeks. Scarring never occurred. Laryngeal tumours as well as laryngeal papillomas were treated by a cylindrical light applicator system and the patients admitted to intensive care unit for 24 hours after laryngoscopy because of risk of laryngeal oedema. 94 patients with tumours of the head and neck with different histological origins were treated photodynamically, as well as 21 patients with laryngeal papillomatosis. Two months after photodynamic laser treatment, controlled biopsies of the former tumour area were performed. 5 patients had a relapse during a maximum follow-up of 4.5 years. This signified a histologically confirmed full response rate of 95%, accompanied by good plastic and functional results.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

[Importance of increased interstitial fluid pressure in therapy of malignant tumors of the head-neck area].

Animal experiments showed that elevated interstitial fluid pressure (IFP) is associated with poor blood supply and inadequate supply of drugs to solid tumours. IFP is approximately 0 mmHg in most normal tissues. Up to now there have been only few studies showing elevated interstitial pressure in human tumours in situ: Mammary carcinomas, cervical carcinomas and colorectal cancers have an elevated IFP. We measured IFP in squamous cell carcinomas of the head and neck region in humans using the "wick-in-needle" technique. In all lesions (n = 25), the IFP was elevated (4-39 mmHg). The IFP increased with tumour size. The highest IFP was 39 mmHg in a 26 ml tumour. These results show that squamous cell carcinomas of the head and neck region in humans have an elevated interstitial fluid pressure. The elevation of IFP associated with inadequate delivery of drugs to the interstitium of malign tumours may reduce the response to therapy.

Carcinoma, Squamous Cell↗

Evaluation of photodynamic therapy-induced heating of hamster melanoma and its effect on local tumour eradication.

To investigate the contribution of hyperthermia on local tumour eradication by photodynamic therapy (PDT) we quantified PDT induced tumour heating and evaluated its biological effect in vivo. Syrian Golden hamsters bearing an amelanotic melanoma implanted into the dorsal skin received intravenous injections of Photofrin (5 mg kg-1). Twenty-four hours later tumours were illuminated by red light (630 nm; total energy: 100 J cm-2) at 100 and 200 mW cm-2 and tumour surface and tumour centre temperature were measured. The tumoricidally threshold temperature of 43 degrees C was exceeded at 200 mW cm-2 only, revealing a calculated equivalent treatment time at 43 degrees C of about 10 min. Melanomas treated by PDT at both light intensities disappeared within 48 h and did not reappear locally within the observation period of 32 days. Tumours treated by hyperthermia (water bath) at the maximum temperatures measured during illumination at 200 mW cm-2 (45.5 degrees C for 500 s) or animals receiving laser light at 200 mW cm-2 alone showed a significant growth delay compared to controls (p < 0.05), whereas illumination at 100 mW cm-2 alone or hyperthermia corresponding to the maximum temperature obtained at 100 mW cm-2 (39.5 degrees C for 1000 s) did not alter tumour growth. These data indicate that tumour temperature increased during PDT and exceeded the hyperthermic threshold temperature of 43 degrees C at 200 mW cm-2. In our tumour model hyperthermia was not necessary for a complete tumour eradication by PDT. Although a combination of PDT and hyperthermia might act in an additive or synergistic manner, an unrecognized overlap of both effects might complicate the interpretation of studies on the mechanisms of PDT.

Animals↗

Basic fibroblast growth factor in serum and urine of patients with head and neck cancer.

Between 1996 and 1997 serum and urine levels of basic fibroblast growth factor (b-FGF) in patients with head and neck cancer were measured to answer the following questions: i) Are increased levels of b-FGF in serum and urine detectable in patients with malignant head and neck tumors? ii) Do these parameters correlate with tumor stage and differentiation of tumors? iii) Is there an association between growth behaviour (local or metastatic growth) and b-FGF levels in serum and/or urine? Eighty-nine patients with head and neck cancer as well as 45 patients with diseases unrelated to cancer were investigated. Detectable levels of b-FGF were found in the serum and urine of patients with malignant head and neck tumors. In addition, there was a significant correlation between tumor size and b-FGF levels in either serum or urine. No association of b-FGF concentrations with degree of histologic differentiation and tumor growth behaviour was observed. The results of this study demonstrate that b-FGF levels are elevated in serum and urine of patients with head and neck cancer. These findings suggest an involvement of b-FGF in the formation of solid tumors.

Biomarkers, Tumor↗