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Biomedical subjects

B M Lippert

Publications and source records attributed to B M Lippert.

At least 73 records · Page 4Linked to original sources

Leiomyosarcoma of the larynx.

Leiomyosarcomas account for approximately 7% of all soft-tissue sarcomas and occur most frequently in the gastrointestinal tract and uterus. Leiomyosarcomas of the larynx are extremely rare with only about 27 cases reported in the available literature. We present a leiomyosarcoma of the left vocal cord that was treated by transoral CO2 laser surgery. To date, the patient has been free of disease for more than 25 months. Since these tumors may be difficult to diagnose, immunohistochemical studies may be necessary for making an unambiguous diagnosis. Primary treatment should be surgical resection, with small tumors suitable for partial laryngectomy or transoral laser surgery.

Humans↗

[Treatment of recurrent epistaxis in Rendu-Osler-Weber disease].

Rendu-Osler-Weber disease is an autosomally dominant inherited disease which affects the connective tissue of blood vessels. The major symptom is recurrent epistaxis for which still exists no generally recommended treatment. Treatment modalities discussed in the literature include bilateral closure of the nostrils, brachytherapy, vessel embolization, hormone therapy, dermoplasties, as well as different kinds of laser therapies. Advantages and disadvantages of single treatment modalities are discussed. Dermoplasty and laser therapy seem to be the most suitable treatment procedures currently available for recurrent epistaxis in affected patients. Treatment carried out with the argon, KTP or ND:YAG laser has proven to be suitable as initial therapy. In most cases the additional use of long-term applications of a soft nasal ointment allows a lasting successful treatment. Our experiences show that dermoplasty should be reserved for cases with continued bleeding despite laser treatment but only rarely offers a long-term cure in the sense of a total recovery from epistaxis.

Aged↗

p53 serum antibodies as prognostic indicator in head and neck cancer.

p53 antibodies are a new serological parameter of unknown potential in patients with malignancies. Their occurrence has been described in various types of cancer patients. The mechanism underlying the immunization process is still unclear. We investigated the incidence of p53 serum antibodies in 143 head and neck cancer patients with an enzyme-linked immunosorbent assay. The posttherapy course of two matched study groups (n = 38 each), one p53-antibody-seropositive and one p53-antibody-seronegative, was followed up for 24 months. Thirty-nine head and neck cancer patients (27.3%) were seropositive for p53 antibodies. During the follow-up, the p53-antibody-seropositive patients accounted for more local tumor recurrences (n = 12 versus n = 8) and more tumor-related deaths (n = 11 versus n = 5) than did seronegative patients, and second primary tumors (n = 9 versus n = 0) occurred exclusively in seropositive patients. In total, therapy failures (recurrences, tumor-related deaths, second primaries) were observed in 17/38 cases (44.7%) in the p53-antibody-seropositive group and in 8/38 cases (21.1%) in the p53-antibody-seronegative group. These results, after a follow-up of 2 years, seem to indicate a prognostic value of p53 serum antibodies for therapy failure in patients with head and neck cancer.

Adult↗

[Chondrosarcoma of the larynx].

BACKGROUND: Manifestation of chondrosarcoma (CS) in the head and neck region is rare but it is the most frequently encountered non-epithelial malignancy of the larynx. Since this tumor entity is frequently neglected, its characteristics including differential diagnosis and therapy will be discussed in the following. PATIENTS: From 1975 to 1995, five cases with CS were diagnosed and treated in the Department of Otorhinolaryngology, Head and Neck Surgery, University of Kiel. RESULTS: The medical history of this five patients (one woman, four men, average age: 71 years) varied from 9 months to 10 years. Three patients had a fixation of the vocal cord; one patient had obviously reduced movement of the vocal cord. Two cases revealed a moderate and three cases a high differentiation in the histological examination. Initially one case was diagnosed as a chondroma. The origin of tumor growth was the cricoid cartilage in four patients and the cartilage of the arytenoid in one patient. Surgical treatment was either by partial or complete laryngectomy in two cases each. One patient refused any therapy. Two patients including the latter died of tumor related causes. CONCLUSIONS: Laryngeal CS grow slowly. Diagnosis is frequently made late in the course of disease. Obtaining of tissue for histological examination and diagnostic delimitation towards a chondroma can be difficult. Therapy depends on the degree of histological differentiation with radical excision of low or moderately differentiated CS and function preserving surgery in case of high differentiation.

Aged↗

[Reproducibility of nonradioactive DDRT-PCR method for detection of gene expression in squamous epithelial carcinoma cells of the upper aerodigestive tract].

BACKGROUND: The analysis of the gene spectrum in tumor and normal cells may provide information about genes involved in the differentiation or in the genesis of tumors. Differential Display Reverse Transcriptase Polymerase Chain Reaction (DDRT-PCR) is an innovative method that enables quick analysis of almost all mRNA molecules expressed in the cells. METHODS: In the trials, the mRNAs of keratinocytes and tumor cells were amplified by a number of oligonucleotide pairs after reverse transcription and resolved on polyacrylamide gel. A modified protocol for the amplification of cDNA probes was devised for detecting PCR products with silver nitrate. RESULTS: After reverse transcription of mRNAs, all cDNA samples were successfully amplified using the protocol devised for the silver nitrate DDRT-PCR, and the differentially expressed fragments were reproducibly demonstrated. CONCLUSIONS: The high reproducibility and feasibility of silver nitrate DDRT-PCR expand the alternatives for analyzing gene expression and detecting selectively expressed genes in different kinds of cells.

Carcinoma, Squamous Cell↗

[Cultivation of human keratinocytes of mucous membranes of the upper aerodigestive tract].

BACKGROUND: Cultivation of benign epithelial cells under standardized conditions is of major interest in many fields of clinical and basic research. A modified fast and simple method for isolation, growth and passage of epidermal cells has been developed with consideration given to the complex environment of the upper aerodigestive tract. METHODS: Normal human mucosa of the upper aerodigestive tract was taken from 15 patients (4-73 years) during diagnostic and therapeutic operations. The epithelium could be separated easily from the mucosa after incubation the biopsies in disease over night. Subsequently, keratinocytes were isolated enzymatically by dissociation of epidermal sheets in trypsin, resulting a suspension of highly proliferating keratinocytes without contaminating fibroblasts (2 x 10(6) keratinocytes/biopsy). The cells were washed several times in fresh fetal calf serum before they were plated in untreated culture flasks. The keratinocytes were cultivated in serum-free medium supplemented with epidermal growth factor, bovine pituitary extract, amphotericin B, and penicillin/ streptomycin. RESULTS: An average plating efficiency of 60% in primary cultures and 85% in subcultures was obtained. Passaging was possible every 10-13 days when keratinocytes reached sufficient confluency. The cells could be subcultured up to eight times (lifespan of 120 days), and exhibited the typical epithelial morphology during cultivation. CONCLUSION: Because of the modified pretreatment of the keratinocytes before plating, this culturing protocol for keratinocytes derived from the upper aerodigestive tract enables easy and fast cultivation of keratinocytes, further simplifying currently available methods.

Adolescent↗

[Mucous membrane melanomas of the upper aerodigestive tract. An analysis of 34 cases].

BACKGROUND: Malignant mucosal melanoma of the upper aerodigestive tract is a rare disease. The prognosis is expected to be significantly worse than the prognosis of cutaneous melanoma and so far no uniform therapeutic concept exists. Publications about mucosal melanoma are scarce and reported patient groups are usually small. PATIENTS: Thirty-four patients have been registered at the ENT Department of the University of Kiel Medical Center with the diagnosis mentioned above. Clinical data were obtained from the patient's charts, the minimum follow-up was three years. RESULTS: Most common site of the tumor was the nasal cavity and paranasal sinuses with 28 of 34 patients. Less frequently affected was the nasopharynx (three cases), oropharynx, larynx, and middle ear (one case each). All patients were caucasians and most of them were of an advanced age (66.9 years +/- 12.3). Treatment of choice was surgical resection in 27 cases, in four cases it was combined with radiation therapy, in one case with radiation therapy and chemotherapy, and in three cases with chemotherapy. Six patients received solely radiation therapy, one patient was only treated by chemotherapy. Patients who were treated by a combined approach had a more favourable outcome than patients who were treated by a monotherapy of surgery, radiation therapy, or chemotherapy. A high number of recurrences were observed, which occurred on an average of 16.6 months after the diagnosis of the primary tumor. Overall 5-year survival was 45.8%, the 10-year survival rate was 22.3%. CONCLUSIONS: Optimized combined therapeutical approaches might possibly improve the prognosis of mucosal melanoma of the upper aerodigestive tract. Intervals between follow-ups should be short to render detection of relapses at an early stage. Repeated therapy of recurrent disease might lengthen survival.

Combined Modality Therapy↗

[Detection of differentially expressed genes in head-neck carcinomas].

BACKGROUND: Carcinogenesis is generally considered a multistage process based on many alterations of the genetic substance. These alterations lead to many qualitative and quantitative changes in gene expression with subsequent malignant transformation of the cell. Only a few of these genetic alterations are identified yet. METHODS: The differential display reverse transcriptase polymerase chain reaction was employed to detect differentially expressed genes in head and neck cancer. The mRNA expression of cultivated keratinocytes of the upper aerodigestive tract was compared to the one of cultivated squamous cell carcinoma cells of the larynx, hypopharynx, and floor of the mouth. RESULTS: A total of 116 differentially expressed gene fragments were identified. They were either solely expressed by the malignant cells or the keratinocytes or in just one carcinoma cell entity. Forty-three of the 116 DNA fragments were sequenced successfully. In four cases the specific differential expression was confirmed by Northern blot hybridisation in comparison to keratinocytes, normal mucosa, and 3 benign tumors from the head and neck region. A gene bank search revealed in three cases a homology of less than 20% to already known human, animal, bacterial or viral gene sequences and in one case a homology of 98% with a human gene sequence. CONCLUSIONS: The detected for squamous cell carcinoma of the head and neck specific genes or gene fragments are the basis for further investigations to better understand carcinogenesis.

Carcinoma, Squamous Cell↗

[Nd:YAG laser therapy of recurrent epistaxis in hereditary hemorrhagic telangiectasia].

BACKGROUND: Epistaxis is the leading symptom of hereditary hemorrhagic teleangiectasia (HHT). Over the last years several laser systems have been used for therapy. Only a few studies have published results of Nd:YAG laser therapy evaluating a larger number of patients. PATIENTS AND METHODS: From 1987 through 1996, forty-one patients with HHT were treated with a Nd:YAG laser due to recurrent epistaxis at the Department of Otorhinolaryngology of Kiel University. Thirty-two patients were followed-up over a period of at least 24 months. A centripetal technique was used for endonasal laser light application (15-25 Watts; 0.1-0.5 s), i.e., the laser light was applied from the periphery towards the center of the angiodysplasia. Intensive preoperative and postoperative nasal care with ointments was performed. RESULTS: Bleeding frequency and intensity decreased in 30 (94%) patients. Duration of the therapeutical success differed individually and varied from seven weeks to 14 months. Repeated laser therapy was necessary in 27 of 32 patients. CONCLUSION: The Nd:YAG laser is a suitable tool in the treatment of epistaxis in HHT. This procedure is less traumatic, less painful, and can be repeated multiple times. Nd:YAG laser therapy and other therapeutic options cannot obtain a lasting cure of Rendu-Osler-Weber syndrome. However, in the vast majority of cases recurrent nasal bleeding as the dominant symptom can be reduced in frequency as well as in intensity.

Adult↗

[Detection of serum soluble fragments of cytokeratins 8 and 18 in patients with squamous epithelial carcinomas of the upper aerodigestive tract].

BACKGROUND: During the development of squamous cell carcinomas of the head and neck (SCCHN), cytokeratin (CK) 18 and 19, which are typical for simple epithelia, show an elevated expression in tumor tissues. CK 8 was found to be overexpressed in cell lines of SCCHN. Epithelial tumors like normal epithelia express characteristic "pairs" of CK. The smallest of these pairs comprises CK 8 and 18. Therefore, the aim of this study was to serologically detect fragments of CK 8 and 18 (cyfra 8/18) in SCCHN patients. METHODS: Sera of 151 patients with SCCHN were tested for cyfra 8/18 (cyfra 8/18 ELISA medac, Hamburg) before treatment. Thirty sera of healthy volunteers and 43 sera of patients with benign diseases of the head and neck region served as control and reference group, respectively. Thirteen patients were followed-up clinically and serologically after surgery. The serum cyfra 8/18 concentrations of those 13 patients were compared to their clinical run. RESULTS: The cut-off value for cyfra 8/18 was determined with a 95% specificity of the reference group and was fixed at 1.1 ng/ml. The sensitivity was 7%. No correlation was found between cyfra 8/18 and clinical parameters like tumor stage, grading, and tumor location. Cyfra 8/18 concentrations could be correlated to the clinical run of 5 of 13 followed-up patients. CONCLUSIONS: Because of its low sensitivity, the serological detection of cyfra 8/18 must not be seen as a sufficient tumor marker for SCCHN. Its clinical applicability for regular post-surgical controls seems to be restricted and appears inferior to the clinical usefulness of cyfra 21-1.

Biomarkers, Tumor↗

Expression of a novel mRNA in human head and neck squamous cell carcinoma cells.

AIMS: The differential display reverse transcription polymerase chain reaction (DDRT-PCR) technique was used to search for differences between the mRNA expression profiles of squamous cell carcinoma (SCC) cell lines established from head and neck tumours and normal keratinocytes from the mucosa of the upper aerodigestive tract. METHODS: Total RNA prepared from both cell types was reverse transcribed into cDNA then amplified in a PCR mixture. To compare the electrophoretic patterns, mRNAs were amplified by nested PCR using specific oligonucleotides. Additionally, using labelled cDNA probes, northern hybridisation was carried out on three cancer cell lines of different origin, a biopsy from a parotid gland pleomorphic adenoma, healthy mucosa, and keratinocytes. RESULTS: Comparison of the separated bands revealed a fragment with a differential expression pattern in the SCC cells. This cloned sequence of a 336 base pair mRNA fragment exhibited no significant homology with known transcripts. Additionally, after amplification and sequencing of the 3' end of the fragment no homology with a known human gene sequence was found. However, low homology with a genomic sequence of a nematode was found. Northern hybridisation confirmed the selective expression of this fragment in SCC cells versus the cancer cell lines of different origin, the biopsy of the pleomorphic adenoma, keratinocytes, and healthy mucosa. CONCLUSIONS: This is the first differentially expressed human genome transcript of squamous cell carcinoma of the head and neck identified by DDRT-PCR. It may prove useful, in the future, to characterise this tumour type.

Base Sequence↗

Comparison of carbon dioxide and neodymium: yttrium-aluminum-garnet lasers in surgery of the inferior turbinate.

At the Department of Otorhinolaryngology-Head and Neck Surgery of the University of Kiel, 533 patients with hyperplastic inferior turbinates were treated between 1987 and 1994 with various carbon dioxide (CO2) and neodymium:yttrium-aluminum-garnet (Nd:YAG) laser techniques. We report on the therapeutic results of both types of laser turbinectomy and compare their long-term results with those of submucosal diathermy. Among the different techniques, we preferred the following approaches. The CO2 laser technique involved the application of a few laser spots (laser energy density 6,100 J/cm2 per lesion) to the head of the turbinate under the operating microscope. In the Nd:YAG laser procedure, diffuse, low-power irradiation (laser energy density < 53 kJ/cm2) of the entire concha was performed under endoscopic control. The CO2 laser procedure involved little bleeding and hardly any pain. It produced a positive effect after only a few days and required no follow-up treatment. The success of Nd:YAG laser treatment, by contrast, only became evident after weeks or months, due to the slow scarring process. Compared to submucosal diathermy, both laser methods produced better long-term results. Two years postoperatively, the overall success rate, as defined by patient satisfaction, was 79.6% for the CO2 laser, 68.3% for the Nd:YAG laser, and 36% for submucosal diathermy.

Adult↗

CO2 laser surgery of hypertrophied inferior turbinates.

The inferior turbinates are responsible for nasal obstruction in patients with allergic and vasomotor rhinitis. Until today there is no satisfactory means of treating hypertrophied turbinates. One hundred and eighty-four patients with nasal obstruction due to hypertrophied inferior turbinates were treated with the CO2 laser using the microscope and a micromanipulator. A few laser spots (1 W, 1 s, laser power density: 2,038 W/cm2) were applied to the head of the turbinate. After a few days a positive effect was present. One hundred and twelve patients were followed for over 2 years. Six months after laser surgery, 87.5% had excellent or good results. After one year, 82.1% of the patients were satisfied, and after 2 years 80.4% were satisfied. The procedure involves little bleeding, no pain and can be done under local anaesthesia in an outpatient setting. Less post-operative wound care is necessary. Therefore, the CO2 laser surgical technique can be considered as an effective method in the treatment of hyperthrophied turbinates.

Adult↗

Optimized differential display and reamplification parameters for silver staining.

Differential display (DD) is a powerful instrument to detect differences in gene expression of malignant and normal cells. An optimized silver staining protocol was used to compare mRNA expression of keratinocytes and squamous cell carcinoma cells of the head and neck. Optimal concentration for upstream and downstream primer was 0.2 microM. Best primer concentrations for reamplification were between 40 and 60 pM. With this optimized protocol nearly 50 differentially expressed transcripts have been identified and differential display can be applied safer, easier, and faster, than by radioactive labeling.

Carcinoma, Squamous Cell↗

Time-resolved fluorescence spectroscopy of a hematoporphyrin derivative used for photodynamic therapy of cancer.

Photodynamic therapy (PDT) is a treatment modality for malignancies that, uses the accumulation of a photosensitizer in tumor tissue and a subsequent laser light irradiation to selectively destroy tumor cells. Usually PDT is carried out with a hematoporphyrin derivative (HPD) as photosensitizer. Fluorescence characteristics of the HPD Photosan-3 were determined at different concentrations with time-resolved fluorescence spectroscopy. Photosan-3 showed a concentration dependent fluorescence with one fluorescence decay time below a concentration of 10 micrograms/ml, two or three decay times at 50 and 100 micrograms/ml Photosan-3 respectively. These findings confirm results of former studies on other HPD that aggregates and dimers are probably more responsible for the photodynamic effect than monomers.

Fluorescence↗

[Antibody formation to cellular p53 protein in patients with squamous cell carcinomas of the upper respiratory and digestive system].

BACKGROUND: The mutated form of the nuclear tumor suppressor protein p53 plays an important role as oncogene in the malignant transformation of cells. A new serologic parameter are antibodies against the p53 protein, that are found in many carcinoma entities and localizations and may have a prognostic relevance. Antibodies against p53 in the serum of patients with squamous cell carcinoma of the head and neck (SCCHN) have not yet been described. METHODS: A set of 117 sera from patients with SCCHN were screened for serum antibodies against p53 with ELISA (Dianova, Hamburg). The serum of 41 healthy blood donors served as controls. Tumor tissue of 45 patients was examined with ELISA for p53 protein accumulation. RESULTS: In 23 patients (19.7%) with SCCHN p53 antibodies were demonstrated. The control sera were all negative for p53 antibodies. No correlation was found between the presence of p53 antibodies and tumorstage, tumor grading, age or sex of the patient or tumorlocalization. Thirteen of the 15 tumor samples from p53 antibody positive patients showed detectable levels of p53 protein. CONCLUSIONS: The frequency of p53 antibodies in patients with SCCHN is comparable with the occurrence of these antibodies in other malignancies. An accumulation of p53 in the tumor tissue seems to be necessary to initiate the antibody production. p53 antibodies seem to be an indicator for malignancy in SCCHN and may be of potential diagnostic and prognostic value.

Adult↗

[Immune response to p53 protein in patients with squamous epithelial carcinoma of the upper aerodigestive tract is independent of p53 point mutation].

OBJECTIVE: Mutations of the p53 gene are the most prevalent genomic changes in human malignancies. The detection of these mutations is usually carried out by gene sequencing or with immunohistochemical methods. A new approach is to search for p53 antibodies in serum of cancer patients. The cause for the production of antibodies against p53 is unclear. The aim of this study was to show the correlation between p53 pointmutations and p53 antibodies in patients with squamous cell carcinoma of the head and neck (SCCHN). METHODS: A semiquantitative ELISA was employed to screen the serum of 117 patients with SCCHN for p53 antibodies. Sixty-one tumor samples were evaluated with SSCP-analysis for point mutations in exons 4 to 9. RESULTS: Twenty-three (19.7%) of the cancer patients had antibodies to p53. There was no significant difference in the frequency of p53 point mutations in exon 4 to 9 between the whole cancer patient group and the p53 antibody positive group. CONCLUSIONS: The accumulation of p53 in the tumor cell is one hypothesis as to how p53 becomes immunogenic. This leads to a decrease in tolerance after a certain amount of time. In contrast to this it is assumed that after a p53 point mutation, important protein determinants are changed and p53 becomes antigenic. The results of this study indicate that p53 point mutations in SCCHN seem to have no influence on the development of p53 antibodies. Therefore this study supports the theory that the loss of tolerance and subsequently the antibody production is induced by an accumulation of p53. The type of p53 point mutations on exon 4-9 seems to have no influence that p53 gains immunogenic potential in SCCHN:

Antibodies, Neoplasm↗