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Biomedical subjects

W Bergler

Publications and source records attributed to W Bergler.

At least 19 recordsLinked to original sources

Expression of basic fibroblast growth factor protein and its down-regulation by interferons in head and neck cancer.

BACKGROUND: Angiogenesis is crucial for tumor growth and metastasis. In several tumors, microvascular density has been shown to correlate with metastasis and aggressiveness. Basic fibroblast growth factor (bFGF) has potent angiogenic activity and has been identified in a wide variety of malignancies including head and neck squamous cell carcinomas (HNSCC). Material and Methods Frozen sections of 50 HNSCC were immunostained for von Willebrand factor and bFGF. Microvessels were counted by light microscopy; bFGF expression was studied at the light and electron microscopic level. Laryngeal cancer cell line HlaC79 was incubated with interferon (IFN) alpha and beta. bFGF quantification was performed by ELISA, and antiproliferative effects were determined by BrdU assay. RESULTS: The mean number of blood vessels (77.5 +/- 23.7) is significantly increased in HNSCC compared with controls (17.1 +/- 5.9). bFGF protein expression was detected in all HNSCC but not in control tissue. An correlation between bFGF expression and mean number of microvessels was found (p <.001). However, no correlation between bFGF expression and the main clinicopathologic features was shown. The long-term exposure (144 hr) of HNSCC cells to noncytostatic concentrations of IFN alpha and beta (>10 U/mL) down-regulated the protein production of bFGF. CONCLUSION: bFGF expression and angiogenesis are enhanced in HNSCC. The higher microvessel density in HNSCC with strong bFGF expression supports the importance of bFGF for tumor angiogenesis. IFN alpha and beta treatment leads to a down-regulation of bFGF expression independent of their antiproliferative effects, suggesting that IFN treatment might result in a reduction of angiogenesis in HNSCC.

Adult↗

[Tonsillectomy with the argon-plasma-coagulation-raspatorium - a prospective randomized single-blinded study].

BACKGROUND: The Argon-Plasma-Coagulation (APC) offers an innovative possibility for the tonsillectomy combined with a high-frequency technology. Aim of our study was to inves-tigate the differences between this high-frequency-technology and the traditional tonsillectomy. No reports exist in the use of the APC in the tonsillectomy. METHODS: Argon-Plasma-Coagulation tonsillectomy (TE-APC) was compared with the traditional blunt dissection tonsillectomy (TE-trad) with hemostasis by compression and bipolar coagulation. 133 patients were stratified in two age groups in a clinical prospective randomised study. RESULTS: Average surgical time and blood loss were markedly decreased in the TE-APC group (p<0,01). There was no significant difference between the two techniques concerning postoperative pain, otalgia, and primary or secondary haemorrhage. In the TE-APC group more extensive fibrin layer appeared after surgery. In the TE-APC patients' group, there was a slightly higher consume of analgetics in some postoperative days. CONCLUSIONS: The one-step dissection and coagulation procedure leads to an almost bloodfree woundground and to a reduction of operation-time. The self-limited and effective coagualative properties of the APC-method leads to a controlled penetration depth. The often associated extensive post operative pain and uncontrolled tissue- damage, known from electrical and lasersurgical techniques, was not found in TE-APC-patients-group.

Adolescent↗

Gabapentin "add-on therapy" for idiopathic chronic hiccup (ICH).

The efficacy of cisapride, omeprazole, and baclofen (COB) for treatment of idiopathic chronic hiccup (ICH). was proven in several studies. The combination is considered, at present, to be "therapy of choice" for this condition. Substituting gabapentin for baclofen in baclofen resistant ICH cases can occasionally be successful. We present here cases where gabapentin was used successfully in combination with cisapride and omeprazole (COG/one patient) or as an "add-on" with cisapride, omeprazole, and baclofen (COBG/three patients). We conclude that, with baclofen and gabapentin, we are in possession of two substances that are, as a part of a combination therapy, quite effective for ICH. Because of the far more extensive experience with baclofen, we use it as a first-line therapy, together with omeprazole and cisapride. In cases where the results are not entirely satisfactory, the addition of gabapentin should be considered.

Acetates↗

Intravenous paraoxon (POX) exposure: coagulation studies in mini pigs.

The in vivo effects of the organophosphorus compound (OPC) paraoxon (POX) on blood coagulation of mini pigs were assessed by measuring the partial thromboplastin time (PTT), prothrombin time (PT), fibrinogen, factor V, factor VII, factor VIII, antithrombin III, protein C, and platelet count. The mini pigs were randomly assigned to a POX-treatment group (n = 9) receiving 54 mg POX kg(-1) BW(-1) or the control group (n = 9). Measurements were carried out over a period of 150 min after poisoning. The exposure to POX did not have any influence on measurements of PT, factor VIII, factor VII, factor V, antithrombin III, protein C, or fibrinogen compared to the control group evaluated by rank order test (ROT) during the time of observation (150 min). Changes seen in the intrinsic coagulation followed a biphasic pattern corresponding to an early sympathomimetic phase with PTT-shortening and a decrease of the platelet count, and a late vagal phase, with PTT-prolongation. The hypercoagulability seen in the sympathomimetic phase is probably due to a massive release of catecholamines from the adrenals. Previous studies showed in vitro no coagulation activating effect of POX. The hypocoagulability in the vagal phase shown by the PTT-protongation is probably due to POX influencing platelet function or its inhibition of clotting factors, which are serine proteases, or a combination of the two.

Animals↗

[Detection of serum concentration of carbohydrate-deficient transferrin (CDT) in patients with head-neck carcinomas].

It is now well known that chronic alcohol abuse is an important factor for developing head and neck squamous cell carcinoma (HNSCC). While hospitalized, these patients are at great risk for developing an unexpected alcohol-withdrawal syndrome. Compared to common markers of alcohol abuse, carbohydrate-deficient transferrin (CDT) has been found to be more sensitive and specific. It is therefore very useful for detecting alcoholism and controlling compliance of alcohol withdrawal. We analyzed the serum concentrations of CDT, liver enzymes and mean corpuscular volume in 49 male patients with HNSCC. Elevated CDT levels were found in more than 25% of patients who earlier denied a history of chronic alcohol abuse. Over one-third of these patients developed an alcohol-withdrawal syndrome. These findings demonstrated that analysis of elevated CDT serum levels was a valuable method for detecting chronic alcohol abuse and recognizing patients at risk for developing an alcohol-withdrawal syndrome post-operatively.

Alcohol Drinking↗

[Controlled cosmetic dermal ablation in the facial region with the erbium:YAG laser].

The erbium: YAG laser (wavelength 2940 nm; pulse duration 0.350 ms; pulse energy 0.1-1.7 J) allows vaporization of very thin skin layers without scarring and minimal lateral thermal injury due to an extremely short pulse duration. It permits exact ablation of relatively large areas of facial skin. We report our results with 216 patients following treatment for different facial lesions (facial wrinkles, acne scars, syringomas, and circumscribed sebaceous gland hyperplasia) using a new erbium: YAG laser system. Good-to-excellent cosmetic results were obtained in these patients. Our findings show that the erbium: YAG laser is an elegant and promising new method for the treatment of facial lesions.

Cicatrix↗

Hereditary hemorrhagic telangiectasias: a challenge for the clinician.

Hereditary hemorrhagic telangiectasia (Osler-Weber-Rendu disease) remains a challenge for all clinicians, as in about 80% of cases nasal bleeding is the first manifestation of this disease, which is characterized by a clinical triad of multiple telangiectasias, recurrent hemorrhages and familial occurrence. Although in the last few years there has been diagnostic and therapeutic progress, a cure for this rarely life-threatening but often burdening and handicapping disease is still not possible. We have reviewed head and neck presentations, diagnostic and therapeutic features, as well as new insights into the molecular genetics of the disease and local treatment now available.

Diagnosis, Differential↗

Age-dependent altered proportions in subpopulations of tonsillar lymphocytes.

Age-related changes in functional subsets of lymphocytes may influence the potential to build up immune responses. In particular, the capacity of tonsillar lymphocytes to counter infections may be altered during ageing. In order to address this question we investigated the proportional distribution of several subsets of tonsillar T and B cells with regard to ageing. Tonsils were derived from 119 patients between 2 and 65 years of age. Lymphocyte subsets were monitored by three-colour fluorescence of relevant CD markers in flow cytometry. As a general tendency the percentage of CD3+ T cells steadily increased whereas that of CD19+ B cells decreased at the same time. No significant differences were observed between lymphocytes of patients with and without inflammatory history of the tonsils. The percentage of CD8+ T cells declined whereas that of CD4+ T cells increased during the same time span. CD45RA+ T cells increased during the first two decades of life and gradually decreased thereafter. In contrast, CD45RO+ T cells showed an opposite trend. No differences were seen in the population of CD3-/CD56+ natural killer (NK) cells. The mature B cell marker CD40 showed no significant changes during ageing. However, CD38+ B cells, representing B cells of late maturation stages, dramatically declined up to the age of 65. In a similar manner the CD5+ subpopulation of B cells decreased during ageing. Substantial changes in major tonsillar T and B cell populations as shown in this study may have an impact on the ageing process of the immune system.

Adolescent↗

Argon plasma coagulation for the treatment of hereditary hemorrhagic telangiectasia.

OBJECTIVES: Patients with (HHT) often suffer from recurrent epistaxis, which poses considerable therapeutic problems. Theoretical considerations render argon plasma coagulation (APC) a promising new therapeutic approach. STUDY DESIGN: In a prospective study 12 patients (aged 8-68 y) who presented with a long history of treatment for epistaxis were treated with telangiectasia in the nasal mucosa. After 2 weeks and again after 4 months the treatment results were evaluated by questionnaire. METHODS: APC is based on high-frequency electric energy transmitted through ionized argon gas to the tissue in a noncontact mode. Coagulation and desiccation of tissue are limited to 1 to 2 mm of penetration and therefore risk of tissue damage is low. Coagulative effects are best in tissue with high electrical conductivity, especially blood vessels. RESULTS: All patients were satisfied with the postoperative results. Frequency and intensity of bleeding were significantly reduced. All patients reported better postoperative results than with any other treatment they had received previously. CONCLUSION: First clinical experience shows that APC is a useful alternative for the treatment of telangiectasia in the nasal mucosa and should be a therapeutic option for this disease.

Adolescent↗

[Argon plasma coagulation in treatment of hereditary hemorrhagic telangiectasia of the nasal mucosa].

Patients with hereditary hemorrhagic telangiectasia (M. Osler-Rendu-Weber disease) often suffer from recurrent epistaxis that poses considerable therapeutic problems. Dermoplasty, electrocoagulation, laser coagulation, iridium brachytherapy and systemic administration of estrogens have been proposed for treatment. Until recently argon plasma coagulation (APC) was not used in ENT surgery, but theoretical considerations render APC a promising therapeutic method for controlling nasal bleeding. Coagulation of tissue is limited to 1-2 mm of penetration and therefore risk of damage to adjacent tissue is low. Effects are best in tissues with high electric conductivity, especially for coagulating bleeding lesions and blood vessels. We have now treated four patients with telangiectasias in the nasal mucosa who had long histories of treatment for epistaxis. The patients were satisfied with the postoperative results and the frequency and intensity of bleeding were significantly reduced. Initial clinical experiences show that APC is a useful alternative for the treatment of bleeding telangiectasias in the nasal mucosa.

Adult↗

[Argon plasma surgery (APC) in the upper aerodigestive tract. Initial results].

Cold knife surgery, electrosurgery and laser surgery all offer techniques, instruments, equipment and systems for resecting and destroying mucosal lesions and for hemostasis in the upper aerodigestive tract. When used in the head and neck, argon plasma surgery (APS) offers a new, contact-free, electrosurgical technique in which high frequency current is applied through ionized, and thus electrically conductive, argon(argon plasma) to the tissue undergoing treatment. Especially noteworthy in APS are its advantages for removing a lesion and controlling bleeding: the technique is easy to control, and the depth of the thermal tissue destruction is limited to a maximum of 3 mm even in wide-area application, so that damage to adjacent or submucosal tissues can be avoided. Initial results with APS in the reduction of hyperplastic nasal turbinates, treatment of hereditary hemorrhagic teleangiectasia (Osler's disease) in the nasal mucosa, and in treating progressive juvenile papillomatosis of the larynx have shown clear advantages for APS over other methods used.

Adolescent↗

Role of sialoglycan structures for the function of the epidermal growth factor receptor and the in vitro proliferation of head and neck cancer.

Squamous cell carcinomas of the head and neck have been found to show a high expression of the receptor for epidermal growth factor (EGF). This overexpression of the receptor has been associated with malignant transformation of cells, although there is still debate as to what extent this receptor takes part in the proliferation of malignant cells and which function it fulfills. The factors which determine receptor-ligand interaction are also not clearly defined. That the extracellular domain of the EGF receptor carries carbohydrate or sialoglycan structures might be important for function of the receptor. Since tumor specific enzymes can possibly alter such structures, it was the aim of our study to investigate the role of these structures on the EGF receptor during the proliferation of head and neck carcinomas. We used the human laryngeal squamous carcinoma cell line HLaC 79 and altered, for the first time, specific glycan structures with sialidase alpha-2,3 and alpha-2,6, causing desialylation. Changes were also produced by endo-beta-galactosidase and sialyltransferase. Findings were monitored by labeling with bromo-deoxyuridine. To determine receptor affinity, 125I-labeled EGF was employed. Results showed that both cell proliferation and receptor affinity depended on the level of sialylation of the receptor carbohydrate side chains. Desialylation led to a statistically significant reduction of tumor cell proliferation to 65 +/- 33% (P < 0.01), while receptor affinity decreased to 70 +/- 26% (P < 0.01). The importance of EGF receptor for the proliferation of malignant cells seems to depend on the level of sialylation of glycan structures on receptor protein. A release of enzymes by tumor cells may then produce auto-control of tumor proliferation on its own.

Binding Sites↗

[Paranasal sinuses: only one of nature's games?].

BACKGROUND: Many theories exist concerning the function of paranasal sinuses, but it is rather difficult to definitively name the right one. Despite the fact that many of them have been proved to be wrong, they are still used. THEORIES: Galen postulated 2000 years ago that they were "porous bones", which helped with weight reduction. Like Galen's theory, most of the others have been refuted as well. A list of these refuted theories covers a range of postulated functions including a relative warming or moistening of the breath, protection against high pressure in the nasal region when sneezing, paranasal sinuses as a place of efficient mucus production, or an aid for smelling, similar to the ethmoidal cells of the porcupine. Others include an isolated function for protection against cold climates and an aid for formulating sound by acting as a resonance chambers. CONCLUSIONS: Two theories still remain. One says that the paranasal sinuses are only the result of the evolutionary processes that have taken place in the skull during human development. The other theory explain that the form of the paranasal sinuses exists through the influence of the forces created during the act of chewing. Small cavities appear as a result of the minimal energy created, and these cavities can be found in the form of paranasal sinuses.

Adaptation, Physiological↗

The influence of an arterial and venous air embolism on the hearing level in laboratory mini pigs.

We examined the influence of an experimental venous and arterial air embolism on the hearing level in laboratory mini pigs. Before and after the injection of air a threshold ABR was measured in anaesthetized mini pigs (n=15). A venous air embolism was performed in 6 animals: no changes in the hearing level or in the interpeak latencies Jewett wave V-I were observed in any of the animals before, during or after the application of air. In 9 animals the arterial embolism was done, 2 animals died and had to be excluded. In 6 animals out of 7 a hearing loss was observed starting after the injection of 40 ml air and finally ending in deafness for these 6 animals. The detected hearing loss is probably of cochlear origin, as no prolongations of the interpeak latencies of Jewett wave V-I at 90 dB HL were observed prior to the deafness. Our results show that air bubbles in the arterial circulation lead to cochlear damage ending in deafness. Our research indicates that decompression sickness, which is comparable to the arterial air embolism, is more often the cause of a sensorineural hearing loss after diving than previously believed.

Animals↗

[ETICS Study: Empirical therapy of idiopathic chronic singultus].

Idiopathic chronic singultus (ICS) describes recurring episodes of persistent hiccuping lasting longer than an arbitrary time limit (e.g. one month) for which no organic cause or consistently effective treatment can be found. It has been suggested that ICS may result from chronic stimulation of a supraspinal "hiccup center" by impulses originating from receptors in the gastrointestinaltract. This hypotesis implies the possibility of treating ICS by reducing gastric acid (via omeprazole), facilitating gastric emptying (via cisapride), or suppressing of the "hiccup centre" (via GABA-ergic offects of baclofen or gabapentin). 29 patients (28 male, one female; age 71 +/- 10 years) suffering from ICS for four to 564 months were treated with a combination of cisapride (30 mg/d), omeprazole (20 mg/d) and baclofen (45 mg/d) (COB). The patients rated the severity of hiccuping on a subjective assessment scale (SAS) that ranged from 0 (= no hiccuping) to 10 (= unbearable hiccuping). Hiccuping ceased in 38% (11/29) of the treated patients and decreased in severity in an additional 24% (7/29). Mean SAS-scores following 20 to 24 weeks of therapy (3.7 +/- 3.4) were significantly lower compared to before therapy (8.8 +/- 1.3) (Mann-Whitney rank order test [p < 0.02]). In the patients that failed to respond to COB, gabapentin (1.200 mg/d) was substituted for baclofen. Hiccuping ceased in one and improved in two of these ten subjects. We conclude that COB is an effective empirical therapy in the majority of patients with ICS. It may be useful to substitute gabapentin for baclofen in those not responding to COB.

Acetates↗

[The treatment of juvenile laryngeal papillomatosis with argon plasma coagulation].

HISTORY AND CLINICAL FINDINGS: At 3 years of age a girl known for one year to have progressive juvenile laryngeal papillomatosis with involvement of the lower respiratory tract was seen by her general practitioner because of increasing hoarseness. As about 20 sessions of CO2-laser treatment and adjuvant administration of interferon-alpha had failed to prevent increasing glottal stenosis and spread of the tracheal involvement, a tracheostomy had to be performed. Removal of the papilloma became progressively more difficult and at the age of 6 years she was admitted for further treatment. INVESTIGATIONS: She had marked inspiratory and expiratory stridor. Results of laboratory tests were unremarkable. Examination of the respiratory tract with a flexible endoscope revealed obstruction of the tracheal lumen by the papilloma. TREATMENT AND COURSE: The papilloma was removed by argon plasma coagulation (APC) under general anaesthesia during intermittent apnoeic phases. After four treatment sessions no papilloma could be seen endoscopically. There were no side effects or complications. The interval between treatments has become progressively longer. Further removal of papilloma is only rarely necessary nowadays. CONCLUSION: APC via a flexible endoscope is a promising method in the treatment of juvenile laryngeal papillomatosis involving the lower respiratory tract. It achieves precise, circumscribed tissue penetration without carbonisation or steaming-up, while bleeding can be controlled.

Child, Preschool↗

In vitro paraoxon (E 600) exposure: no activating effect on human blood coagulation.

The in vitro effects of the organophosphorus compound (OPC) paraoxon (POX) on human blood coagulation were assessed by fibrin monomer (FM) concentration measurements and thrombelastographic (TEG) determinations. Increasing doses of POX dissolved in alcohol (POX + ALO) or alcohol (ALO) only in corresponding quantities were added to blood drawn from six human volunteers. In both series (POX + ALO and ALO-only) FM concentrations increased in comparison to the baseline levels. No statistically significant differences exist, however, between FM measurements performed on blood with POX + ALO and those performed on blood with ALO-only. No coagulation-activating effect of POX in vitro was demonstrable; the changes seen in vitro are due to the ALO used as a vehicle. The thrombelastographic parameters showed several changes in the POX + ALO series as dosage increased. At high POX levels, reaction time r and clot formation time k became longer than in the baseline measurements, the clot formation rate alpha and the maximum amplitude MA were reduced. The TEG changes indicate a hypocoagulable state, probably due to the POX effect on platelet function and/or inhibition of clotting factors (serine proteases).

Blood Coagulation↗

A new histobiochemical method to analyze sialylation on cell-surface glycoproteins of head and neck squamous-cell carcinomas.

Oncogenic transformation is often accompanied by alterations of glycosylation on a tumor cell's surface, which may contribute to uncontrolled cell growth. The sialoglycans and degree of sialylation on the cell surface are of increasing interest because of their possible role in metastasis and tissue invasion. Since primary tumors and metastases may differ in the degree of sialylation, we examined the expression of sialic acid as a terminal constituent of lactosaminyl glycans on the cell surfaces of 30 cervical lymph-node metastases and 30 squamous-cell carcinomas of the oropharynx and oral cavity. Cell-surface sialylation was determined by a new histobiochemical assay on cryostat sections and was based on the enzymatic introduction of a fluorescence-labelled sialic acid into lactosaminyl type (Gal-beta 1-4 GlcNAc) oligosaccharide chains of cell-surface-expressed glycoproteins. To this end, tissues were incubated in the presence of 5-acetamido-9-deoxy-9-fluoresceinyl-thioureido neuraminic acid (CMP-9-fluoresceinyl-NeuAc) and alpha-2,6-sialyltransferase. In order to compare the degree of sialylation with the potential total amount of sialylation sites, pretreatment with sialidase for desialylation was required. We observed a significantly higher amount of lactosaminyl-type binding sites for sialic acid on metastases compared to the primary tumors (P = 0.001), indicating a lower degree of sialylation in metastases. In primary tumors no correlation was seen between the amount of binding sites and tumor localization, TNM stage or histologic grading. Pretreatment of specimens with sialidase demonstrated a significant degree of sialylation on both primary tumors and lymph-node metastases, but no difference between primary tumors and metastases. When tumor stroma of primary tumors and metastases was compared, tumor cells showed a higher degree of free binding sites for sialic acid, but a low degree of sialylation. Our results suggest that differences in the degree of sialylation of glycoconjugates on a tumor cell's surface may play an important role in the process of cell metastasis. Our histobiochemical method turned out to be very reliable, effective and readily performed.

Binding Sites↗