[Recommendations of the Working Group 'Supportive Massnahmen in der Onkologie' concerning the Clinical Use of Cytoprotectives].
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Amifostine↗
Biomedical subjects
W Wagner
Publications and source records attributed to W Wagner.
Frameless neuronavigation in intracranial endoscopic neurosurgery.
OBJECT: Frameless computerized neuronavigation has been increasingly used in intracranial endoscopic neurosurgery. However, clear indications for the application of neuronavigation in neuroendoscopy have not yet been defined. The purpose of this study was to determine in which intracranial neuroendoscopic procedures frameless neuronavigation is necessary and really beneficial compared with a free-hand endoscopic approach. METHODS: A frameless infrared-based computerized neuronavigation system was used in 44 patients who underwent intracranial endoscopic procedures, including 13 third ventriculostomies, nine aqueductoplasties, eight intraventricular tumor biopsy procedures or resections, six cystocistemostomies in arachnoid cysts, five colloid cyst removals, four septostomies in multiloculated hydrocephalus, four cystoventriculostomies in intraparenchymal cysts, two aqueductal stent placements, and fenestration of one pineal cyst and one cavum veli interpositi. All interventions were successfully accomplished. In all procedures, the navigational system guided the surgeons precisely to the target. Navigational tracking was helpful in entering small ventricles, in approaching the posterior third ventricle when the foramen of Monro was narrow, and in selecting the best approach to colloid cysts. Neuronavigation was essential in some cystic lesions lacking clear landmarks, such as intraparenchymal cysts or multiloculated hydrocephalus. Neuronavigation was not necessary in standard third ventriculostomies, tumor biopsy procedures, and large sylvian arachnoid cysts, or for approaching the posterior third ventricle when the foramen of Monro was enlarged. CONCLUSIONS: Frameless neuronavigation has proven to be accurate, reliable, and extremely useful in selected intracranial neuroendoscopic procedures. Image-guided neuroendoscopy improved the accuracy of the endoscopic approach and minimized brain trauma.
Adolescent↗
Control of SIV rebound through structured treatment interruptions during early infection.
In a randomized controlled trial with acute simian immunodeficiency virus (SIV)-infected macaques, both highly active antiretroviral therapy (HAART) and HAART with fixed-schedule structured treatment interruption (STI-HAART; alternating 3 weeks on and 3 weeks off therapy) suppressed viral load. In the STI-HAART group, T cell virus-specific immune response (VIR) and control of viral rebound increased concurrently during subsequent interruptions. In contrast, VIR did not increase and SIV rebounded after permanent treatment withdrawal in all animals on continuous HAART. Fixed-schedule STI-HAART appears to be an effective alternative to continuous HAART for the early treatment of retroviral infection.
Adenine↗
Control of viremia and prevention of clinical AIDS in rhesus monkeys by cytokine-augmented DNA vaccination.
With accumulating evidence indicating the importance of cytotoxic T lymphocytes (CTLs) in containing human immunodeficiency virus-1 (HIV-1) replication in infected individuals, strategies are being pursued to elicit virus-specific CTLs with prototype HIV-1 vaccines. Here, we report the protective efficacy of vaccine-elicited immune responses against a pathogenic SHIV-89.6P challenge in rhesus monkeys. Immune responses were elicited by DNA vaccines expressing SIVmac239 Gag and HIV-1 89.6P Env, augmented by the administration of the purified fusion protein IL-2/Ig, consisting of interleukin-2 (IL-2) and the Fc portion of immunoglobulin G (IgG), or a plasmid encoding IL-2/Ig. After SHIV-89.6P infection, sham-vaccinated monkeys developed weak CTL responses, rapid loss of CD4+ T cells, no virus-specific CD4+ T cell responses, high setpoint viral loads, significant clinical disease progression, and death in half of the animals by day 140 after challenge. In contrast, all monkeys that received the DNA vaccines augmented with IL-2/Ig were infected, but demonstrated potent secondary CTL responses, stable CD4+ T cell counts, preserved virus-specific CD4+ T cell responses, low to undetectable setpoint viral loads, and no evidence of clinical disease or mortality by day 140 after challenge.
AIDS Vaccines↗
Magnetic correlations in nanostructured ferromagnets
Small-angle neutron scattering experiments on nanostructured Fe, Co, and Ni reveal grain-size dependent magnetic correlations across grain boundaries. In Fe, a minimum of the correlation length is observed for grain sizes of the order of the bulk domain-wall width where the coercive field has a maximum. The results are explained within a generalization of the random-anisotropy model that takes into account domain-wall formation within grains and reduced interface coupling.
Journal Article↗
In vitro senescence models for human T lymphocytes.
Immunosenescence is an age-associated dysregulation of immune function which may contribute to the increased susceptibility of the elderly to infectious disease. Although age-associated changes are measurable in the innate immune system, it is the adaptive arm of the immune system which is particularly susceptible to the deleterious effects of ageing, especially the T cell compartment. In this review, the characteristics of longitudinal ageing in cultured monoclonal human T cell populations will be summarized. It will be argued that parallels between this in vitro model and T cell senescence in vivo suggest the use of such models to screen for interventions ameliorating immunosenescence in vivo.
Adult↗
[A simple method for transposing MRI information to simulation films. Technical note].
BACKGROUND: The use of MRI information in the treatment planning process is still expensive and time consuming. Electro-optical devices or specially designed post-processing software in here the risk of picture distortion. PATIENTS AND METHODS: Between June 1998 and June 1999 in 48 patients with brain tumors and 11 patients with carcinoma of the prostate CT treatment planning and MRI were performed with identical patient positioning using the same devices as in the simulation. The transposition of organ and tumor volumes between MRI and simulation film takes place by overlying both on the brightening screen by using a grid. MRI and simulation films must be produced using an identical magnification factor. RESULTS: For 9 patients with brain tumors and 2 patients with a carcinoma of the prostate the transposition of MRI information on the simulation films showed the necessity of a modification of the shielding or the treatment portals. CONCLUSIONS: The simple method of direct transposition of MRI structures into simulation films allows to accomplish a verification of the portals and conformation which result of the treatment planning process. Moreover an individualized shielding can also directly be realized.
Brain Neoplasms↗
Prognostic value of hemoglobin concentrations in patients with advanced head and neck cancer treated with combined radio-chemotherapy and surgery.
PURPOSE: Hemoglobin levels are currently the focus of interest as prognostic factors in patients with head and neck cancer. Most published clinical trials have confirmed hemoglobin to possess a significant influence on survival in patients treated with radiotherapy. In our study we have investigated the prognostic value of hemoglobin in a combined modality schedule. PATIENTS AND METHODS: Forty-three patients with advanced head and neck tumors were treated with combined radio-chemotherapy. The therapy comprised 2 courses of induction chemotherapy with ifosfamide (1,500 mg/m2, day 1 to 5) and cisplatin (60 mg/m2, day 5) followed by hyperfractionated accelerated radiotherapy with a total dose of only 30 Gy. Surgery involved tumor resection and neck dissection. RESULTS: The 1-year overall survival rate and the 2-year survival rate were 79% and 56%, respectively. The 1- and 2-year recurrence-free survival rates were 68% and 49%, respectively. Prognostic factors with an impact on survival were seen in tumor size (T3 vs T4, p = 0.0088), response to radio-chemotherapy at the primary site (no vital tumor rest vs vital tumor rest, p = 0.045), response to lymph node radio-chemotherapy (no vital tumor cells vs vital tumor cells, p = 0.013) and level of hemoglobin after radio-chemotherapy (Hb > or = 11.5 g/dl vs < 11.5 g/dl, p = 0.0084). CONCLUSION: In our study hemoglobin level after radio-chemotherapy was identified for the first time to be also a significant prognostic factor (univariate analysis) in head and neck cancer patients who underwent combined radio-chemotherapy. Besides chemotherapy plus low-dose irradiation achieved similar results in comparison with radical resection and high-dose radiotherapy at least for the first 2 years after therapy. Relapsing disease could be treated with 1 additional course of radiotherapy which is supposed to be well tolerated.
Adult↗
Diagnostic radiation oncology: malignant cystosarcoma phylloides.
BACKGROUND: Cystosarcoma phylloides is a rare, mostly benign tumor of the breast. In most cases curative treatment is possible with complete surgical excision of the lesions. However, there is a high local recurrence rate up to 46%. There are only few reported successful treatments with radiotherapy in cystosarcoma phylloides. Radiotherapy is indicated in patients with locoregional recurrent disease and those with symptomatic metastases. PATIENT: We present a case of a 54-year-old woman with a painless mass in the right breast. Clinical examination showed a large, firm tumor and axillary lymph node metastases. The patient underwent mastectomy and axillary lymph node dissection. Histopathology showed a cystosarcoma phylloides measuring 30 x 25 x 19 cm as well as lymph node metastases measuring 9.5 cm. Despite a R0 resection the patient developed 4 thoracic wall recurrences within 2 years. At 18 months there were additional multiple pulmonary and pleural lesions with a maximum diameter of 6.5 cm. Subsequently the patient received polychemotherapy. There was a significant response of the thoracic wall disease as well as of the pulmonary and pleural lesions. Six months later there was further progress of the thoracic wall disease and the pulmonary lesions. Following this the patient underwent radiation therapy of her right thoracic wall with 50 Gy which lead clinically to a quick response. For the past 5 months there has been no evidence of thoracic wall disease recurrence. CONCLUSION: This is an unusual case of cystosarcoma phylloides and response to different therapeutic modalities. Cystosarcoma phylloides showed to be a radiosensitive tumor. Thus postopertive radiation therapy is indicated to prevent local recurrences.
Breast Neoplasms↗
[Comments on articles by K.H. Gebhardt, "What has been proven in homeopathy?" and K. Linde, "Are there evidence-based therapies in homeopathy?"].
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Clinical Trials as Topic↗
Using ultrasound transmission velocity to analyse the mechanical properties of teeth after in vitro, in situ, and in vivo irradiation.
Ultrasound transmission velocity (UTV) in isotropic material as a measure for the modulus of elasticity was correlated to mechanical properties. Changes in micromechanical properties of radiated teeth and influence of the oral cavity were to be evaluated nondestructively. UTV was measured in extracted teeth after 36 Gy and 62 Gy of in situ (enorally, with no contact to the oral cavity) and in vitro irradiation. Relative to controls, teeth subjected to 62 Gy in vivo showed higher UTV values for dentine and enamel. Sound teeth irradiated with 60 Gy in situ also showed higher UTV values for enamel, whereas dentine values were not significantly different from those of control. The mechanical properties of teeth irradiated in vitro were affected only after high experimental doses of up to 500 Gy. The difference between in vivo and in vitro mechanical properties may be due to radioxerostomia-induced damages as well as the status of dentine vitality. This supports the concept of direct radiation-induced damage in synergy with radioxerostomia-induced caries.
Cranial Irradiation↗
Terminal end of the human odontoblast processes.
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Dental Enamel↗
[Retrospective analysis of the prognostic significance of the manner of mandibular resection and adjuvant radiotherapy in para-mandibular carcinomas].
The prognostic effect of bone resection (continuous vs non-continuous) was analysed in a retrospective study of 100 patients who were treated for squamous cell carcinoma located close to the lower jaw, between 1983 and 1994. Tumour stage, type of bone resection, extent of lymphatic node resection, dose of radiotherapy and chemotherapy were documented. Prognosis was characterised by the statistical end points "death", "metastasis" and "relapse". Thirty-two stage pT2 carcinomas, half of which were treated by continuous and half by non-continuous resection of the lower jaw, showed the same occurrence of the statistical end points death, metastasis or relapse. There was a trend towards a significantly longer survival time and metastasis-free interval in the group of continuous resection. The hazard ratios, however, showed no effect depending on the type of resection. However, both tumour stage (pTNM) and dose of radiation independently influenced prognosis in multivariate analysis. Consequently, three groups were defined. Univariate analysis of 62 patients without radiotherapy vs 19 with low-dose radiotherapy (36 Gy) and 19 with high-dose (62 Gy) showed a positive effect on the rate and time of survival in the group treated with high-dose radiotherapy. This was confirmed by multivariate analysis showing significantly lower hazard ratios for death and metastasis in the high-dose radiotherapy group after adjusting to cofactors (e.g. tumour stage). The data of this study challenge the current concept of resection of the lower jaw. However, due to the low number of patients and the retrospective character of the study, it is not possible to give suggestions regarding established therapy concepts. The advances of a high-dose radiotherapy in this study should be the subject of further multicentre retrospective and prospective randomised trials.
Adult↗
[Cytokeratin expression in botryoid odontogenic cyst. A rare differential keratocyst and ameloblastoma diagnosis].
The botryoid odontogenic cyst (BOC) is considered a rare multilocular variant of the lateral periodontal cyst. The origin of the BOC can be seen in aberrant odontogenic tissue. The BOC is found especially in the premolar region of the mandible, as well as in the frontal region of the maxilla of patients aged between 60 and 70 years. Most of the 11 published articles of BOC have shown high rates of recurrence. Histopathologically the BOC is marked by multilocular cysts lined by a thin, nonkeratinized epithelium. Clusters of glycogen-rich epithelial cells may be noted in nodular thickenings of the cyst lining. For the clinician, the differentiation of the BOC from the keratocyst and ameloblastoma is relevant. One case of a large BOC (65-year-old male, BOC regio 33-45, diameter 5 cm, radiographically and histologically multilocular) is presented with a review of the literature, including the therapeutic management, and the possible diagnostic criteria are discussed. The immunohistochemically determined expression of cytokeratin (CK) 13 implicates the histogenetic origin of the BOC from the squamous epithelium of the oral cavity and excludes the origin from the small salivary glands. The expression of CK 19 and the lack of expression of p53, as well as the higher proliferation rate of the basal epithelial cell layer by the BOC, may be useful for distinction between the keratocyst.
Ameloblastoma↗
[(18F)-2-fluorodeoxyglucose PET. Prospects for secondary prevention of mouth cavity carcinoma].
AIMS: The predominant cause of death due to oral cancer is the failure to control local tumor due to regional tumor recurrence. The sequelae of surgical resection and high-dose irradiation cause substantial changes in head and neck anatomy, leading to considerable problems in the early morphological detection of recurrent disease. Therefore, this study evaluates the verification of cancer recurrence by means of its pathologic glucose metabolism. MATERIALS AND METHODS: We reviewed a total of 50 [18F]-2-fluordeoxyglucose positron emission tomography (18FDG-PET) investigations performed in 44 patients who had undergone surgical resection of oral cancer. In 23 cases, re-staging (group A) was indicated due to suspicion of recurrent or secondary tumor manifestation. In 27 cases, PET served as a screening procedure (group B). Statistic evaluation included sensitivity, specificity, positive/negative predictive value and accuracy of 18FDG-PET for the detection of tumor manifestation. RESULTS: 18FDG-PET correctly identified 23 of 26 tumor sites (88%) in the re-staging group and 9 of 10 tumor sites (90%) in the screening group. We encountered a total number of 16 false-positive foci with an increased 18FDG-uptake. In six patients, 18FDG-PET detected tumor recurrence several months before a morphological correlative could be identified. In 5 of these 6 patients, the PET findings for the latter tumor sites determined the patient's fate. Specificity was 63% for local recurrence, 97% for secondary lymph node involvement and 90% for distant metastasis. CONCLUSION: According to these data, 18FDG-PET is the most effective diagnostic tool in the follow-up of oral cancer patients to date. Due to the high prevalence of recurrent disease in the follow-up of oral cancer, either the detection of early recurrence or the identification of additional, incurable tumors may add substantially to a rational therapeutic management. We therefore recommend 18FDG-PET for screening and re-staging of recurrent oral cancer.
Blood Glucose↗
[Determining the size of the specific surface of bone substitutes with gas adsorption].
The surface area and the microporosity of bone regeneration materials influence their chemical and biological properties. Therefore, the size of the specific surface area and the distribution of the pore diameters (pores < 1 micron) of bone regeneration materials were analyzed within this study. The analyzed hydroxyapatites were of synthetic, bovine, and phytotroph origin. The tricalcium phosphates and the bioglasses included only synthetic materials. The gas adsorption of each specimen was analyzed using a volumetric N2/Kr system (ASAP 2010, Micromeritics). Additionally, for materials with a specific surface area (> 2 m2/g) the pore size distribution was evaluated by the BJH-method. Two of the materials evaluated astonishingly large dimensions of the specific surface area (BioOss 79.7 m2/g, Algipore new 14.6 m2/g). A medium surface area was found for Algipore old (4.9 m2/g) and Interpore200 (2.64 m2/g). All other included materials showed only small sizes of the specific surface area (Ceros80 1.8 m2/g, Ceros82 1.31 m2/g, Cerasorb 1.2 m2/g, Biobase 0.7 m2/g, Endobone 0.7 m2/g, Perioglas 0.6 m2/g, Allotropat50 0.23 m2/g, Biogran 0.2 m2/g). The materials with large and medium sizes of the specific surface area evaluated the following pore diameters: BioOss 2-50 nm, Algipore new 2-100 nm, Algipore old 5-50 nm, Interpore200 2-100 nm. Pore sizes less than 2 nm were not found in relevant numbers. The materials BioOss, old and new Algipore, and Interpore200 contain a large interconnecting mesopore system (diameter < 1 micron). For the materials Biobase, Endobone, Perioglas, Allotropat 50, and Biogran this cannot be assumed. The materials Ceros80, Ceros82, and Cerasorb evaluated a specific surface area between those and might include only a small part of these interconnecting pores. An influence of the interconnecting porosity and the different sizes of the specific surface areas on the biological behavior of the bone regeneration materials can be suggested.
Adsorption↗
Biotechnology and the European public.
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Biotechnology↗
Low levels of Ypt protein prenylation cause vesicle polarization defects and thermosensitive growth that can be suppressed by genes involved in cell wall maintenance.
The Rab/Ypt small G proteins are essential for intracellular vesicle trafficking in mammals and yeast. The vesicle-docking process requires that Ypt proteins are located in the vesicle membrane. C-terminal geranylgeranyl anchors mediate the membrane attachment of these proteins. The Rab escort protein (REP) is essential for the recognition of Rab/Ypt small G proteins by geranylgeranyltransferase II (GGTase II) and for their delivery to acceptor membranes. What effect an alteration in the levels of prenylated Rab/Ypt proteins has on vesicle transport or other cellular processes is so far unknown. Here, we report the characterization of a yeast REP mutant, mrs6-2, in which reduced prenylation of Ypt proteins occurs even at the permissive temperature. A shift to the restrictive temperature does not alter exponential growth during the first 3 h. The amount of Sec4p, but not Ypt1p, bound to vesicle membranes is reduced 2.5 h after the shift compared with wild-type or mrs6-2 cells incubated at 25 degrees C. In addition, vesicles fail to be polarized towards the bud and small budded binucleate cells accumulate at this time point. Growth in 1 M sorbitol or overexpression of MLC1, encoding a myosin light chain able to bind the unconventional type V myosin Myo2, or of genes involved in cell wall maintenance, such as SLG1, GFA1 and LRE1, suppresses mrs6-2 thermosensitivity. Our data suggest that, at least at high temperature, a critical minimal level of Ypt protein prenylation is required for maintaining vesicle polarization.
Adaptor Proteins, Signal Transducing↗