[Surgical treatment of skeletal metastases]. / Chirurgische Therapie der Skelettmetastasen.

The prevalence of cancerous diseases in Germany is rising. The skeletal system represents the third most common localization for metastases. Nearly two thirds of metastases are found in the region of the spine. Due to longer survival times of tumor patients in the metastasis stage, an increase in the number of patients with bone metastases is to be expected. The treatment of patients with osseus metastases is nowadays an integral component of orthopedic trauma surgery practices. This article presents the principles of the diagnostics, provides aids for estimation of the prognosis and danger of fractures and discusses the various surgical treatment procedures for skeletal metastases with the accompanying advantages and disadvantages.

Loss of heterozygosity at 11p15 and p53 alterations in malignant gliomas.

PURPOSE: Malignant gliomas are the most frequent primary brain tumors. Recent studies defined several genetic markers, which might characterize molecular-biological subsets of glioblastomas with prognostic implications. In the later steps of tumor-progression, deletions on chromosome 11p15 and mutations of the tumor suppressor gene p53 were determined for different malignancies. To elucidate the involvement of 11p15 deletions in the tumorigenesis of malignant gliomas, we analyzed a series of 50 glioblastomas for loss of heterozygosity (LOH). METHODS: Paired tissue and blood samples from 50 patients with glioblastoma multiforme were included. Microsatellite markers located on 11p15.1-11p15.5 were used for LOH analysis. Additionally, mutation analysis of the tumor suppressor gene p53 was performed, which might correlate with favorable survival in glioblastomas. RESULTS: The region 11p15.4-5 was deleted heterozygously in 28% of cases representing 15 cM. Twenty-six glioblastomas did not show allelic loss for any locus. Our data revealed close association of LOH 11p15 with p53 mutations, and survival analysis showed a trend indicating better prognosis in glioblastomas characterized by LOH 11p15. CONCLUSION: In the tumorigenesis of malignant gliomas, p53 mutations and 11p15 deletions seem to indicate a genetic subset of tumors with favorable prognostic value.

Irradiation of histiocytosis X confined to the oral mucosa.

BACKGROUND: Histiocytosis X is a rare granulomatous disease and it is still under debate as to whether this disease has to be counted among malignant tumors or benign immunologic lesions. The typical localization is confined to the bone. In rare cases histiocytosis X may be localized in the oropharyngeal mucosa. PATIENTS AND METHODS: We report about a case of a 75-year-old woman presenting with histiocytosis X lesions solely located in the oral cavity. A total dose of 19.5 Gy was administered without any side effects. RESULTS: Two weeks after completion of irradiation a rapid regression of mucosal ulcerations and improvement of symptoms occurred. In a follow-up of 24 months the patient is still in complete remission observed. CONCLUSION: Review of the literature revealed only casuistic reports about solitary lesions of histiocytosis X without bone involvement in the adulthood. External beam radiotherapy with total doses between 10 and 20 Gy seems to be effective for local control of this disease.

CT-based virtual simulation using the AdvantageSim 4.1. system. Description of reliability and accuracy.

BACKGROUND: CT simulation systems provide integration of CT-based planning target volumes, which allows to operate without the conventional simulator. The aim of our study was the quantitative assessment of the accuracy of field alignment and isocenter position using the new virtual simulation system AdvantageSim 4.1. for different treatment regions. PATIENTS AND METHODS: Twenty-seven patients with prostate cancer, 23 patients with head and neck cancer and 30 lung cancer patients were included in this prospective trial. CT-based virtual simulation was performed to define treatment isocenter position. The linear discrepancies of the digitally reconstructed beam's eye views were compared with the conventional simulation and first treatment verification images. RESULTS: Among all patients the mean difference of isocenter position between conventional and virtual simulation was 3.5 mm. The isocenter displacements ranged from 0 to 6 mm. There was no significant difference in isocenter accuracy between the different treatment regions. CONCLUSIONS: Virtual simulation with AdvantageSim 4.1. is feasible in daily routine and allows to replace conventional simulation for different target volumes with a reliable accuracy of isocenter and field alignment. The beam's eye views allow the precise evaluation of the coverage of the planning target volume and the shielding of organs at risk.

Analysis of mdm2 and p53 gene alterations in glioblastomas and its correlation with clinical factors.

Malignant gliomas are the most frequent primary brain tumors. Recent studies defined several genetic markers, which might characterize molecular-biological subsets of glioblastomas with probably prognostic implications. To elucidate the involvement of murine-double-minute (mdm)2 gene amplifications and mutations of the tumor suppressor gene p53 in the tumorigenesis of malignant gliomas we analyzed a series of 75 glioblastomas. The p53 mutations occur in one-third of glioblastomas, mdm2 amplifications were found in 13% of cases. Our analysis revealed a hot spot in the p53 gene locus in codon 156, the same point mutation was detected in 4 tumor samples. None of the mdm2 amplified tumors had p53 mutations, supporting the hypothesis, that mdm2 amplifications are alternative mechanisms for p53 inactivation. Patients with p53 mutated tumors were significantly younger characterized by a mean age of 44 years. Additionally association with longer overall survival could be detected for this subgroup of patients. In our study, survival estimation revealed a significant correlation of mdm2 gene amplification with shorter survival time, and support the hypothesis, that mdm2 oncogene activation appears to occur late in tumor progression and may be characteristic as negative prognostic marker.

On identification of Na(+) channel gating schemes using moving-average filtered hidden Markov models.

Transitions between distinct kinetic states of an ion channel are described by a Markov process. Hidden Markov models (HMM) have been successfully applied in the analysis of single ion channel recordings with a small signal-to-noise ratio. However, we have recently shown that the anti-aliasing low-pass filter misleads parameter estimation. Here, we show for the case of a Na(+) channel recording that the standard HMM do neither allow parameter estimation nor a correct identification of the gating scheme. In particular, the number of closed and open states is determined incorrectly, whereas a modified HMM considering the anti-aliasing filter (moving-average filtered HMM) is able to reproduce the characteristic properties of the time series and to perform gating scheme identification.

UFT plus calcium folinate plus radiotherapy for recurrent rectal cancer.

Uracil and tegafur (in a molar ratio of 4:1 [UFT]) plus calcium folinate comprise the components of the oral agent, Orzel, which appears to have activity comparable to intravenously administered 5-fluorouracil. This article describes the design of an open-label, disease-oriented, phase I trial of UFT plus calcium folinate in combination with simultaneous pelvic radiation for recurrent rectal cancer. This trial is designed to determine the maximum tolerated dose and dose-limiting toxicity of this regimen.

A human muscle Na+ channel mutation in the voltage sensor IV/S4 affects channel block by the pentapeptide KIFMK.

1. Whole cell patch clamping of transfected HEK293 cells was used to examine the effects of a pentapeptide (KIFMK) containing the proposed inactivation particle of the Na+ channel on two mutations causing myotonia. One mutation (R1448P) is located in the voltage sensor IV/S4, and the other one (G1306E) near the postulated inactivation gate within the III-IV linker. 2. In the absence of peptide, currents of wild-type (WT) and mutant human muscle Na+ channels decayed monoexponentially with inactivation time constants that were 5-fold (R1448P) and 3-fold (G1306E) larger for the mutants. Upon intracellular application of KIFMK (0.3-1 mM) the current decay became biexponential with an additional fast decaying component that increased in amplitude with depolarization. 3. Furthermore, the peptide induced large tail currents upon repolarization, indicating that KIFMK prevents inactivation by blocking open Na+ channels. The peak of this tail current decreased only slowly with depolarizations of increasing duration. The voltage dependence of this decline indicated that the dissociation rate of the charged peptide decreased with depolarization. Increased external [Na+] ([Na+]e) antagonized block by KIFMK, consistent with a pore-blocking mechanism. 4. The results are discussed with regard to a three-state model for one open, an absorbing inactivated and one blocked state with voltage-dependent on- and off-rates for peptide binding. The peptide had qualitatively similar effects on WT and both mutants, indicating that the freely diffusible peptide accelerates the current decay in all three clones. However, for the R1448P mutation the affinity for KFIMK was decreased and the voltage dependence of peptide block was changed in a similar way to the voltage dependence of inactivation. These data suggest that the mutation R1448P affects the voltage-dependent formation of a receptor site for both the inactivation particle and KIFMK.

Mitomycin C-related hemolytic uremic syndrome in cancer patients.

In rare cases mitomycin C (MMC) may induce cancer-associated hemolytic uremic syndrome, which is characterized by hemolytic anemia, thrombocytopenia and progressive renal failure. Treatment possibilities of this multisystem disease up to now remain disappointing. We report a case of MMC-related hemolytic uremic syndrome, and discuss the etiologic parameters, clinical aspects, prognosis and treatment modalities of this severe syndrome.

[A remote access system for inquiry of centrally stored data on patients suspected of malignant hyperthermia . A prototypical development for the Internet]. / for the Internet] zur Ermittlung zentral gespeicherter Daten von Patienten mit Verdacht auf Maligne Hyperthermie--Prototypische Entwicklung für das Internet.

OBJECTIVES: Malignant hyperthermia (MH) is an inherited, potentially life-threatening syndrome of the skeletal muscles. It is a life-threatening complication of anaesthesia with a high mortality (8-10%). The risk of the patient during anaesthesia due to an overlooked predisposition for MH can be reduced by organisational measures, such as, all data of MH-susceptible patients and their families known in Germany must be brought together in a central register, MH-relevant data of patients must be readily retrievable, optional oral advice for those making an inquiry must be available. METHODS: To achieve this goal, a client-server system has been implemented: Standard Multimedia personal computers installed at the user's (anaesthetist's) site, linked to the Internet, will act as clients. On a server, relevant data of patients concerning MH-susceptibility are integrated in a central database. The newly developed software of this project ensures the legally prescribed data security on the server and the data routes. At the client's site, standard software together with automatically installed programmes from the server using Java applets ensure easy use and maintenance. IMPLEMENTATION: The total system was implemented and tested. Its functionality and high availability was demonstrated during this test period. Relevant aspects of data security were successfully examined by the data security officer of the University Hospitals of Baden-Württemberg. The user can optionally call a multifunctional teleconference which secures on-line advice if needed. This system demonstrates a safe and quick retrieval of MH relevant data of patients via Internet while at the same time guaranteeing all aspects of data protection and security. CONCLUSION: A prototypical database access system is described. It ensures safe access to patient data via Internet, while guaranteeing all aspects of data security.

Protein kinase C is required for long-lasting synaptic enhancement by the neuropeptide DRNFLRFamide in crayfish.

The FMRFamide-related neuropeptide AspArgAsnPheLeuArgPhe-NH2 (DRNFLRFamide, DF2) induces a long-lasting enhancement of synaptic transmission at neuromuscular junctions on the crayfish deep abdominal extensor muscles. Here we investigated the function of protein kinase C (PKC) in this effect because PKC has been implied in the control of long-term synaptic modulation in other systems. The general kinase antagonist staurosporine reduced both the initial increase in excitatory postsynaptic potential (EPSP) amplitude and the duration of synaptic enhancement. Unlike staurosporine, the selective PKC inhibitors, chelerythrine and bisindolylmaleimide, augmented the initial EPSP increase. However, like staurosporine, they also reduced the duration of synaptic enhancement. The PKC activator, phorbol-12-myristate 13-acetate, induced a long-lasting synaptic enhancement that was blocked by chelerythrine. These results show that synaptic enhancement by DF2 is mediated by different intracellular signaling systems that act in temporal sequence. The initial increase in EPSP amplitudes is negatively regulated by PKC and involves another, staurosporine-sensitive, kinase; whereas, the maintenance of synaptic enhancement requires PKC.

Radiotherapy in the treatment of uterine sarcomas. A retrospective analysis of 54 cases.

BACKGROUND: In the general population, uterine sarcoma (US) is an uncommon tumor, which accounts for approximately 1-3% of all uterine neoplasms. Its biological behavior is characterized by hematogenous metastases and local recurrent growth including the pelvis and peritoneal cavity. In the management of US, surgery is the primary form of treatment. Up to now the role of adjuvant radiotherapy has not been clearly established. PATIENTS AND METHODS: We report about 54 patients with US treated from 1954 to 1994 by surgical resection alone (22) or a combination of surgery and irradiation (32) and evaluate the influence of histology, stage and different treatment options on survival. RESULTS AND CONCLUSIONS: Our data indicate an increased disease-free survival for patients treated with adjuvant radiotherapy, especially if poor prognostic factors are present (advanced tumor stage, histopathological grade II or III of leiomyosarcoma and mixed mesodermal sarcoma). Postoperative irradiation using doses between 50 and 60 Gy is recommended, in selected cases brachytherapy should be added. Prospective multicentric trials including a statistically evaluable number of patients are necessary to further clarify the role of multimodality treatment programs for US.

[The clinical picture and therapy of malignant pleural mesothelioma]. / Klinik und Therapie des malignen Pleuramesothelioms.

BACKGROUND: In the general population malignant pleural mesothelioma is an uncommon tumor with an average annual incidence of 15 cases per million. Its biological behavior is characterized by an infiltrating and aggressive growth. Median survival ranges between 6 and 12 months. There are different therapeutic modalities (surgical treatment, radiotherapy, chemotherapy), which are used alone or in combination to influence the poor outcome of pleural mesothelioma. PATIENTS AND METHODS: We report about 7 of our own cases, treated with surgery and radiotherapy (4) or with a combination of surgery, radiotherapy and chemotherapy (3) and discuss the clinical aspects, diagnosis and the different ways of treatment of malignant pleural mesothelioma and its influence on survival. RESULTS AND CONCLUSION: The extrapleural pleuropneumonectomy should be reserved to patients with stage I disease. Radical operation here offers some prospect of long-term survival. Palliative surgery such as pleurectomy is the treatment of choice for extended disease. Radiotherapy using doses between 45 and 50 Gy is useful in a palliative setting. Anthracyclin or cisplatin based chemotherapy may be helpful in cases with disseminated disease. Prospective trials are necessary to further clarify the role of multimodality treatment programs for malignant pleural mesothelioma.

Pericardial peptides enhance synaptic transmission and tension in phasic extensor muscles of crayfish.

Two identified peptides, which are structurally related to FMRF-NH2 and are known to be associated with lobster pericardial organs, increase nerve-evoked tension and excitatory postsynaptic potentials (EPSPs) recorded from crayfish deep abdominal extensor muscles. At low stimulus frequencies, which produce marked depression of muscle twitches with successive stimuli, the peptides quickly and reversibly restore tension. Increased quantal content of transmitter release, rather than changes in postsynaptic input resistance, accounted for most of the increase in EPSP amplitude. The results support earlier suggestions that these two peptides may act as circulating neurohormones and provide the first evidence for peptidergic modulation of a phasic neuromuscular system in a crustacean.

Characterization and partial purification of different factors with contraction-potentiating activities from neurohaemal organs of the locust.

Phe-Met-Arg-Phe (FMRF-NH2) and structurally related peptides enhance neuromuscular transmission and contraction of the M. extensor tibiae preparations of the locusts Locusta migratoria and Schistocerca gregaria (Walther et al.: Neurosci. Lett. 45:99-104, '84). Similar effects could also be obtained with extracts of locust ganglia (Walther and Schiebe: Neurosci. Lett. 77:209-214, '87). By using two HPLC systems, we have partially purified extracts of the unpaired median nerves (including their neurohaemal organs) of different locust ganglia. The biological activity of the extracts served as an estimate for the degree of purification. Six different bioactive fractions were identified migrating at and close to retention times of known -RFamide peptides with similar bioactivity. No fraction coeluted with authentic FMRF-NH2 or FLRF-NH2. We demonstrate that extensor tibiae muscle contractions were potentiated by HPLC fractions from raw material with -RF-NH2 immunoreactivity, but also by HPLC fractions from raw material without such immunoreactivity.

FMRF-NH2-like factor from neurohaemal organ modulates neuromuscular transmission in the locust.

YGGFMRFamide, FMRFamide and related peptides potentiate transmission at locust slow motor synapses. Since immunohistochemical evidence points to neurohaemal organs (NHO) as potential sources for endogenous RFamide-like peptides we have applied extracts from the metathoracic NHO, equivalent to 1/3 NHO, to the metathoracic extensor tibiae muscle. NHO-extract depolarizes the muscle fibre and increases its membrane resistance; enhances transmitter release; and increases the amplitude of contraction and the rate of relaxation. These effects are in good qualitative and quantitative agreement with those of YGGFMRFamide (5 X 10(-8) to 10(-7) M). Octopamine which partly acts like YGGFMRFamide cannot account for the NHO-effects.

Night-time plasma cortisol secretion is associated with specific sleep stages.

Polysomnographic recordings were obtained in 16 healthy male subjects in order to evaluate temporal interrelationships between concentrations of plasma cortisol and sleep at night. The pattern of nocturnal cortisol secretion appeared to be synchronized with the periodicity of sleep: rapid eye movement (REM) sleep was found to be primarily present when cortisol concentrations were decreasing, indicating a diminished or absent secretory activity of the adrenals at that time; wakefulness and Stage 1 sleep, by contrast, were associated with increasing plasma cortisol concentrations. Furthermore, the enhanced adrenal secretory activity usually preceded the occurrence of light sleep or wakefulness, which is in accord with a wakening effect of plasma cortisol. Just prior to the onset of the first pronounced rise in plasma cortisol during sleep, episodes of slow wave sleep (SWS) became more frequent. This suggests that the offset of episodes of SWS may act as a trigger for the first pronounced nocturnal rise in plasma cortisol.