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41.
Most mechanisms of drugs which are used in brain tumor chemotherapy are well characterized: alkylation of DNA components (nitrosoureas), binding with tubulin protein resulting in metaphase arrest (vincristine), chromatid breaks and chromosome translocations (procarbazine), or inhibition of ribonucleotide reductase (hydroxyurea) [1]. These drugs exert their effects mainly during certain cell cycle phases of proliferating cells, particularly when DNA is synthesized. From this it can be assumed that the efficacy of these drugs depends on the fraction of proliferating cells. Thus it would be of great importance to estimate the proliferation rate of brain tumors which could guide chemotherapy in individual patients. Positron emission tomography (PET) measures quantitatively the in vivo tissue uptake of tracer substances. In tumors, the uptake appears to be altered in a characteristic way determined by biochemical properties of tumor tissue. Some aspects of brain tumor metabolism which are theoretically related to proliferation have been investigated with PET. In the following, the literature is reviewed with regard to: 1) tracer substances whose uptake has been thought to reflect tumor malignancy (11C-methionine, 18F-fluoro-deoxyglucose), and 2) tracers which theoretically could reflect mechanisms specifically related to DNA synthesis (11C-putrescine, ligands for peripheral benzodiazepine receptors).  相似文献   
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A 80-year-old man with cobalamin deficiency and no history of epilepsy developed a partial complex epileptic confusional status (ECS) unresponsive to acute i.v. diazepam. Brain CT scan and MRI investigation ruled out a focal cerebral lesion. Therapy with high doses (10,000 micrograms i.m. daily) of cobalamin alone was started, and the patient fully recovered in the following 72-hour. Control EEGs repeatedly performed days and weeks later showed progressive disappearance of the frontal interictal spiking, while the patient was on monotherapy with cobalamin (5,000 micrograms i.m. weekly). A month later the patient unfortunately discontinued replacement therapy and 13 weeks later he developed a fatal convulsive epileptic status. To our knowledge the association of ECS and cobalamin deficiency has not been previously reported.  相似文献   
44.
We consider the problem of recovering a band-limited signal f(t) from noisy data yk=f(kτ)+≫epsilon/k, where τ is the sampling rate. Starting from the truncated Whittaker-Shannon cardinal expansion with or without sampling windows (both cases yield inconsistent estimates of f(t)) we propose estimators that are convergent to f(t) in the pointwise and uniform sense. The basic idea is to cut down high frequencies in the data and to use suitable oversampling τ⩽π/Ω, Ω being the bandwidth (maximum frequency) of f(t). The simplest estimator we propose is given by fˆn(t)=τ Σ/|t-kτ|⩽nτ yksin(Ω(t-kτ))/π(t-kτ),|t|⩽nτ. Generalizations of fˆn including sampling windows are also examined. The main aim is to examine the mean squared error (MSE) properties of such estimators in order to determine the optimal choice of the sampling rate τ yielding the fastest possible rate of convergence. The best rate for the MSE we obtain is O(In(n)/n)  相似文献   
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PURPOSE: Expression of the multidrug resistance gene (MDR1) p170 protein is frequent in leukemic blasts from patients with relapsed acute myelogenous leukemia (AML). A phase I study using the nonimmunosuppressive MDR1 blocker SDZ PSC-833 (PSC) in combination with mitoxantrone (MITO) and etoposide (VP) was performed. PATIENTS AND METHODS: Starting doses (LVL0) of MITO (3.25 mg/m2/d on days 1 and 3 to 6) and VP (210 mg/m2/d on days 1 and 3 to 5) were 40% of the maximal-tolerated dose (MTD) from a prior study. A 1.5-mg/kg loading dose of PSC was followed by a 120-hour continuous infusion of 10 mg/kg/d on days 2 to 6. Blood samples for PSC, MITO, and VP pharmacokinetics (PK) were taken on days 1 and 3, and samples for MDR1 expression were taken on day 0. RESULTS: Severe mucositis developed in all patients at LVL0; therefore, MITO and VP doses were reduced to 2.5 and 170 mg/m2 (LVL-1) for the next seven patients, and this dose proved to be MTD. All LVL0 and three LVL-1 patients had transient elevations in the serum bilirubin level to > or = 4 mg/dL. Serum creatinine level increased to greater than 2 mg/dL in one case. There were no other grade 3 or 4 nonhematologic toxicities observed. The peripheral blood was cleared of leukemia in three LVL0 and four LVL-1 patients. The marrow was cleared of leukemic cells in one LVL0 and five LVL-1 patients, and a significant reduction in marrow leukemic infiltrate was observed in eight of 10. No patient achieved complete remission (CR), and all died of progressive disease (n = 8) or infection (n = 2). MDR1 expression was detected by fluorescent-activated cell sorter (FACS) analysis in five of seven cases. An elevated MDR1 mRNA level was detected by quantitative polymerase chain reaction (Q-PCR) in six of eight cases studied. Clearing of leukemia cells from the marrow occurred in four of six MDR1-positive and one of three MDR1-negative patients. Despite the fact that LVL0 doses had to be reduced due to toxicity, coadministration of PSC did not produce a consistent effect on MITO PK; however, it did repeatedly lead to increased levels of VP in the serum. CONCLUSION: We conclude that PSC-MITO-VP is a tolerable regimen with antileukemic activity. Addition of PSC necessitated a 66% reduction in MITO and VP doses from a prior study without PSC.  相似文献   
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It is often assumed that blind separation of dynamically mixed sources cannot be done with second-order statistics. It is shown that separation of dynamically mixed sources indeed can be performed using second-order statistics only. A criterion based on second-order statistics for the purpose of separating crosswise mixtures is stated. The criterion is used in order to derive a gradient-based separation algorithm, as well as a Newton-type separation algorithm. The uniqueness of the solution representing the separation is also investigated. This reveals that (1) the channel system is parameter identifiable under weak conditions, and (2) if the sources have the same color, there exists at most two solutions. The local convergence behavior of the proposed algorithm is studied and reveals a sufficient condition for local convergence. Furthermore, the estimates of the channel system are shown to be consistent or to locally minimize the criterion  相似文献   
49.
45 patients with occlusive peripheral vascular disease were examined by MR angiography in a retrospective study. A FISP 3D sequence was used by acquiring a rephased and a dephased data set. The individual slices were post-processed by using a maximum-intensity-projection algorithm. The MRA results of the popliteal and tibioperoneal arteries were compared to conventional or digital angiography. In comparing these techniques MR angiography cannot be accepted for pre- and postoperative staging of patients with occlusive peripheral vascular disease. In future new MRA techniques may be useful in postoperative staging of patients with peripheral vascular stenosis.  相似文献   
50.
Safety, local and systemic immunomodulation, and tumor response to treatment with aerosolized natural interleukin 2 (nIL-2) applied five times a day were studied in a Phase I trial in 16 patients with pulmonary malignancies refractory to conventional therapy. The toxicity of inhaled nIL-2 was different from that observed after systemic administration. Reversible airway irritation causing a nonproductive cough represented the dose-limiting toxicity. Mild to moderate reduction of the vital capacity and forced expiratory volume (FEV1) with minor effects on relative FEV1, peak expiratory flow, airway resistance, and PaO2 was experienced by individual patients. In 14 patients suffering from pulmonary metastases due to renal cell cancer, one durable complete response, one partial response, and one mixed response were observed. Inhalation of nIL-2 aerosol resulted in a dose-dependent expansion of pulmonary immunocompetent cells in bronchoalveolar lavage fluid. Posttreatment bronchoalveolar lavage showed an activated lymphocyte phenotype with increased HLA-DR expression. The only systemic biological effect detectable in peripheral blood was a marked increase of soluble interleukin 2 receptor serum levels. We conclude that treatment with aerosolized nIL-2 is an effective means for site-specific immunomodulation and deserves further investigation for the treatment of malignant and inflammatory lung disease.  相似文献   
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