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Träfflista för sökning "WFRF:(Tabatabaei Pedram) ;spr:eng"

Sökning: WFRF:(Tabatabaei Pedram) > Engelska

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1.
  • Björkblom, Benny, et al. (författare)
  • Metabolic response patterns in brain microdialysis fluids and serum during interstitial cisplatin treatment of high-grade glioma
  • 2020
  • Ingår i: British Journal of Cancer. - : Nature Publishing Group. - 0007-0920 .- 1532-1827. ; 122:2, s. 221-232
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: High-grade gliomas are associated with poor prognosis. Tumour heterogeneity and invasiveness create challenges for effective treatment and use of systemically administrated drugs. Furthermore, lack of functional predictive response-assays based on drug efficacy complicates evaluation of early treatment responses.METHODS: We used microdialysis to deliver cisplatin into the tumour and to monitor levels of metabolic compounds present in the tumour and non-malignant brain tissue adjacent to tumour, before and during treatment. In parallel, we collected serum samples and used multivariate statistics to analyse the metabolic effects.RESULTS: We found distinct metabolic patterns in the extracellular fluids from tumour compared to non-malignant brain tissue, including high concentrations of a wide range of amino acids, amino acid derivatives and reduced levels of monosaccharides and purine nucleosides. We found that locoregional cisplatin delivery had a strong metabolic effect at the tumour site, resulting in substantial release of glutamic acid, phosphate, and spermidine and a reduction of cysteine levels. In addition, patients with long-time survival displayed different treatment response patterns in both tumour and serum. Longer survival was associated with low tumour levels of lactic acid, glyceric acid, ketoses, creatinine and cysteine. Patients with longer survival displayed lower serum levels of ketohexoses, fatty acid methyl esters, glycerol-3-phosphate and alpha-tocopherol, while elevated phosphate levels were seen in both tumour and serum during treatment.CONCLUSION: We highlight distinct metabolic patterns associated with high-grade tumour metabolism, and responses to cytotoxic cisplatin treatment.
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2.
  • Tabatabaei, Pedram, et al. (författare)
  • Bilateral T12 dorsal root ganglion stimulation for the treatment of low back pain with 20-Hz and 4-Hz stimulation : a retrospective study
  • 2024
  • Ingår i: Neuromodulation. - : Elsevier. - 1094-7159 .- 1525-1403. ; 27:1, s. 141-150
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives: Chronic low back pain (CLBP) is one of the most common chronic pain conditions that cause both individual suffering and a burden to society. For these patients, several interventional treatment options such as surgery, blocks, radiofrequency, and spinal cord stimulation are available. Lately, dorsal root ganglion stimulation (DRG-S) also has been mentioned as an option by targeting bilateral T12 dorsal ganglia. In this study, we present the outcome of 11 patients with CLBP treated with bilateral T12 DRG-S.Materials and Methods: Thirteen patients with CLBP with and without leg pain were treated with bilateral T12 DRG-S. Three of the patients also received a third lumbar lead owing to leg pain. Eleven of the patients had >50% pain relief during the peri- or/and postoperative testing and received a fully implantable neurostimulator. Pain intensity, general health status, quality of life, pain catastrophizing, mental status, sleeping disorder, physical activity, and patient satisfaction were followed using numeric rating scale (NRS), Patient-Reported Outcomes Measurement Information System 29 version 2.1, Pain Catastrophizing Score, Generalized Anxiety Disorder 7-item scale, Patient Health Questionnaire Depression Module, Insomnia Severity Index, and Patient Satisfaction Questionnaire at baseline before implantation and at three months and six months. The results were analyzed on the basis of six domains: pain relief, sleeping disorder, social ability, mental status, physical activity, and satisfaction. To be identified as a responder, the patients should show a significant improvement in the pain relief domain together with at least two other domains. All responders also were given the opportunity to test 4-Hz DRG-S and compare it with traditional 20-Hz stimulation.Results: All 11 patients were identified as responders at six months. Five of the patients had >80% pain relief, with an average NRS score reduction of 71% for the whole group. Significant improvement could be observed in three domains for one patient, four domains for three patients, five domains for six patients, and six domains for one patient. Seven patients chose to try 4-Hz stimulation. All seven identified 4-Hz stimulation as at least as good as or better than 20-Hz stimulation and chose to continue with 4-Hz stimulation.Conclusions: Bilateral T12 DRG-S seems to be an effective treatment for chronic low back pain, with significant beneficial effect not only on pain but also on quality of life, pain catastrophizing, mental status, sleeping disorder, and physical activity. 4-Hz DRG-S gave a result comparable with or better than 20-Hz stimulation.
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3.
  • Tabatabaei, Pedram, et al. (författare)
  • Glucose metabolites, glutamate and glycerol in malignant glioma tumours during radiotherapy
  • 2008
  • Ingår i: Journal of Neuro-Oncology. - : Springer. - 0167-594X .- 1573-7373. ; 90:1, s. 35-39
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: The metabolism of malignant glioma was studied in 13 patients. The main objective was to perform a study of the metabolic pattern of glucose, lactate, pyruvate, glutamate and glycerol in tumour tissue during base-line conditions and to detect any changes in the metabolism during radiotherapy.METHOD: During a stereotactic biopsy, two microdialysis catheters were implanted: one in tumour and one in peri-tumoural tissue. Fasting samples were analysed daily, before and during 5 days of radiotherapy given with 2 Gy fractions.RESULTS: Base-line levels of glucose and pyruvate were significantly lower in tumour compared to peri-tumoural tissue (P = 0.04 and 0.023, respectively). The lactate/pyruvate ratio was significantly higher in tumour tissue (P = 0.022). In general, the levels of lactate, glutamate and glycerol were higher in tumour tissue, although not statistically significant. Further, we could not detect any significant changes during the 5 days of radiotherapy in any of the metabolites analysed.CONCLUSION: Radiotherapy up to 10 Gy given in five fractions does not influence the glucose metabolism nor does it induce any acute cytotoxic effect detected with glutamate or glycerol in malignant glioma, as assessed by microdialysis. The study confirms the glycolytic properties of glucose metabolism in malignant glioma.
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4.
  • Tabatabaei, Pedram, et al. (författare)
  • Intratumoral retrograde microdialysis treatment of high-grade glioma with cisplatin
  • 2020
  • Ingår i: Acta Neurochirurgica. - : Springer. - 0001-6268 .- 0942-0940. ; 162:12, s. 3043-3053
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose: This study evaluates the application of a microdialysis technique for interstitial chemotherapy using cisplatin in high-grade glioma.Method: An in vitro study demonstrated that cisplatin can be administered through retrograde microdialysis and defined the recovery for cisplatin. In a subsequent phase I study, 1–4 microdialysis catheters were implanted in tumor tissue, brain adjacent to tumor (BAT) tissue, and subcutaneous tissue in 10 patients with recurrent high-grade glioma. Cisplatin was administered continuously in daily doses between 0.3 and 3.9 mg for 4 to12 days. Microdialysis samples were continuously collected and analyzed for glucose metabolites, glutamate, glycerol, and cisplatin concentrations. Treatment tolerability was evaluated through clinical monitoring. Quality of life was assessed using the EORTC-QLQ-C30 questionnaire for up to 3 months after treatment.Results: This in vitro study showed that cisplatin could be administrated with a recovery of 41–97%, depending on flowrate, type of catheter, and cisplatin concentration. During the treatment, patients were exposed to a total dose of 1.2–36.8 mg cisplatin. The concentration of cisplatin in BAT, serum, and subcutaneous tissue was close to detection level in all but two patients. A transient neurologic deterioration due to edema was commonly observed, but no systemic side effects were recorded. After onset of treatment, concentrations of glutamate and glycerol were significantly increased in tumor tissue but not in BAT, with a peak after 3 days, and consistent for the rest of the treatment. Five of the patients survived between 153 and 492 days after treatment.Conclusion: This phase I study demonstrates that retrograde microdialysis can be used to administer cisplatin interstitially into high-grade glioma tissue. A high cytotoxicity was detected in tumor tissue, but not in the surrounding brain. Retrograde microdialysis appears to be a clinically useful method for intratumoral drug administration in high-grade glioma.
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5.
  • Tabatabaei, Pedram, et al. (författare)
  • Radiotherapy induces an immediate inflammatory reaction in malignant glioma : a clinical microdialysis study
  • 2017
  • Ingår i: Journal of Neuro-Oncology. - : Springer. - 0167-594X .- 1573-7373. ; 131:1, s. 83-92
  • Tidskriftsartikel (refereegranskat)abstract
    • The knowledge of response to radiation in the immuno-microenvironment of high grade gliomas is sparse. In vitro results have indicated an inflammatory response of myeloid cells after irradiation. Therefore, microdialysis was used to verify whether this is operative in tumor tissue and brain adjacent to tumor (BAT) after clinical radiotherapy of patients with high grade glioma. Stereotactic biopsies and implantation of microdialysis catheters in tumor tissue and BAT were performed in eleven patients with high-grade glioma. The patients were given daily radiation fractions of 2-3.4 Gy. Microdialysis samples were collected before radiotherapy and during the first five days of radiation. Cytokines, glucose metabolites, glutamate and glycerol were analyzed. Immunohistochemistry was performed to detect macrophages (CD68) and monocytes (CD163) as well as IL-6, IL-8 and MCP-1. A significant increase of IL-8, MCP-1 and MIP-1a were detected in tumor tissue already after the first dose of radiation and increased further during 5 days of radiation. IL-6 did also increase but after five fractions of radiation. In BAT, the cytokine response was modest with significant increase of IL-8 after third dose of radiation. We found a positive correlation between baseline IL-8 and IL-6 microdialysis levels in tumor tissue and survival. Glucose metabolites or glycerol and glutamate did not change during radiation. In all tumors staining for macrophages was demonstrated. IL-6 was found in viable tumor cells while MCP-1 was demonstrated in macrophages or tumor matrix. Our findings suggest that radiation induces a rapid enhancement of the prevailing inflammation in high-grade glioma tissue. The microdialysis technique is feasible for this type of study and could be used to monitor metabolic changes after different interventions.
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6.
  • Tabatabaei, Pedram, 1978- (författare)
  • Stereotactic microdialysis for metabolic assessment and experimental treatment of malignant glioma
  • 2020
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Glioblastoma multiforme, the most common primary brain tumor, has a dire prognosis despite multimodal treatments that include surgery and radio-chemotherapy. To improve the outcome of this destructive disease, we need to improve our understanding of its tumor biology. Furthermore, the development of new treatment strategies will improve with a better understanding of the interplay between malignant cells and their direct surrounding microenvironment.This thesis aims to increase the understanding of the processes within high-grade glioma and its microenvironment during normal conditions as well as during the distress associated with treatment. Specifically, we have investigated the metabolic response to radiotherapy (study I and II), the immunologic response to radiotherapy (study II), and the metabolic response pattern to loco-regional treatment with cisplatin (study III and IV). Using microdialysis, we collected samples from the extracellular space in both normal brain and tumor tissue during radiotherapy (study I and II) and loco-regional cisplatin treatment (study III and IV). Theses samples were analyzed for glucose metabolites, glycerol, and glutamate (study I, II, and III) and for cytokines (study II). In addition, we analyzed the global metabolism with mass spectrometry to identify and assess the response pattern of malignant glioma cells to loco-regional cisplatin treatment (study IV).In study I and II, we found that malignant glioma cells used glucose at a higher rate than normal cells and preferred glycolysis for glucose metabolism. The given radiation dose (2 Gray (Gy) daily for five days) did not significantly affect glucose metabolism, glycerol levels, or glutamate levels in tumor tissue or the microenvironment. However, in study II, we observed an induced inflammatory effect due to the given radiation dose as several of the cytokines investigated showed significantly increased levels during radiotherapy. In study IV, we observed a complex and strong metabolic response to the loco-regional cisplatin therapy. At baseline, we found a metabolic pattern corresponding well with highly proliferating tumor tissue–i.e., high levels of amino acids, their metabolites, and other metabolic end products and low levels of sugar derivatives, antioxidants, and nucleotides. During the loco-regional therapy, we observed a clearly localized cytotoxic effect within the tumor and a metabolic response pattern corresponding with cisplatin’s complex mechanism of action, affecting several metabolic pathways within the malignant cell. Glutamate and glycerol also increased in tumor tissue following loco-regional treatment, a finding that further supported the observation of local toxicity.In study III, we investigated microdialysis as a method to assess the microenvironment in high-grade glioma and as a method for drug delivery (retrograde microdialysis). All studies demonstrated the usefulness of microdialysis as a tool for in vivo real-time assessment of molecular events in malignant glioma tissue. Although the method is invasive, no complications related to the surgical procedure or assessment were noted. In study III, we also demonstrated that retrograde microdialysis is a feasible method for locally delivering clinically significant doses of drugs such as cisplatin to tumor tissue in the brain. However, in addition to having a cytotoxic effect on tumor cells, cisplatin may induce clinically significant edema.
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7.
  • Tronnier, Volker M., et al. (författare)
  • The appropriate management of persisting pain after spine surgery : a European panel study with recommendations based on the RAND/UCLA method
  • 2019
  • Ingår i: European spine journal. - : Springer. - 0940-6719 .- 1432-0932. ; 28:1, s. 31-45
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose: Management of patients with persisting pain after spine surgery (PPSS) shows significant variability, and there is limited evidence from clinical studies to support treatment choice in daily practice. This study aimed to develop patient-specific recommendations on the management of PPSS.Methods: Using the RAND/UCLA appropriateness method (RUAM), an international panel of 6 neurosurgeons, 6 pain specialists, and 6 orthopaedic surgeons assessed the appropriateness of 4 treatment options (conservative, minimally invasive, neurostimulation, and re-operation) for 210 clinical scenarios. These scenarios were unique combinations of patient characteristics considered relevant to treatment choice. Appropriateness had to be expressed on a 9-point scale (1 = extremely inappropriate, 9 = extremely appropriate). A treatment was considered appropriate if the median score was ≥ 7 in the absence of disagreement (≥ 1/3 of ratings in each of the opposite sections 1–3 and 7–9).Results: Appropriateness outcomes showed clear and specific patterns. In 48% of the scenarios, exclusively one of the 4 treatments was appropriate. Conservative treatment was usually considered appropriate for patients without clear anatomic abnormalities and for those with new pain differing from the original symptoms. Neurostimulation was considered appropriate in the case of (predominant) neuropathic leg pain in the absence of conditions that may require surgical intervention. Re-operation could be considered for patients with recurrent disc, spinal/foraminal stenosis, or spinal instability.Conclusions: Using the RUAM, an international multidisciplinary panel established criteria for appropriate treatment choice in patients with PPSS. These may be helpful to educate physicians and to improve consistency and quality of care.
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