liu.seSök publikationer i DiVA
Ändra sökning
Avgränsa sökresultatet
1 - 10 av 10
RefereraExporteraLänk till träfflistan
Permanent länk
Referera
Referensformat
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • oxford
  • Annat format
Fler format
Språk
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Annat språk
Fler språk
Utmatningsformat
  • html
  • text
  • asciidoc
  • rtf
Träffar per sida
  • 5
  • 10
  • 20
  • 50
  • 100
  • 250
Sortering
  • Standard (Relevans)
  • Författare A-Ö
  • Författare Ö-A
  • Titel A-Ö
  • Titel Ö-A
  • Publikationstyp A-Ö
  • Publikationstyp Ö-A
  • Äldst först
  • Nyast först
  • Skapad (Äldst först)
  • Skapad (Nyast först)
  • Senast uppdaterad (Äldst först)
  • Senast uppdaterad (Nyast först)
  • Disputationsdatum (tidigaste först)
  • Disputationsdatum (senaste först)
  • Standard (Relevans)
  • Författare A-Ö
  • Författare Ö-A
  • Titel A-Ö
  • Titel Ö-A
  • Publikationstyp A-Ö
  • Publikationstyp Ö-A
  • Äldst först
  • Nyast först
  • Skapad (Äldst först)
  • Skapad (Nyast först)
  • Senast uppdaterad (Äldst först)
  • Senast uppdaterad (Nyast först)
  • Disputationsdatum (tidigaste först)
  • Disputationsdatum (senaste först)
Markera
Maxantalet träffar du kan exportera från sökgränssnittet är 250. Vid större uttag använd dig av utsökningar.
  • 1.
    Barranco, Isabel
    et al.
    University of Murcia, Spain.
    Roca, Jordi
    University of Murcia, Spain.
    Tvarijonaviciute, Asta
    University of Murcia, Spain.
    Rubér, Marie
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Medicinska fakulteten.
    Vicente Carrillo, Alejandro
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Hälsouniversitetet.
    Atikuzzaman, Mohammad
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Medicinska fakulteten.
    Ceron, Jose J.
    University of Murcia, Spain.
    Martinez, Emilio A.
    University of Murcia, Spain.
    Rodriguez-Martinez, Heriberto
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Medicinska fakulteten.
    Measurement of Activity and Concentration of Paraoxonase 1 (PON-1) in Seminal Plasma and Identification of PON-2 in the Sperm of Boar Ejaculates2015Ingår i: Molecular Reproduction and Development, ISSN 1040-452X, E-ISSN 1098-2795, Vol. 82, nr 1, s. 58-65Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    This study revealed and characterised the presence of the antioxidant enzymes paraoxonase (PON) type 1 (PON-1, extracellular) and type 2 (PON-2, intracellular) in boar semen. To evaluate PON-1, an entire ejaculate from each of ten boars was collected and the seminal plasma was harvested after double centrifugation (1,500g for 10min). Seminal plasma was analysed for concentration as well as enzymatic activity of PON-1 and total cholesterol levels. Seminal-plasma PON-1 concentration ranged from 0.961 to 1.670ng/ml while its enzymatic activity ranged from 0.056 to 0.400 IU/ml, which represent individual variance. Seminal-plasma PON-1 concentration and enzymatic activity were negatively correlated (r=-0.763; Pless than0.01). The activity of seminal-plasma PON-1 negatively correlated with ejaculate volume (r=-0.726, Pless than0.05), but positively correlated with sperm concentration (r=0.654, Pless than0.05). Total seminal-plasma cholesterol concentration positively correlated with PON-1 activity (r=0.773; Pless than0.01), but negatively correlated with PON-1 concentration (r=-0.709; Pless than0.05). The presence of intracellular PON-2 was determined via immunocytochemistry in spermatozoa derived from artificial insemination. PON-2 localised to the post-acrosomal area of the sperm head and principal piece of the tail in membrane-intact spermatozoa. In summary, PON is present in boar semen, with PON-1 at low levels in seminal plasma and PON-2 within the spermatozoa. Further studies are needed to characterise the relationship between antioxidant PONs with sperm and other seminal-plasma parameters. Mol. Reprod. Dev. 82: 58-65, 2015. (c) 2014 Wiley Periodicals, Inc.

  • 2.
    Ghareh Baghi, Ghareh Baghi
    Linköpings universitet, Institutionen för medicinsk teknik. Linköpings universitet, Tekniska högskolan.
    Assessment of Valvular Aortic Stenosis by Signal Analysis of the Phonocardiogram2014Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    Aortic stenosis (AS) is one of the most prevalent valvular heart diseases in elderly people. According to the recommendations of both the American Heart Association and the European Society of Cardiology, severity assessment of AS is primarily based on echocardiographic findings. The experience of the investigator here play important roles in the accuracy of the assessment, and therefore in the disease management. However, access to the expert physicians could be limited, especially in rural health care centers of developing countries.

    This thesis aims to develop processing algorithms tailored for phonocardiographic signal with the intension to obtain a noninvasive diagnostic tool for AS assessment and severity grading. The algorithms employ a phonocardiogram as input signal and perform analysis for screening and diagnostics. Such a decision support system, which we call “the intelligent phonocardiography”, can be widely used in primary healthcare centers.

    The main contribution of the thesis is to present innovative models for the phonocardiographic analysis by taking the segmental characteristics of the signal into consideration. Three novel methodologies are described, based on the presented models, to perform robust classification. In the first attempt, a novel pattern recognition framework is presented for screening of AS-related murmurs. The framework offers a hybrid model for classifying cyclic time series in general, but is tailored to detect the murmurs as a special case study. The time growing neural network is another method that we use to classify short time signals with abrupt frequency transition. The idea of the growing frames is extended to the cyclic signals with stochastic properties for the screening purposes. Finally, a combined statistical and artificial intelligent classifier is proposed for grading the severity of AS.

    The study suggests comprehensive statistical validations not only for the evaluation and representation of systolic murmurs but also for setting the methodology design parameters, which can be considered as one of the significant features of the study. The resulting methodologies can be implemented by using web and mobile technologies to be utilized in distributed healthcare system.

    Delarbeten
    1. A pattern recognition framework for detecting dynamic changes on cyclic time series
    Öppna denna publikation i ny flik eller fönster >>A pattern recognition framework for detecting dynamic changes on cyclic time series
    2015 (Engelska)Ingår i: Pattern Recognition, ISSN 0031-3203, E-ISSN 1873-5142, Vol. 48, nr 3, s. 696-708Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    This paper proposes a framework for binary classification of the time series with cyclic characteristics. The framework presents an iterative algorithm for learning the cyclic characteristics by introducing the discriminative frequency bands (DFBs) using the discriminant analysis along with k-means clustering method. The DFBs are employed by a hybrid model for learning dynamic characteristics of the time series within the cycles, using statistical and structural machine learning techniques. The framework offers a systematic procedure for finding the optimal design parameters associated with the hybrid model. The proposed  model is optimized to detect the changes of the heart sound recordings (HSRs) related to aortic stenosis. Experimental results show that the proposed framework provides efficient tools for classification of the HSRs based on the heart murmurs. It is also evidenced that the hybrid model, proposed by the framework, substantially improves the classification performance when it comes to detection of the heart disease.

    Ort, förlag, år, upplaga, sidor
    Elsevier, 2015
    Nyckelord
    Hybrid model, cyclic time series, time series, phonocardiogram, systolic murmurs
    Nationell ämneskategori
    Biomedicinsk laboratorievetenskap/teknologi Medicinsk bioteknologi
    Identifikatorer
    urn:nbn:se:liu:diva-110177 (URN)10.1016/j.patcog.2014.08.017 (DOI)000347747000008 ()
    Tillgänglig från: 2014-09-04 Skapad: 2014-09-04 Senast uppdaterad: 2017-12-05Bibliografiskt granskad
    2. Detection of systolic ejection click using time growing neural network
    Öppna denna publikation i ny flik eller fönster >>Detection of systolic ejection click using time growing neural network
    2014 (Engelska)Ingår i: Medical Engineering and Physics, ISSN 1350-4533, E-ISSN 1873-4030, Vol. 36, nr 4, s. 477-483Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    In this paper, we present a novel neural network for classification of short-duration heart sounds: the time growing neural network (TGNN). The input to the network is the spectral power in adjacent frequency bands as computed in time windows of growing length. Children with heart systolic ejection click (SEC) and normal children are the two groups subjected to analysis. The performance of the TGNN is compared to that of a time delay neural network (TDNN) and a multi-layer perceptron (MLP), using training and test datasets of similar sizes with a total of 614 normal and abnormal cardiac cycles. From the test dataset, the classification rate/sensitivity is found to be 97.0%/98.1% for the TGNN, 85.1%/76.4% for the TDNN, and 92.7%/85.7% for the MLP. The results show that the TGNN performs better than do TDNN and MLP when frequency band power is used as classifier input. The performance of TGNN is also found to exhibit better immunity to noise.

    Ort, förlag, år, upplaga, sidor
    Elsevier, 2014
    Nyckelord
    Systolic ejection click; Time growing neural network; Time delay neural network; Heart sound
    Nationell ämneskategori
    Teknik och teknologier
    Identifikatorer
    urn:nbn:se:liu:diva-106865 (URN)10.1016/j.medengphy.2014.02.011 (DOI)000334976800008 ()
    Tillgänglig från: 2014-05-28 Skapad: 2014-05-23 Senast uppdaterad: 2017-12-05
    3. A novel method for discrimination between innocent and pathological heart murmurs
    Öppna denna publikation i ny flik eller fönster >>A novel method for discrimination between innocent and pathological heart murmurs
    2015 (Engelska)Ingår i: Medical Engineering and Physics, ISSN 1350-4533, E-ISSN 1873-4030, Vol. 37, nr 7, s. 674-682Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    This paper presents a novel method for discrimination between innocent and pathological murmurs using the growing time support vector machine (GTSVM). The proposed method is tailored for characterizing innocent murmurs (IM) by putting more emphasis on the early parts of the signal as IMs are often heard in early systolic phase. Individuals with mild to severe aortic stenosis (AS) and IM are the two groups subjected to analysis, taking the normal individuals with no murmur (NM) as the control group. The AS is selected due to the similarity of its murmur to IM, particularly in mild cases. To investigate the effect of the growing time windows, the performance of the GTSVM is compared to that of a conventional support vector machine (SVM), using repeated random sub-sampling method. The mean value of the classification rate/sensitivity is found to be 88%/86% for the GTSVM and 84%/83% for the SVM. The statistical evaluations show that the GTSVM significantly improves performance of the classification as compared to the SVM.

    Ort, förlag, år, upplaga, sidor
    Elsevier, 2015
    Nyckelord
    Growing-time support vector machine, support vector machine, phonocardiogram signal, heart murmurs, innocent murmurs.
    Nationell ämneskategori
    Medicinteknik
    Identifikatorer
    urn:nbn:se:liu:diva-117825 (URN)10.1016/j.medengphy.2015.04.013 (DOI)000357354400007 ()26003286 (PubMedID)
    Anmärkning

    At the time for thesis presentation publication was in status: Manuscript

    Tillgänglig från: 2015-05-08 Skapad: 2015-05-08 Senast uppdaterad: 2017-12-04Bibliografiskt granskad
    4. An Automatic Tool for Pediatric Heart Sounds Segmentation
    Öppna denna publikation i ny flik eller fönster >>An Automatic Tool for Pediatric Heart Sounds Segmentation
    Visa övriga...
    (Engelska)Manuskript (preprint) (Övrigt vetenskapligt)
    Abstract [en]

    In this paper, we present a novel algorithm for pediatric heart sound segmentation, incorporated into a graphical user interface. The algorithm employs both the Electrocardiogram (ECG) and Phonocardiogram (PCG) signals for an efficient segmentation under pathological circumstances.First, the ECG signal is invoked in order to determine the beginning and end points of each cardiac cycle by using wavelet transform technique. Then, first and second heart sounds within the cycles are identified over the PCG signal by paying attention to the spectral properties of the sounds. The algorithm is applied on 120 recordings of normal and pathological children, totally containing 1976 cardiac cycles. The accuracy of the segmentation algorithm is 97% for S1 and 94% for S2 identification while all the cardiac cycles are correctly determined.

    Nationell ämneskategori
    Biomedicinsk laboratorievetenskap/teknologi Medicinsk bioteknologi
    Identifikatorer
    urn:nbn:se:liu:diva-110179 (URN)
    Tillgänglig från: 2014-09-04 Skapad: 2014-09-04 Senast uppdaterad: 2014-09-04Bibliografiskt granskad
    5. Severity assessments of aortic stenosis using intelligent phonocardiography
    Öppna denna publikation i ny flik eller fönster >>Severity assessments of aortic stenosis using intelligent phonocardiography
    Visa övriga...
    (Engelska)Manuskript (preprint) (Övrigt vetenskapligt)
    Abstract [en]

    Objectives: To study capabilities of the intelligent phonocardiography (IPCG) in automatic grading severity of the aortic stenosis (AS).

    Methods: Phonocardiogram signals were recorded from the patients with AS, as diagnosed by echocardiography. The patient group is comprised of signals, recorded from 5 patients (2 recordings from each), mostly elderly referrals (>60 years) with mild to severe AS. An advanced processing algorithm, consisted of the wavelet transform and the stepwise regression analysis, characterizes the systolic murmur caused by the AS in order to predict the 5 indicators; mean pressure gradient over the aortic valve (MPG), maximum jet velocity (MJV), aortic valve area (AVA), velocity time integral and the ejection period. The automatic assessment is performed by an artificial neural network using the predicted values of the indicators as the input data. Reliability of the IPCG is validated by applying repeated random sub-sampling (RRSS) with 70%/30% of the training/testing data, and calculating the accuracy. The RRSS is also employed to validate reproducibility of the IPCG by using 70% of the signals for training and the second recording of the same individuals for  testing.

    Results: Accuracy of the IPCG is estimated to be and (95% confidence interval) for the reliability and the reproducibility, respectively. Linear correlation between the characterized systolic murmur and the MPG (r>0.81), the MJV (r>0.82) and the AVA (r>0.85) is observed.

    Conclusions: The IPCG has the potential to objectively serve as a clinical tool for grading severity of the aortic stenosis.

    Nationell ämneskategori
    Biomedicinsk laboratorievetenskap/teknologi Medicinsk bioteknologi
    Identifikatorer
    urn:nbn:se:liu:diva-110181 (URN)
    Tillgänglig från: 2014-09-04 Skapad: 2014-09-04 Senast uppdaterad: 2014-09-04Bibliografiskt granskad
  • 3.
    Lee, Francis
    Linköpings universitet, Institutionen för tema, Tema teknik och social förändring. Linköpings universitet, Filosofiska fakulteten.
    Purity and interest: on relational work and epistemic value in the biomedical sciences2015Ingår i: Value practice in the life sciences and medicine / [ed] Isabelle Dussauge, Claes-Fredrik Helgesson, Francis Lee, oxford: Oxford University Press, 2015, s. 207-223Kapitel i bok, del av antologi (Refereegranskat)
  • 4.
    Malmström, Annika
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Närsjukvården i centrala Östergötland, LAH Linköping.
    Studies for Better Treatment of Patients with Glioma2019Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    In Sweden annually over 500 people will be diagnosed with the malignant brain tumor glioma. They are graded from I-IV. The majority are glioblastoma (grade IV) (GBM), these being the most aggressive type. Median survival for those treated with standard of care is expected to be around 15 months. This tumor will mainly affect those 60 years or older.

    The studies in this thesis focus on treatment of patients with malignant gliomas grade III and IV. The aim of the studies is to improve the care of glioma patients. Papers I and II explored different therapeutic options in randomized trials, to facilitate individualized treatment recommendations. Findings from studies I and II, together with additional trials, demonstrated the importance of analyzing the tumor marker O6-methylguanine DNA methyltransferase (MGMT) methylation status for survival of GBM patients treated with Temozolomide (TMZ). The third paper investigated how the analysis of this marker is implemented internationally.

    The first study (paper I, Nordic trial) investigated treatment options for patients 60 years or older with GBM. The trial compared standard radiotherapy (SRT) over 6 weeks versus hypofractionated radiotherapy (HRT) over 2 weeks versus single agent TMZ administered in up to six 4 weekly cycles. In all, 342 patients were included in the trial. This study demonstrated that those randomized to TMZ had superior survival as compared to SRT. In addition, quality of life (QoL) data also suggested a better QoL for TMZ treatment than for radiotherapy. The benefit of TMZ treatment seemed to be limited to those with the tumor molecular marker MGMT methylated (inactivated).

    The second trial (paper II, Neoadjuvant trial) studied whether integrating TMZ treatment with SRT for patients younger than 60 years with GBM (grade IV) and astrocytoma grade III would confer a survival benefit, if administered postoperatively, before the start of SRT (neoadjuvant). TMZ was provided for 2-3 four weekly cycles followed by SRT to patients randomized to neoadjuvant treatment and was compared to postoperative SRT alone. Although this trial could not illustrate any advantage of delaying the start of SRT while administering TMZ for the study cohort in general, for those included as astrocytoma grade III the median survival was found to be superior by 5 years when randomized to neoadjuvant TMZ. This trial also confirmed the importance of MGMT promoter methylation for the efficacy of TMZ.

    The third study (paper III) investigated international practices for analyzing tumor MGMT promoter methylation status. MGMT analysis can be conducted by various laboratory methods, which in some cases can provide opposing results regarding the MGMT methylation status of the patient´s tumor. This can lead to incorrect treatment recommendations. To establish which methods and cut-offs that are regularly used to determine tumor MGMT status in the clinic, an international survey was provided to those working in the field. We also inquired about opinions regarding an international consensus on how MGMT should be tested. The 152 respondents reported several methodologies and different cut-off levels also for the same method. A majority of respondents warrant international guidelines.

    In conclusion, the results of the 2 randomized trials contribute to individualized treatment recommendations for patients affected by GBM or astrocytoma grade III. The results of the survey regarding analyses of MGMT clarify the current problematic situation. The request of the respondents regarding international guidelines might contribute to their future development, so that personalized treatment recommendations can be improved.

    Delarbeten
    1. Temozolomide versus standard 6-week radiotherapy versus hypofractionated radiotherapy in patients older than 60 years with glioblastoma: the Nordic randomised, phase 3 trial
    Öppna denna publikation i ny flik eller fönster >>Temozolomide versus standard 6-week radiotherapy versus hypofractionated radiotherapy in patients older than 60 years with glioblastoma: the Nordic randomised, phase 3 trial
    Visa övriga...
    2012 (Engelska)Ingår i: The Lancet Oncology, ISSN 1470-2045, E-ISSN 1474-5488, Vol. 13, nr 9, s. 916-926Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    Background Most patients with glioblastoma are older than 60 years, but treatment guidelines are based on trials in patients aged only up to 70 years. We did a randomised trial to assess the optimum palliative treatment in patients aged 60 years and older with glioblastoma. less thanbrgreater than less thanbrgreater thanMethods Patients with newly diagnosed glioblastoma were recruited from Austria, Denmark, France, Norway, Sweden, Switzerland, and Turkey. They were assigned by a computer-generated randomisation schedule, stratified by centre, to receive temozolomide (200 mg/m(2) on days 1-5 of every 28 days for up to six cycles), hypofractionated radiotherapy (34.0 Gy administered in 3.4 Gy fractions over 2 weeks), or standard radiotherapy (60.0 Gy administered in 2.0 Gy fractions over 6 weeks). Patients and study staff were aware of treatment assignment. The primary endpoint was overall survival. Analyses were done by intention to treat. This trial is registered, number ISRCTN81470623. less thanbrgreater than less thanbrgreater thanFindings 342 patients were enrolled, of whom 291 were randomised across three treatment groups (temozolomide n=93, hypofractionated radiotherapy n=98, standard radiotherapy n=100) and 51 of whom were randomised across only two groups (temozolomide n=26, hypofractionated radiotherapy n=25). In the three-group randomisation, in comparison with standard radiotherapy, median overall survival was significantly longer with temozolomide (8.3 months [95% CI 7.1-9.5; n=93] vs 6.0 months [95% CI 5.1-6.8; n=100], hazard ratio [HR] 0.70; 95% CI 0.52-0.93, p=0.01), but not with hypofractionated radiotherapy (7.5 months [6.5-8.6; n=98], HR 0.85 [0.64-1.12], p=0.24). For all patients who received temozolomide or hypofractionated radiotherapy (n=242) overall survival was similar (8.4 months [7.3-9.4; n=119] vs 7.4 months [6.4-8.4; n=123]; HR 0.82, 95% CI 0.63-1.06; p=0.12). For age older than 70 years, survival was better with temozolomide and with hypofractionated radiotherapy than with standard radiotherapy (HR for temozolomide vs standard radiotherapy 0.35 [0.21-0.56], pandlt;0.0001; HR for hypofractionated vs standard radiotherapy 0.59 [95% CI 0.37-0.93], p=0.02). Patients treated with temozolomide who had tumour MGMT promoter methylation had significantly longer survival than those without MGMT promoter methylation (9.7 months [95% CI 8.0-11.4] vs 6.8 months [5.9-7.7]; HR 0.56 [95% CI 0.34-0.93], p=0.02), but no difference was noted between those with methylated and unmethylated MGMT promoter treated with radiotherapy (HR 0.97 [95% CI 0.69-1.38]; p=0.81). As expected, the most common grade 3-4 adverse events in the temozolomide group were neutropenia (n=12) and thrombocytopenia (n=18). Grade 3-5 infections in all randomisation groups were reported in 18 patients. Two patients had fatal infections (one in the temozolomide group and one in the standard radiotherapy group) and one in the temozolomide group with grade 2 thrombocytopenia died from complications after surgery for a gastrointestinal bleed. less thanbrgreater than less thanbrgreater thanInterpretation Standard radiotherapy was associated with poor outcomes, especially in patients older than 70 years. Both temozolomide and hypofractionated radiotherapy should be considered as standard treatment options in elderly patients with glioblastoma. MGMT promoter methylation status might be a useful predictive marker for benefit from temozolomide.

    Ort, förlag, år, upplaga, sidor
    Elsevier, 2012
    Nationell ämneskategori
    Medicin och hälsovetenskap
    Identifikatorer
    urn:nbn:se:liu:diva-84333 (URN)10.1016/S1470-2045(12)70265-6 (DOI)000308425600019 ()
    Anmärkning

    Funding Agencies|Merck||Lions Cancer Research Foundation||University of Umea||Swedish Cancer Society||Schering-Plough||University of Umea, Sweden||Cancer Fonden, Sweden||

    Tillgänglig från: 2012-10-05 Skapad: 2012-10-05 Senast uppdaterad: 2019-11-06
    2. Postoperative neoadjuvant temozolomide before radiotherapy versus standard radiotherapy in patients 60 years or younger with anaplastic astrocytoma or glioblastoma: a randomized trial
    Öppna denna publikation i ny flik eller fönster >>Postoperative neoadjuvant temozolomide before radiotherapy versus standard radiotherapy in patients 60 years or younger with anaplastic astrocytoma or glioblastoma: a randomized trial
    Visa övriga...
    2017 (Engelska)Ingår i: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 56, nr 12, s. 1776-1785Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    Introduction: A pilot study of temozolomide (TMZ) given before radiotherapy (RT) for anaplastic astrocytoma (AA) and glioblastoma (GBM) resulted in prolonged survival compared to historical controls receiving RT alone. We therefore investigated neoadjuvant TMZ (NeoTMZ) in a randomized trial. During enrollment, concomitant and adjuvant radio-chemotherapy with TMZ became standard treatment. The trial was amended to include concurrent TMZ.Patients and methods: Patients, after surgery for GBM or AA, age 60 years and performance status (PS) 0-2, were randomized to either 2-3 cycles of TMZ, 200mg/m(2) days 1-5 every 28 days, followed by RT 60Gy in 30 fractions or RT only. Patients without progressive disease after two TMZ cycles, received the third cycle. From March 2005, TMZ 75mg/m(2) was administered daily concomitant with RT. TMZ was recommended first-line treatment at progression. Primary endpoint was overall survival and secondary safety.Results: The study closed prematurely after enrolling 144 patients, 103 with GBM and 41 with AA. Median age was 53 years (range 24-60) and 89 (62%) were male. PS was 0-1 for 133 (92%) patients, 53 (37%) had complete surgical resection and 18 (12%) biopsy. Ninety-two (64%) received TMZ concomitant with RT. Seventy-two (50%) were randomized to neoadjuvant treatment. For the overall study population survival was 20.3 months for RT and 17.7 months for NeoTMZ (p=.76), this not reaching the primary objective. For the preplanned subgroup analysis, we found that NeoTMZ AA patients had a median survival of 95.1 months compared to 35.2 months for RT (p=.022). For patients with GBM, no difference in survival was observed (p=.10). MGMT and IDH status affected outcome.Conclusions: No advantage of NeoTMZ was noted for the overall study population or subgroup of GBM, while NeoTMZ resulted in 5 years longer median survival for patients diagnosed as AA.

    Ort, förlag, år, upplaga, sidor
    TAYLOR & FRANCIS LTD, 2017
    Nationell ämneskategori
    Kirurgi
    Identifikatorer
    urn:nbn:se:liu:diva-144005 (URN)10.1080/0284186X.2017.1332780 (DOI)000418118800016 ()28675067 (PubMedID)
    Anmärkning

    Funding Agencies|Merck; Linkoping University Hospital for Neuro-research; Lions Cancer Foundation; Cancer Foundation Norrland, Umea, Sweden; LIUCancer; South-East Sweden FORSS

    Tillgänglig från: 2018-01-02 Skapad: 2018-01-02 Senast uppdaterad: 2019-11-06
    3. Do we really know who has an MGMT methylated glioma?: Results of an international survey regarding use of MGMT analyses for glioma
    Öppna denna publikation i ny flik eller fönster >>Do we really know who has an MGMT methylated glioma?: Results of an international survey regarding use of MGMT analyses for glioma
    Visa övriga...
    2019 (Engelska)Ingår i: Neuro-Oncology Practice, ISSN 2054-2577, s. 1-9Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    Glioma O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation status informs clinical decision making. Worldwide different methods and cutoff levels are used, which can lead to discordant methylation results.We conducted an international survey to clarify which methods are regularly used and why. We also explored opinions regarding international consensus on methods and cutoff.The survey had 152 respondents from 25 countries. MGMT methylation status is determined for all glioblastomas in 37% of laboratories. The most common methods are methylation-specific polymerase chain reaction (msPCR) (37%) and pyrosequencing (34%). A method is selected for simplicity (56%), cost-effectiveness (50%), and reproducibility of results (52%). For sequencing, the number of CpG sites analyzed varies from 1–3 up to more than 16. For 50% of laboratories, the company producing the kit determines which CpG sites are examined, whereas 33% select the sites themselves. Selection of cutoff is equally distributed among a cutoff defined in the literature, by the local laboratory, or by the outside laboratory performing the analysis. This cutoff varies, reported from 1% to 30%, and in 1 laboratory tumor is determined as methylated in case of 1 methylated CpG site of 17 analyzed. Some report tumors as unmethylated or weakly vs highly methylated. An international consensus on MGMT methylation method and cutoff is warranted by 66% and 76% of respondents, respectively. The method preferred would be msPCR (45%) or pyrosequencing (42%), whereas 18% suggest next-generation sequencing.Although analysis of MGMT methylation status is routine, there is controversy regarding laboratory methods and cutoff level. Most respondents favor development of international consensus guidelines.

    Ort, förlag, år, upplaga, sidor
    Oxford: Oxford University Press, 2019
    Nationell ämneskategori
    Medicinsk biovetenskap Klinisk laboratoriemedicin
    Identifikatorer
    urn:nbn:se:liu:diva-160808 (URN)10.1093/nop/npz039 (DOI)
    Tillgänglig från: 2019-10-09 Skapad: 2019-10-09 Senast uppdaterad: 2019-11-06Bibliografiskt granskad
  • 5.
    Malmström, Annika
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten.
    Lysiak, Malgorzata
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten.
    Winther Kristensen, Bjarne
    Department of Pathology, Odense University Hospital, Institute of Clinical Research, University of Southern Denmark, Denmark.
    Hovey, Elizabeth
    Department of Medical Oncology, Nelune Comprehensive Cancer Centre, Prince of Wales Hospital , Randwick, Sydney, NSW, Australia University of New South Wales , Sydney, Australia.
    Henriksson, Roger
    Department of Radiation Sciences, University of Umeå , Sweden.
    Söderkvist, Peter
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten.
    Do we really know who has an MGMT methylated glioma?: Results of an international survey regarding use of MGMT analyses for glioma2019Ingår i: Neuro-Oncology Practice, ISSN 2054-2577, s. 1-9Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Glioma O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation status informs clinical decision making. Worldwide different methods and cutoff levels are used, which can lead to discordant methylation results.We conducted an international survey to clarify which methods are regularly used and why. We also explored opinions regarding international consensus on methods and cutoff.The survey had 152 respondents from 25 countries. MGMT methylation status is determined for all glioblastomas in 37% of laboratories. The most common methods are methylation-specific polymerase chain reaction (msPCR) (37%) and pyrosequencing (34%). A method is selected for simplicity (56%), cost-effectiveness (50%), and reproducibility of results (52%). For sequencing, the number of CpG sites analyzed varies from 1–3 up to more than 16. For 50% of laboratories, the company producing the kit determines which CpG sites are examined, whereas 33% select the sites themselves. Selection of cutoff is equally distributed among a cutoff defined in the literature, by the local laboratory, or by the outside laboratory performing the analysis. This cutoff varies, reported from 1% to 30%, and in 1 laboratory tumor is determined as methylated in case of 1 methylated CpG site of 17 analyzed. Some report tumors as unmethylated or weakly vs highly methylated. An international consensus on MGMT methylation method and cutoff is warranted by 66% and 76% of respondents, respectively. The method preferred would be msPCR (45%) or pyrosequencing (42%), whereas 18% suggest next-generation sequencing.Although analysis of MGMT methylation status is routine, there is controversy regarding laboratory methods and cutoff level. Most respondents favor development of international consensus guidelines.

    Publikationen är tillgänglig i fulltext från 2020-09-25 08:00
  • 6.
    Nyman, Erika
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Hälsouniversitetet. Region Östergötland, Sinnescentrum, Hand- och plastikkirurgiska kliniken US.
    Guided Regeneration of the Human Skin: in vitro and in vivo studies2015Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    Every day and in all parts of the world, humans experience different grades of wounding and tissue loss of the skin, thus initiating one of the most complex biological processes. Acute and chronic wounds, as well as the additional problem of skin scarring, involve not only great suffering for the patient but also extensive health care costs for the society. Although the wound-healing process is a wellstudied field much knowledge must be gained to unlock the door to regenerative pathways in humans.

    Epidermis heals by complete regeneration, but dermal and full thickness injuries heal with fibrosis and scar formation. In Papers I and II, we studied whether dermal scarring could be turned into regeneration by using two different types of threedimensional dermal scaffolds. In Paper I, we studied a solid scaffold made of poly(urethane urea), initially in vitro then followed by in vivo studies. In Paper II, we intradermally injected a liquid three-dimensional scaffold consisting of porous gelatin spheres in human healthy volunteers. Both materials showed ingrowth of functional fibroblasts and blood vessels and appeared to stimulate regeneration while slowly degrading. This finding could be of significant clinical importance, for example in burn wound care or after cancer surgery.

    In Papers III and IV, we wanted to study the effects of amniotic fluid and hyaluronic acid on adult wound healing, because early fetal wounds re-epithelialize rapidly and naturally heal dermis by regeneration without the need of a dermal scaffold. Amniotic fluid, naturally rich in hyaluronic acid, induced an accelerated reepithelialization of adult human wounds in vitro, and hyaluronic acid seemed to be important for this effect. Stimulation with exogenous hyaluronic acid in vivo induced accelerated re-epithelialization and an altered protein expression in healthy human volunteers. The inflammatory phase of wound healing, as measured by tissue viability imaging, was not affected by hyaluronic acid. Elucidating the effects of amniotic fluid and hyaluronic acid on the wound-healing process may allow improved treatment of wounds with impaired healing.

    Studies on finding new dermal scaffolds and studies on the positive effect of amniotic fluid or hyaluronic acid on the wound-healing process are two different ways of gaining insight that may lead to regeneration and improved wound healing for the patient.

    Delarbeten
    1. Characterisation of a new degradable polymer scaffold for regeneration of the dermis: In vitro and in vivo human studies
    Öppna denna publikation i ny flik eller fönster >>Characterisation of a new degradable polymer scaffold for regeneration of the dermis: In vitro and in vivo human studies
    Visa övriga...
    2008 (Engelska)Ingår i: Organogenesis, ISSN 1547-6278, Vol. 4, nr 3, s. 195-200Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    Full thickness skin wounds in humans heal with scars, but without regeneration of the dermis. A degradable poly(urethane urea) scaffold (PUUR), Artelon® is already used to reinforce soft tissues in orthopaedics, and for treatment of osteoarthritis of the hand, wrist and foot. In this paper we have done in vitro experiments followed by in vivo studies to find out whether the PUUR is biocompatible and usable as a template for dermal regeneration. Human dermal fibroblasts were cultured on discs of PUUR, with different macrostructures (fibrous and porous). They adhered to and migrated into the scaffolds, and produced collagen. The porous scaffold was judged more suitable for clinical applications and 4 mm Ø, 2 mm-thick discs of porous scaffold (12% w/w or 9% w/w polymer solution) were inserted intradermally in four healthy human volunteers. The implants were well tolerated and increasing ingrowth of fibroblasts was seen over time in all subjects. The fibroblasts stained immunohistochemically for procollagen and von Willebrand factor, indicating neocollagenesis and angiogenesis within the scaffolds. The PUUR scaffold may be a suitable material to use as a template for dermal regeneration. ©2008 Landes Bioscience.

    Nationell ämneskategori
    Medicin och hälsovetenskap
    Identifikatorer
    urn:nbn:se:liu:diva-44440 (URN)76642 (Lokalt ID)76642 (Arkivnummer)76642 (OAI)
    Tillgänglig från: 2009-10-10 Skapad: 2009-10-10 Senast uppdaterad: 2015-03-17Bibliografiskt granskad
    2. Use of macroporous gelatine spheres as a biodegradable scaffold for guided tissue regeneration of healthy dermis in humans: An in vivo study
    Öppna denna publikation i ny flik eller fönster >>Use of macroporous gelatine spheres as a biodegradable scaffold for guided tissue regeneration of healthy dermis in humans: An in vivo study
    2010 (Engelska)Ingår i: Journal of Plastic, Reconstructive & Aesthetic Surgery, ISSN 1748-6815, E-ISSN 1532-1959, Vol. 63, nr 5, s. 848-857Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    If a biodegradable scaffold is applied, the dermis can be regenerated by guided tissue regeneration. Scaffolds can stimulate in-growth of cells from the surroundings that migrate into them and start to produce autologous extracellular matrix as the scaffold is degraded. Several materials are available, but most of them are in the form of sheets and need to be laid on an open wound surface. A number of injectable fillers have been developed to correct soft-tissue defects. However, none of these has been used for guided tissue regeneration. We present a new technique that could possibly be used to correct dermal defects by using macroporous gelatine spheres as a biodegradable scaffold for guided tissue regeneration. In eight healthy volunteers, intradermal injections of macroporous gelatine spheres were compared with injections of saline and hyaluronic acid (Restylane (R)). Full-thickness skin biopsy specimens of the implants and surrounding tissue were removed 2, 8, 12 and 26 weeks after injection, and the (immuno) histological results were analysed. The Restylane (R) merely occupied space. It shattered the dermal tissue and compressed collagen fibres and cells at the interface between the implant and the dermis. No regeneration of tissue was found with this material at any time. The macroporous gelatine spheres were populated with fibroblasts already after 2 weeks. After 8 weeks the spheres were completely populated by fibroblasts producing dermal tissue. After 12 and 26 weeks, the gelatine spheres had been more or less completely resorbed and replaced by vascularised neodermis. There were no signs of capsular formation, rejection or adverse events in any subject. Further in vivo studies in humans are needed to evaluate the effect of the macroporous spheres fully as a matrix for guided tissue regeneration with and without cellular pre-seeding. However, the results of this study indicate the possibility of using macroporous gelatine spheres as an injectable, three-dimensional, degradable matrix for guided tissue regeneration.

    Ort, förlag, år, upplaga, sidor
    Elsevier Science B.V.amsterdam, 2010
    Nyckelord
    Filler, Soft-tissue defect, Guided tissue regeneration, Tissue engineering, Plastic surgery, Human
    Nationell ämneskategori
    Medicin och hälsovetenskap
    Identifikatorer
    urn:nbn:se:liu:diva-54859 (URN)10.1016/j.bjps.2009.01.068 (DOI)000276199700021 ()
    Tillgänglig från: 2010-04-16 Skapad: 2010-04-16 Senast uppdaterad: 2017-12-12Bibliografiskt granskad
    3. Hyaluronic acid, an important factor in the wound healing properties of amniotic fluid: In vitro studies of re-epithelialisation in human skin wounds
    Öppna denna publikation i ny flik eller fönster >>Hyaluronic acid, an important factor in the wound healing properties of amniotic fluid: In vitro studies of re-epithelialisation in human skin wounds
    Visa övriga...
    2013 (Engelska)Ingår i: Scandinavian Journal of Plastic and Reconstructive Surgery and Hand Surgery, ISSN 2000-656X, E-ISSN 2000-6764, Vol. 47, nr 2, s. 89-92Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    Foetal wounds are unique in their ability to heal rapidly without forming scars. The amniotic fluid, rich in nutrients, growth factors, and hyaluronic acid, surrounds the foetus and is essential to foetal wound healing. The wound healing properties of foetal wounds may be the result of high concentrations of hyaluronic acid. This study aimed to verify that amniotic fluid induces re-epithelialisation in human skin wounds in vitro and to study whether this ability is dependent on hyaluronic acid. Standard deep dermal wounds were produced in vitro in human skin. The skin samples, with a central wound, were incubated in different culture media. Varying concentrations of amniotic fluid and amniotic fluid with added hyaluronidase were tested, and re-epithelialisation was assessed at 3, 7, and 12 days using light microscopy, after staining with haematoxylin and eosin. Amniotic fluid 50% resulted in a significantly higher (p andlt; 0.05) grade of re-epithelialisation than Dulbeccos modified Eagles medium and 10% amniotic fluid at all time points. When 50% amniotic fluid was compared with 10% foetal calf serum, no significant difference was found in grades of re-epithelialisation on days 3 and 12 and significantly higher grades of re-epithelialisation on day 7 (p andlt; 0.05). Degradation of hyaluronic acid in the medium that contained 50% amniotic fluid gave significantly impaired re-epithelialisation (p andlt; 0.05) on culture days 3 and 7. In conclusion, amniotic fluid promotes accelerated re-epithelialisation and hyaluronic acid is an important ingredient.

    Ort, förlag, år, upplaga, sidor
    Informa Healthcare, 2013
    Nyckelord
    Amniotic fluid, fibroblasts, human, hyaluronic acid, hyaluronidase, in vitro, keratinocytes, wound healing
    Nationell ämneskategori
    Medicin och hälsovetenskap
    Identifikatorer
    urn:nbn:se:liu:diva-91006 (URN)10.3109/2000656X.2012.733169 (DOI)000316362300002 ()
    Anmärkning

    Funding Agencies|Swedish Fund for Research without Animal Experiments||

    Tillgänglig från: 2013-04-11 Skapad: 2013-04-11 Senast uppdaterad: 2019-01-07Bibliografiskt granskad
    4. Exogenous hyaluronic acid induces accelerated re-epithelialization and altered protein expression in adult human skin wounds in vivo
    Öppna denna publikation i ny flik eller fönster >>Exogenous hyaluronic acid induces accelerated re-epithelialization and altered protein expression in adult human skin wounds in vivo
    Visa övriga...
    (Engelska)Manuskript (preprint) (Övrigt vetenskapligt)
    Abstract [en]

    Background

    Hyaluronic acid, a large glycosaminoglycan involved in proliferation, migration, and tissue repair, is suggested to play an important role in ideal scarless fetal wound healing. This study aimed to investigate the effect of exogenous hyaluronic acid intradermal during deep dermal wound healing. Study parameters were erythema, re-epithelialization, and protein expression examined by using a previously described, minimally invasive in vivo human wound model in combination with tissue viability imaging, histology, and proteomics.

    Methods

    Standardized deep dermal wounds were created in the ventral forearm in ten healthy volunteers using blood collection lancets. The wound sites were injected with hyaluronic acid or saline solution, prior to wounding, or were left untreated. To quantify changes in red blood cell concentration as a measurement of inflammation, the study sites were photographed daily for two weeks using a tissue viability imaging system. At 24 hours and after 14 days, biopsy specimens were taken for histology and proteomics analysis.

    Results

    The inflammatory response was not affected by the injection of hyaluronic acid, as measured by tissue viability imaging. Hyaluronic acid significantly induced (p < 0.05) accelerated reepithelialization at 24 hours, and wounds treated with hyaluronic acid showed an altered protein expression.

    Conclusion

    The results from the present study are in concordance with  previous in vitro findings and suggest that exogenous hyaluronic acid has a  positive effect on the healing process of cutaneous wounds. We conclude that hyaluronic acid injected intradermally induces accelerated re-epithelialization and alters protein expression in vivo in human deep dermal skin wounds.

    Nyckelord
    Hyaluronic acid, hyaluronan, hyaluronate, Amniotic fluid, Wound healing, Human wound model, In vivo, Tissue viability imaging, Protein expression, proteomics
    Nationell ämneskategori
    Medicinsk bioteknik Cell- och molekylärbiologi
    Identifikatorer
    urn:nbn:se:liu:diva-115593 (URN)
    Tillgänglig från: 2015-03-17 Skapad: 2015-03-17 Senast uppdaterad: 2018-10-08Bibliografiskt granskad
  • 7.
    Wårdell, Karin
    et al.
    Linköpings universitet, Institutionen för medicinsk teknik. Linköpings universitet, Tekniska högskolan.
    Kefalopoulou, Zinovia
    Unit of Functional Neurosurgery, Institute of Neurology, University College London, London, UK.
    Diczfalusy, Elin
    Linköpings universitet, Institutionen för medicinsk teknik, Biomedicinsk instrumentteknik. Linköpings universitet, Tekniska högskolan.
    Andersson, Mats
    Linköpings universitet, Institutionen för medicinsk teknik. Linköpings universitet, Centrum för medicinsk bildvetenskap och visualisering, CMIV. Linköpings universitet, Tekniska högskolan.
    Åström, Mattias
    Linköpings universitet, Institutionen för medicinsk teknik. Linköpings universitet, Tekniska högskolan.
    Limousin, Patricia
    Unit of Functional Neurosurgery, Institute of Neurology, University College London, London, UK.
    Zrinzo, Ludvic
    Unit of Functional Neurosurgery, Institute of Neurology, University College London, London, UK.
    Hariz, Marwan
    Unit of Functional Neurosurgery, Institute of Neurology, University College London, London, UK / Department of Clinical Neuroscience, Umeå University, Umeå, Sweden.
    Deep Brain Stimulation of the Pallidum Internum for Gilles de la Tourette Syndrome: A Patient-Specific Model-Based Simulation Study of the Electric Field2015Ingår i: Neuromodulation (Malden, Mass.), ISSN 1094-7159, E-ISSN 1525-1403, nr 2, s. 90-96Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objectives

    The aim of this study was to investigate the deep brain stimulation (DBS) electric field distribution in proton-density MRI scans visualizing the globus pallidus internus (GPi) of patients with Gilles de la Tourette syndrome (GTS), along with its relation to the anatomy.

    Methods

    Patient-specific brain tissue models (n = 7) with bilateral DBS electrodes in the GPi were set up using the finite element method in five patients who had undergone stereotactic proton-density MRI-guided surgery and showed variable improvement with DBS. Simulations (n = 27) of the electric field were performed and the results visualized on the respective preoperative stereotactic MRI scans. The mean electric field volumes (n = 81) within the 0.1, 0.15, and 0.2 V/mm isosurfaces were calculated and compared with the anatomy.

    Results

    Visualization of the simulated electric field confirmed that the anteromedial limbic GPi was the main stimulated target for four of the patients and the posteromedial sensorimotor GPi for one. Larger volumes extended asymmetrically, with parts of fields stretching into the lamina between GPi and globus pallidus externus and into the internal capsule. There was a high correlation (r = 0.994, n = 54) between volumes and brain sides, but with a systematic shift toward the right side, especially for the larger volumes. Simulations with homogeneous tissue models showed no differences.

    Conclusions

    Patient-specific DBS electric field simulations in the GPi as visualized on proton-density MR scans can be implemented in patients with GTS. Visualization of electric fields together with stereotactic thin-slice MRI can provide further support when predicting anatomical structures possibly influenced by DBS in this complex disorder.

  • 8.
    Zsigmond, Peter
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neurovetenskap. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Sinnescentrum, Neurokirurgiska kliniken US.
    Nord, Maria
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neurovetenskap. Linköpings universitet, Hälsouniversitetet.
    Kullman, Anita
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Hälsouniversitetet.
    Diczfalusy, Elin
    Linköpings universitet, Institutionen för medicinsk teknik, Biomedicinsk instrumentteknik. Linköpings universitet, Tekniska högskolan.
    Wårdell, Karin
    Linköpings universitet, Institutionen för medicinsk teknik. Linköpings universitet, Tekniska högskolan. Linköpings universitet, Centrum för medicinsk bildvetenskap och visualisering, CMIV.
    Dizdar (Dizdar Segrell), Nil
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neurovetenskap. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Närsjukvården i centrala Östergötland, Neurologiska kliniken.
    Neurotransmitter levels in basal ganglia during levodopa and deep brain stimulation treatment in Parkinson’s disease2014Ingår i: Neurology and Clinical Neuroscience, ISSN 2049-4173, Vol. 2, nr 5, s. 149-155Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background The mechanism by which deep brain stimulation of the nucleus subthalamicus improves Parkinson’s disease symptoms remains unclear. In a previous perioperative study, we showed that there might be alterations of neurotransmitter levels in the globus pallidum interna during deep brain stimulation of the nucleus subthalamicus. Aim In this study, we examined whether deep brain stimulation of the nucleus subthalamicus and levodopa infusion interact and affect the levels of neurotransmitters. Methods Five patients with advanced Parkinson’s disease took part in the study. During subthalamic nucleus surgery, microdialysis catheters were inserted bilaterally in the globus pallidum interna and unilaterally in the right putamen. A study protocol was set up and was followed for 3 days. Levodopa infusion with and without concomitant bilateral deep brain stimulation of the nucleus subthalamicus was also carried out. Results The putaminal dopamine levels increased during deep brain stimulation of the nucleus subthalamicus. In addition, an increase of gamma amino buturic acid concentrations in the globus pallidum interna during deep brain stimulation of the nucleus subthalamicus and during levodopa infusion was found. Conclusions These findings provide evidence that the subthalamic nucleus has a direct action on the substantia nigra pars compacta, and that deep brain stimulation of the nucleus subthalamicus might indirectly release putaminal dopamine. There is also evidence that deep brain stimulation of the nucleus subthalamicus interferes with levodopa therapy resulting in higher levels of levodopa in the brain, explaining why it is possible to decrease levodopa medication after deep brain stimulation surgery.

  • 9.
    Zuiderent-Jerak, Teun
    et al.
    Linköpings universitet, Institutionen för tema, Tema teknik och social förändring. Linköpings universitet, Filosofiska fakulteten.
    Grit, Kor
    Department of Health Policy and Management, Erasmus University, Rotterdam.
    Grinten, Tom van der
    Department of Health Policy and Management, Erasmus University, Rotterdam.
    Critical composition of public values: on the enactment and disarticulation of what counts in health-care markets2015Ingår i: Value practices in the life sciences and medicine / [ed] Isabelle Dussauge, Claes-Fredrik Helgesson, Francis Lee, Oxford: Oxford University Press, 2015, s. 119-135Kapitel i bok, del av antologi (Refereegranskat)
  • 10.
    Åström, Mattias
    et al.
    Linköpings universitet, Institutionen för medicinsk teknik. Linköpings universitet, Tekniska högskolan. Sapiens Steering Brain Stimulation BV, NL-5656 Eindhoven, Netherlands.
    Diczfalusy, Elin
    Linköpings universitet, Institutionen för medicinsk teknik. Linköpings universitet, Tekniska högskolan.
    Martens, Hubert
    Sapiens Steering Brain Stimulation B.V., Eindhoven, The Netherlands.
    Wårdell, Karin
    Linköpings universitet, Institutionen för medicinsk teknik. Linköpings universitet, Tekniska högskolan.
    Relationship between Neural Activation and Electric Field Distribution during Deep Brain Stimulation2015Ingår i: IEEE Transactions on Biomedical Engineering, ISSN 0018-9294, E-ISSN 1558-2531, Vol. 62, nr 2, s. 664-72Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Models and simulations are commonly used to study deep brain stimulation (DBS). Simulated stimulation fields are often defined and visualized by electric field isolevels or volumes of tissue activated (VTA). The aim of the present study was to evaluate the relationship between stimulation field strength as defined by the electric potential V, the electric field E, and the divergence of the electric field ∇(2) V, and neural activation. Axon cable models were developed and coupled to finite-element DBS models in three-dimensional (3-D). Field thresholds ( VT , ET, and ∇(2) VT ) were derived at the location of activation for various stimulation amplitudes (1 to 5 V), pulse widths (30 to 120 μs), and axon diameters (2.0 to 7.5 μm). Results showed that thresholds for VT and ∇(2) VT were highly dependent on the stimulation amplitude while ET were approximately independent of the amplitude for large axons. The activation field strength thresholds presented in this study may be used in future studies to approximate the VTA during model-based investigations of DBS without the need of computational axon models.

1 - 10 av 10
RefereraExporteraLänk till träfflistan
Permanent länk
Referera
Referensformat
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • oxford
  • Annat format
Fler format
Språk
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Annat språk
Fler språk
Utmatningsformat
  • html
  • text
  • asciidoc
  • rtf