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Sökning: WFRF:(Karlsson Jan)

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41.
  • Joerger, Markus, et al. (författare)
  • Population pharmacokinetics and pharmacodynamics of paclitaxel and carboplatin in ovarian cancer patients : a study by the European organization for research and treatment of cancer-pharmacology and molecular mechanisms group and new drug development group.
  • 2007
  • Ingår i: Clinical Cancer Research. - 1078-0432 .- 1557-3265. ; 13:21, s. 6410-6418
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose: Paclitaxel and carboplatin are frequently used in advanced ovarian cancer following cytoreductive surgery. Threshold models have been used to predict paclitaxel pharmacokinetic-pharmacodynamics, whereas the time above paclitaxel plasma concentration of 0.05 to 0.2 μmol/L (tC > 0.05−0.2) predicts neutropenia. The objective of this study was to build a population pharmacokinetic-pharmacodynamic model of paclitaxel/carboplatin in ovarian cancer patients. Experimental Design: One hundred thirty-nine ovarian cancer patients received paclitaxel (175 mg/m2) over 3 h followed by carboplatin area under the concentration-time curve 5 mg/mL*min over 30 min. Plasma concentration-time data were measured, and data were processed using nonlinear mixed-effect modeling. Semiphysiologic models with linear or sigmoidal maximum response and threshold models were adapted to the data. Results: One hundred five patients had complete pharmacokinetic and toxicity data. In 34 patients with measurable disease, objective response rate was 76%. Neutrophil and thrombocyte counts were adequately described by an inhibitory linear response model. Paclitaxel tC > 0.05 was significantly higher in patients with a complete (91.8 h) or partial (76.3 h) response compared with patients with progressive disease (31.5 h; P = 0.02 and 0.05, respectively). Patients with paclitaxel tC > 0.05 > 61.4 h (mean value) had a longer time to disease progression compared with patients with paclitaxel tC > 0.05 < 61.4 h (89.0 versus 61.9 weeks; P = 0.05). Paclitaxel tC > 0.05 was a good predictor for severe neutropenia (P = 0.01), whereas carboplatin exposure (Cmax and area under the concentration-time curve) was the best predictor for thrombocytopenia (P < 10−4). Conclusions: In this group of patients, paclitaxel tC > 0.05 is a good predictive marker for severe neutropenia and clinical outcome, whereas carboplatin exposure is a good predictive marker for thrombocytopenia.
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42.
  • Johansson, Birgitta, 1957, et al. (författare)
  • Mindfulness-Based Stress Reduction (MBSR) Delivered Live on the Internet to Individuals Suffering from Mental Fatigue After an Acquired Brain Injury
  • 2015
  • Ingår i: Mindfulness. - : Springer Science and Business Media LLC. - 1868-8527 .- 1868-8535. ; 6:6, s. 1356-1365
  • Tidskriftsartikel (refereegranskat)abstract
    • An acquired brain injury often leads to long-lasting mental fatigue, which can have a considerable effect on work and social interactions. Fortunately, the Mindfulness-Based Stress Reduction (MBSR) program has been found to alleviate mental fatigue. The purpose of this feasibility study was to evaluate the success of an interactive MBSR program delivered live online to individuals who have experienced a traumatic brain injury or stroke. We included the following three groups in our study: an Internet group, a face-to-face MBSR group, and an active control group who took weekly walks in natural environments. Thirty-four participants completed the study, and all were suffering from long-lasting mental fatigue after either a traumatic brain injury (16 participants) or a stroke (18 participants). However, seven did not accept to attend an Internet MBSR, and Internet was the only choice for others. We found that, according to the Mental Fatigue Scale (MFS), the program leads to significantly reduced mental fatigue in the Internet group compared with the face-to-face and the control group. Individuals in the MBSR groups also exhibited an improved ability to process two temporally close targets (attentional blink task), while this was not detected in the control group. In conclusion, we believe that it is possible for individuals suffering from mental fatigue after an acquired brain injury to obtain positive results through enrollment in a live, interactive, online MBSR program. This is promising, as the Internet is accessible to many individuals, irrespective of where they live. Further randomized control studies comparing are warranted.
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43.
  • Karlsson, Bengt, et al. (författare)
  • Thyroid dysfunction in Down's syndrome : relation to age and thyroid autoimmunity
  • 1998
  • Ingår i: Archives of Disease in Childhood. - 0003-9888 .- 1468-2044. ; 79:3, s. 242-245
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: The prevalence of thyroid disease is increased in Down's syndrome. Most available data come from cross sectional studies. AIMS: To study longitudinally thyroid function in patients with Down's syndrome in Uppsala county (85 patients) up to the age of 25 years. METHODS: Observational study based on yearly follow up in a children's clinic. Thyroid function tests were performed at each visit to the clinic. RESULTS: Hypothyroidism was found in 30 and hyperthyroidism was found in two of the 85 patients. No sex difference was seen. Half of the patients with hypothyroidism acquired the condition before the age of 8 years, but only one of them displayed thyroid autoantibodies at diagnosis. Most patients who developed hypothyroidism after this age had thyroid autoantibodies. In the prepubertal patients with hypothyroidism, growth velocity was lower during the year before the start of thyroxine treatment than during the year after treatment began; it was also lower than that of sex and age matched euthyroidic children with Down's syndrome. CONCLUSION: Thyroid dysfunction in patients with Down's syndrome is common in childhood. Consequently, annual screening is important. Autoimmune thyroid disease is uncommon in young children with Down's syndrome but is common after 8 years of age.
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44.
  • Karlsson, Daniel, et al. (författare)
  • Experimental and theoretical study of the photodissociation of bromo-3-fluorobenzene
  • 2008
  • Ingår i: Journal of Chemical Physics. - : AIP Publishing. - 0021-9606 .- 1089-7690. ; 128:3, s. 034307-
  • Tidskriftsartikel (refereegranskat)abstract
    • The UV photodissociation of bromo-3-fluorobenzene under collisionless conditions has been studied as a function of the excitation wavelength between 255 and 265 nm. The experiments were performed using ultrafast pump-probe laser spectroscopy. To aid in the interpretation of the results, it was necessary to extend the theoretical framework substantially compared to previous studies, to also include quantum dynamical simulations employing a two-dimensional nuclear Hamiltonian. The nonadiabatic potential energy surfaces (PES) were parameterized against high-level MS-CASTP2 quantum chemical calculations, using both the C–Br distance and the out-of-plane bending of the bromine as nuclear parameters. We show that the wavelength dependence of the photodissociation via the S0→1ππ*→1πσ* channel, accessible with a ∼ 260 nm pulse, is captured in this model. We thereby present the first correlation between experiments and theory within the quantitative regime.
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45.
  • Karlsson, Fredrik, 1975-, et al. (författare)
  • Articulatory closure proficiency in Parkinson's disease patients following deep brain stimulation of the subthalamic nucleus and caudal zona incerta.
  • 2014
  • Ingår i: Journal of Speech, Language and Hearing Research. - 1092-4388 .- 1558-9102. ; 57, s. 1178-1190
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVEThe present study aimed at comparing the effects of deep brain stimulation (DBS) treatment of the subthalamic nucleus (STN) and the caudal zona incerta (cZi) on Parkinson's disease patients' proficiency in achieving oral closure and release during plosive production. METHODS Nineteen patients were evaluated preoperatively and 12 months after DBS surgery. Nine patients were implanted in the STN, seven bilaterally and two unilaterally (left). Ten were bilaterally implanted in the cZi. Postoperative examinations were made off and on stimulation. All patients received simultaneous L-dopa treatment in all conditions. For a series of plosives extracted from a reading passage, absolute and relative measures of duration of frication and amplitude of plosive release were compared between conditions within each treatment group. RESULTS Relative duration of frication increased in voiceless plosives in the on stimulation condition in cZi patients. Similar trends were observed across the data set. Duration of pre-release frication and the release peak prominence increased in voiceless plosives on stimulation for both groups. CONCLUSIONS The increased release prominence suggests that patients achieved a stronger closure gesture due to DBS, but that the increased energy available resulted in increased frication.
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46.
  • Karlsson, Fredrik, 1975-, et al. (författare)
  • Control of phonatory onset and offset in Parkinson patients following deep brain stimulation of the subthalamic nucleus and caudal Zona Incerta
  • 2012
  • Ingår i: Parkinsonism & Related Disorders. - : Elsevier. - 1353-8020 .- 1873-5126. ; 18:7, s. 824-827
  • Tidskriftsartikel (refereegranskat)abstract
    • Laryngeal hypokinesia is a common symptom in Parkinson’s disease (PD) that affects quality of life. Deep brain stimulation (DBS) is well recognized as a complementary method for treatment of motor symptoms in PD but the outcomes on patients’ control over phonatory alternation have yet not been clearly elucidated. The present study examined the effect of subthalamic nucleus STN-DBS (n=8, aged 51-72 yrs; median=63 yrs) and caudal Zona incerta cZi-DBS (n=8,aged 49-71 yrs; median=61 yrs) on control of onset and offset of phonation in connected speech. The patients were evaluated in a preoperatively (Med ON, 1.5 times the ordinary Levodopa dose) and 12 months postoperatively (Med ON, ordinary Levodopa dose). The results provided evidence of a progressive reduction in the ability to manifest alternations between voicing and voiceless states in a reading task. Mean proportion produced with inappropriate voicing increased from 47.6% to 55.3% and from 62.9% to 68.6% of the total duration for the two groups of patients between Pre-op and Post-op, Stim OFF evaluations. The medial and final parts of the fricative were more affected than the initial part, indicating an increased voicing lead into the following vowel. We propose that this reduction in phonatory control is be due to either progression of the disease, an effect of reduced Levodopa dosage or a microlesional effect. Patients’ proficiency in alternating between voiced and voiceless states in connected speech remained unaffected by both STN-DBS and cZi-DBS.
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47.
  • Karlsson, Fredrik, 1975-, et al. (författare)
  • Deep brain stimulation of caudal zona incerta and subthalamic nucleus in patients with Parkinson’s disease : effects on diadochokinetic rate
  • 2011
  • Ingår i: Parkinson's Disease. - : Hindawi Publishing Corporation. - 2090-8083 .- 2042-0080. ; 2011, s. 605607-
  • Tidskriftsartikel (refereegranskat)abstract
    • The hypokinetic dysarthria observed in Parkinson's disease (PD) affects the range, speed, and accuracy of articulatory gestures in patients, reducing the perceived quality of speech acoustic output in continuous speech. Deep brain stimulation (DBS) of the subthalamic nucleus (STN-DBS) and of the caudal zona incerta (cZi-DBS) are current surgical treatment options for PD. This study aimed at investigating the outcome of STN-DBS (7 patients) and cZi-DBS (7 patients) in two articulatory diadochokinesis tasks (AMR and SMR) using measurements of articulation rate and quality of the plosive consonants (using the percent measurable VOT metric). The results indicate that patients receiving STN-DBS increased in articulation rate in the Stim-ON condition in the AMR task only, with no effect on production quality. Patients receiving cZi-DBS decreased in articulation rate in the Stim-ON condition and further showed a reduction in production quality. The data therefore suggest that cZi-DBS is more detrimental for extended articulatory movements than STN-DBS.
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48.
  • Karlsson, Fredrik, 1975-, et al. (författare)
  • Pitch variability in patients with Parkinson’s disease : effects of deep brain stimulation of caudal zona incerta and subthalamic nucleus
  • 2013
  • Ingår i: Journal of Speech, Language and Hearing Research. - : American Speech-Language-Hearing Association. - 1092-4388 .- 1558-9102. ; 56:1, s. 150-158
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective The purpose of the present study was to examine the effect of deep brain stimulation (DBS) of the subthalamic nucleus (STN) and the caudal zona incerta (cZi) pitch characteristics of con- nected speech in patients with Parkinson’s disease (PD).Methods Sixteen patients were evaluated preoperatively and 12 months after DBS surgery. Eight pa- tients were implanted in the STN (aged 51-72 yrs; xC=63 yrs). Six received bilateral implanta- tion and two unilateral (left) implantation. Eight patients were bilaterally implanted in the cZi (aged 49-71 yrs; xC=60.8 yrs). Preoperative assessments were made after an L-Dopa challenge (approximately 1.5 times the ordinary dose). All postoperative examinations were made off and on stimulation, with a clinically optimized dose of L-dopa. Measurements of pitch range and var- iability were obtained from each utterance in a recorded read speech passage.Results Pitch range and coefficient of variation showed an increase in patients under STN-DBS. Patients under cZi-DBS showed no significant effects of treatment on investigated pitch properties.Conclusions STN-DBS was shown to increase pitch variation and range. The results provided no evidence of cZi-DBS having a beneficial effect on PD patients’ pitch variability. 
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49.
  • Karlsson, Ingrid, et al. (författare)
  • Coevolution of RANTES sensitivity and mode of CCR5 receptor use by human immunodeficiency virus type 1 of the R5 phenotype.
  • 2004
  • Ingår i: Journal of Virology. - 1098-5514 .- 0022-538X. ; 78:21, s. 11807-11815
  • Tidskriftsartikel (refereegranskat)abstract
    • The evolution of human immunodeficiency virus type 1 (HIV-1) coreceptor use has been described as the acquisition of CXCR4 use linked to accelerated disease progression. However, CXCR4-using virus can be isolated only from approximately one-half of individuals with progressive HIV-1 disease. The other half continue to yield only CCR5-using viruses (R5 phenotype) throughout the course of disease. In the present work, the use of receptor chimeras between CCR5 and CXCR4 allowed us to study the evolution of HIV-1 with the R5 phenotype, which was not revealed by studies of wild-type coreceptor use. All together, 246 isolates (173 with the R5 phenotype) from 31 individuals were tested for their ability to infect cells through receptor chimeras. R5narrow virus was able to use only wild-type CCR5, whereas R5broad(1) to R5broad(3) viruses were able to use one to three chimeric receptors, respectively. Broad use of chimeric receptors was interpreted as an increased flexibility in the mode of receptor use. R5broad isolates showed higher infectivity in cells expressing wild-type CCR5 than R5narrow isolates. Also, the increased flexibility of R5broad isolates was concomitant with a lower sensitivity to inhibition by the CC chemokine RANTES. Our results indicate a close relationship between HIV-1 phenotypic changes and the pathogenic process, since the mode and efficiency of CCR5 use as well as the decrease in the RANTES sensitivities of isolated viruses are significantly correlated with CD4+-T-cell decline in a patient. One possible explanation is that ligand competition at the CCR5 receptor or changed CCR5 availability may shape the outcome of HIV-1 infection.
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50.
  • Karlsson, Ingrid, et al. (författare)
  • Differential pathogenesis of primary CCR5-using human immunodeficiency virus type 1 isolates in ex vivo human lymphoid tissue.
  • 2005
  • Ingår i: Journal of Virology. - 1098-5514 .- 0022-538X. ; 79:17, s. 11151-11160
  • Tidskriftsartikel (refereegranskat)abstract
    • In the course of human immunodeficiency virus (HIV) disease, CCR5-utilizing HIV type 1 (HIV-1) variants (R5), which typically transmit infection and dominate its early stages, persist in approximately half of the infected individuals (nonswitch virus patients), while in the other half (switch virus patients), viruses using CXCR4 (X4 or R5X4) emerge, leading to rapid disease progression. Here, we used a system of ex vivo tonsillar tissue to compare the pathogeneses of sequential primary R5 HIV-1 isolates from patients in these two categories. The absolute replicative capacities of HIV-1 isolates seemed to be controlled by tissue factors. In contrast, the replication level hierarchy among sequential isolates and the levels of CCR5(+) CD4(+) T-cell depletion caused by the R5 isolates seemed to be controlled by viral factors. R5 viruses isolated from nonswitch virus patients depleted more target cells than R5 viruses isolated from switch virus patients. The high depletion of CCR5(+) cells by HIV-1 isolates from nonswitch virus patients may explain the steady decline of CD4(+) T cells in patients with continuous dominance of R5 HIV-1. The level of R5 pathogenicity, as measured in ex vivo lymphoid tissue, may have a predictive value reflecting whether, in an infected individual, X4 HIV-1 will eventually dominate.
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