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Sökning: WFRF:(Lindholm Johan) > Karolinska Institutet

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1.
  • Cardinale, Daniele A., 1982-, et al. (författare)
  • Influence of Hyperoxic-Supplemented High-Intensity Interval Training on Hemotological and Muscle Mitochondrial Adaptations in Trained Cyclists.
  • 2019
  • Ingår i: Frontiers in Physiology. - : Frontiers Media S.A.. - 1664-042X. ; 10
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Hyperoxia (HYPER) increases O2 carrying capacity resulting in a higher O2 delivery to the working muscles during exercise. Several lines of evidence indicate that lactate metabolism, power output, and endurance are improved by HYPER compared to normoxia (NORM). Since HYPER enables a higher exercise power output compared to NORM and considering the O2 delivery limitation at exercise intensities near to maximum, we hypothesized that hyperoxic-supplemented high-intensity interval training (HIIT) would upregulate muscle mitochondrial oxidative capacity and enhance endurance cycling performance compared to training in normoxia. Methods: 23 trained cyclists, age 35.3 ± 6.4 years, body mass 75.2 ± 9.6 kg, height 179.8 ± 7.9 m, and VO2max 4.5 ± 0.7 L min-1 performed 6 weeks polarized and periodized endurance training on a cycle ergometer consisting of supervised HIIT sessions 3 days/week and additional low-intensity training 2 days/week. Participants were randomly assigned to either HYPER (FIO2 0.30; n = 12) or NORM (FIO2 0.21; n = 11) breathing condition during HIIT. Mitochondrial respiration in permeabilized fibers and isolated mitochondria together with maximal and submaximal VO2, hematological parameters, and self-paced endurance cycling performance were tested pre- and posttraining intervention. Results: Hyperoxic training led to a small, non-significant change in performance compared to normoxic training (HYPER 6.0 ± 3.7%, NORM 2.4 ± 5.0%; p = 0.073, ES = 0.32). This small, beneficial effect on the self-paced endurance cycling performance was not explained by the change in VO2max (HYPER 1.1 ± 3.8%, NORM 0.0 ± 3.7%; p = 0.55, ES = 0.08), blood volume and hemoglobin mass, mitochondrial oxidative phosphorylation capacity (permeabilized fibers: HYPER 27.3 ± 46.0%, NORM 16.5 ± 49.1%; p = 0.37, ES = 3.24 and in isolated mitochondria: HYPER 26.1 ± 80.1%, NORM 15.9 ± 73.3%; p = 0.66, ES = 0.51), or markers of mitochondrial content which were similar between groups post intervention. Conclusions: This study showed that 6 weeks hyperoxic-supplemented HIIT led to marginal gain in cycle performance in already trained cyclists without change in VO2max, blood volume, hemoglobin mass, mitochondrial oxidative phosphorylation capacity, or exercise efficiency. The underlying mechanisms for the potentially meaningful performance effects of hyperoxia training remain unexplained and may raise ethical questions for elite sport.
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2.
  • Carrero, Juan Jesus, et al. (författare)
  • Albuminuria changes are associated with subsequent risk of end-stage renal disease and mortality
  • 2017
  • Ingår i: Kidney International. - : Elsevier BV. - 0085-2538 .- 1523-1755. ; 91:1, s. 244-251
  • Tidskriftsartikel (refereegranskat)abstract
    • Current guidelines for chronic kidney disease (CKD) recommend using albuminuria as well as estimated glomerular filtration rate (eGFR) to stage CKD. However, CKD progression is solely defined by change in eGFR with little regard to the risk implications of change in albuminuria. This is an observational study from the Stockholm CREAtinine Measurements (SCREAM) project, a health care utilization cohort from Stockholm, Sweden, with laboratory measures from 2006-2011 and follow-up through December 2012. Included were 31,732 individuals with two or more ambulatory urine albumin to creatinine ratio (ACR) tests. We assessed the association between change in ACR during a baseline period of 1, 2, or 3 years and end-stage renal disease (ESRD) or death. Using a 2-year baseline period, there were 378 ESRD events and 1712 deaths during a median of 3 years of follow-up. Compared to stable ACR, a 4-fold increase in ACR was associated with a 3.08-times (95% confidence interval 2.59 to 3.67) higher risk of ESRD while a 4-fold decrease in ACR was associated with a 0.34-times (0.26 to 0.45) lower risk of ESRD. Similar associations were found in people with and without diabetes mellitus, with and without hypertension, and also when adjusted for the change in eGFR during the same period. The association between change in ACR and mortality was weaker: ACR increase was associated with mortality, but the relationship was largely flat for ACR decline. Results were consistent for 1-, 2-, and 3-year ACR changes. Thus, changes in albuminuria are strongly and consistently associated with the risk of ESRD and death.
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4.
  • Chapman, Mark A., et al. (författare)
  • Skeletal Muscle Transcriptomic Comparison between Long-Term Trained and Untrained Men and Women
  • 2020
  • Ingår i: Cell Reports. - : Elsevier BV. - 2211-1247. ; 31:12
  • Tidskriftsartikel (refereegranskat)abstract
    • To better understand the health benefits of lifelong exercise in humans, we conduct global skeletal muscle transcriptomic analyses of long-term endurance- (9 men, 9 women) and strength-trained (7 men) humans compared with age-matched untrained controls (7 men, 8 women). Transcriptomic analysis, Gene Ontology, and genome-scale metabolic modeling demonstrate changes in pathways related to the prevention of metabolic diseases, particularly with endurance training. Our data also show prominent sex differences between controls and that these differences are reduced with endurance training. Additionally, we compare our data with studies examining muscle gene expression before and after a months-long training period in individuals with metabolic diseases, This analysis reveals that training shifts gene expression in individuals with impaired metabolism to become more similar to our endurance-trained group. Overall, our data provide an extensive examination of the accumulated transcriptional changes that occur with decades-long training and identify important "exercise-responsive" genes that could attenuate metabolic disease.
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5.
  • Cordtz, Rene Lindholm, et al. (författare)
  • Haematological malignancies in patients with psoriatic arthritis overall and treated with TNF inhibitors : a Nordic cohort study
  • 2022
  • Ingår i: RMD Open. - : BMJ Publishing Group Ltd. - 2056-5933. ; 8:2
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives To evaluate the risk of haematological malignancies in patients with psoriatic arthritis (PsA) overall, and in relation to treatment with tumour necrosis factor inhibitors (TNFi).Methods We identified that patients with PsA starting a first TNFi from the clinical rheumatology registers (CRR) in the five Nordic countries (n=10 621) and biologics-naive PsA patients from (1) the CRR (n=18 705) and (2) the national patient registers (NPR, n=27 286, Sweden and Denmark) from 2006 through 2019. For Sweden and Denmark, general population comparators were matched 5:1 to PsA patients on birth year, year at start of follow-up and sex. By linkage to the national cancer registers in all countries, we collected information on haematological malignancies overall, and categorised into lymphoid or myeloid types. We estimated incidence rate ratios (IRRs) with 95% CIs using modified Poisson regression for TNFi-treated versus biologics-naive PsA patients and versus the general population adjusted for age, sex, calendar period and country.Results During 59 827 person-years, 40 haematological malignancies occurred among TNFi-treated patients with PsA resulting in a pooled IRR of 0.96 (0.68-1.35) versus biologics-naive PsA from CRR and an IRR of 0.84 (0.64-1.10) versus biologics-naive PsA from NPR. The IRR of haematological malignancies in PsA overall versus general population comparators was 1.35 (1.17-1.55). The estimates were largely similar for lymphoid and myeloid malignancies.Conclusions Treatment with TNFi in patients with PsA was not associated with an increased incidence of haematological malignancies. Conversely, a moderately increased underlying risk was seen in patients with PsA compared with the general population.
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6.
  • Dahlgren, Liselotte, et al. (författare)
  • Human papillomavirus is more common in base of tongue than in mobile tongue cancer and is a favorable prognostic factor in base of tongue cancer patients.
  • 2004
  • Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 112:6, s. 1015-9
  • Tidskriftsartikel (refereegranskat)abstract
    • The frequency of human papilloma virus (HPV) and its influence on clinical outcome was analyzed retrospectively in pre-treatment paraffin embedded biopsies from 110 patients with tongue cancer. The presence of HPV DNA was examined in 85 mobile tongue tumors and 25 base of tongue tumors by a polymerase chain reaction (PCR) with 2 general primer pairs, GP5+/6+ and CPI/IIG. When HPV-DNA was found, HPV-type specific primers and direct sequencing were used for HPV sub-type verification. Twelve of 110 (10.9%) samples were HPV-positive; 9 for HPV-16, 1 for HPV-33, 1 for HPV-35 and 1 could not be analyzed because of shortage of DNA. HPV was significantly more common in base of tongue tumors (10/25, 40.0%) compared to tumors of the mobile tongue (2/85, 2.3%). The influence of HPV on clinical outcome in mobile tongue cancer could not be studied, due to that HPV was present in too few cases. Of the 19 patients with base of tongue cancer that were included in the survival analysis, however, 7 patients with HPV-positive base of tongue cancer had a significantly favorable 5-year survival rate compared to the 12 HPV-negative patients. In conclusion, HPV is significantly more common in base of tongue cancer than in mobile tongue cancer, and has a positive impact on disease-specific survival in patients with base of tongue cancer.
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7.
  • Emanuelsson, Eric B., et al. (författare)
  • Remodeling of the human skeletal muscle proteome found after long-term endurance training but not after strength training
  • 2024
  • Ingår i: iScience. - : Elsevier BV. - 2589-0042. ; 27:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Exercise training has tremendous systemic tissue-specific health benefits, but the molecular adaptations to long-term exercise training are not completely understood. We investigated the skeletal muscle proteome of highly endurance-trained, strength-trained, and untrained individuals and performed exercise- and sex-specific analyses. Of the 6,000+ proteins identified, >650 were differentially expressed in endurance-trained individuals compared with controls. Strikingly, 92% of the shared proteins with higher expression in both the male and female endurance groups were known mitochondrial. In contrast to the findings in endurance-trained individuals, minimal differences were found in strength-trained individuals and between females and males. Lastly, a co-expression network and comparative literature analysis revealed key proteins and pathways related to the health benefits of exercise, which were primarily related to differences in mitochondrial proteins. This network is available as an interactive database resource where investigators can correlate clinical data with global gene and protein expression data for hypothesis generation.
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8.
  • Hansen, Tomas, et al. (författare)
  • Normal radiological lymph node appearance in the thorax
  • 2019
  • Ingår i: Diseases of the esophagus. - : OXFORD UNIV PRESS INC. - 1120-8694 .- 1442-2050. ; 32:10, s. 1-6
  • Tidskriftsartikel (refereegranskat)abstract
    • Modern treatment of esophageal cancer is multimodal and highly dependent on a detailed diagnostic assessment of clinical stage, which includes nodal stage. Clinical appraisal of nodal stage is highly dependent on knowledge of normal radiological appearance, information of which is scarce. We aimed to describe lymph node appearance on computed tomography (CT) investigations in a randomly selected cohort of healthy subjects. In a sample of the Swedish Cardiopulmonary bioimage study, which investigates a sample of the Swedish population aged 50-64 years, the CT scans of 426 subjects were studied in detail concerning intrathoracic node stations relevant in clinical staging of esophageal cancer. With stratification for sex, the short axis of visible lymph nodes was measured and the distribution of lymph node sizes was calculated as well as proportion of patients with visible nodes above 5 and 10 millimeters for each station. Probability of having any lymph node station above 5 and 10 millimeters was calculated with a logistic regression model adjusted for age and sex. In the 214 men (aged: 57.3 +/- 4.1 years) and 212 women (aged: 57.8 +/- 4.4 years) included in this study, a total of 309 (72.5%) had a lymph node with a short axis of 5 mm or above was seen in at least one of the node stations investigated. When using 10 mm as a cutoff, nodes were visible in 29 (6.81%) of the subjects. Men had higher odds of having any lymph node with short axis 5 mm or above (OR 3.03 95% CI 1.89-4.85, P < 0.001) as well as 10 mm or above (OR 2.31 95% CI 1.02-5.23, P = 0.044) compared to women. Higher age was not associated with propensity for lymph nodes above 5 or 10 millimeters in this sample. We conclude that, in a randomly selected cohort of patients between 50 and 64 years, almost 10% of the men and 4% of the women had lymph nodes above 10 millimeters, most frequently in the subcarinal station (station 107). More than half of the patients had nodes above 5 millimeters on CT and men were much more prone to have this finding. The probability of finding lymph nodes in specific stations relevant of esophageal cancer is now described.
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9.
  • Heaf, James, et al. (författare)
  • Choice of dialysis modality among patients initiating dialysis : results of the Peridialysis study
  • 2021
  • Ingår i: Clinical Kidney Journal. - : Oxford University Press (OUP). - 2048-8505 .- 2048-8513. ; 14:9, s. 2064-2074
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: In patients with end-stage kidney disease (ESKD), home dialysis offers socio-economic and health benefits compared with in-centre dialysis but is generally underutilized. We hypothesized that the pre-dialysis course and institutional factors affect the choice of dialysis modality after dialysis initiation (DI).Methods: The Peridialysis study is a multinational, multicentre prospective observational study assessing the causes and timing of DI and consequences of suboptimal DI. Clinical and biochemical data, details of the pre-dialytic course, reasons for DI and causes of the choice of dialysis modality were registered.Results: Among 1587 included patients, 516 (32.5%) were judged unsuitable for home dialysis due to contraindications [384 ( 24.2%)] or no assessment [106 (6.7%); mainly due to late referral and/or suboptimal DI] or death [26 (1.6%)]. Older age, comorbidity, late referral, suboptimal DI, acute illness and rapid loss of renal function associated with unsuitability. Of the remaining 1071 patients, 700 (65.4%) chose peritoneal dialysis (61.7%) or home haemodialysis (HD; 3.6%), while 371 (34.6%) chose in-centre HD. Somatic differences between patients choosing home dialysis and in-centre dialysis were minor; factors linked to the choice of in-centre dialysis were late referral, suboptimal DI, acute illness and absence of a 'home dialysis first' institutional policy.Conclusions: Given a personal choice with shared decision making, 65.4% of ESKD patients choose home dialysis. Our data indicate that the incidence of home dialysis potentially could be further increased to reduce the incidence of late referral and unplanned DI and, in acutely ill patients, by implementing an educational programme after improvement of their clinical condition.
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10.
  • Heaf, James, et al. (författare)
  • First-year mortality in incident dialysis patients : results of the Peridialysis study
  • 2022
  • Ingår i: BMC Nephrology. - : Springer Science and Business Media LLC. - 1471-2369. ; 23:1
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Controversy surrounds which factors are important for predicting early mortality after dialysis initiation (DI). We investigated associations of predialysis course and circumstances affecting planning and execution of DI with mortality following DI.METHODS: Among 1580 patients participating in the Peridialysis study, a study of causes and timing of DI, we registered features of predialysis course, clinical and biochemical data at DI, incidence of unplanned suboptimal DI, contraindications to peritoneal dialysis (PD) or hemodialysis (HD), and modality preference, actual choice, and cause of modality choice. Patients were followed for 12 months or until transplantation. A flexible parametric model was used to identify independent factors associated with all-cause mortality.RESULTS: First-year mortality was 19.33%. Independent factors predicting death were high age, comorbidity, clinical contraindications to PD or HD, suboptimal DI, high eGFR, low serum albumin, hyperphosphatemia, high C-reactive protein, signs of overhydration and cerebral symptoms at DI. Among 1061 (67.2%) patients who could select dialysis modality based on personal choice, 654 (61.6%) chose PD, 368 (34.7%) center HD and 39 (3.7%) home HD. The 12-months survival did not differ significantly between patients receiving PD and in-center HD.CONCLUSIONS: First-year mortality in incident dialysis patients was in addition to high age and comorbidity, associated with clinical contraindications to PD or HD, clinical symptoms, hyperphosphatemia, inflammation, and suboptimal DI. In patients with a "free" choice of dialysis modality based on their personal preferences, PD and in-center HD led to broadly similar short-term outcomes.
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