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Sökning: FÖRF:(Johan Molin)

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1.
  • Molin, Carl Johan, 1989- (författare)
  • New Biomarkers for Neuromuscular Function and Myasthenia Gravis
  • 2018
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Myasthenia gravis (MG) is an autoimmune disorder, which is caused by autoantibodies against the acetylcholine receptor (AChR). The cardinal symptom is muscle fatigue, which can range from slight weakness of the extraocular muscles (causing droopy eyelids or double vision), to paralysis of the respiratory muscles. Antibodies towards other muscle proteins have been discovered, and MG is now considered a very heterogeneous disease with several subgroups. The severity of symptoms in MG patients is often fluctuating, and the antibody titers do not correlate with disease severity or treatment response. Therefore, there is a great need for reliable biomarkers in MG, both for assessing neuromuscular function, but also for clinical aspects such as disease progression and subgrouping.In Study I, the use of compound motor action potential (CMAP) as a biomarker for muscle status was examined in trained and untrained individuals. We found that trained individuals have a higher CMAP in proximal muscles, and the CMAP value in the biceps correlate with muscle strength in these individuals, indicating that CMAP can be used as a biomarker for muscle function. In Study II, subjects from study I were examined with ultrasound to assess the effect of high-resistance strength training (HRST) on peripheral nerves, and to compare muscle thickness. We did not find a difference in nerve cross-sectional area between the two groups. Trained individuals had thicker biceps muscles. The results from study I and II has led to CMAP and ultrasound being used to evaluate the result of physical exercise as an intervention in MG patients.In Study III, the expression of inflammatory proteins in the sera of MG patients was compared to healthy controls, in search for possible biomarkers. We found eleven proteins to be elevated, which provide new insight to the inflammatory response in MG and have possible functions as new biomarkers of inflammatory activity.In Study IV, the effect of thymectomy on the potential microRNA MG biomarkers miR-150-5p and miR-21-5p was examined. A decrease in miR-150-5p was seen 24 months after thymectomy, which further validate the use of miR-150-5p as a disease-specific biomarker for clinical outcome in AChR positive MG patients.
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2.
  • Molin, Carl Johan, et al. (författare)
  • Thymectomy lowers the myasthenia gravis biomarker miR-150-5p
  • 2018
  • Ingår i: Neurology. - 2332-7812. ; 5:3
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: The aim of the study was to analyze the effect of thymectomy on the proposed disease-specific microRNA (miRNA) biomarkers miR-150-5p and miR-21-5p in patients from the prospective randomized trial of thymectomy in myasthenia gravis (MGTX trial) and to evaluate the longitudinal changes in clinical patterns compared with these miRNA levels.Methods: Serum samples were obtained from 80 patients with MG who were included in the MGTX trial. Thirty-eight patients were randomized to thymectomy plus prednisone treatment, and 42 patients were randomized to prednisone treatment. Serum samples were analyzed for the expression of miR-150-5p and miR-21-5p, with quantitative reverse transcriptase PCR at baseline and at 12, 24, and 36 months after randomization. The inclusion criteria for participation in the MGTX trial were age 18-65 years, generalized myasthenia gravis (Myasthenia Gravis Foundation of America Class II-IV), disease duration of less than 5 years, and seropositivity for acetylcholine receptor antibodies (AChR+).Results: Patients treated with thymectomy had lower levels of miR-150-5p at 24 months, both compared with baseline values (p = 0.0011) and the prednisone group (p = 0.04). No change in miRNA levels was found in the prednisone group. Levels of miR-21-5p displayed a negative correlation with the prednisone dose within the prednisone-only group (p ≤ 0.001).Conclusions: Thymectomy lowers the levels of the proposed biomarker miR-150-5p, which strengthens its position as a potential disease-specific biomarker for AChR+ MG.
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3.
  • Westerberg, Elisabet, 1971-, et al. (författare)
  • The impact of physical exercise on neuromuscular function in Myasthenia gravis patients : A single-subject design study
  • 2018
  • Ingår i: Medicine. - : Lippincott Williams & Wilkins. - 0025-7974 .- 1536-5964. ; 97:31
  • Tidskriftsartikel (refereegranskat)abstract
    • There is a need for tailored exercise recommendations to patients with Myasthenia Gravis (MG). A few pilot studies have recently shown that physical exercise in accordance with general recommendations to healthy adults can be applied safely to patients with mild MG symptoms. How physical exercise affects muscle parameters and risk factors for life-style diseases in patients with MG is, however, only poorly known. We evaluated functional skeletal muscle parameters in 11 MG patients, before and after conducting a 12-week supervised physical therapy regimen of aerobic and high-resistance strength training. After the training program, parameters of the proximal leg muscle rectus femoris improved: compound motor action potential (from 4.5 ± 2.6 to 5.3 ± 2.8 mV, p=0.016), isometric muscle force (from 25.2 ± 4.4 to 30.2 ± 3.8 kg; p=0.014) and ultrasound muscle thickness (from 19.6 ± 5.6 to 23.0 ± 3.9 mm, p=0.0098) all increased. Further, physical performance-based measures improved, including the 30-Second Chair Stand Test (median change +2, p=0.0039) as well as the clinical MG composite score (from 3[2-5] to 2 [0-4], p=0.043). These findings indicate that MG patients can improve their functional muscle status as a result of aerobic and high-resistance strength training, especially in proximal leg muscles. This is important knowledge when physical therapy is considered for this patient group, for whom no guidelines on physical exercise currently exist.
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4.
  • Molin, Carl Johan, et al. (författare)
  • High-resistance strength training does not affect nerve cross sectional area – An ultrasound study
  • 2017
  • Ingår i: Clinical Neurophysiology Practice. - : Elsevier BV. - 2467-981X. ; 2, s. 163-169
  • Tidskriftsartikel (refereegranskat)abstract
    • ObjectiveThe aim was to study the effect of high-resistance strength training on peripheral nerve morphology, by examining properties of peripheral nerves as well as distal and proximal muscle thickness with ultrasound, comparing healthy individuals who perform and do not perform high-resistance strength training.MethodsNeuromuscular ultrasound was used to examine cross sectional area (CSA) of the median and musculocutaneous nerves, and muscle thickness of the abductor pollicis brevis muscle, biceps brachii muscle, quadriceps muscle and extensor digitorum brevis muscle, in 44 healthy individuals, of whom 22 performed regular high-resistance strength training.ResultsNo difference in nerve CSA was found between trained and untrained individuals although trained individuals had thicker biceps brachii muscles. The CSA of the median nerve in the forearm correlated with participants’ height and was significantly larger in men than women.ConclusionsIn this cohort, CSA of the median and musculocutaneous nerves was not affected by strength training, whereas gender had a prominent effect both on CSA and muscle thickness.SignificanceThis is the first study to examine the effect of high-resistance strength training on peripheral nerves with neuromuscular ultrasound.
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5.
  • Molin, Carl Johan, et al. (författare)
  • Profile of upregulated inflammatory proteins in sera of Myasthenia Gravis patients.
  • 2017
  • Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 7
  • Tidskriftsartikel (refereegranskat)abstract
    • This study describes specific patterns of elevated inflammatory proteins in clinical subtypes of myasthenia gravis (MG) patients. MG is a chronic, autoimmune neuromuscular disease with antibodies most commonly targeting the acetylcholine receptors (AChRab), which causes fluctuating skeletal muscle fatigue. MG pathophysiology includes a strong component of inflammation, and a large proportion of patients with early onset MG additionally present thymus hyperplasia. Due to the fluctuating nature and heterogeneity of the disease, there is a great need for objective biomarkers as well as novel potential inflammatory targets. We examined the sera of 45 MG patients (40 AChRab seropositive and 5 AChRab seronegative), investigating 92 proteins associated with inflammation. Eleven of the analysed proteins were significantly elevated compared to healthy controls, out of which the three most significant were: matrix metalloproteinase 10 (MMP-10; p = 0.0004), transforming growth factor alpha (TGF-α; p = 0.0017) and extracellular newly identified receptor for advanced glycation end-products binding protein (EN-RAGE) (also known as protein S100-A12; p = 0.0054). Further, levels of MMP-10, C-X-C motif ligand 1 (CXCL1) and brain derived neurotrophic factor (BDNF) differed between early and late onset MG. These novel targets provide valuable additional insight into the systemic inflammatory response in MG.
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6.
  • Westerberg, Elisabet, et al. (författare)
  • Physical exercise in Myasthenia Gravis is safe and improves neuromuscular parameters and physical performance-based measures : A pilot study
  • 2017
  • Ingår i: Muscle and Nerve. - : Wiley. - 0148-639X .- 1097-4598. ; 56:2, s. 207-214
  • Tidskriftsartikel (refereegranskat)abstract
    • INTRODUCTION: Due to the shortage of exercise-related research in Myasthenia Gravis (MG), there are no consensus guidelines on physical exercise for MG patients.METHODS: In this prospective pilot study, 10 MG patients with mild disease performed supervised aerobic and resistance training twice weekly for 12 weeks. The Myasthenia Gravis Composite (MGC) score, compound motor action potential (CMAP), repetitive nerve stimulation, muscle force, physical performance-based measures, serum levels of interleukin-6, muscle enzymes as well as immuno-microRNAs miR-150-5p and miR-21-5p were assessed before and after the training period.RESULTS: Physical exercise was well tolerated, and the MGC score was unchanged. Muscle resistance weights and CMAP amplitudes increased for biceps brachii and rectus femoris muscles, and physical performance-based measures improved. Muscle enzymes remained normal, whereas disease-specific microRNAs miR-150-5p and miR-21-5p were reduced after the training period.CONCLUSIONS: We propose that general recommendations regarding physical exercise safely can be applied to well-regulated MG patients.
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7.
  • Molin, Carl Johan, et al. (författare)
  • Compound Motor Action Potential : Electrophysiological Marker for Muscle Training
  • 2016
  • Ingår i: Journal of clinical neurophysiology. - 0736-0258 .- 1537-1603. ; 33:4, s. 340-345
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose:The compound motor action potential (CMAP) represents the summated action potentials of all stimulated motor endplates and potentially reflects muscle hypertrophy and increased muscle contractions. Since electrophysiological biomarkers for high-resistance strength training are lacking, the authors evaluated whether the CMAP of distal and proximal muscles differs between healthy men and women who perform and do not perform high-resistance muscle training.Methods:Motor neurography was performed with stimulation of the median nerve (recording of abductor pollicis brevis muscle), peroneal nerve (recording of extensor digitorum brevis muscle), femoral nerve (recording of rectus femoris muscle) and musculocutaneous nerve (recording of biceps brachii muscle), and isometric muscle strength, measured with a hand-held dynamometer, were performed on 83 healthy subjects (52 women).Results:Trained women had 25% higher CMAP amplitude in the rectus femoris muscle than untrained women (P < 0.001), whereas CMAP amplitude in the trained male cohort was 25% higher in the biceps (P = 0.005) compared with untrained men. In the trained group, CMAP amplitude in the biceps correlated with isometric muscle strength (R = 0.30; P = 0.046).Conclusions:The authors' propose the CMAP as an objective neurophysiological parameter for proximal muscle status and training effects in future interventional studies of patients with neuromuscular disorders.
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8.
  • Wangel, Anne-Marie, et al. (författare)
  • Emergency cesarean sections can be predicted by markers for stress, worry and sleep disturbances in first-time mothers
  • 2011
  • Ingår i: Acta Obstetricia et Gynecologica Scandinavica. - : Wiley-Blackwell. - 0001-6349 .- 1600-0412. ; 90:3, s. 238-244
  • Tidskriftsartikel (refereegranskat)abstract
    • Abstract Objective: To identify predictors as free-text markers for mental ill-health from an electronic perinatal record (EMR) system and the association for emergency cesarean section (CS) in nulliparous women. Design: Population-based study using an EMR system. Setting: The catchment area of Malmö University Hospital in Sweden. Population: 6 467 women with complete perinatal electronic records (EMR) were selected of 10 662 nulliparous women presenting with a singleton cephalic baby for vaginal delivery between 2001 and 2006. Methods: Free-text search of markers for mental ill-health and multivariate logistic regression. Main Outcome Measures: Eleven markers for mental ill-health were tested with Cohen’s kappa for agreement and used as exposure variables. Odds ratios (OR) with 95% confidence interval (CI) were calculated for emergency CS, and adjusted for maternal age, diabetes, epidural anesthesia, and gestational weeks <37 and >41 by a multivariate logistic regression model with vaginal delivery as the reference. Results: Three markers identified from the EMR system reached statistically significant associations with an increased risk for emergency CS in nulliparous women: stress adjusted OR 1.66 (95% CI 1.34–2.06), sleep adjusted OR 1.57 (1.14–2.16), and worry adjusted OR 1.41 (1.10–1.79). Conclusions: Free-text words in medical records, indicating stress, sleep disturbances, or worry predicted increased adjusted OR for emergency CS in first-time mothers. Recognizing pregnant women’s reporting of their mental health status could have a predictive bearing on delivery outcomes.
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9.
  • Wangel, Anne-Marie, et al. (författare)
  • Prior psychiatric inpatient care and risk of cesarean sections: a registry study
  • 2011
  • Ingår i: Journal of Psychosomatic Obstetrics and Gynecology. - : Informa Healthcare. - 0167-482X .- 1743-8942. ; 32:4, s. 189-197
  • Tidskriftsartikel (refereegranskat)abstract
    • This study of 17,443 childbearing women, investigated the relationship between hospital admissions 5 years prior to index birth, type of mental disorders and risk factors for mode of delivery. Hospital based electronic perinatal medical records between 2001 and 2006, were linked with the Swedish National Inpatient Care Registry 1996-2006. Of all the women, 39.3% had had inpatient care prior to index birth (27.3% had had obstetric, 10.1% somatic, and 1.9% psychiatric inpatient care). Diagnoses of mental disorders at psychiatric admission (n = 333) were categorized into five groups: personality/behavioral/unspecified disorder (30.9%), affective disorders and 'suicide attempt' (28.9%), neurotic/somatoform disorders (18.9%), substance use (17.1%) and schizophrenia (4.2%). Women with history of psychiatric care were more often smokers, below age 24 and single (p < 0.001, respectively), had more markers of mental ill-health in pregnancy records (p = 0.001), compared to women without such previous care, and fewer were nulliparous (p < 0.001). The results show that women with prior psychiatric inpatient care and those with identified mental ill-health in pregnancy records, were associated with increased adjusted risks of cesarean sections. Identifying a woman's mental health status in pregnancy may predict and prevent emergency cesarean section.
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10.
  • Wedin, Kathe, et al. (författare)
  • Group antenatal care: new pedagogic method for antenatal care-a pilot study.
  • 2010
  • Ingår i: Midwifery. - : Elsevier BV. - 1532-3099 .- 0266-6138. ; 26, s. 389-393
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: to investigate how women who attended group antenatal care experienced the information they received, compared with women who attended traditional antenatal care, and their satisfaction with the form of care. The aim was also to determine the effect of group antenatal care on women's social networks compared with traditional antenatal care. DESIGN AND SETTING: a pilot study with an intervention group (group antenatal care) and a control group (traditional antenatal care). Both groups were selected through informed choice. A questionnaire and a follow-up telephone call, using a structured questionnaire, were used to evaluate both groups. PARTICIPANTS: for each woman who had chosen to be in the intervention group, two women who had chosen traditional antenatal care were selected from the same antenatal clinic and given the same questionnaire. FINDINGS: 35/45 (77%) women in the intervention group returned a completed questionnaire, compared with 40/85 (48%) women in the control group. There was little difference in satisfaction with information between the two groups, and overall satisfaction was high. KEY CONCLUSIONS: at six months post partum, the women who attended group antenatal care still met others from the group more regularly than the women who attended traditional antenatal care. IMPLICATIONS FOR PRACTICE: group antenatal care is well accepted by women, and can better utilise midwives' time.
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