| 1. |
- Alping, P., et al.
(författare)
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Rituximab versus Fingolimod after Natalizumab in Multiple Sclerosis Patients
- 2016
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Ingår i: Annals of Neurology. - : Wiley. - 0364-5134 .- 1531-8249. ; 79:6, s. 950-958
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Many JC virus antibody-positive relapsing-remitting multiple sclerosis (RRMS) patients who are stable on natalizumab switch to other therapies to avoid progressive multifocal leukoencephalopathy. Methods: We compared outcomes for all RRMS patients switching from natalizumab due to JC virus antibody positivity at 3 Swedish multiple sclerosis centers with different preferential use of rituximab and fingolimod (Stockholm, n = 156, fingolimod 51%; Gothenburg, n = 64, fingolimod 88%; Umea, n = 36, fingolimod 19%), yielding a total cohort of N = 256 (fingolimod 55%). Results: Within 1.5 years of cessation of natalizumab, 1.8% (rituximab) and 17.6% (fingolimod) of patients experienced a clinical relapse (hazard ratio for rituximab = 0.10, 95% confidence interval [CI] = 0.02-0.43). The hazard ratio (favoring rituximab) for adverse events (5.3% vs 21.1%) and treatment discontinuation (1.8% vs 28.2%) were 0.25 (95% CI = 0.10-0.59) and 0.07 (95% CI = 0.02-0.30), respectively. Furthermore, contrast-enhancing lesions were found in 1.4% (rituximab) versus 24.2% (fingolimod) of magnetic resonance imaging examinations (odds ratio = 0.05, 95% CI = 0.00-0.22). Differences remained when adjusting for possible confounders (age, sex, disability status, time on natalizumab, washout time, follow-up time, and study center). Interpretation: Our findings suggest an improved effectiveness and tolerability of rituximab compared with fingolimod in stable RRMS patients who switch from natalizumab due to JC virus antibody positivity. Although residual confounding factors cannot be ruled out, the shared reason for switching from natalizumab and the preferential use of either rituximab or fingolimod in 2 of the centers mitigates these concerns.
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| 2. |
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| 3. |
- Axelsson, Jonatan, et al.
(författare)
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Association between paternal smoking at the time of pregnancy and the semen quality in sons
- 2018
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 13:11, s. 0207221-0207221
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Maternal smoking during pregnancy has repeatedly been associated with decreased sperm counts in sons. Nevertheless, our team recently detected a lower total sperm count in the sons of smoking fathers as compared to sons of non-smoking fathers. Since paternal and maternal tobacco smoking often coincide, it is difficult to discriminate whether effects are mediated paternally or maternally when using questionnaire- or register-based studies. Therefore, getting an objective measure of the maternal nicotine exposure level during pregnancy might help disentangling the impact of paternally and maternally derived exposure. OBJECTIVES: Our aim was to study how paternal smoking at the time of the pregnancy was associated with semen quality in the sons after adjusting for the maternal levels of nicotine exposure during pregnancy. METHODS: We recruited 104 men (17-20 years old) from the general Swedish population. The participants answered a questionnaire about paternal smoking. Associations between smoking and semen volume, total sperm count, sperm concentration, morphology and motility were adjusted for levels of the nicotine metabolite cotinine in stored maternal serum samples obtained from rubella screening between the 6th and 35th week of pregnancy. We additionally adjusted for the estimated socioeconomic status. RESULTS: After adjusting for the maternal cotinine, the men of smoking fathers had 41% lower sperm concentration and 51% lower total sperm count than the men of non-smoking fathers (p = 0.02 and 0.003, respectively). This was robust to the additional adjustment. CONCLUSIONS: Our results suggest a negative association between paternal smoking and sperm counts in the sons, independent of the level maternal nicotine exposure during the pregnancy.
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| 4. |
- Axelsson, Jonatan, et al.
(författare)
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Exposure to polychlorinated compounds and cryptorchidism; A nested case-control study
- 2020
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 15:7
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Maldescended testes or cryptorchidism is a genital birth defect that affects 2-9% of all male new-borns. Over the last 40 years there have been reports of increased prevalence in countries like the US, the UK and the Scandinavian countries. This possible increase has in some studies been linked to a foetal exposure to chemical pollutants. In this matched case-control study, we analysed maternal serum samples in early pregnancy for three different organochlorine compounds, to investigate whether the levels were associated with the risk of cryptorchidism. METHOD: Maternal serum samples taken during the first trimester of pregnancy from 165 cases (boys born with cryptorchidism) and 165 controls, matched for birth year and maternal age, parity and smoking habits during the pregnancy, were retrieved from the Southern Sweden Maternity Biobank. The samples were analysed for 2,2',4,4',5,5'-hexachlorobiphenyl (PCB-153), dichlorodiphenyltrichloroethane (p,p'-DDE) and hexachlorobenzene (HCB), using gas chromatography mass spectrometry. Associations between exposure and cryptorchidism were evaluated by conditional logistic regression. RESULTS: We found no statistically significantly associations between exposure to these compounds and cryptorchidism, either when the exposure variables were used as a continuous variable, or when the exposure levels were divided in quartiles. CONCLUSION: We found no evidence of an association between maternal levels of PCB-153, p,p'-DDE or HCB during the pregnancy and the risk of having cryptorchidism in the sons.
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| 5. |
- Axelsson, Jonatan, et al.
(författare)
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Exposure to polycyclic aromatic hydrocarbons and nicotine, and associations with sperm DNA fragmentation
- 2022
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Ingår i: Andrology. - : Wiley. - 2047-2919 .- 2047-2927. ; 10:4, s. 740-748
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Tidskriftsartikel (refereegranskat)abstract
- Background: Tobacco smoking has been reported to cause DNA fragmentation and has been suggested to cause mutations in spermatozoa. These effects have been ascribed to the action of polycyclic aromatic hydrocarbons (PAH) present in the smoke. Simultaneously, DNA fragmentation has been associated with mutagenesis. Objective: The aim of this study was to investigate whether levels of urinary biomarkers of PAH and nicotine exposure were associated with sperm DNA fragmentation. Methods: In the urine of 381 men recruited from two cohorts of young men (17–21 years old) from the general Swedish population, the PAH metabolites 1-hydroxypyrene and 2-hydroxyphenanthrene, as well as the nicotine metabolite cotinine, were measured. The sperm DNA fragmentation index (DFI) was analysed using the sperm chromatin structure assay. Associations between the DFI, and PAH metabolite levels as continuous variables as well as in quartiles, were studied by general linear models adjusted for abstinence time. A similar analysis was carried out for cotinine levels, according to which the men were categorised as “non-smoking” (n = 216) and “smoking” (n = 165). Results: No association was found between levels of any of the three biomarkers and DFI, either as a continuous variable (p = 0.87–0.99), or when comparing the lowest and the highest quartiles (p = 0.11–0.61). The same was true for comparison of men categorised as non-smoking or smoking (DFI 11.1% vs. 11.8%, p = 0.31). Discussion: We found no evidence of PAH or nicotine exposure to be associated with DFI, which does not exclude that these exposures may have other effects on sperm DNA. Conclusion: In these young men, levels of biomarkers of nicotine and PAH exposure were not associated with DFI.
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| 6. |
- Axelsson, Jonatan, et al.
(författare)
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Gene-environment interaction and male reproductive function.
- 2010
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Ingår i: Asian Journal of Andrology. - : Medknow. - 1008-682X .- 1745-7262. ; 12, s. 298-307
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Tidskriftsartikel (refereegranskat)abstract
- As genetic factors can hardly explain the changes taking place during short time spans, environmental and lifestyle-related factors have been suggested as the causes of time-related deterioration of male reproductive function. However, considering the strong heterogeneity of male fecundity between and within populations, genetic variants might be important determinants of the individual susceptibility to the adverse effects of environment or lifestyle. Although the possible mechanisms of such interplay in relation to the reproductive system are largely unknown, some recent studies have indicated that specific genotypes may confer a larger risk of male reproductive disorders following certain exposures. This paper presents a critical review of animal and human evidence on how genes may modify environmental effects on male reproductive function. Some examples have been found that support this mechanism, but the number of studies is still limited. This type of interaction studies may improve our understanding of normal physiology and help us to identify the risk factors to male reproductive malfunction. We also shortly discuss other aspects of gene-environment interaction specifically associated with the issue of reproduction, namely environmental and lifestyle factors as the cause of sperm DNA damage. It remains to be investigated to what extent such genetic changes, by natural conception or through the use of assisted reproductive techniques, are transmitted to the next generation, thereby causing increased morbidity in the offspring.
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| 7. |
- Axelsson, Jonatan, et al.
(författare)
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No secular trend over the last decade in sperm counts among Swedish men from the general population.
- 2011
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Ingår i: Human Reproduction. - : Oxford University Press (OUP). - 0268-1161 .- 1460-2350. ; 26, s. 1012-1016
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION Based on historical data, a decline in sperm counts during the years 1940-1990 has been suggested and aetiologically linked to a concomitant increase in the incidence of testicular cancer. This study, focusing on possible changes in sperm parameters among young Swedish men, during the past 10 years, was specifically designed in order to answer the question of whether there is a continuing decline in sperm counts. METHODS During the period 2008-2010, 295 young (17-20 years; median 18) men born and raised in Sweden were recruited at the age they were supposed to undergo medical examination prior to military service. The participants filled in questionnaires, underwent andrological examination and delivered an ejaculate. Their semen parameters were compared with those of a similar cohort of men (n = 216) recruited in the year 2000-2001. RESULTS No significant changes (means; 2000-2001 versus 2008-2010) in sperm concentration (78 × 10(6)/ml versus 82 × 10(6)/ml; P = 0.54), semen volume (3.1 ml versus 3.0 ml; P = 0.26) or total sperm counts (220 × 10(6) versus 250 × 10(6); P = 0.18) were found. The proportion of progressively motile spermatozoa also remained unchanged. CONCLUSIONS Between the years 2000 and 2010 we found no evidence of time-related deterioration of semen parameters among young Swedish men from the general population. This finding does not exclude that such a decrease may have taken place before year 2000. If the risk of testicular cancer is linked to the sperm counts, the increase in incidence of this malignancy should be levelling off in southern Sweden in the next 10-15 years.
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| 8. |
- Axelsson, Jonatan, et al.
(författare)
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Phthalate exposure and reproductive parameters in young men from the general Swedish population.
- 2015
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Ingår i: Environment International. - : Elsevier BV. - 1873-6750 .- 0160-4120. ; 85, s. 54-60
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Tidskriftsartikel (refereegranskat)abstract
- In animals, exposure to certain phthalates negatively affects the male reproductive function. Human results are conflicting and mostly based on subfertile males, in whom the association between exposure and reproductive function may differ from the general population.
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| 9. |
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| 10. |
- Axelsson, Jonatan
(författare)
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Reproductive function in young Swedish men - Time trend, prenatal and adult exposure to smoking and phthalates
- 2015
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- A decrease in male reproductive function, including sperm counts, during the second half of the 20th century, has been postulated. During this period, testicular cancer has increased several-fold. Environmental and lifestyle-related factors have been proposed as explanations for a possible negative trend in male reproductive function. One important lifestyle factor is smoking. However, smoking during pregnancy appears to play a greater role for a man's reproductive function than smoking by the man himself. As regards environmental chemicals, one type of compound to which humans are exposed is phthalates. These are often used as plasticizers in different consumer products. Several phthalates have been reported as decreasing male reproductive function in laboratory animals, especially when given during the foetal period. Between 2008 and 2010, 314 men from the general Swedish population were recruited. Their semen quality was compared with a group of men recruited in a similar manner between 2000 and 2001. The participants also delivered serum and urinary samples and answered questionnaires concerning maternal and paternal smoking during pregnancy. Data on maternal smoking was additionally assessed through the Swedish Medical Birth Register. Through a Swedish screening program for rubella, maternal serum samples were retrieved from the men's prenatal period. We analysed metabolites of phthalates as exposure markers both in the maternal sera and in urine and serum of the men. Associations between parental smoking during pregnancy as well as phthalate metabolite levels, and parameters of male reproductive function were studied. In summary, we found no change in semen quality between 2000-2001 and 2008-2010. However, both maternal and paternal smoking during pregnancy were associated with reduced sperm counts in men whose other parent did not smoke. In addition, prenatal exposure to diethylhexyl phthalate (DEHP) and diisononyl phthalate (DiNP) appeared to be associated with decreased semen volume, and exposure to DiNP as well with smaller testicular size. Finally, adult exposure to DEHP and dibutyl phthalate (DBP) were associated with decreased progressive sperm motility, and DEHP exposure was also linked to a higher proportion of immature sperm. Thus, although no change in semen quality appeared to have occurred in Swedish men during the last decade, parental smoking and prenatal and adult exposure to certain phthalates may play a role in the male reproductive function.
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