| 1. |
- Alping, P., et al.
(författare)
-
Rituximab versus Fingolimod after Natalizumab in Multiple Sclerosis Patients
- 2016
-
Ingår i: Annals of Neurology. - : Wiley. - 0364-5134 .- 1531-8249. ; 79:6, s. 950-958
-
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.
|
|
| 2. |
|
|
| 3. |
- Axelsson, Jonatan, et al.
(författare)
-
Association between paternal smoking at the time of pregnancy and the semen quality in sons
- 2018
-
Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 13:11, s. 0207221-0207221
-
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.
|
|
| 4. |
- Axelsson, Jonatan, et al.
(författare)
-
Exposure to polychlorinated compounds and cryptorchidism; A nested case-control study
- 2020
-
Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 15:7
-
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.
|
|
| 5. |
- Axelsson, Jonatan, et al.
(författare)
-
Exposure to polycyclic aromatic hydrocarbons and nicotine, and associations with sperm DNA fragmentation
- 2022
-
Ingår i: Andrology. - : Wiley. - 2047-2919 .- 2047-2927. ; 10:4, s. 740-748
-
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.
|
|
| 6. |
- Axelsson, Jonatan, et al.
(författare)
-
Gene-environment interaction and male reproductive function.
- 2010
-
Ingår i: Asian Journal of Andrology. - : Medknow. - 1008-682X .- 1745-7262. ; 12, s. 298-307
-
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.
|
|
| 7. |
- Axelsson, Jonatan, et al.
(författare)
-
No secular trend over the last decade in sperm counts among Swedish men from the general population.
- 2011
-
Ingår i: Human Reproduction. - : Oxford University Press (OUP). - 0268-1161 .- 1460-2350. ; 26, s. 1012-1016
-
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.
|
|
| 8. |
- Axelsson, Jonatan, et al.
(författare)
-
Phthalate exposure and reproductive parameters in young men from the general Swedish population.
- 2015
-
Ingår i: Environment International. - : Elsevier BV. - 1873-6750 .- 0160-4120. ; 85, s. 54-60
-
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.
|
|
| 9. |
|
|
| 10. |
- Axelsson, Jonatan
(författare)
-
Reproductive function in young Swedish men - Time trend, prenatal and adult exposure to smoking and phthalates
- 2015
-
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.
|
|
| 11. |
|
|
| 12. |
|
|
| 13. |
- Axmon, Anna, et al.
(författare)
-
Tidstrender för perfluorerade ämnen i plasma från svenska kvinnor 1987-2007
- 2014
-
Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Perfluorerade kemikalier (PFC) är en stor grupp ämnen som är misstänkt hormon- störande. De är svårnedbrytbara och stannar länge i både miljö och människa. De mest kända PFC är PFOS och PFOA. Dessa användes under många år för att im- pregnera textilier, skor, möbler och mattor, i golv- och bilvax och målarfärger, mm. Användningen började minska i början av detta århundrade då PFOS och PFOA ersattes av andra PFC. Vi använde sparade plasmaprover från 80 kvinnor. Proven togs ursprungligen mellan 1987 och 2007 i samband med bröstförminskningsoperationer, från kvinnor som vi- sade sig friska vid screening för ärftlig cancer och från kvinnor vars äkta män hade cancer. Proverna analyserades för ett antal olika PFC (se textruta nedan), och vi undersökte därefter tidstrender för varje kemikalie. Vi tittade dels på linjära tidstrender, dvs vi an- tog att förändringen i halter var lika stor för varje år, och dels på förändringar mellan perioderna före 1990, 1990-2000 och efter 2000. • PFNA och PFDA ökade över hela tidsperioden, men allra mest efter 2000. Från 1987 till 2007 ökade PFNA med 305% och PFDA med 312%. • PFUnDA ökade med 155% från 1987 till 2007. Detta berodde framför allt på en stor ökning från 2000 och framåt. • PFOS och PFOA låg som högst under perioden 1990-2000. Sett över hela studieperioden, dvs 1987 till 2007, minskade PFOS med 36% och PFOA med 7%. • Även PFHxS låg som högst under perioden 1990-2000. Till skillnad från PFOS och PFOA uppvisade PFHxS en ökning – 142% – mellan 1987 och 2007.
|
|
| 14. |
- Axmon, Anna, et al.
(författare)
-
Time trends between 1987 and 2007 for perfluoroalkyl acids in plasma from Swedish women.
- 2014
-
Ingår i: Chemosphere. - : Elsevier BV. - 1879-1298 .- 0045-6535. ; 102, s. 61-67
-
Tidskriftsartikel (refereegranskat)abstract
- Perfluoroalkyl acids (PFAAs) are a large group of chemicals which are highly persistent in both nature and humans. The use of the most prominent ones, perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA), was reduced in the early 21st century, and since then levels in human matrices have decreased. However, these two compounds have been exchanged by other PFAAs, for which time trends have not been as extensively investigated. By the use of 80 plasma samples collected between 1987 and 2007 from healthy women (n=1-9 yearly for 1987-2001, n=15 from 2006, and n=10 from 2007), possible time trends of six PFAAs were assessed. Time trends were evaluated for the entire study period, as well as for three sub-periods. As seen in previous studies, levels of perfluorohexane sulfonate (PFHxS), PFOS, and PFOA peaked during the middle time period (1990-2000), with medians of 0.98ngmL(-1), 18.06ngmL(-1), and 3.73ngmL(-1), respectively. However, levels of perfluorononanic acid (PFNA), perfluorodecanic acid (PFDA), and perfluoroundecanoic acid (PFUnDA) increased over the whole study period and most markedly so after year 2000, with medians of 0.73ngmL(-1), 0.28ngmL(-1), and 0.24ngmL(-1), respectively, during the last study period.
|
|
| 15. |
|
|
| 16. |
- Boremalm, Malin, et al.
(författare)
-
Natalizumab, rituximab and fingolimod as escalation therapy in multiple sclerosis
- 2019
-
Ingår i: European Journal of Neurology. - : Wiley. - 1351-5101 .- 1468-1331. ; 26:8, s. 1060-1067
-
Tidskriftsartikel (refereegranskat)abstract
- Background and purpose Breakthrough disease on first-line injectables in relapsing-remitting multiple sclerosis (RRMS) is a common clinical situation where comparative studies between different escalation therapies are lacking. The aim of this study was to compare the efficacy, safety and medication persistence of natalizumab (NTZ), rituximab (RTX) and fingolimod (FGL) as escalation therapy in RRMS. Methods Patients switching from interferon or glatiramer acetate to NTZ, RTX or FGL due to breakthrough disease were identified through the Swedish multiple sclerosis (MS) registry at four large MS centers in this retrospective observational study. Data were collected from the MS registry and medical charts. Hazard ratios (HRs) for relapses, adverse events and drug discontinuation with 95% confidence interval (CI) were calculated using multivariable confounder-adjusted Cox proportional hazard models. Results A total of 241 patients were included. The annualized relapse rates were 0.02 for NTZ, 0.03 for RTX and 0.07 for FGL. Compared with NTZ, the adjusted HR for relapse was 1.0 (95% CI, 0.2-5.6) for RTX and 3.4 (95% CI, 1.3-9.2) for FGL. The annualized drug discontinuation rates were 0.15, 0.01 and 0.15 for NTZ, RTX and FGL, respectively. The adjusted HR for drug discontinuation was 0.05 (95% CI, 0.01-0.38) for RTX and 1.0 (95% CI, 0.6-1.7) for FGL vs. NTZ. Conclusions In patients with RRMS on interferon/glatiramer acetate with breakthrough disease, switching to NTZ or RTX was associated with less disease activity compared with FGL. RTX displayed superior medication persistence compared with both NTZ and FGL.
|
|
| 17. |
|
|
| 18. |
|
|
| 19. |
- Jönsson, Bo AG, et al.
(författare)
-
Tidstrender för och halter av persistenta fluorerade, klorerade och bromerade organiska miljögifter i serum samt ftalater i urin hos unga svenska män – Resultat från den tredje uppföljningsundersökningen år 2009-2010.
- 2010
-
Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Bakgrund:Studier av tidstrender för miljögifter är viktiga för riskvärdering och åtgärder för att minska exponeringen. Studiens huvudsyfte har varit att fortsatt undersöka halter och tidstrender för klorerade, bromerade och fluorerade POPar i serum och ftalatmetaboliter i urin hos mönstrande unga män. För detta har vi valt att använda oss av mönstringsundersökningen, som de flesta svenska män hittills har genomgått vid omkring 18 års ålder.Metoder:Mönstrande från fyra olika år har studerats. År 2000 samlades serumprover från 274 mönstrande och urinprover från 234, år 2004 samlades serum- och urinprover från 200 mönstrande, år 2006 serumprover från 200 mönstrande och till sist åren 2009-2010 serumprover från 100 mönstande och urinprover från 50. Serumproverna analyserades med gaskromatografi-masspektrometri (CG-MS) med avseende på 2,2’,4,4’,5,5’-hexaklorobifenyl (CB-153), p,p’-diklordifenyldikloreten (p,p´-DDE) samt bromerade difenyletrar (BDE). Urinproverna analyserades med vätskekromatografi-tandem MS med avseende på monoetylftalat (MEP), monobutylftalat (MBP), monobutylbenzylftalat (MBzP) och monoetylhexylftalat (MEHP). I urinproverna från 2009-2010 analyserades dessutom oxiderade ftalatmetaboliter till dietylhexylftalat: 5-hydroxy-MEHP, 5-oxo-MEHP och 5- karboxy-monoetylpentylftalat (5-cx-MEPP) samt diisononylftalat: 7-hydroxy-MiNP, 7-oxo- MiNP och 7-karboxy-monometylheptylftalat (7cx-MMeHP). Trender analyserades med Jonckheere-Terpstra testet.Resultat:Medianhalten i serum för CB-153 för åren 2000, 2004, 2006 och 2009/2010 var 65, 19, 34 och 22 ng/g fett. Medianhalten för p,p´-DDE för åren 2000, 2004, 2006 och 2009/2010 var 88, mindre än detektionsgränsen (De kreatininjusterade medianurinhalterna för åren 2000, 2004 och 2009-2010 var för MEP 83, 24 respektive 12 nmol/mmol, för MBP 24, 20 respektive 5 nmol/mmol samt för MBzP 4, 4 respektive 1 nmol/mmol. För MEHP var värdena Medianhalterna för BDE-47 var 1,32 (2006), respektive 0,63 ng/g blodfett (2009/2010), för BDE-99 0,38 ng/g blodfett respektive Även halter av perfluorerade ämnen bestämdes i proverna från år 2009/2010.Konklusion:Det har skett en påtaglig minskning av serumhalterna av CB-153 och p,p’-DDE hos unga män mellan 2000 och 2010 och beror säkerligen på att dessa ämnen inte längre används i Sverige sedan lång tid tillbaka. De minskade koncentrationerna av ftalatmetaboliter i urin avspeglar troligen en lägre exponeringsnivå till följd av en minskad användning av ftalater i olika produkter ute i samhället. Det finns dock andra ftalater där exponeringen i stället ökar enligt litteraturen. Halterna av de bromerade föreningarna minskade i de flesta fall vilket även detta beror på en minskad eller avslutad användning.
|
|
| 20. |
|
|
| 21. |
- Kimblad, Agnes, et al.
(författare)
-
Decreased sperm counts in Swedish users of oral tobacco
- 2022
-
Ingår i: Andrology. - : Wiley. - 2047-2919 .- 2047-2927. ; 10:6, s. 1181-1188
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Smoke-free tobacco via moist oral snuff (snus) is used daily in more than 20% of Swedish men. Negative effects of cigarette smoking on sperm parameters are well documented, unlike for snuff, despite relevance also for other smoke-free nicotine products. Objectives: We wanted to investigate whether reproductive parameters differed between users and non-users of snuff, and whether the amount of snuff and nicotine exposure mattered. Materials and methods: Men (n = 613) from the general population, recruited 2000–2010, were physically examined, answered questions on smoking and snuff use, and delivered urine, blood and semen samples. Sperm concentration, total sperm count, semen volume, percent morphologically normal and progressively motile sperm, and DNA fragmentation index (by the Sperm Chromatin Structure Assay) and reproductive hormones were analysed. Nicotine exposure was measured through urinary levels of cotinine. We used general linear models, with adjustments including cigarette smoking, and for semen parameters also abstinence time. Results: After adjustments, total sperm count was 24% lower (P = 0.03) and testosterone 14% higher (P < 0.001) in 109 users of snuff than in non-users, whereas cotinine was positively associated with testosterone and oestradiol (P < 0.001). Numbers of boxes of snuff used per week were associated with testosterone and FSH (P < 0.001). Discussion: Applied to the general population, the consumption of smoke-free tobacco by the use of snuff was associated with a lower sperm count and a higher testosterone, for which the extent seemed to play a role. Conclusions: Independent of smoking, consumption of snuff was associated with lower total sperm count and different hormone levels. Applying these results to a reported association between sperm count and the chance of pregnancy, men who used snuff would have about a 10% lower chance of fathering a child.
|
|
| 22. |
- Lindgren, Ida, et al.
(författare)
-
Association between follicle-stimulating hormone receptor polymorphisms and reproductive parameters in young men from the general population.
- 2012
-
Ingår i: Pharmacogenetics & Genomics. - 1744-6872. ; 22:9, s. 667-672
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Follicle-stimulating hormone (FSH) regulates gametogenesis through binding to its receptor (FSHR). In women, the Thr307Ala and Asn680Ser polymorphisms in the FSHR gene affect reproductive function, but it is not clear whether they have any impact on spermatogenesis and have mainly been investigated in infertile men of varying ages. The aim of the present study was therefore to examine whether these genetic variants of the FSHR influence reproductive parameters in men from the general population. METHODS: Men aged 17-20 years (n=313) were genotyped. All men provided a semen sample and a blood sample for hormonal measurements and DNA extraction. They underwent a medical examination and analyses of possible associations between Thr307Ala and Asn680Ser polymorphisms and hormonal and sperm parameters were subsequently carried out. RESULTS: Men homozygous for Thr307/Asn680 had a lower mean serum FSH concentration (3.07 vs. 3.65 IU/l, P=0.009), and higher mean serum estradiol (94.0 vs. 86.1 pmol/l, P=0.001), sex hormone-binding globulin (33.6 vs. 31.3 nmol/l, P<0.0001), and total testosterone (19.1 vs.17.9 nmol/l, P<0.0001) concentrations compared with men with other genotypes. In addition, sperm concentrations (71.9×10 vs. 70.8×10/ml, P=0.040) and the total sperm counts were higher (212×10 vs. 206×10, P<0.0001) and their testes volumes were larger (left: 11.5 vs. 11.0 ml, P<0.0001; right: 12.4 vs. 11.6 ml, P=0.002). CONCLUSION: As in women, the results from the present study indicate that variants of the FSHR influence reproductive parameters in men.
|
|
| 23. |
- Littorin, Margareta, et al.
(författare)
-
Kemiska bekämpningsmedel
- 2019. - Fjärde upplagan
-
Ingår i: Arbets- och miljömedicin : - en lärobok om hälsa och miljö - - en lärobok om hälsa och miljö. - 9789144127460 ; , s. 339-350
-
Bokkapitel (refereegranskat)
|
|
| 24. |
- Lu, Viktor, et al.
(författare)
-
The association between serum estradiol levels and sperm DNA integrity
- 2022
-
Ingår i: Environmental and Molecular Mutagenesis. - : Wiley. - 0893-6692 .- 1098-2280. ; 63:6, s. 268-274
-
Tidskriftsartikel (refereegranskat)abstract
- In men from the general population, BMI has been associated with a lower sperm DNA fragmentation index (DFI). We wondered whether this could be due to estradiol, which is associated with BMI and reported important for sperm function. Our objective was to investigate the association between estradiol and DFI. In 2008–2010, we recruited 284 young men from the general population to deliver samples of semen and blood and answer questionnaires. Serum concentrations of reproductive hormones and DFI were analyzed, the latter using the Sperm Chromatin Structure Assay. Associations were studied using general linear models. The first model utilized metric values of estradiol, whereas the second model compared men with high and low levels, dichotomized by the median value. A possible interaction between estradiol and testosterone was also examined. When investigating metric estradiol levels and DFI, an inverse association was seen without adjustments (p =.02), but the statistical significance was lost at adjustments for potential confounders (p =.08). Men with lower estradiol levels (<88 pmol/L, mean 71 pmol/L) had a statistically significantly higher DFI than men with higher levels of estradiol (≥88 pmol/L, mean 110 pmol/L). Mean ratio difference was 1.21 (p =.002) without adjustments and 1.18 (p =.01) with adjustments. A statistically significant difference in DFI was observed in men with testosterone levels below median when comparing high and low estradiol (p <.001). This study supports the idea that serum estradiol levels are protective for sperm DNA integrity, at least at lower testosterone levels.
|
|
| 25. |
- Norén, Erika, et al.
(författare)
-
Concentrations and temporal trends in pesticide biomarkers in urine of Swedish adolescents, 2000–2017
- 2020
-
Ingår i: Journal of Exposure Science and Environmental Epidemiology. - : Springer Science and Business Media LLC. - 1559-0631 .- 1559-064X. ; 30:4, s. 756-767
-
Tidskriftsartikel (refereegranskat)abstract
- Agricultural pesticides are extensively used for weed- and pest control, resulting in residues of these compounds in food. The general population is mainly exposed through dietary intake. Exposure to certain pesticides has been associated with adverse human health outcomes. Our aim was to assess urinary concentrations and temporal trends in the biomarkers of commonly used pesticides. Samples were collected from adolescents (n = 1060) in Scania, Sweden, from 2000 to 2017. Concentrations of 14 pesticide biomarkers were analyzed in urine using LC–MS/MS. Temporal trends in biomarker concentrations (ln-transformed) were evaluated using linear regression. Biomarkers of pyrethroids (3-PBA and DCCA), chlorpyrifos (TCPy), chlormequat (CCC), thiabendazole (OH-TBZ), and mancozeb (ETU) were detected in >90% of the population all sampling years. The biomarkers CCC and TCPy had the highest median concentrations (>0.8 µg/L), whereas the biomarkers of cyfluthrin (4F-3-PBA) and two pyrethroids (CFCA) had the lowest median concentrations (<0.02 µg/L). Increasing temporal trends were found for the biomarkers 3-PBA (3.7%/year), TCPy (1.7%/year) and biomarkers of pyrimethanil (11.9%/year) and tebuconazole (12.2%/year). Decreasing trends were found for CCC (–5.5%/year), OH-TBZ (−5.5%/year), and ETU (−3.9%/year). Our results suggest that Swedish adolescents are commonly exposed to pesticides in low concentrations (median concentrations <3.88 µg/L).
|
|
| 26. |
- Priskorn, Lærke, et al.
(författare)
-
RUBIC (ReproUnion Biobank and Infertility Cohort) : A binational clinical foundation to study risk factors, life course, and treatment of infertility and infertility-related morbidity
- 2021
-
Ingår i: Andrology. - : Wiley. - 2047-2919 .- 2047-2927. ; 9:6, s. 1828-1842
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Infertility affects 15%–25% of all couples during their reproductive life span. It is a significant societal and public health problem with potential psychological, social, and economic consequences. Furthermore, infertility has been linked to adverse long-term health outcomes. Despite the advanced diagnostic and therapeutic techniques available, approximately 30% of infertile couples do not obtain a live birth after fertility treatment. For these couples, there are no further options to increase their chances of a successful pregnancy and live birth. Objectives: Three overall questions will be studied: (1) What are the risk factors and natural life courses of infertility, early embryonic loss, and adverse pregnancy outcomes? (2) Can we develop new diagnostic and prognostic biomarkers for fecundity and treatment success? And (3) what are the health characteristics of women and men in infertile couples at the time of fertility treatment and during long-term follow-up?. Material and Methods: ReproUnion Biobank and Infertility Cohort (RUBIC) is established as an add-on to the routine fertility management at Copenhagen University Hospital Departments in the Capital Region of Denmark and Reproductive Medicine Centre at Skåne University Hospital in Sweden. The aim is to include a total of 5000 couples equally distributed between Denmark and Sweden. The first patients were enrolled in June 2020. All eligible infertile couples are prospectively asked to participate in the project. Participants complete an extensive questionnaire and undergo a physical examination and collection of biospecimens (blood, urine, hair, saliva, rectal swabs, feces, semen, endometrial biopsies, and vaginal swabs). After the cohort is established, the couples will be linked to the Danish and Swedish national registers to obtain information on parental, perinatal, childhood, and adult life histories, including disease and medication history. This will enable us to understand the causes of infertility and identify novel therapeutic options for this important societal problem.
|
|
| 27. |
- Salzer, Jonatan, et al.
(författare)
-
Rituximab in multiple sclerosis : a retrospective observational study on safety and efficacy
- 2016
-
Ingår i: Neurology. - 0028-3878 .- 1526-632X. ; 87:20, s. 2074-2081
-
Tidskriftsartikel (refereegranskat)abstract
- Objective: To investigate the safety and efficacy of rituximab in multiple sclerosis (MS). Methods: In this retrospective uncontrolled observational multicenter study, off-label rituximab-treated patients with MS were identified through the Swedish MS register. Outcome data were collected from the MS register and medical charts. Adverse events (AEs) grades 2-5 according to the Common Terminology Criteria for Adverse Events were recorded. Results: A total of 822 rituximab-treated patients with MS were identified: 557 relapsing-remitting MS (RRMS), 198 secondary progressive MS (SPMS), and 67 primary progressive MS (PPMS). At baseline, 26.2% had contrast-enhancing lesions (CELs). Patients were treated with 500 or 1,000 mg rituximab IV every 6-12 months, during a mean 21.8 (SD 14.3) months. During treatment, the annualized relapse rates were 0.044 (RRMS), 0.038 (SPMS), and 0.015 (PPMS), and 4.6% of patients displayed CELs. Median Expanded Disability Status Scale remained unchanged in RRMS (p = 0.42) and increased by 0.5 and 1.0 in SPMS and PPMS, respectively (p = 0.10 and 0.25). Infusion-related AEs occurred during 7.8% of infusions and most were mild. A total of 89 AEs grades >= 2 (of which 76 infections) were recorded in 72 patients. No case of progressive multifocal leukoencephalopathy was detected. Conclusions: This is the largest cohort of patients with MS treated with rituximab reported so far. The safety, clinical, and MRI findings in this heterogeneous real-world cohort treated with different doses of rituximab were similar to those reported in previous randomized controlled trials on B-cell depletion therapy in MS. Classification of evidence: This study provides Class IV evidence that for patients with MS, rituximab is safe and effective.
|
|
| 28. |
- Svenningsson, Anders, et al.
(författare)
-
Safety and efficacy of rituximab versus dimethyl fumarate in patients with relapsing-remitting multiple sclerosis or clinically isolated syndrome in Sweden: a rater-blinded, phase 3, randomised controlled trial
- 2022
-
Ingår i: Lancet Neurology. - : ELSEVIER SCIENCE INC. - 1474-4422 .- 1474-4465. ; 21:8, s. 693-703
-
Tidskriftsartikel (refereegranskat)abstract
- Background B-cell depleting therapies are highly efficacious in relapsing-remitting multiple sclerosis but one such therapy, rituximab, is not approved for multiple sclerosis and no phase 3 trial data are available. We therefore examined the safety and efficacy of rituximab compared with dimethyl fumarate in patients with relapsing-remitting multiple sclerosis to obtain data that might allow inclusion of rituximab in treatment guidelines. Methods RIFUND-MS was a multicentre, rater-blinded, active-comparator, phase 3, randomised controlled trial done at 17 Swedish university and community hospitals. Key inclusion criteria for participants were: age 18-50 years; relapsing-remitting multiple sclerosis or clinically isolated syndrome according to prevailing McDonald criteria; 10 years or less since diagnosis; untreated or only exposed to interferons or glatiramer acetate; and with clinical or neuroradiological disease activity in the past year. Patients were automatically randomly assigned (1:1) by the treating physician using a randomisation module in the Swedish multiple sclerosis registry, without stratification, to oral dimethyl fumarate 240 mg twice daily or to intravenous rituximab 1000 mg followed by 500 mg every 6 months. Relapse evaluation, Expanded Disability Status Scale rating, and assessment of MRI scans were done by examining physicians and radiologists masked to treatment allocation. The primary outcome was the proportion of patients with at least one relapse (defined as subacute onset of new or worsening neurological symptoms compatible with multiple sclerosis with a duration of more than 24 h and preceded by at least 30 days of clinical stability), assessed in an intention-to-treat analysis using log-binomial regression with robust standard errors. This trial is registered at ClinicalTrials.gov, NCT02746744. Findings Between July 1, 2016, and Dec 18, 2018, 322 patients were screened for eligibility, 200 of whom were randomly assigned to a treatment group (100 assigned to rituximab and 100 assigned to dimethyl fumarate). The last patient completed 24-month follow-up on April 21, 2021. 98 patients in the rituximab group and 97 patients in the dimethyl fumarate group were eligible for the primary outcome analysis. Three (3%) patients in the rituximab group and 16 (16%) patients in the dimethyl fumarate group had a protocol-defined relapse during the trial, corresponding to a risk ratio of 0.19 (95% CI 0.06-0.62; p=0.0060). Infusion reactions (105 events [40.9 per 100 patient-years]) in the rituximab group and gastrointestinal reactions (65 events [47.4 per 100 patient-years]) and flush (65 events [47.4 per 100 patient-years]) in the dimethyl fumarate group were the most prevalent adverse events. There were no safety concerns. Interpretation RIFUND-MS provides evidence that rituximab given as 1000 mg followed by 500 mg every 6 months is superior to dimethyl fumarate in preventing relapses over 24 months in patients with early relapsing-remitting multiple sclerosis. Health economic and long-term safety studies of rituximab in patients with multiple sclerosis are needed.
|
|
