| 1. |
- Kappos, Ludwig, et al.
(författare)
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Siponimod versus placebo in secondary progressive multiple sclerosis (EXPAND): a double-blind, randomised, phase 3 study
- 2018
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Ingår i: The Lancet. - 0140-6736 .- 1474-547X. ; 391, s. 1263-1273
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Tidskriftsartikel (refereegranskat)abstract
- © 2018 Elsevier Ltd Background: No treatment has consistently shown efficacy in slowing disability progression in patients with secondary progressive multiple sclerosis (SPMS). We assessed the effect of siponimod, a selective sphingosine 1-phosphate (S1P) receptor 1,5 modulator, on disability progression in patients with SPMS. Methods: This event-driven and exposure-driven, double-blind, phase 3 trial was done at 292 hospital clinics and specialised multiple sclerosis centres in 31 countries. Using interactive response technology to assign numbers linked to treatme nt arms, patients (age 18–60 years) with SPMS and an Expanded Disability Status Scale score of 3·0–6·5 were randomly assigned (2:1) to once daily oral siponimod 2 mg or placebo for up to 3 years or until the occurrence of a prespecified number of confirmed disability progression (CDP) events. The primary endpoint was time to 3-month CDP. Efficacy was assessed for the full analysis set (ie, all randomly assigned and treated patients); safety was assessed for the safety set. This trial is registered with ClinicalTrials.gov, number NCT01665144. Findings: 1651 patients were randomly assigned between Feb 5, 2013, and June 2, 2015 (1105 to the siponimod group, and 546 to the placebo group). One patient did not sign the consent form, and five patients did not receive study drug, all of whom were in the siponimod group. 1645 patients were included in the analyses (1099 in the siponimod group and 546 in the placebo). At baseline, the mean time since first multiple sclerosis symptoms was 16·8 years (SD 8·3), and the mean time since conversion to SPMS was 3·8 years (SD 3·5); 1055 (64%) patients had not relapsed in the previous 2 years, and 918 (56%) of 1651 needed walking assistance. 903 (82%) patients receiving siponimod and 424 (78%) patients receiving placebo completed the study. 288 (26%) of 1096 patients receiving siponimod and 173 (32%) of 545 patients receiving placebo had 3-month CDP (hazard ratio 0·79, 95% CI 0·65–0·95; relative risk reduction 21%; p=0·013). Adverse events occurred in 975 (89%) of 1099 patients receiving siponimod versus 445 (82%) of 546 patients receiving placebo; serious adverse events were reported for 197 (18%) patients in the siponimod group versus 83 (15%) patients in the placebo group. Lymphopenia, increased liver transaminase concentration, bradycardia and bradyarrhythmia at treatment initiation, macular oedema, hypertension, varicella zoster reactivation, and convulsions occurred more frequently with siponimod than with placebo. Initial dose titration mitigated cardiac first-dose effects. Frequencies of infections, malignancies, and fatalities did not differ between groups. Interpretation: Siponimod reduced the risk of disability progression with a safety profile similar to that of other S1P modulators and is likely to be a useful treatment for SPMS. Funding: Novartis Pharma AG.
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| 2. |
- Lissbrant, Erik, et al.
(författare)
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Effects of haemorrhagic hypotension on the subcapsular artery and microvasculature of the rat testis.
- 2006
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Ingår i: Int J Androl. - : Wiley. ; 29:3, s. 434-440
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Tidskriftsartikel (refereegranskat)abstract
- Developing germ cells may be sensitive to even moderate reductions in blood flow. Surprisingly, however, experimental evidence suggests that the rat testis may be unable to maintain its blood flow during a decrease in systemic blood pressure. This study was therefore performed in order to answer the following questions: Is the testis able to maintain its blood flow during moderate to major reductions in blood pressure and, if so, at which level of the testicular vasculature (main artery or microcirculation) does this compensatory response take place? Moderate (−20%) and major (−40%) reductions in blood pressure were induced in anaesthetized rats by haemorrhage and the effects on testicular microvascular blood flow and subcapsular testicular artery diameter were examined by using laser Doppler flowmetry and in vivo video-microscopy respectively. Haemorrhagic hypotension led to decreased local testicular blood flow, but the relative reductions in flow were generally only half as large as the reductions in blood pressure. Hypotension also decreased the diameter of the main subcapsular testicular artery. During large reductions in blood pressure the subcapsular testicular artery constricts and testicular blood flow decreases. However, blood flow is reduced proportionally less than the mean arterial pressure, suggesting that local regulatory mechanisms are present in the testicular microvasculature, which may prevent blood flow from falling below a critical level.
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| 3. |
- Bartfay, Sven-Erik, et al.
(författare)
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Heart transplantation in patients bridged with mechanical circulatory support: outcome comparison with matched controls
- 2023
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Ingår i: Esc Heart Failure. - 2055-5822. ; 10:4, s. 2621-2629
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Tidskriftsartikel (refereegranskat)abstract
- AimsDue to the shortage of heart donors, increasing numbers of heart transplantation (HTx) candidates are receiving long-term mechanical circulatory support (MCS) as bridge-to-transplantation. Treatment with MCS is associated with increased formation of anti-human leukocyte antigen antibodies (allosensitization), but whether this affects post-HTx outcomes is unclear. Methods and resultsWe included all adult patients who received long-term MCS as bridge-to-transplantation and underwent subsequent HTx at our centre between 2008 and 2018. We also enrolled medically treated HTx recipients without prior MCS as controls. These controls were matched by age, sex, diagnosis, and transplantation era. Outcome parameters were compared between the two study groups. A total of 126 patients (48 +/- 15 years, 84% male) were included of whom 64 were bridged with MCS and 62 were matched controls. Pre-HTx allosensitization occurred more frequently in the MCS group than in the control group (27% vs. 11%, P = 0.03). At post-HTx year 10, the overall survival probability was 84% among patients treated with MCS and 90% among those medically managed (P = 0.32). At post-HTx year 1, freedom from treated rejections (>= ISHLT 2R) was 69% in the MCS group and 70% in the control group (P = 0.94); and freedom from any rejection was 8% and 5%, respectively (P = 0.98). There were no differences in renal function or cardiac allograft vasculopathy (grade >= 1) between groups at 1, 3, and 5 years post-HTx. ConclusionsAlthough patients treated with MCS had a higher frequency of pre-HTx allosensitization, there were no significant differences in post-HTx graft survival, biopsy-proven rejections, or renal function as compared with patients not bridged with MCS.
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| 4. |
- Bellner, Lars, 1973, et al.
(författare)
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A proinflammatory peptide from herpes simplex virus type 2 glycoprotein G affects neutrophil, monocyte, and NK cell functions
- 2005
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Ingår i: J Immunol. - : American Association of Immunologists. ; 174:4, s. 2235-2241
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Tidskriftsartikel (refereegranskat)abstract
- We have identified a synthetic peptide derived from the secreted portion of HSV type 2 glycoprotein G, denoted gG-2p20, which has proinflammatory properties in vitro. The gG-2p20 peptide, corresponding to aa 190-205 of glycoprotein G-2, was a chemoattractant for both monocytes and neutrophils in a dose-dependent fashion, and also induced the release of reactive oxygen from these cells. The receptor mediating the responses was identified as the formyl peptide receptor. The gG-2p20-induced activation of phagocytes had a profound impact on NK cell functions. The reactive oxygen species produced by gG-2p20-activated phagocytes both inhibited NK cell cytotoxicity and accelerated the apoptotic cell death in NK cell-enriched lymphocyte populations. Hence, we have for the first time been able to identify a potential function of the secreted portion of HSV-2 glycoprotein G. We propose that the proinflammatory gG-2p20 peptide identified could contribute to a reduced function and viability of NK cells during HSV-2 infection due to its ability to recruit and activate phagocytic cells.
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| 5. |
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| 6. |
- Bergh, Jan-Erik, et al.
(författare)
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Anoxic treatment of a moth-infected saddle
- 2000
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Ingår i: Nordisk Museologi. - Sorö, Danmark : Museumshöjskolen. - 1103-8152. ; :2, s. 119-122
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Pest insects pose a continuous and serious threat to museum objects that are organic in origin. Traditionally various chemical substances have been used for insect control, but in recent decades there has been increased concern about the disadvantages of this type of control strategy (Dawson 1988). Among the alternative control methods developed for museum use in recent decades, low oxygen treatment (Gilberg 1991)is of special interest. Using nitrogen or argon to replace oxygen, produces no residues and allows a conditioning of the gas regarding temperature and relative humidity. The first practical application in the Nordic countries of this method took place at Skokloster Castle in Central Sweden.
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| 7. |
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| 8. |
- Bergh, Jan-Erik, et al.
(författare)
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Barns bilder av forskare
- 2005
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Ingår i: Rikskonferensen för ämnesdidaktik. - Karlstad.
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)
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| 9. |
- Bergh, Jan-Erik, et al.
(författare)
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Insect DNA Exposed to Two Insecticides
- 2007
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Ingår i: International Conference Directions in Preventive Conservation Sibiu. - Sibiu, Rumänien.
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Analyses of DNA is now a standard method in exploring taxonomical relationships between taxa or when studying intraspecific genetic variation. For these purposes museum specimen are often used. During their “museum history”, biological collections often have been treated with various insecticides to avoid museum pest attacks. There is a risk that some insecticides have more or less destroyed the specimen DNA, and thus it is important to know to what extent this happens to be able to estimate if old collection are useful for DNA screening and also to avoid future mistakes. Kigawa et al. (2003) showed that methyl bromide, methyl bromide/ethylene oxide (mixed), ethylene oxide, propylene oxide and methyl iodide all caused degradation of DNA in samples of mushroom and chicken muscle. We have tested possible negative effects on insect DNA from exposure of paradichlorobenzene and diclorvos. Species used were Schistocerca gregaria (Orthoptera), Musca domestica (Diptera), Dermestes hemeroidalis (Coleoptera), Periplaneta americana (Blattodea). The specimens were cut into two parts before completely dried in silica gel in closed containers for about 2 weeks. Three serials were set up in sealed, small glass containers for each species: (1) paradichlorobenzene (0.5g ±0.02g, representing saturated concentration); (2) diclorvos (0.5g ±0.02g, representing saturated concentration); and (3) no chemicals (blank). Each serial was sampled after 1 and 4 weeks. Immediately after sampling, the insect tissues were exposed to clean air for 8 hours in order to eliminate chemicals from the tissue before subsequent treatment. Together with the blank samples, the exposed tissues were stored in deep freezers before extracted for DNA after the last tissue sampling. After extraction, a 658 bp (base pair) COI gene fragment of the DNA was amplified using the forward and reverse primers HCO2198 (TAA ACT TCA GGG TGA CCA AAA AAT CA) and HCOout (CCA GGT AAA ATT AAA ATA TAA ACT TC), respectively. Electrophoresis of the PCR products was run for about 2h and presence or absence of the amplified COI gene fragment showed as band or absence of band in UV light. The gel was photographed for documentation of the results. For S. gregaria we did not obtain any clear results, probably because the primer did not work for the COI gene of this species. For the other three species no effect could be seen from the exposure of paradichlorobenzene, while dichlorvos destroyed the COI gene fragment after 28 days. For M. domestica a band was present after one week exposure. Our conclusion is that dichlorvos has a deteriorating effect on DNA. A more extensive experimental series on M. domestica has been started at the Swedish Museum of Natural History. Reference: Kigawa, R., Nochide, H., Kimura, H. and Miura, S., Effects of various fumigants, thermal methods and carbon dioxide treatment on DNA extraction and amplification: A case study on freeze-dried mushroom and free-dried muscle specimens. Collection Forum 2003, 18 (1-2): 74-89.
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