| 1. |
|
|
| 2. |
- Dahl, F, et al.
(författare)
-
Imaging single DNA molecules for high precision NIPT
- 2018
-
Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 8:1, s. 4549-
-
Tidskriftsartikel (refereegranskat)abstract
- Cell-free DNA analysis is becoming adopted for first line aneuploidy screening, however for most healthcare programs, cost and workflow complexity is limiting adoption of the test. We report a novel cost effective method, the Vanadis NIPT assay, designed for high precision digitally-enabled measurement of chromosomal aneuploidies in maternal plasma. Reducing NIPT assay complexity is achieved by using novel molecular probe technology that specifically label target chromosomes combined with a new readout format using a nanofilter to enrich single molecules for imaging and counting without DNA amplification, microarrays or sequencing. The primary objective of this study was to assess the Vanadis NIPT assay with respect to analytical precision and clinical feasibility. Analysis of reference DNA samples indicate that samples which are challenging to analyze with low fetal-fraction can be readily detected with a limit of detection determined at <2% fetal-fraction. In total of 286 clinical samples were analysed and 30 out of 30 pregnancies affected by trisomy 21 were classified correctly. This method has the potential to make cost effective NIPT more widely available with more women benefiting from superior detection and false positive rates.
|
|
| 3. |
|
|
| 4. |
- Bill-Axelson, Anna, et al.
(författare)
-
Radical prostatectomy versus watchful waiting in localized prostate cancer : the Scandinavian prostate cancer group-4 randomized trial
- 2008
-
Ingår i: Journal of the National Cancer Institute. - : Oxford University Press. - 0027-8874 .- 1460-2105. ; 100:16, s. 1144-1154
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The benefit of radical prostatectomy in patients with early prostate cancer has been assessed in only one randomized trial. In 2005, we reported that radical prostatectomy improved prostate cancer survival compared with watchful waiting after a median of 8.2 years of follow-up. We now report results after 3 more years of follow-up.METHODS: From October 1, 1989, through February 28, 1999, 695 men with clinically localized prostate cancer were randomly assigned to radical prostatectomy (n = 347) or watchful waiting (n = 348). Follow-up was complete through December 31, 2006, with histopathologic review and blinded evaluation of causes of death. Relative risks (RRs) were estimated using the Cox proportional hazards model. Statistical tests were two-sided.RESULTS: During a median of 10.8 years of follow-up (range = 3 weeks to 17.2 years), 137 men in the surgery group and 156 in the watchful waiting group died (P = .09). For 47 of the 347 men (13.5%) who were randomly assigned to surgery and 68 of the 348 men (19.5%) who were not, death was due to prostate cancer. The difference in cumulative incidence of death due to prostate cancer remained stable after about 10 years of follow-up. At 12 years, 12.5% of the surgery group and 17.9% of the watchful waiting group had died of prostate cancer (difference = 5.4%, 95% confidence interval [CI] = 0.2 to 11.1%), for a relative risk of 0.65 (95% CI = 0.45 to 0.94; P = .03). The difference in cumulative incidence of distant metastases did not increase beyond 10 years of follow-up. At 12 years, 19.3% of men in the surgery group and 26% of men in the watchful waiting group had been diagnosed with distant metastases (difference = 6.7%, 95% CI = 0.2 to 13.2%), for a relative risk of 0.65 (95% CI = 0.47 to 0.88; P = .006). Among men who underwent radical prostatectomy, those with extracapsular tumor growth had 14 times the risk of prostate cancer death as those without it (RR = 14.2, 95% CI = 3.3 to 61.8; P < .001).CONCLUSION: Radical prostatectomy reduces prostate cancer mortality and risk of metastases with little or no further increase in benefit 10 or more years after surgery.
|
|
| 5. |
|
|
| 6. |
|
|
| 7. |
- Hagell, Peter, et al.
(författare)
-
Apomorphine formulation may influence subcutaneous complications from continuous subcutaneous apomorphine infusion in Parkinson's disease
- 2020
-
Ingår i: Journal of Neurology. - 0340-5354 .- 1432-1459. ; 267:11, s. 3411-3417
-
Tidskriftsartikel (refereegranskat)abstract
- Continuous subcutaneous (s.c.) apomorphine infusion is an effective therapy for Parkinson's disease (PD), but a limitation is the formation of troublesome s.c. nodules. Various chemically non-identical apomorphine formulations are available. Anecdotal experiences have suggested that shifting from one of these (Apo-Go PumpFill®; apoGPF) to another (Apomorphine PharmSwed®; apoPS) may influence the occurrence and severity of s.c. nodules. We, therefore, followed 15 people with advanced PD (median PD-duration, 15 years; median "off"-phase Hoehn and Yahr, IV) on apoGPF and with troublesome s.c. nodules who were switched to apoPS. Data were collected at baseline, at the time of switching, and at a median of 1, 2.5, and 7.3 months post-switch. Total nodule numbers (P < 0.001), size (P < 0.001), consistency (P < 0.001), skin changes (P = 0.058), and pain (P ≤ 0.032) improved over the observation period. PD severity and dyskinesias tended to improve and increase, respectively. Apomorphine doses were stable, but levodopa doses increased by 100 mg/day. Patient-reported apomorphine efficacy tended to increase and all participants remained on apoPS throughout the observation period; with the main patient-reported reason being improved nodules. These observations suggest that patients with s.c. nodules caused by apoGPF may benefit from switching to apoPS in terms of s.c. nodule occurrence and severity. Alternatively, observed benefits may have been due to the switch itself. As nodule formation is a limiting factor in apomorphine treatment, a controlled prospective study comparing local tolerance with different formulations is warranted.
|
|
| 8. |
|
|
| 9. |
|
|
| 10. |
|
|
| 11. |
|
|
| 12. |
|
|
| 13. |
|
|
| 14. |
|
|
| 15. |
- Nowak, K, et al.
(författare)
-
Engineering Af1521 improves ADP-ribose binding and identification of ADP-ribosylated proteins
- 2020
-
Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11:1, s. 5199-
-
Tidskriftsartikel (refereegranskat)abstract
- Protein ADP-ribosylation is a reversible post-translational modification that regulates important cellular functions. The identification of modified proteins has proven challenging and has mainly been achieved via enrichment methodologies. Random mutagenesis was used here to develop an engineered Af1521 ADP-ribose binding macro domain protein with 1000-fold increased affinity towards ADP-ribose. The crystal structure reveals that two point mutations K35E and Y145R form a salt bridge within the ADP-ribose binding domain. This forces the proximal ribose to rotate within the binding pocket and, as a consequence, improves engineered Af1521 ADPr-binding affinity. Its use in our proteomic ADP-ribosylome workflow increases the ADP-ribosylated protein identification rates and yields greater ADP-ribosylome coverage. Furthermore, generation of an engineered Af1521 Fc fusion protein confirms the improved detection of cellular ADP-ribosylation by immunoblot and immunofluorescence. Thus, this engineered isoform of Af1521 can also serve as a valuable tool for the analysis of cellular ADP-ribosylation under in vivo conditions.
|
|
| 16. |
|
|
| 17. |
- Rockström, Johan, et al.
(författare)
-
A safe operating space for humanity
- 2013
-
Ingår i: The Future of Nature. - : Yale University Press. - 9780300184617 ; , s. 491-501
-
Bokkapitel (refereegranskat)
|
|
| 18. |
|
|
| 19. |
- Alm, Erik, 1980-, et al.
(författare)
-
Vibrational overtone combination spectroscopy (VOCSY)—a new way of using IR and NIR data
- 2007
-
Ingår i: Analytical and Bioanalytical Chemistry. - : Springer Science and Business Media LLC. - 1618-2642 .- 1618-2650. ; 388:1, s. 179-188
-
Tidskriftsartikel (refereegranskat)abstract
- This work explores a novel method for rearranging 1st order (one-way) infra-red (IR) and/or near infra-red (NIR) ordinary spectra into a representation suitable for multi-way modelling and analysis. The method is based on the fact that the fundamental IR absorption and the first, second, and consecutive overtones of NIR absorptions represent identical chemical information. It is therefore possible to rearrange these overtone regions of the vectors comprising an IR and NIR spectrum into a matrix where the fundamental, 1st, 2nd, and consecutive overtones of the spectrum are arranged as either rows or columns in a matrix, resulting in a true three-way tensor of data for several samples. This tensorization facilitates explorative analysis and modelling with multi-way methods, for example parallel factor analysis (PARAFAC), N-way partial least squares (N-PLS), and Tucker models. The vibrational overtone combination spectroscopy (VOCSY) arrangement is shown to benefit from the “order advantage”, producing more robust, stable, and interpretable models than, for example, the traditional PLS modelling method. The proposed method also opens the field of NIR for true peak decomposition—a feature unique to the method because the latent factors acquired using PARAFAC can represent pure spectral components whereas latent factors in principal component analysis (PCA) and PLS usually do not.
|
|
| 20. |
|
|
| 21. |
- Andersson, S O, et al.
(författare)
-
Prevalence of lower urinary tract symptoms in men aged 45-79 years : a population-based study of 40,000 Swedish men
- 2004
-
Ingår i: BJU International. - Karolinska Inst, Natl Inst Environm Med, SE-17177 Stockholm, Sweden. Univ Hosp Orebro, Dept Urol, Orebro, Sweden. Univ Hosp Orebro, Ctr Assessment Med Technol, Orebro, Sweden. Vasteras Hosp, Dept Urol, Vasteras, Sweden. : WILEY. - 1464-4096 .- 1464-410X. ; 94:3, s. 327-331
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE To estimate the age-specific prevalence and severity of lower urinary tract symptoms (LUTS) among Swedish men, the intercorrelations between different symptoms, and to assess quality of life and health-seeking behaviour among men with LUTS. SUBJECTS AND METHODS In 1997, an International Prostate Symptom Score (IPSS) questionnaire, together with other questions about lifestyle, was mailed to all men aged 45-79 years living in two counties in Sweden; the analyses included 39 928 men. RESULTS Overall, 18.5% and 4.8% of the men were moderately and severely symptomatic; the prevalence of at least one symptom was 83%. LUTS were strongly age-dependent, with 1.8% of severe symptoms among men aged 45-49 years and increasing to 9.7% among those 75-79 years old. Frequent urination was the most common symptom among men aged <70 years and nocturia among those aged >70 years. Symptoms like hesitancy, poor flow and intermittency were highly correlated with each other (Spearman coefficients 0.56-0.60). There was a high correlation between the IPSS and a poor score for quality of life resulting from the bothersomeness of LUTS (r = 0.70). Among symptomatic subjects, 36% reported a poor quality of life (fairly bad, very bad or terrible). Only 29% of symptomatic subjects (IPSS >7) reported that they had been diagnosed previously for their urinary problems, and only 11% received medication for that. CONCLUSION Although the prevalence of LUTS in Sweden is high, the percentage of men whose quality of life is substantially affected is much lower.
|
|
| 22. |
- Andrén, Lennart, 1946, et al.
(författare)
-
Circulatory effects of noise.
- 1983
-
Ingår i: Acta medica Scandinavica. - : Wiley. - 0001-6101. ; 213:1, s. 31-5
-
Tidskriftsartikel (refereegranskat)abstract
- Thirteen patients with mild essential hypertension, mean age 44 years (range 21-59), were studied during "stress" before and after postsynaptic alpha-adrenoceptor blockade and combined postsynaptic alpha- and non-selective beta-adrenoceptor blockade. Loud broad band noise (100 dBA for 10 min) was used as the stress stimulus. Exposure to noise caused a significant increase in systolic (7%, p less than 0.05), diastolic (9%, p less than 0.01) and mean arterial pressure (6%, p less than 0.01). The blood pressure elevation was caused by an increase in total peripheral resistance (12%, p less than 0.05). There was no significant change in heart rate, stroke volume or cardiac output. The blood pressure response during noise stimulation was not affected by postsynaptic alpha-adrenoceptor blockade (prazosin, 2 mg orally). The hemodynamic reaction pattern, however, was totally reversed. Thus, the cardiac output increased significantly (9%, p less than 0.05), while the total peripheral resistance tended to decrease. Combined postsynaptic alpha- and non-selective beta-adrenoceptor blockade (labetalol, 200 mg orally) inhibited the increase in systolic blood pressure caused by noise, while the diastolic and mean arterial pressures still increased significantly (5%, p less than 0.01). Labetalol effectively blocked the stress-induced increase in total peripheral resistance and there was no significant increase in cardiac output after combined alpha- and beta-adrenoceptor blockade. Exposure to noise caused a significant increase in circulating noradrenaline (20%, p less than 0.05). Plasma adrenaline and plasma renin activity were not affected by noise stimulation. These results suggest that blood pressure elevation is essential during "stress" but that the hemodynamic pattern causing blood pressure elevation may vary and may be affected by pharmacological blockade of various parts of the sympathetic nervous system.
|
|
| 23. |
- Barnett, A.H., et al.
(författare)
-
Angiotensin-receptor blockade versus converting-enzyme inhibition in type 2 diabetes and nephropathy
- 2004
-
Ingår i: New England Journal of Medicine. - 0028-4793 .- 1533-4406. ; 351:19, s. 1952-1961
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Few studies have directly compared the renoprotective effects of angiotensin II-receptor blockers and angiotensin-converting-enzyme (ACE) inhibitors in persons with type 2 diabetes. METHODS: In this prospective, multicenter, double-blind, five-year study, we randomly assigned 250 subjects with type 2 diabetes and early nephropathy to receive either the angiotensin II-receptor blocker telmisartan (80 mg daily, in 120 subjects) or the ACE inhibitor enalapril (20 mg daily, in 130 subjects). The primary end point was the change in the glomerular filtration rate (determined by measuring the plasma clearance of iohexol) between the baseline value and the last available value during the five-year treatment period. Secondary end points included the annual changes in the glomerular filtration rate, serum creatinine level, urinary albumin excretion, and blood pressure, the rates of end-stage renal disease and cardiovascular events, and the rate of death from all causes. RESULTS: After five years, the change in the glomerular filtration rate was -17.9 ml per minute per 1.73 m2 of body-surface area, where the minus sign denotes a decrement, with telmisartan (in 103 subjects), as compared with -14.9 ml per minute per 1.73 m2 with enalapril (in 113 subjects), for a treatment difference of -3.0 ml per minute per 1.73 m2 (95 percent confidence interval, -7.6 to 1.6 ml per minute per 1.73 m2). The lower boundary of the confidence interval, in favor of enalapril, was greater than the pre-defined margin of -10.0 ml per minute per 1.73 m2, indicating that telmisartan was not inferior to enalapril. The effects of the two agents on the secondary end points were not significantly different after five years. CONCLUSIONS: Telmisartan is not inferior to enalapril in providing long-term renoprotection in persons with type 2 diabetes. These findings do not necessarily apply to persons with more advanced nephropathy, but they support the clinical equivalence of angiotensin II-receptor blockers and ACE inhibitors in persons with conditions that place them at high risk for cardiovascular events. Copyright © 2004 Massachusetts Medical Society.
|
|
| 24. |
|
|
| 25. |
|
|
| 26. |
- Delaine, Tamara, 1981, et al.
(författare)
-
A structure activity relationship study of geranial derivatives
- 2012
-
Ingår i: Contact Dermatitis 11th congress of the European society of contact dermatitis (ESCD) 13-16 june 2012, Malmö, Sweden. - : Wiley. ; 66:Suppl. 2
-
Konferensbidrag (refereegranskat)abstract
- Background: Fragrances are common causes of contact allergy. Skin exposure to geranial is frequent since citral (mixture of geranial and neral) is commonly used in fragrances and flavors and is considered as a moderate allergen. Previous studies according to the local lymphnodeassay (LLNA)in micehaverevealed large variations in the sensitizing capacity of different geranial derivatives. Objectives: For a better understanding of these variations, a structure-activity relationship (SAR) study on a series of derivatives of geranial was carried out. Methods: The chemical reactivity of the compounds towards a model peptide was investigated using LC-MS. The adduct formation and the non-reacted peptide depletion were monitored. Adducts formed with model amino acids were investigated and structural determination was performed. Additional derivatives were synthesized and their sensitization potencies were evaluated in relation to their physicochemical and reactivity properties. Results: Most of the derivatives were shown to bind covalently to the cysteine residue of the model peptide. The percentage of depletion of the non-reacted peptide ranged from 0% to 100% after 24 hr, constant rate of depletion revealed a large difference between the fastest and lowest reacting derivatives. These resultswere congruent with the skin sensitization potencies obtained with the LLNA. Conclusions: A good correlation between the reactivity and the sensitizing potency was observed. Small changes in the chemical structure of geranial result in significant differences in sensitizing capacity and chemical reactivity. Conflicts of interest: The authors have declared no conflicts.
|
|
| 27. |
- Delaine, Tamara, 1981, et al.
(författare)
-
Epoxyalcohols: bioactivation and conjugation required for skin sensitization.
- 2014
-
Ingår i: Chemical research in toxicology. - : American Chemical Society (ACS). - 1520-5010 .- 0893-228X. ; 27:10, s. 1860-70
-
Tidskriftsartikel (refereegranskat)abstract
- Allylic alcohols, such as geraniol 1, are easily oxidized by varying mechanisms, including the formation of both 2,3-epoxides and/or aldehydes. These epoxides, aldehydes, and epoxy-aldehydes can be interconverted to each other, and the reactivity of them all must be considered when considering the sensitization potential of the parent allylic alcohol. An in-depth study of the possible metabolites and autoxidation products of allylic alcohols is described, covering the formation, interconversion, reactivity, and sensitizing potential thereof, using a combination of in vivo, in vitro, in chemico, and in silico methods. This multimodal study, using the integration of diverse techniques to investigate the sensitization potential of a molecule, allows the identification of potential candidate(s) for the true culprit(s) in allergic responses to allylic alcohols. Overall, the sensitization potential of the investigated epoxyalcohols and unsaturated alcohols was found to derive from metabolic oxidation to the more potent aldehyde where possible. Where this is less likely, the compound remains weakly or nonsensitizing. Metabolic activation of a double bond to form a nonconjugated, nonterminal epoxide moiety is not enough to turn a nonsensitizing alcohol into a sensitizer, as such epoxides have low reactivity and low sensitizing potency. In addition, even an allylic 2,3-epoxide moiety is not necessarily a potent sensitizer, as shown for 2, where formation of the epoxide weakens the sensitization potential.
|
|
| 28. |
- Delaine, Tamara, 1981, et al.
(författare)
-
Structure-Activity Relationship between the in Vivo Skin Sensitizing Potency of Analogues of Phenyl Glycidyl Ether and the Induction of Nrf2-Dependent Luciferase Activity in the KeratinoSens in Vitro Assay.
- 2011
-
Ingår i: Chemical research in toxicology. - : American Chemical Society (ACS). - 1520-5010 .- 0893-228X. ; 24:8, s. 1312-8
-
Tidskriftsartikel (refereegranskat)abstract
- Because of regulatory constraints and ethical considerations, research on alternatives to animal testing to predict the skin sensitization potential of novel chemicals has become a high priority. Ideally, these alternatives should not only predict the hazard of novel chemicals but also rate the potency of skin sensitizers. Currently, no alternative method gives reliable potency estimations for a wide range of chemicals in differing structural classes. Performing potency estimations within specific structural classes has thus been proposed. Detailed structure-activity studies for the in vivo sensitization capacity of a series of analogues of phenyl glycidyl ether (PGE) were recently published. These studies are part of an investigation regarding the allergenic activity of epoxy-resin monomers. Here we report data on the same chemicals in the KeratinoSens in vitro assay, which is based on a stable transgenic keratinocyte cell line with a luciferase gene under the control of an antioxidant response element. A strong correlation between the EC3 values in the local lymph node assay (LLNA) and both the luciferase-inducing concentrations and the cytotoxicity in the cell-based assay was established for six analogues of PGE. This correlation allowed the potency in the LLNA of two novel structurally closely related derivatives to be predicted by read-across with errors of 1.4- and 2.6-fold. However, the LLNA EC3 values of two structurally different bifunctional monomers were overpredicted on the basis of this data set, indicating that accurate potency estimation by read-across based on in vitro data might be restricted to a relatively narrow applicability domain.
|
|
| 29. |
- Dellve, Lotta, et al.
(författare)
-
Macrosocioeconomic determinants of occupational injuries and diseases among home care workers in Sweden : An ecosocial study
- 2003
-
Ingår i: Safety science monitor. - : International Network on Prevention of Accidents & Trauma at Work.
-
Konferensbidrag (refereegranskat)abstract
- The purpose of this study was to identify macro-socioeconomic determinants for the incidence of occupational injuries and diseases among home care workers. The study base was the total workforce of home care workers in Sweden during 1994-1998. In an ecological study design, data from three national databases were combined by record linkage. Descriptive and analytical statistics were used to estimate and interpret macro-socioeconomic determinants (economic resources, age structures of inhabitants and home care workers, unemployment, type of employment, size and location of municipality) for the incidence of occupational disorders among home care workers.
|
|
| 30. |
- Dellve, Lotta, et al.
(författare)
-
Socioeconomic determinants of occupational injuries and diseases among the total work force of home care workers in Sweden -An eco-epidemiological study
- 2003
-
Ingår i: Safety Science Monitor. - : IPSO Australia. - 1443-8844. ; 7:IV-I, s. 1-11
-
Tidskriftsartikel (refereegranskat)abstract
- The purpose of this study was to identify macro-socioeconomic determinants for the incidence of occupational injuries and diseases among home care workers. The study base was the total workforce of home care workers in Sweden during 1994-1998. In an ecological study design, data from three national databases were combined by record linkage. Descriptive and analytical statistics were used to estimate and interpret macro-socioeconomic determinants (economic resources, age structures of inhabitants and home care workers, unemployment, type of employment, size and location of municipality) for the incidence of occupational disorders among home care workers. A great variation in municipal incidence of occupational disorders was found when comparing various municipalities (10-184 occupational disorders/1000 full-time equivalent workers per year and municipality). The relation between the incidence of occupational disorders and macro-socioeconomic factors is complex. The investigated socioeconomic factors together explained 12-19 % of the differences in mean municipal occupational disorders but there were different explanations related to metropolitan regions and sparsely populated areas. The factors that had a potential to explain the differences were the age structure of inhabitants and home care workers, and unemployment. The economic resources, e.g. the gross expenses for the care of the elderly and handicapped, and the average income, or the employment conditions among the home care workers did not give any explanation for differences in occupational disorders. The group of privately employed home care workers (1-3 %) had a lower incidence of occupational disorders and were younger. The great difference in incidence of occupational disorders which appears when municipalities in Sweden are compared indicates a preventive potential. However, the relation between the incidence and macro-socioeconomic factors is complex. In order to better understand socio-environment phenomena related to occupational injuries, further studies are needed to explore the possible influence of the work system at the macro-, organisational- and micro-level.
|
|
| 31. |
|
|
| 32. |
|
|
| 33. |
- Hagvall, Lina, 1978, et al.
(författare)
-
Assessment of cross-reactivity of new less sensitizing epoxy resin monomers in epoxy resin-allergic individuals
- 2016
-
Ingår i: Contact Dermatitis. - : Wiley. - 0105-1873. ; 75:3, s. 144-150
-
Tidskriftsartikel (refereegranskat)abstract
- BackgroundMeasures to prevent occupational exposure to epoxy resins, including education, medical examination, and voluntary agreements between employers and workers, have not been effective enough to protect against skin sensitization. Therefore, alternatives to the major epoxy resin haptens that have been found to be less sensitizing in the local lymph node assay have been developed. ObjectivesTo study the cross-reactivity of two newly designed epoxy resin monomers, with decreased skin-sensitizing potency and good technical properties as compared with diglycidyl ether of bisphenol A (DGEBA), in subjects with known contact allergy to epoxy resin of DGEBA type. Patients and MethodsEleven individuals with previous positive patch test reactions to epoxy resin of DGEBA participated in the study. The two alternative epoxy resin monomers were synthesized and patch tested in dilution series in parallel with epoxy resin of DGEBA from the baseline series (containing 92% DGEBA). ResultsAll participants reacted to epoxy resin of DGEBA on retesting. Three participants reacted to monomer 1. No reactions were seen to monomer 2. ConclusionsThe alternative monomers studied showed little or no cross-reactivity with epoxy resin of DGEBA. Decreasing the risk of sensitization by using less sensitizing compounds is important, as contact allergy to epoxy resins is common in spite of thorough preventive measures.
|
|
| 34. |
- Hagvall, Lina, 1978, et al.
(författare)
-
Can the epoxides of cinnamyl alcohol and cinnamal show new cases of contact allergy?
- 2018
-
Ingår i: Contact dermatitis. - : Wiley. - 1600-0536 .- 0105-1873. ; 78:6, s. 399-405
-
Tidskriftsartikel (refereegranskat)abstract
- Cinnamyl alcohol is considered to be a prohapten and prehapten with cinnamal as the main metabolite. However, many individuals who are allergic to cinnamyl alcohol do not react to cinnamal. Sensitizing epoxides of cinnamyl alcohol and cinnamal have been identified as metabolites and autoxidation products of cinnamyl alcohol.To investigate the clinical relevance of contact allergy to epoxycinnamyl alcohol and epoxycinnamal.Irritative effects of the epoxides were investigated in 12 dermatitis patients. Epoxycinnamyl alcohol and epoxycinnamal were patch tested in 393 and 390 consecutive patients, respectively. In parallel, cinnamyl alcohol and cinnamal were patch tested in 607 and 616 patients, respectively.Both epoxides were irritants, but no more positive reactions were detected than when testing was performed with cinnamyl alcohol and cinnamal. Late allergic reactions to epoxycinnamyl alcohol were observed. In general, patients with late reactions showed doubtful or positive reactions to cinnamal and fragrance mix I at regular patch testing.The investigated epoxides are not important haptens in contact allergy to cinnamon fragrance. The high frequency of fragrance allergy among patients included in the irritancy study showed the difficulty of suspecting fragrance allergy on the basis of history; patch testing broadly with fragrance compounds is therefore important.
|
|
| 35. |
|
|
| 36. |
|
|
| 37. |
|
|
| 38. |
|
|
| 39. |
- Hansson, L, et al.
(författare)
-
Randomised trial of effects of calcium antagonists compared with diuretics and beta-blockers on cardiovascular morbidity and mortality in hypertension : the Nordic Diltiazem (NORDIL) study
- 2000
-
Ingår i: The Lancet. - 0140-6736 .- 1474-547X. ; 356:9227, s. 359-365
-
Tidskriftsartikel (refereegranskat)abstract
- Background Calcium antagonists are a first-line treatment for hypertension. The effectiveness of diltiazem, a nondihydropyridine calcium antagonist, in reducing cardiovascular morbidity or mortality is unclear. We compared the effects of diltiazem with that of diuretics, beta-blockers, or both on cardiovascular morbidity and mortality in hypertensive patients. Methods In a prospective, randomised, open, blinded endpoint study, we enrolled 10 881 patients, aged 50-74 years, at health centres in Norway and Sweden, who had diastolic blood pressure of 100 mm Hg or more. We randomly assigned patients diltiazem, or diuretics, beta-blockers, or both. The combined primary endpoint was fatal and non-fatal stroke, myocardial infarction, and other cardiovascular death. Analysis was done by intention to treat. Findings Systolic and diastolic blood pressure were lowered effectively in the diltiazem and diuretic and beta-blocker groups (reduction 20.3/18.7 vs 23.3/18.7 mm Hg, difference in systolic reduction p<0.001). A primary endpoint occurred in 403 patients in the diltiazem group and in 400 in the diuretic and beta-blocker group (16.6 vs 16.2 events per 1000 patient-years, relative risk 1.00 [95% CI 0.87-1.15], p=0.97). Fatal and non-fatal stroke occurred in 159 patients in the diltiazem group and in 196 in the diuretic and beta-blocker group (6.4 vs 7.9 events per 1000 patient-years, 0.80 [0.65-0.99], p=0.04) and fatal and non-fatal myocardial infarction in 183 and 157 patients (7.4 vs 6.3 events per 1000 patient-years, 1.16 [0.94-1.44], p=0.17). Interpretation Diltiazem was as effective as treatment based on diuretics, beta-blockers, or both in preventing the combined primary endpoint of all stroke, myocardial infarction, and other cardiovascular death.
|
|
| 40. |
|
|
| 41. |
|
|
| 42. |
|
|
| 43. |
|
|
| 44. |
- Högbom, Martin, et al.
(författare)
-
Crystal Structure of Conserved Domains 1 and 2 of the Human DEAD-box Helicase DDX3X in Complex with the Mononucleotide AMP
- 2007
-
Ingår i: Journal of Molecular Biology. - : Elsevier BV. - 0022-2836 .- 1089-8638. ; 372:1, s. 150-159
-
Tidskriftsartikel (refereegranskat)abstract
- DExD-box helicases are involved in all aspects of cellular RNA metabolism. Conserved domains 1 and 2 contain nine signature motifs that are responsible for nucleotide binding, RNA binding and ATP hydrolysis. The human DEAD-box helicase DDX3X has been associated with several different cellular processes, such as cell-growth control, mRNA transport and translation, and is suggested to be essential for the export of unspliced/partially spliced HIV mRNAs from the nucleus to the cytoplasm. Here, the crystal structure of conserved domains 1 and 2 of DDX3X, including a DDX3-specific insertion that is not generally found in human DExD-box helicases, is presented. The N-terminal domain 1 and the C-terminal domain 2 both display RecA-like folds comprising a central β-sheet flanked by α-helices. Interestingly, the DDX3X-specific insertion forms a helical element that extends a highly positively charged sequence in a loop, thus increasing the RNA-binding surface of the protein. Surprisingly, although DDX3X was crystallized in the presence of a large excess of ADP or the slowly hydrolyzable ATP analogue ATPγS the contaminant AMP was seen in the structure. A fluorescent-based stability assay showed that the thermal stability of DDX3X was increased by the mononucleotide AMP but not by ADP or ATPγS, suggesting that DDX3X is stabilized by AMP and elucidating why AMP was found in the nucleotide-binding pocket.
|
|
| 45. |
|
|
| 46. |
- Jendle, Johan, 1963-, et al.
(författare)
-
An exploration of intrapulmonary insulin administration in anaesthetized and mechanically ventilated pigs
- 1996
-
Ingår i: Scandinavian Journal of Clinical and Laboratory Investigation. - : Taylor & Francis. - 0036-5513 .- 1502-7686. ; 56:3, s. 251-258
-
Tidskriftsartikel (refereegranskat)abstract
- We investigated the efficacy of intrapulmonary administration of short-acting porcine insulin in anaesthetized pigs (n = 14) in a randomized intervention study. Insulin was administered by a new jet nebulizer (Maxin) in a random order at different doses, 0 (saline), 10 or 40 U. The hypoglycaemic effect was compared to control (0.9% saline). Blood glucose and serum insulin concentrations were followed at specified time intervals for 90 min. Plasma catecholamine concentrations were measured in order to estimate the concurrent stress. Nebulized insulin caused a significant decrease in blood glucose concentrations (p < 0.0001) (n = 28) at all doses used. The decrease in mean blood glucose concentration from the start of nebulization was 39 +/- 3% (mean +/- SEM), falling from 4.6 +/- 0.1 to 2.8 +/- 0.2 mmol 1(-1), with a nadir at 40 min after the 40 U insulin dose (n = 10). Serum insulin concentration rose from (mean +/- SEM) 5.2 +/- 0.1 to 25 +/- 9 mU 1(-1) after the insulin dose of 40 U (n = 10), the peak value occurred at 30 min. The plasma catecholamine concentrations increased significantly (p < 0.0001) (n = 28) from 0 to 60 min, this increase was similar for control and for different insulin doses. We conclude that intrapulmonary administration of insulin can cause a significant decrease in blood glucose concentrations in anaesthetized and mechanically ventilated pigs and results in clinically relevant serum insulin levels. Similar effects in humans would make inhaled insulin possible for clinical use.
|
|
| 47. |
- Jendle, Johan, 1963-, et al.
(författare)
-
Effects of intrapulmonary insulin in patients with non-insulin-dependent diabetes
- 1996
-
Ingår i: Scandinavian Journal of Clinical and Laboratory Investigation. - : Informa UK Limited. - 0036-5513 .- 1502-7686. ; 56:6, s. 555-561
-
Tidskriftsartikel (refereegranskat)abstract
- The effects of intrapulmonary insulin administration in non-insulin-dependent diabetes mellitus (NIDDM) were studied in 12 patients in a double-blind randomized placebo-controlled intervention study. Regular human insulin, 100 U ml-1, was given as an aerosol by oral inhalation after a 12-h fasting. A significant decrease in blood glucose concentration, from 10.2 +/- 0.5 to 6.1 +/- 0.5 mmol l-1 (p < 0.0001) and a significant rise in serum insulin concentration, from 11.2 +/- 1.8 to 28.0 +/- 2.6 mU ml-1 (p < 0.0001), was seen. Serum C-peptide levels decreased from 1.6 +/- 0.2 to 1.0 +/- 0.1 nmol l-1 (p < 0.0001). No side-effects were reported following aerosol inhalation. If similar results can be obtained when using this route for insulin administration to insulin-dependent diabetes mellitus patients, this may be a useful complement to traditional subcutaneous insulin injections in these patients.
|
|
| 48. |
- Jendle, Johan, 1963-, et al.
(författare)
-
Intrapulmonary administration of insulin to healthy volunteers
- 1996
-
Ingår i: Journal of Internal Medicine. - : Blackwell Science Ltd.. - 0954-6820 .- 1365-2796. ; 240:2, s. 93-98
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: To study the biological effects of nebulized insulin, administered intrapulmonary, to healthy volunteers.DESIGN: A double-blind, randomized, controlled intervention study.SETTING: The department of Internal Medicine, University Hospital, Linköping, Sweden.SUBJECTS: Eight healthy, non-smoking volunteers, with a mean age of 28 (range 22 to 56) years.INTERVENTIONS: Regular human insulin 100 U mL-1 (Actrapid) or 0.9% saline was given randomly as an oral inhalation. Insulin was given in three different doses (40, 80 and 160 U). Aerosol was generated by a new jet nebulizer.MAIN OUTCOME MEASURES: Blood glucose, serum insulin, and serum C-peptide.RESULTS: After the 160 U insulin dose the blood glucose concentration (mean +/- SE) fell from 4.3 +/- 0.2 to 2.8 +/- 0.2 mmol L-1 (P < 0.001), concomitant with an increase in mean serum insulin concentrations, rising from 9.5 +/- 1.5 to 26.1 +/- 2.5 mU L-1 (P < 0.001). Serum C-peptide concentrations simultaneously decreased from 0.48 +/- 0.03 to 0.12 +/- 0.02 mmol L-1 (P < 0.001). All changes were dose dependent. No adverse reactions were noted and no significant changes in lung function tests.CONCLUSIONS: Intrapulmonary insulin administration to healthy subjects can induce a significant hypoglycaemia and cause a clinically relevant increase in serum insulin concentrations. If similar results can be obtained when administering insulin to diabetic subjects, this insulin administration route can be a future complement to certain groups of patients.
|
|
| 49. |
|
|
| 50. |
- Karlberg, B, et al.
(författare)
-
DAC tries a new format, TrAC
- 2008
-
Ingår i: Trends in Analytical Chemistry. ; 27, s. 97-100
-
Tidskriftsartikel (refereegranskat)
|
|
