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- Axén, Jakob, et al.
(författare)
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An investigation of peak-broadening effects arising when combining CE with MS.
- 2007
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Ingår i: Electrophoresis. - : Wiley. - 0173-0835 .- 1522-2683. ; 28:18, s. 3207-3213
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Tidskriftsartikel (refereegranskat)abstract
- In this study, peak-broadening effects caused by nebulizing gas flow and lack of temperature control have been investigated for separation capillaries with three different inner diameters. The study was performed with serial UV/ESI-MS detection in an effort to distinguish between peak broadening arising in the separation and peak broadening arising in the ion source. The nebulizing gas was found to significantly affect both migration time and separation efficiency when using capillaries with 50 and 75 µm id. If the nebulizing gas is on during injection, the injection volume increases to such an extent that significant peak broadening is induced. Reducing the id to 25 µm minimizes the parabolic flow induced by the nebulizing gas. Results indicate that the nebulizing gas pressure can be optimized to minimize peak broadening in the ion source. A decrease in detection sensitivity, possibly related to the orthogonal design of the interface, was observed when the nebulizing gas pressure was increased. A tapered capillary tip was found to provide superior separation efficiency as well as sensitivity.
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- Axén, Jakob, et al.
(författare)
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Efforts to improve detection sensitivity for capillary electrophoresis coupled to atmospheric pressure photoionization mass spectrometry.
- 2010
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Ingår i: Rapid Communications in Mass Spectrometry. - : John Wiley & Sons Ltd. - 0951-4198 .- 1097-0231. ; 24:9, s. 1260-1264
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Tidskriftsartikel (refereegranskat)abstract
- Electrospray ionization performs best with volatile buffers. However, generally the best separation performance for capillary electrophoresis (CE) is achieved with non-volatile buffers. Hyphenation of CE with mass spectrometry (MS) utilizing atmospheric pressure photoionization (APPI) enables use of a wider range of separation buffers without compromising detection sensitivity. As APPI is considered to be mass flow sensitive, the use of a larger inner diameter separation capillary (75 microm) allows larger volumes to be injected, without decreased separation performance, thus providing improved sensitivity (approx. a factor of 10), compared to the use of a 25 microm capillary. However, nebulizing gas flow and position of capillary tip in the sprayer have to be carefully optimized to prevent excessive band broadening. Further improvement in sensitivity (approx. a factor of 2) was obtained by decreasing the distance between the sprayer and ionization region, indicating that a specially designed CE/APPI-MS interface for low flow rates will be favourable.
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- Eriksson, Carl, 1981-, et al.
(författare)
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Real-world effectiveness of vedolizumab in inflammatory bowel disease : week 52 results from the Swedish prospective multicentre SVEAH study
- 2021
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Ingår i: Therapeutic Advances in Gastroenterology. - : Sage Publications. - 1756-283X .- 1756-2848. ; 14
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Tidskriftsartikel (refereegranskat)abstract
- Background: Prospectively and systematically collected real-world data on vedolizumab are scarce. We aimed to assess the long-term clinical effectiveness of vedolizumab in inflammatory bowel disease (IBD).Methods: This study was a prospective, observational, multicentre study. Overall, 286 patients with active IBD were included (Crohn's disease, n = 169; ulcerative colitis, n = 117). The primary outcomes were clinical response at week 12 and clinical remission at week 52, based on the Harvey Bradshaw Index and the partial Mayo Clinic score. Secondary outcomes included clinical remission at week 12, clinical response at week 52, corticosteroid-free clinical remission at week 52, changes in biochemical measures, and health-related quality of life (HRQoL).Results: At baseline, 88% of the patients were exposed to anti-TNF and 41% of the patients with Crohn's disease had undergone ⩾1 surgical resection. At week 12, clinical response was 27% and remission 47% in Crohn's disease; corresponding figures in ulcerative colitis were 52% and 34%. Clinical response, remission and corticosteroid-free remission at week 52 were 22%, 41% and 40% in Crohn's disease and 49%, 47% and 46% in ulcerative colitis, respectively. A statistically significant decrease in median faecal-calprotectin and C-reactive protein was observed at 12 and 52 weeks in patients with Crohn's disease and ulcerative colitis. The HRQoL measures Short Health Scale and EuroQol 5-Dimensions improved in both Crohn's disease and ulcerative colitis patients (p < 0.001). Clinical disease activity at baseline was inversely associated with clinical remission at week 52.Conclusion: Vedolizumab proved effective for the treatment of refractory IBD in clinical practice.
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- Essén, Birgitta, et al.
(författare)
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Are some perinatal deaths in immigrant groups linked to sub-optimal perinatal care services? Perinatal audit of infants to women from Africa’s Horn delivered in Sweden 1990-96
- 2002
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Ingår i: BJOG: An International Journal of Obstetrics & Gynaecology. - : Wiley. - 1471-0528 .- 1470-0328. ; 109:6, s. 677-682
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To test the hypothesis that sub-optimal factors in perinatal care services resulting in perinatal deaths were more common among immigrant mothers from the Horn of Africa, as compared to Swedish mothers. Design: A perinatal audit, comparing cases of perinatal deaths among children of African immigrants residing in Sweden, with a stratified sample of cases among native Swedish women. Setting: Sixty-three cases of perinatal deaths among immigrant east African women delivered in Swedish hospitals in 1990–1996, and 126 cases of perinatal deaths among native Swedish women. Time of death and type of hospital were stratified. Main outcome measures: Sub-optimal factors in perinatal care services, categorised as maternal, medical care, and communication. Results: The rate of sub-optimal factors likely to result in potentially avoidable perinatal death was significantly higher among African immigrants. In the group of antenatal deaths, the OR was 6.2 (CI 1.9-20); the OR for intrapartal deaths was 13 (CI 1.1-166); and the OR for neonatal deaths was 18 (CI 3.3-100), when compared with Swedish mothers. The most common factors were delay in seeking health care, mothers refusing caesarean sections, insufficient surveillance of IUGR (intrauterine growth restriction), inadequate medication, misinterpretation of CTG (cardiotocography), and interpersonal miscommunication. Conclusions: Sub-optimal factors in perinatal care likely to result in perinatal death were significantly more common among east African than native Swedish mothers, affording insight into socio-cultural differences in pregnancy strategies, but also the sub-optimal performance of certain health-care routines in the Swedish perinatal care system.
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- Essén, Birgitta, et al.
(författare)
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Is there an association between female circumcision and perinatal death?
- 2002
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Ingår i: Bulletin of the World Health Organization. - 0042-9686. ; 80:8, s. 629-632
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: In Sweden, a country with high standards of obstetric care, the high rate of perinatal mortality among children of immigrant women from the Horn of Africa raises the question of whether there is an association between female circumcision and perinatal death. METHODS: To investigate this, we examined a cohort of 63 perinatal deaths of infants born in Sweden over the period 1990–96 to circumcised women. FINDINGS: We found no evidence that female circumcision was related to perinatal death. Obstructed or prolonged labour, caused by scar tissue from circumcision, was not found to have any impact on the number of perinatal deaths. CONCLUSION: The results do not support previous conclusions that genital circumcision is related to perinatal death, regardless of other circumstances, and suggest that other, suboptimal factors contribute to perinatal death among circumcised migrant women.
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- Gerde, Per, et al.
(författare)
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Regional lung targeting with a fluticasone/salmeterol aerosol using a bolus breath hold method of the PreciseInhale® system : A first evaluation in humans
- 2024
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Ingår i: European Journal of Pharmaceutical Sciences. - : Elsevier. - 0928-0987 .- 1879-0720. ; 196
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundIn development of inhaled drugs- and formulations the measured concentration in the systemic circulation is often used as a surrogate for local dosimetry in the lungs. To further elucidate regional differences in the fate of drugs in the lungs, different aerodynamic sizes of aerosols have been used to target major airway regions. An alternative approach to achieve regional targeting of aerosols, is to use a defined aerosol bolus together with a bolus breath hold strategy. A small volume of test aerosol is intercalated and stopped at different penetration depths, to achieve increased drug deposition at chosen lung locations. Drug permeation from the lung regions is then investigated by repeatedly sampling venous blood from the systemic circulation.The PreciseInhale® (PI) exposure platform was developed to allow generation of aerosols from different sources, including clinical inhalers, into a holding chamber, for subsequent use with alternative exposure modules in vitro and in vivo. In the current first-in-human study was investigated the feasibility of a new clinical exposure module added to the PI system. By extracting aerosol puffs from a medical inhaler for subsequent delivery to volunteers, it was possible to administer whole lung exposures, as well as regional targeting exposures.MethodsAerosols containing 250 µg/25 µg fluticasone propionate (FP)/salmeterol xinafoate (SMX) were automatically actuated and extracted from the pressurized Metered Dose Inhaler (pMDI) Evohaler Seretide forte into the PI system's holding chamber, then administered to the healthy volunteers using controlled flowrate and volume exposure cycles.Two main comparisons were made by measuring the systemic PK response: I. One label dose directly from the inhaler to the subject was compared to the same dose extracted from the pMDI into the PI system and then administered to the subject. II A small aerosol bolus at a penetration level in the central airways was compared to a small aerosol bolus at a penetration level in the peripheral lung.Results and ConclusionsWhen one inhaler dose was administered via the PI system, the absorbed dose, expressed as AUC24, was approximately twice as high and the CV was less than half, compared to direct inhalation from the same pMDI. Bolus breath hold targeting of drugs from the same aerosol mixture to the peripheral lung and the central airways showed a difference in their appearance in the systemic circulation. Normalized to the same deposited dose, SMX had a 57 % higher Cmax in the peripheral lung compared to the central airways. However, from 6 to 24 h after dosing the systemic concentrations of SMX from both regions were quite similar. FP had parallel concentrations curves with a 23 % higher AUC24 in the peripheral lung with no noticeable elevation around Cmax. The permeability of these two substances from similar sized aerosols was indeed higher in the thinner air/blood barriers of the peripheral lung compared to the central airways, but differences as measured on the venous side of the circulation were not dramatic. In conclusion, the PI system provided better control of actuation, aspiration, and dispensation of aerosols from the clinical inhaler and thereby delivered higher quality read outs of pharmacokinetic parameters such as tmax, Cmax, and AUC. Improved performance, using PI system, can likely also be employed for studying regional selectivity of other responses in the lungs, for use in drug development.
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