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  • 1. Döring, Gerd
    et al.
    Elborn, J. Stuart
    Johannesson, Marie
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa.
    de Jonge, Hugo
    Griese, Matthias
    Smyth, Alan
    Heijerman, Harry
    Clinical trials in cystic fibrosis2007Inngår i: Journal of Cystic Fibrosis, ISSN 1569-1993, E-ISSN 1873-5010, Vol. 6, nr 2, s. 85-99Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    In patients with cystic fibrosis (CF), clinical trials are of paramount importance. Here, the current status of drug development in CF isdiscussed and future directions highlighted. Methods for pre-clinical testing of drugs with potential activity in CF patients including relevantanimal models are described. Study design options for phase II and phase III studies involving CF patients are provided, including requiredpatient numbers, safety issues and surrogate end point parameters for drugs, tested for different disease manifestations. Finally, regulatoryissues for licensing new therapies for CF patients are discussed, including new directives of the European Union and the structure of aEuropean clinical trial network for clinical studies involving CF patients is proposed.

  • 2.
    Gustafsson, Ingegerd
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk bakteriologi.
    Sjölund, Maria
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk bakteriologi.
    Torell, Erik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Infektionssjukdomar.
    Johannesson, Marie
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa.
    Engstrand, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk bakteriologi.
    Cars, Otto
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk bakteriologi.
    Andersson, Dan I.
    Bacteria with increased mutation frequency and antibiotic resistance are enriched in the commensal flora of patients with high antibiotic usage2003Inngår i: Journal of Antimicrobial Chemotherapy, ISSN 0305-7453, E-ISSN 1460-2091, Vol. 52, nr 4, s. 645-650Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: We examined how prolonged antibiotic treatment affected the resistance and mutation frequency of human microflora isolated from intestine (Escherichia coli, enterococci spp.), pharynx (alpha-streptococci) and nostril (coagulase-negative staphylococci, CoNS).

    METHODS: Samples were collected from patients at the Center of Cystic Fibrosis (n=18) and the haematology ward (n=18) of the University Hospital, Uppsala, Sweden. The individually used amount of antibiotics for 1 year was recorded as the defined daily dose (DDD). Primary health care patients (n=30), with no antibiotic treatment for 1 year before sampling, were used as controls. Three isolates of each bacterium from each patient were examined. Antibiotic susceptibilities were determined by disc diffusion. Mutation frequencies to rifampicin resistance were measured on 30 independent cultures of each bacterial species from each individual by plating on rifampicin agar plates. For alpha-streptococci the mutation frequency to streptomycin resistance was also determined.

    RESULTS: Isolates from patients with high antibiotic use showed a pronounced shift towards increased resistance and a small but significant increase in the mutation frequency compared with isolates from the controls. For E. coli, enterococci and CoNS the increase in geometric mean mutation frequency in the patient group was 3-, 1.8- and 1.5-fold, respectively (P values 0.0001, 0.016 and 0.012). For alpha-streptococci there was a significant difference in geometric mean mutation frequency between patient and control groups for streptomycin resistance (P=0.024) but not for rifampicin resistance (P=0.74).

    CONCLUSIONS: High antibiotic use selected for commensals with highly increased resistance and a slight increase in mutation frequency.

  • 3.
    Johannesson, M
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa.
    Effects of pregnancy on health: certain aspects of importance for women with cystic fibrosis2002Inngår i: Journal of Cystic Fibrosis, Vol. 1, s. 9-Artikkel i tidsskrift (Fagfellevurdert)
  • 4.
    Johannesson, M
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa.
    Services for adults with cystic fibrosis¹. Meeting report2002Inngår i: Journal of Cystic Fibrosis, Vol. 1, s. 103-Artikkel i tidsskrift (Fagfellevurdert)
  • 5.
    Johannesson, M
    et al.
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa.
    Lask, B
    Survival against the odds.2003Inngår i: Journal of Cystic Fibrosis, Vol. 2, s. 46-Artikkel i tidsskrift (Fagfellevurdert)
  • 6.
    Johannesson, M
    et al.
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa.
    Odegaard, I
    Maternal and fetal morbidity in pregnancies of Norwegian and Swedish women with cystic fibrosis.2003Inngår i: Pediatrics Review Journal, Vol. 3, s. 20-Artikkel i tidsskrift (Fagfellevurdert)
  • 7.
    Johannesson, Marie
    et al.
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa.
    Berglund, Eva Gil
    [The Medical Products Agency's preparations prior to the new EU regulation on children and drugs]2007Annet (Annet (populærvitenskap, debatt, mm))
  • 8.
    Johannesson, Marie
    et al.
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa.
    Vebert Olesen, Hanne
    Mehta, Gita
    Mehta, Anil
    Settin up a European registry for Cystic fibrosis -Lessons Learned2007Rapport (Annet (populærvitenskap, debatt, mm))
  • 9.
    Kollberg, Hans
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa.
    Carlander, David
    Olesen, Hanne
    Wejåker, Per-Erik
    Johannesson, Marie
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa.
    Larsson, Anders
    Oral administration of specific yolk antibodies (IgY) may prevent Pseudomonas aeruginosa infections in patients with cystic fibrosis: a phase I feasibility study2003Inngår i: Pediatric Pulmonology, ISSN 8755-6863, E-ISSN 1099-0496, Vol. 35, nr 6, s. 433-40Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Respiratory infection is the major cause of morbidity and mortality in cystic fibrosis (CF) patients. Chronic Pseudomonas aeruginosa (PA) infections ultimately occur in virtually all patients. It is impossible to eradicate PA when a patient has been chronically colonized. Immunotherapy with specific egg-yolk antibodies (IgY) may be an alternative to antibiotics for the prevention of PA infections. We wanted to determine if treatment with specific IgY can prolong the period between the first and the second PA colonization? And long-term, can the treatment diminish the number of positive PA cultures and postpone the onset of chronic colonization? CF patients gargled daily with an IgY-antibody preparation, purified from eggs of hens immunized with PA bacteria. They were compared to a group of patients who did not gargle with the preparation. Both groups had their first colonization with PA eradicated by antibiotics. The basic treatment was essentially the same in both groups. In the initial study, the period between the first and second colonization with PA was significantly prolonged for the treated vs. the control group (Kaplan-Meier P = 0.015, Breslow test). In the prolonged study, the treated group had only 2.5 sputum cultures positive for PA per 100 months of observation, and none of these patients became chronically colonized with PA. No adverse events were reported. In the control group, 13.7 cultures per 100 months of observation were positive for PA, and 5 (24%) patients became chronically colonized with PA. This feasibility study shows that antipseudomonal IgY has the potential to effectively prevent PA colonization without any severe adverse effects. A phase III study should be initiated.

  • 10.
    Kozlova, Inna
    et al.
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi.
    Vanthanouvong, Viengphet
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi.
    Johannesson, Marie
    Institutionen för kvinnors och barns hälsa.
    Roomans, Godfried M
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi.
    Composition of airway surface liquid determined by X-ray microanalysis.2006Inngår i: Ups J Med Sci, ISSN 0300-9734, Vol. 111, nr 1, s. 137-53Artikkel i tidsskrift (Fagfellevurdert)
  • 11.
    Nilsson, Elin
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk kemi.
    Kollberg, Hans
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa.
    Johannesson, Marie
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa.
    Wejåker, Per-Erik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk kemi.
    Carlander, David
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk kemi.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk kemi.
    More than 10 years' continuous oral treatment with specific immunoglobulin Y for the prevention of Pseudomonas aeruginosa infections: a case report2007Inngår i: Journal of Medicinal Food, ISSN 1096-620X, E-ISSN 1557-7600, Vol. 10, nr 2, s. 375-378Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Immunotherapy with specific antibodies is an alternative to antibiotics for the prevention of infections in humans and animals. We have used orally administered immunoglobulin Y (IgY) preparations, purified from eggs of hens immunized with Pseudomonas aeruginosa bacteria, to prevent pulmonary P. aeruginosa infections in a group of patients with cystic fibrosis (CF). Respiratory infections are major problems for CF patients because of the thick mucus in the airways, and chronic P. aeruginosa lung infections occur in virtually all CF patients and cause morbidity and mortality. The IgY-treated group had only 2.5 P. aeruginosa-positive sputum cultures per 100 months, and none of the IgY-treated patients became chronically colonized with P. aeruginosa. In the control group, 13.7 of the cultures per 100 months were positive for P. aeruginosa, and 24% of patients became chronically colonized with P. aeruginosa. The first enrolled patient in this study has now been treated continuously for more than 10 years. During the first 8 years she only had four P. aeruginosa-positive cultures. After 8 years she became chronically infected, but still after 10 years the bacteria have not turned mucoid. No negative side effects of IgY treatment have been noted during these 10 years. To our knowledge this is the longest treatment with specific yolk antibodies for therapeutic purposes.

  • 12.
    Nilsson, Harriet
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi.
    Dragomir, Anca
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi.
    Ahlander, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi.
    Johannesson, Marie
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi.
    Roomans, Godfried M.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi.
    Effects of hyperosmotic stress on cultured airway epithelial cells2007Inngår i: Cell and Tissue Research, ISSN 0302-766X, E-ISSN 1432-0878, Vol. 330, nr 2, s. 257-269Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Inhalation of hyperosmotic solutions (salt, mannitol) has been used in the treatment of patients with cystic fibrosis or asthma, but the mechanism behind the effect of hyperosmotic solutions is unclear. The relation between osmolarity and permeability changes was examined in an airway cell line by the addition of NaCl, NaBr, LiCl, mannitol, or xylitol (295–700 mOsm). Transepithelial resistance was measured as an indicator of the tightness of the cultures. Cell-cell contacts and morphology were investigated by immunofluorescence and by transmission electron microscopy, with lanthanum nitrate added to the luminal side of the epithelium to investigate tight junction permeability. The electrolyte solutions caused a significant decrease in transepithelial resistance from 450 mOsm upwards, when the hyperosmolar exposure was gradually increased from 295 to 700 mOsm; whereas the nonelectrolyte solutions caused a decrease in transepithelial resistance from 700 mOsm upwards. Old cultures reacted in a more rigid way compared to young cultures. Immuno-fluorescence pictures showed weaker staining for the proteins ZO-1, claudin-4, and plakoglobin in treated samples compared to the control. The ultrastructure revealed an increased number of open tight junctions as well as a disturbed morphology with increasing osmolarity, and electrolyte solutions opened a larger proportion of tight junctions than nonelectrolyte solutions. This study shows that hyperosmotic solutions cause the opening of tight junctions, which may increase the permeability of the paracellular pathway and result in increased transepithelial water transport.

  • 13. Odegaard, I
    et al.
    Stray-Pedersen, B
    Hallberg, K
    Haanaes, OC
    Storrosten, OT
    Johannesson, M
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa.
    Maternal and fetal morbidity in pregnancies of Norwegian and Swedish women with cystic fibrosis.2002Inngår i: Acta Obstet Gynecol Scand, Vol. 81, s. 698-Artikkel i tidsskrift (Fagfellevurdert)
  • 14. Odegaard, I
    et al.
    Stray-Pedersen, B
    Hallberg, K
    Haanaes, OC
    Storrosten, OT
    Johannesson, M
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa.
    Prevalence and outcome of pregnancies in Norwegian and Swedish women with cystic fibrosis.2002Inngår i: Acta Obstet Gynecol Scand, Vol. 81, s. 693-Artikkel i tidsskrift (Fagfellevurdert)
  • 15. Roomans, Godfried M
    et al.
    Ivanovs, Andrejs
    Shebani, Eyman B
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi. Institutionen för kvinnors och barns hälsa.
    Johannesson, Marie
    Institutionen för kvinnors och barns hälsa.
    Transmission electron microscopy in the diagnosis of primary ciliary dyskinesia.2006Inngår i: Ups J Med Sci, ISSN 0300-9734, Vol. 111, nr 1, s. 155-68Artikkel i tidsskrift (Fagfellevurdert)
  • 16. Schaedel, Charlotta
    et al.
    de Monestrol, I.
    Hjelte, L.
    Johannesson, Marie
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa.
    Kornfält, R.
    Lindblad, A.
    Strandvik, B.
    Wahlgren, L.
    Holmberg, L.
    Predictors of deterioration of lung function in cystic fibrosis2002Inngår i: Pediatric Pulmonology, ISSN 8755-6863, E-ISSN 1099-0496, Vol. 33, nr 6, s. 483-491Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The severity of lung disease in cystic fibrosis (CF) may be related to the type of mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, and to environmental and immunological factors. Since pulmonary disease is the main determinant of morbidity and mortality in CF, it is important to identify factors that can explain and predict this variation. The aim of this longitudinal study of the whole Swedish CF population over age 7 years was to correlate genetic and clinical data with the rate of decline in pulmonary function. The statistical analysis was performed using the mixed model regression method, supplemented with calculation of relative risks for severe lung disease in age cohorts.The severity of pulmonary disease was to some extent predicted by CFTR genotype. Furthermore, the present investigation is the first long-term study showing a significantly more rapid deterioration of lung function in patients with concomitant diabetes mellitus. Besides diabetes mellitus, pancreatic insufficiency and chronic Pseudomonas colonization were found to be negative predictors of pulmonary function. In contrast to several other reports, we found no significant differences in lung function between genders. Patients with pancreatic sufficiency have no or only a slight decline of lung function with age once treatment is started, but an early diagnosis in this group is desirable.

  • 17.
    Vanthanouvong, V
    et al.
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi.
    Kozlova, I
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi.
    Johannesson, M
    Institutionen för kvinnors och barns hälsa.
    Nääs, E
    Nordvall, L
    Institutionen för kvinnors och barns hälsa.
    Dragomir, A
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi.
    Roomans, G M
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi.
    Composition of nasal airway surface liquid in cystic fibrosis and other airway diseases determined by X-ray microanalysis.2006Inngår i: Microsc Res Tech, ISSN 1059-910X, Vol. 69, nr 4, s. 271-6Artikkel i tidsskrift (Fagfellevurdert)
  • 18.
    Varelogianni, Georgia
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi.
    Oliynyk, Igor
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi.
    Roomans, Godfried M.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi.
    Johannesson, Marie
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Allmänmedicin och preventivmedicin.
    The effect of N-acetylcysteine on chloride efflux from airway epithelial cells2010Inngår i: Cell Biology International, ISSN 1065-6995, E-ISSN 1095-8355, Vol. 34, nr 3, s. 245-252Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Defective chloride transport in epithelial cells increases mucus viscosity and leads to recurrent infections with high oxidative stress in patients with CF (cystic fibrosis). NAC (N-acetylcysteine) is a well known mucolytic and antioxidant drug, and an indirect precursor of glutathione. Since GSNO (S-nitrosoglutathione) previously has been shown to be able to promote Cl- efflux from CF airway epithelial cells, it was investigated whether NAC also could stimulate Cl- efflux from CF and non-CF epithelial cells and through which mechanisms. CFBE (CF bronchial epithelial cells) and normal bronchial epithelial cells (16HBE) were treated with 1 mM, 5 mM, 10 mM or 15 mM NAC for 4 h at 37 degrees C. The effect of NAC on Cl- transport was measured by Cl- efflux measurements and by X-ray microanalysis. Cl- efflux from CFBE cells was stimulated by NAC in a dose-dependent manner, with 10 mM NAC causing a significant increase in Cl- efflux with nearly 80% in CFBE cells. The intracellular Cl- concentration in CFBE cells was significantly decreased up to 60% after 4 h treatment with 10 mM NAC. Moreover immunocytochemistry and Western blot experiments revealed expression of CFTR channel on CFBE cells after treatment with 10 mM NAC. The stimulation of Cl- efflux by NAC in OF airway epithelial cells may improve hydration of the mucus and thereby be beneficial for OF patients.

  • 19. Wexler, Isaiah D
    et al.
    Johannesson, Marie
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa.
    Edenborough, Frank P
    Sufian, Beth S
    Kerem, Eitan
    Pregnancy and chronic progressive pulmonary disease.2007Inngår i: American Journal of Respiratory and Critical Care Medicine, ISSN 1073-449X, E-ISSN 1535-4970, Vol. 175, nr 4, s. 300-305Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Progressive pulmonary disease may preclude the option of pregnancy for a number of women in their child-bearing years due to the severity of the disease. For a subset of women with chronic lung disease including cystic fibrosis, pregnancy is possible, but can have a devastating effect both on the prospective mother and fetus. The potential hazards of pregnancy in cystic fibrosis or other progressive pulmonary diseases may trigger a moral conflict between physician and patient. The female patient may argue that her autonomy cannot be circumscribed and that the physician is obliged to assist her reproductive efforts. The physician can counter that his/her participation in potentially harmful interventions is not consistent with professional norms requiring adherence to the principles of beneficence and nonmaleficence. Whenever possible, the ethical conflict between physician and patient should be resolved before initiation of pregnancy. We propose that this best be done through structured negotiations between physician and patient with the goal of constructing an ethical framework for reducing the moral tension between the two. Steps in the negotiating process include defining the therapeutic alliance, information exchange, dialog, and deliberation. As part of the information exchange, it is important to discuss alternatives to pregnancy such as adoption and surrogacy, especially when there are strong contraindications to pregnancy. If negotiations reach a satisfactory conclusion for both sides, there should be a well-delineated consensual agreement to commence the pregnancy with the full support of the medical team.

  • 20. Zetterberg W,
    et al.
    Marteus, H
    Johannesson, M
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa.
    Nordvall, L
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa.
    Ihre, E
    Alving, K
    Exhaled carbon monoxide is not elevated in patients with asthma and cystic fibrosis.2002Inngår i: European Resp Journal., Vol. 1, s. 92-Artikkel i tidsskrift (Fagfellevurdert)
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