| 1. |
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| 2. |
- Stenberg, Å M, et al.
(författare)
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Lack of distant migration after injection of a 125iodine labeled dextranomer based implant into the rabbit bladder
- 1997
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Ingår i: Journal of Urology. - 0022-5347 .- 1527-3792. ; 158:5, s. 1937-1941
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE:In recent years endoscopic treatment of stress incontinence and vesicoureteral reflux has been introduced. Reports of possible particle migration of the injected material to distant organs in humans and experimental animals have led to a search for biological nonmigration products. An implant found to have a good clinical effect in these conditions is dextranomer in hyaluronan. We performed this study in rabbits to investigate the possible migration of dextranomer particles.MATERIALS AND METHODS:125Iodine labeled dextranomer particles were injected into the submucosal space of rabbit bladders, and samples of blood and various tissues were examined for radioactivity at scheduled intervals during a 28-day period. Furthermore, whole body autoradiography was performed 1 day, and 1 and 4 weeks after injection.RESULTS:Radioactivity was found in blood samples and in all tissues but it remained at the background activity level except in the thyroid, where uptake representing free 125iodine was detected. In the bladder 41 and 45% of the injected dose remained within the bladder wall 1 day and 4 weeks, respectively, after injection. The remainder of the dose probably disappeared from the bladder wall by leakage into the urine shortly after deposition, as indicated by the finding of 10-fold higher urine radioactivity levels at day 1 than at day 28 after injection.CONCLUSIONS:No distant migration of dextranomer particles occurs after submucosal injection of such an implant in the rabbit bladder wall.
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| 3. |
- Al-Mashhadi, Ammar, et al.
(författare)
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Changes of arterial pressure following relief of obstruction in adults with hydronephrosis
- 2018
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Ingår i: Upsala Journal of Medical Sciences. - : Uppsala Medical Society. - 0300-9734 .- 2000-1967. ; 123:4, s. 216-224
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Tidskriftsartikel (refereegranskat)abstract
- Background: As much as 20% of all cases of hypertension are associated with kidney malfunctions. We have previously demonstrated in animals and in pediatric patients that hydronephrosis causes hypertension, which was attenuated by surgical relief of the ureteropelvic junction (UPJ) obstruction. This retrospective cohort study aimed to investigate: (1) the proposed link between hydronephrosis, due to UPJ obstruction, and elevated arterial pressure in adults; and (2) if elevated blood pressure in patients with hydronephrosis might be another indication for surgery.Materials and methods: Medical records of 212 patients undergoing surgical management of hydronephrosis, due to UPJ obstruction, between 2000 and 2016 were assessed. After excluding patients with confounding conditions and treatments, paired arterial pressures (i.e. before/after surgery) were compared in 49 patients (35 years old; 95% CI 29–39). Split renal function was evaluated by using mercaptoacetyltriglycine (MAG3) renography before surgical management of the hydronephrotic kidney.Results: Systolic (−11 mmHg; 95% CI 6–15 mmHg), diastolic (−8 mmHg; 95% CI 4–11 mmHg), and mean arterial (-9 mmHg; 95% CI 6–12) pressures were significantly reduced after relief of the obstruction (p < 0.001). Split renal function of the hydronephrotic kidney was 39% (95% CI 37–41). No correlations were found between MAG3 and blood pressure level before surgery or between MAG3 and the reduction of blood pressure after surgical management of the UPJ obstruction.Conclusions: In adults with hydronephrosis, blood pressure was reduced following relief of the obstruction. Our findings suggest that elevated arterial pressure should be taken into account as an indication to surgically correct hydronephrosis.
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| 4. |
- Al-Mashhadi, Ammar Nadhom Farman, et al.
(författare)
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Changes in arterial pressure and markers of nitric oxide homeostasis and oxidative stress following surgical correction of hydronephrosis in children
- 2018
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Ingår i: Pediatric nephrology (Berlin, West). - : Springer. - 0931-041X .- 1432-198X. ; 33:4, s. 639-649
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Tidskriftsartikel (refereegranskat)abstract
- Objective Recent clinical studies have suggested an increased risk of elevated arterial pressure in patients with hydronephrosis. Animals with experimentally induced hydronephrosis develop hypertension, which is correlated to the degree of obstruction and increased oxidative stress. In this prospective study we investigated changes in arterial pressure, oxidative stress, and nitric oxide (NO) homeostasis following correction of hydronephrosis.Methods Ambulatory arterial pressure (24 h) was monitored in pediatric patients with hydronephrosis (n = 15) before and after surgical correction, and the measurements were compared with arterial pressure measurements in two control groups, i.e. healthy controls (n = 8) and operated controls (n = 8). Markers of oxidative stress and NO homeostasis were analyzed in matched urine and plasma samples.Results The preoperative mean arterial pressure was significantly higher in hydronephrotic patients [83 mmHg; 95% confidence interval (CI) 80–88 mmHg] than in healthy controls (74 mmHg; 95% CI 68–80 mmHg; p < 0.05), and surgical correction of ureteral obstruction reduced arterial pressure (76 mmHg; 95% CI 74–79 mmHg; p < 0.05). Markers of oxidative stress (i.e., 11- dehydroTXB2, PGF2α, 8-iso-PGF2α, 8,12-iso-iPF2α-VI) were significantly increased (p < 0.05) in patients with hydronephrosis compared with both control groups, and these were reduced following surgery (p < 0.05). Interestingly, there was a trend for increased NO synthase activity and signaling in hydronephrosis, which may indicate compensatory mechanism(s).Conclusion This study demonstrates increased arterial pressure and oxidative stress in children with hydronephrosis compared with healthy controls, which can be restored to normal levels by surgical correction of the obstruction. Once reference data on ambulatory blood pressure in this young age group become available, we hope cut-off values can be defined for deciding whether or not to correct hydronephrosis surgically.Keywords Blood pressure . Hydronephrosis . Hypertension . Nitric oxide . Oxidative stress . Ureteral obstruction
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| 5. |
- Al-Mashhadi, Ammar Nadhom Farman, et al.
(författare)
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Surgical treatment reduces blood pressure in children with unilateral congenital hydronephrosis
- 2015
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Ingår i: Journal of Pediatric Urology. - : Elsevier BV. - 1477-5131 .- 1873-4898. ; 11:2, s. 91.e1-91.e6
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Tidskriftsartikel (refereegranskat)abstract
- Objective Renal disorders can cause hypertension, but less is known about the influence of hydronephrosis on blood pressure. Hydronephrosis due to pelvo-ureteric junction obstruction (PUJO) is a fairly common condition (incidence in newborns of 0.5-1%). Although hypertensive effects of hydronephrosis have been suggested, this has not been substantiated by prospective studies in humans [1-3]. Experimental studies with PUJO have shown that animals with induced hydronephrosis develop salt-sensitive hypertension, which strongly correlate to the degree of obstruction [4-7]. Moreover, relief of the obstruction normalized blood pressure [8]. In this first prospective study our aim was to study the blood pressure pattern in pediatric patients with hydronephrosis before and after surgical correction of the ureteral obstruction. Specifically, we investigated if preoperative blood pressure is reduced after surgery and if split renal function and renographic excretion curves provide any prognostic information. Patients and methods Twelve patients with unilateral congenital hydronephrosis were included in this prospective study. Ambulatory blood pressure (24 h) was measured preoperatively and six months after surgery. Preoperative evaluations of bilateral renal function by Tc99m-MAG3 scintigraphy, and renography curves, classified according to O'Reilly, were also performed. Results As shown in the summary figure, postoperative systolic (103 +/- 2 mmHg) and diastolic (62 +/- 2 mmHg) blood pressure were significantly lower than those obtained preoperatively (110 +/- 4 and 69 +/- 2 mmHg, respectively), whereas no changes in circadian variation or pulse pressure were observed. Renal functional share of the hydronephrotic kidney ranged from 11 to 55%. There was no correlation between the degree of renal function impairment and the preoperative excretory pattern, or between the preoperative excretory pattern and the blood pressure reduction postoperatively. However, preoperative MAG3 function of the affected kidney correlated with the magnitude of blood pressure change after surgery. Discussion Correction of the obstruction lowered blood pressure, and the reduction in blood pressure appeared to correlate with the degree of renal functional impairment, but not with the excretory pattern. Thus, in the setting of hypertension, it appears that the functional share of the hydronephrotic kidney should be considered an indicator of the need for surgery, whereas the renography curve is less reliable. The strength of the present study is the prospective nature and that ambulatory blood pressure monitoring was used. Future longitudinal prolonged follow-up studies are warranted to confirm the present findings, and to understand if a real nephrogenic hypertension with potential necessity of treatment will develop. Conclusion This novel prospective study in patients with congenital hydronephrosis demonstrates a reduction in blood pressure following relief of the obstruction. Based on the present results, we propose that the blood pressure level should also be taken into account when deciding whether to correct hydronephrosis surgically or not.
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| 6. |
- Anderberg, Magnus, et al.
(författare)
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Laparoskopi och robotassisterad kirurgi
- 2015
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Ingår i: Grottes Barnkirurgi och barnurologi. - 9789144071510 ; , s. 51-54
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Bokkapitel (populärvet., debatt m.m.)
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| 7. |
- Arnell, Henrik, et al.
(författare)
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The genetics of primary nocturnal enuresis: inheritance and suggestion of a second major gene on chromosome 12q
- 1997
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Ingår i: Journal of Medical Genetics. - : BMJ. - 0022-2593 .- 1468-6244. ; 34:5, s. 360-5
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Tidskriftsartikel (refereegranskat)abstract
- Primary nocturnal enuresis (PNE), or bedwetting at night, affects approximately 10% of 6 year old children. Genetic components contribute to the pathogenesis and recently one locus was assigned to chromosome 13q. We evaluated the genetic factors and the pattern of inheritance for PNE in 392 families. Dominant transmission was observed in 43% and an apparent recessive mode of inheritance was observed in 9% of the families. Among the 392 probands the ratio of males to females was 3:1 indicating sex linked or sex influenced factors. Linkage to candidate regions was tested in 16 larger families segregating for autosomal dominant PNE. A gene for PNE was excluded from chromosome 13q in 11 families, whereas linkage to the interval D13S263-D13S291 was suggested (Zmax = 2.1) in three families. Further linkage analyses excluded about 1/3 of the genome at a 10 cM resolution except the region around D12S80 on chromosome 12q that showed a positive two point lod score in six of the families (Zmax = 4.2). This locus remains suggestive because the material was not sufficiently large to give evidence for heterogeneity. Our pedigree analysis indicates that major genes are involved in a large proportion of PNE families and the linkage results suggest that such a gene is located on chromosome 12q.
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| 8. |
- Barker, G. M., et al.
(författare)
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Distal shunt obstruction in children with meningomyelocele after bladder perforation
- 2006
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Ingår i: Journal of Urology. - : Ovid Technologies (Wolters Kluwer Health). - 0022-5347 .- 1527-3792. ; 176:4 Pt 2, s. 1726-1728
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: We studied short-term complications and particularly the signs of shunt dysfunction after augmented bladder perforation in patients with myelomeningocele and ventriculoperitoneal shunts. MATERIALS AND METHODS: In our series of bladder augmentations in 27 patients with myelomeningocele and a ventriculoperitoneal shunt in the last 10 years (1994 to 2004) we noted 4 who were 8 to 16 years old at our institute with bladder perforation 2 to 5 years after augmentation. Three patients received a colonic augmentation and 1 received an ileal augmentation. One patient underwent surgery for small bowel obstruction 2 years after the primary operation, when a hole in the augmented bladder was identified and oversewn. The other 3 bladder perforations occurred spontaneously or after failure to catheterize. An additional patient with spontaneous perforation underwent auto-augmentation elsewhere. RESULTS: After primary open abdominal surgery and enterocystoplasty there was no sign of shunt dysfunction in any patient. Bladder perforation and leakage of free urine into the abdominal cavity occurred in 4 of the 5 patients. In those patients severe symptoms of shunt dysfunction, including headache and high intracranial pressure, were noted 2 to 7 days after perforation. In patient 1 there was only urine leakage into a small cavity close to the bladder and no acute signs of post-perforation shunt dysfunction. In all cases the shunt was externalized for 1 to 6 weeks without further complications. CONCLUSIONS: In patients with myelodysplasia who have bladder perforation and free urine in the abdominal cavity the peritoneum is chemically inflamed by urine. Resorption of cerebral liquor may be disturbed, leading to shunt dysfunction and high intracranial pressure. Therefore, it is important for the urologist to recognize and evaluate postoperative signs and symptoms of increased intracerebral pressure in patients with bladder perforation. If found, early computerized tomography of the brain is recommended.
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| 9. |
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| 10. |
- Fors, Ronny, 1969-
(författare)
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Nickel allergy in a Swedish adolescent population and its relation to orthodontic treatment and lifestyle factors
- 2008
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Nickel stands out as the main cause of contact allergy in both children and adults, which has given rise to concern and the introduction of regulations by official bodies. Today´s youths are frequently exposed to body piercing and orthodontic treatment. Changes in youth lifestyle practices are also likely to influence nickel exposure and thus, the occurrence of nickel allergy. However, against patient and parental concern regarding nickel exposure to orthodontic appliances, often evoked by allergies following piercing, stand results from studies indicating that early orthodontic appliance treatment may reduce, rather than increase, prevalence of nickel allergy; a finding that has been suggested to result from tolerance induction by early exposure to nickel via the oral route. The objective of the present thesis was to investigate the association between nickel allergy and exposure to different orthodontic appliances and lifestyle, in particular piercing, as well as to study nickel release from orthodontic appliances into the oral cavity. Furthermore, one objective was to establish baseline prevalence data of nickel allergy in a Swedish adolescent population. Data was generated from a cross-sectional survey, in which about 6000 youths completed a questionnaire and almost 4500 of these were patch-tested for contact allergy. Information on exposure to orthodontic appliances was verified by dental records, whilst nickel content in saliva and dental biofilm was measured in a clinical study. Questionnaire data demonstrated a reduced risk of nickel allergy when orthodontic treatment preceded piercing (OR 0.5; 95 % CI 0.3-0.8) and similar results were found for data verified from dental records, however statistical significance was lost when adjusting for background factors (OR 0.6, 95 % CI 0.4-1.0). Exposure to full fixed appliances with NiTi-containing alloys, as well as a pooled ‘high nickel-releasing’ appliance group prior to piercing correlated with a significantly reduced risk of nickel allergy and a trend towards a reduced risk with exposure duration. Nickel could also be found in significantly higher concentrations from dental plaque samples, but not saliva samples, in orthodontic patients who were well into treatment compared to patients who had not been exposed to orthodontic appliances. The effect was not found to be due to differences in estimated dietary nickel intake between the two groups. Significantly more girls than boys (13.3 % versus 2.5 %) were found to be patch-test positive to nickel. Positive nickel tests were also most prevalent in occupational programmes and least prevalent in natural science programmes, indicating differences in lifestyle and exposure to nickel. Dropout from testing was handled using a missing-value analysis. This internal validation showed that our results overestimated the occurrence of nickel allergy to a minor degree. More girls than boys reported piercing, vegetarian/vegan diet, and smoking practices, whereas an interesting shift in tattooing prevalence was observed with a larger proportion of girls reporting this practice compared to boys. Sex, number of piercings, smoking and orthodontic appliance treatment prior to piercing were found to influence weighted risk estimates of nickel allergy. To conclude, although orthodontic patients are exposed to nickel intraorally, we found no increased risk of sensitising adolescents to nickel by the use of oral orthodontic appliances. On the contrary, early orthodontic treatment preceding piercing reduced the risk of nickel allergy by a factor of 1.5-2.0. This reduced risk appears to be associated with estimated nickel release of the appliance and duration of treatment, in all supporting a hypothesised induction of immunological tolerance via oral administration of nickel. Our study also showed a strong association between lifestyle and nickel allergy. Although there have been changes in lifestyle over time, as indicated by the strong shift in tattooing practices, no large change in nickel allergy prevalence was found compared with previous Swedish data. Our data will serve as a baseline for future studies of the effect of nickel exposure regulations, such as the Nickel Directive, and for studies of lifestyle changes and their effects on nickel allergy.
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| 11. |
- Gjuvsland, Arne B, et al.
(författare)
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Disentangling genetic and epigenetic determinants of ultrafast adaptation.
- 2016
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Ingår i: Molecular systems biology. - : EMBO. - 1744-4292. ; 12:12
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Tidskriftsartikel (refereegranskat)abstract
- A major rationale for the advocacy of epigenetically mediated adaptive responses is that they facilitate faster adaptation to environmental challenges. This motivated us to develop a theoretical-experimental framework for disclosing the presence of such adaptation-speeding mechanisms in an experimental evolution setting circumventing the need for pursuing costly mutation-accumulation experiments. To this end, we exposed clonal populations of budding yeast to a whole range of stressors. By growth phenotyping, we found that almost complete adaptation to arsenic emerged after a few mitotic cell divisions without involving any phenotypic plasticity. Causative mutations were identified by deep sequencing of the arsenic-adapted populations and reconstructed for validation. Mutation effects on growth phenotypes, and the associated mutational target sizes were quantified and embedded in data-driven individual-based evolutionary population models. We found that the experimentally observed homogeneity of adaptation speed and heterogeneity of molecular solutions could only be accounted for if the mutation rate had been near estimates of the basal mutation rate. The ultrafast adaptation could be fully explained by extensive positive pleiotropy such that all beneficial mutations dramatically enhanced multiple fitness components in concert. As our approach can be exploited across a range of model organisms exposed to a variety of environmental challenges, it may be used for determining the importance of epigenetic adaptation-speeding mechanisms in general.
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| 12. |
- Hagnerud, Sven, et al.
(författare)
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Deficit of CD47 results in a defect of marginal zone dendritic cells, blunted immune response to particulate antigen and impairment of skin dendritic cell migration.
- 2006
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Ingår i: Journal of Immunology. - 0022-1767. ; 176:10, s. 5772-8
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Tidskriftsartikel (refereegranskat)abstract
- CD47 is a ubiquitously expressed cell surface glycoprotein that associates with integrins and regulates chemotaxis, migration, and activation of leukocytes. CD47 is also a ligand for signal regulatory protein alpha, a cell surface receptor expressed on monocytes, macrophages, granulocytes, and dendritic cell (DC) subsets that regulates cell activation, adhesion, and migration. Although the function of CD47 in macrophages and granulocytes has been studied in detail, little is known about the role of CD47 in DC biology in vivo. In this study we demonstrate that CD47(-/-) mice exhibit a selective reduction of splenic CD11c(high)CD11b(high)CD8alpha(-)CD4(+) DCs. These DCs correspond to marginal zone DCs and express signal regulatory protein alpha, possibly explaining their selective deficiency in CD47(-/-) mice. Deficiency of marginal zone DCs resulted in impairment of IgG responses to corpusculate T cell-independent Ags. Although epidermal DCs were present in normal numbers in CD47(-/-) mice, their migration to draining lymph nodes in response to contact sensitization was impaired, while their maturation was intact. In vitro, CD47(-/-) mature DCs showed normal CCR7 expression but impaired migration to CCL-19, whereas immature DC response to CCL-5 was only slightly impaired. These results demonstrate a fundamental role of CD47 in DC migration in vivo and in vitro and in the function of marginal zone DCs.
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| 13. |
- Ibstedt, Sebastian, 1983, et al.
(författare)
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Concerted Evolution of Life Stage Performances Signals Recent Selection on Yeast Nitrogen Use.
- 2015
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Ingår i: Molecular biology and evolution. - : Oxford University Press (OUP). - 1537-1719 .- 0737-4038. ; 32:1, s. 153-161
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Tidskriftsartikel (refereegranskat)abstract
- Exposing natural selection driving phenotypic and genotypic adaptive differentiation is an extraordinary challenge. Given that an organism's life stages are exposed to the same environmental variations, we reasoned that fitness components, such as the lag, rate, and efficiency of growth, directly reflecting performance in these life stages, should often be selected in concert. We therefore conjectured that correlations between fitness components over natural isolates, in a particular environmental context, would constitute a robust signal of recent selection. Critically, this test for selection requires fitness components to be determined by different genetic loci. To explore our conjecture, we exhaustively evaluated the lag, rate, and efficiency of asexual population growth of natural isolates of the model yeast Saccharomyces cerevisiae in a large variety of nitrogen-limited environments. Overall, fitness components were well correlated under nitrogen restriction. Yeast isolates were further crossed in all pairwise combinations and coinheritance of each fitness component and genetic markers were traced. Trait variations tended to map to quantitative trait loci (QTL) that were private to a single fitness component. We further traced QTLs down to single-nucleotide resolution and uncovered loss-of-function mutations in RIM15, PUT4, DAL1, and DAL4 as the genetic basis for nitrogen source use variations. Effects of SNPs were unique for a single fitness component, strongly arguing against pleiotropy between lag, rate, and efficiency of reproduction under nitrogen restriction. The strong correlations between life stage performances that cannot be explained by pleiotropy compellingly support adaptive differentiation of yeast nitrogen source use and suggest a generic approach for detecting selection.
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| 14. |
- Kasetty, Gopinath, et al.
(författare)
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Osteopontin protects against pneumococcal infection in a murine model of allergic airway inflammation
- 2019
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Ingår i: Allergy: European Journal of Allergy and Clinical Immunology. - : Wiley. - 0105-4538. ; 74:4, s. 663-674
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Tidskriftsartikel (refereegranskat)abstract
- Background: In atopic asthma, chronic Th2-biased inflammation is associated with an increased risk of pneumococcal infection. The anionic phosphoglycoprotein osteopontin (OPN) is highly expressed in asthma and has been ascribed several roles during inflammation. This study aimed to investigate whether OPN affects inflammation and vulnerability to pneumococcal infection in atopic asthma. Methods: House dust mite (HDM) extract was used to induce allergic airway inflammation in both wild-type (Spp1+/+) and OPN knockout (Spp1−/−) C57BL/6J mice, and the airway was then infected with Streptococcus pneumoniae. Parameters reflecting inflammation, tissue injury, and bacterial burden were measured. In addition, samples from humans with allergic asthma were analyzed. Results: Both allergen challenge in individuals with allergic asthma and the intranasal instillation of HDM in mice resulted in increased OPN levels in bronchoalveolar lavage fluid (BALF). More immune cells (including alveolar macrophages, neutrophils, eosinophils, and lymphocytes) and higher levels of proinflammatory cytokines were found in Spp1−/− mice than in Spp1+/+ mice. Moreover, OPN-deficient mice exhibited increased levels of markers reflecting tissue injury. Upon infection with S. pneumoniae, Spp1+/+ mice with allergic airway inflammation had a significantly lower bacterial burden in both BALF and lung tissue than did Spp1−/− mice. Furthermore, Spp1−/− mice had higher levels of cytokines and immune cells in BALF than did Spp1+/+ mice. Conclusion: OPN reduces inflammation, decreases tissue injury, and reduces bacterial loads during concurrent pneumococcal infection and allergic airway inflammation in a murine model. These findings suggest that OPN significantly affects vulnerability to pneumococcal infection in atopic asthma.
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| 15. |
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| 16. |
- Koskinen, Cecilia, et al.
(författare)
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Lack of CD47 impairs bone cell differentiation and results in an osteopenic phenotype in vivo due to impaired signal regulatory protein α (SIRPα) signaling
- 2013
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Ingår i: Journal of Biological Chemistry. - 0021-9258 .- 1083-351X. ; 288:41, s. 29333-29344
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Tidskriftsartikel (refereegranskat)abstract
- Here, we investigated whether the cell surface glycoprotein CD47 was required for normal formation of osteoblasts and osteoclasts and to maintain normal bone formation activity in vitro and in vivo. In parathyroid hormone or 1α,25(OH)2-vitamin D3 (D3)-stimulated bone marrow cultures (BMC) from CD47(-/-) mice, we found a strongly reduced formation of multinuclear tartrate-resistant acid phosphatase (TRAP)(+) osteoclasts, associated with reduced expression of osteoclastogenic genes (nfatc1, Oscar, Trap/Acp, ctr, catK, and dc-stamp). The production of M-CSF and RANKL (receptor activator of nuclear factor κβ ligand) was reduced in CD47(-/-) BMC, as compared with CD47(+/+) BMC. The stromal cell phenotype in CD47(-/-) BMC involved a blunted expression of the osteoblast-associated genes osterix, Alp/Akp1, and α-1-collagen, and reduced mineral deposition, as compared with that in CD47(+/+) BMC. CD47 is a ligand for SIRPα (signal regulatory protein α), which showed strongly reduced tyrosine phosphorylation in CD47(-/-) bone marrow stromal cells. In addition, stromal cells lacking the signaling SIRPα cytoplasmic domain also had a defect in osteogenic differentiation, and both CD47(-/-) and non-signaling SIRPα mutant stromal cells showed a markedly reduced ability to support osteoclastogenesis in wild-type bone marrow macrophages, demonstrating that CD47-induced SIRPα signaling is critical for stromal cell support of osteoclast formation. In vivo, femoral bones of 18- or 28-week-old CD47(-/-) mice showed significantly reduced osteoclast and osteoblast numbers and exhibited an osteopenic bone phenotype. In conclusion, lack of CD47 strongly impairs SIRPα-dependent osteoblast differentiation, deteriorate bone formation, and cause reduced formation of osteoclasts.
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| 17. |
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| 18. |
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| 19. |
- Lundberg, Pernilla, et al.
(författare)
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Osteoclast formation is strongly reduced both in vivo and in vitro in the absence of CD47/SIRPalpha-interaction.
- 2007
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Ingår i: Biochemical and biophysical research communications. - : Elsevier BV. - 0006-291X .- 1090-2104. ; 352:2, s. 444-8
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Tidskriftsartikel (refereegranskat)abstract
- Physical interaction between the cell surface receptors CD47 and signal regulatory protein alpha (SIRPalpha) was reported to regulate cell migration, phagocytosis, cytokine production, and macrophage fusion. However, it is unclear if the CD47/SIRPalpha-interaction can also regulate macrophage colony-stimulating factor (M-CSF) and receptor activator of nuclear factor (NF)-kappaB ligand (RANKL)-stimulated formation of osteoclasts. Here, we show that functional blocking antibodies to either CD47 or SIRPalpha strongly reduced formation of multinucleated tartrate-resistant acid phosphatase (TRAP)+ osteoclasts in cultures of murine hematopoietic cells, stimulated in vitro by M-CSF and RANKL. In addition, the numbers of osteoclasts formed in M-CSF/RANKL-stimulated bone marrow macrophage cultures from CD47-/- mice were strongly reduced, and bones of CD47-/- mice exhibited significantly reduced osteoclast numbers, as compared with wild-type controls. We conclude that the CD47/SIRPalpha interaction is important for M-CSF/RANKL-stimulated osteoclast formation both in vivo and in vitro, and that absence of CD47 results in decreased numbers of osteoclasts in CD47-/- mice.
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| 20. |
- Lundmark, Elisabet, et al.
(författare)
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Effects of antidepressant therapy on voiding chart data andnocturnal urine production in children with enuresis – a randomized controlled study
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Introduction:Since a substantial minority of enuretic children does not respond to either first- or second-line treatment, there is still need for antidepressants in therapy-resistant enuresis. We recently published the results of a placebo-controlled study of the noradrenergic antidepressant reboxetine in this patient group. The drug was found to have a modest but statistically significant antienuretic effect. Aim:To determine whether reboxetine exerts its antienuretic effect via modulation of either bladder function or nocturnal urine production, as reflected by the voiding chart.Patients and Methods:The study had a randomized, double-blind cross-over design, with three treatment periods of four weeks each. The therapies given were 1) placebo, 2) reboxetine 4 mg + placebo and 3) reboxetine 4 mg + desmopressin 0.4 mg, all drugs given orally in the evening. During the last two weeks of each treatment period, the families were asked to complete a voiding chart in which day-time voiding frequency and voided volumes were documented during 48 hours. Nocturnal urine production was assessed via weighing of diapers. Results:No clear and consistent reboxetine effects were seen on either voiding parameters or nocturnal urine production. Neither did we find any significant difference in the voiding chart data of responders to active treatment, compared to that of non-responders.Discussion:This observation may have several different, non-exclusive explanations, one of which is that the anti-enuretic action of reboxetine is explained by the drug’s noradrenergic effects on arousal. It may also be the case that the voiding chart is too blunt an instrument to detect nocturnal, or indeed daytime, detrusor overactivity. It is thus not ascertained that the lack of reboxetine influence on the bladder variables actually precludes that the drug can affect detrusor function. The lack of difference in nocturnal urine production between treatment periods with and without desmopressin may indicate that nocturnal polyuria is of minor importance in therapy-resistant enuresis.Finally, it may obviously be the case that the number of patients was too small, since the power calculations underlying the determination of sample size in this study were made based on treatment response, not voiding chart variables.Conclusion:In this randomized, placebo-controlled study we found no effect on daytime voiding parameters or nocturnal urine production that can explain the antienuretic effect of reboxetine. This may indicate that the drug exerts its beneficial effects via noradrenergic modulation of arousal.
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| 21. |
- Lundmark, Elisabet, et al.
(författare)
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Reboxetine in therapy-resistant enuresis : a randomized placebo-controlled study
- 2016
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Ingår i: Journal of Pediatric Urology. - : Elsevier. - 1477-5131 .- 1873-4898. ; 12:6, s. 397.e1-397.e5
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: A significant minority of children with enuresis do not respond to either desmopressin or the enuresis alarm. Anticholinergics have not proven as successful as expected. The fourth evidence-based treatment, the tricyclic antidepressant imipramine, is cardiotoxic when overdosed, which has led to diminished use. Aim: The aim was to determine whether there is a role for the noradrenergic antidepressant reboxetine, as monotherapy or combined with desmopressin, in the treatment of enuresis in children who have not responded to standard therapy, and whether there are side effects involved. We also sought prognostic factors in anamnestic data and in the voiding chart. Patients and methods: The study was a randomized placebo-controlled study with a double-blind cross-over design, in which all patients underwent treatment during three 4-week periods, one with reboxetine 4 mg and placebo, one with reboxetine 4 mg and desmopressin, and one with double placebo treatment. The proportion of wet nights out of 14 was compared before treatment and during the last 2 weeks of each treatment period. Results: Eighteen patients were included. The reduction of wet nights was much better with either reboxetine in monotherapy or in combination with desmopressin than during the placebo period (p = 0.002) (Figure). However, only one patient achieved complete dryness, this during monotherapy. There were three intermediate responders to monotherapy and five to combination treatment. With reboxetine in monotherapy, six children experienced negative side effects compared with three with combination therapy, and two with placebo. All of these side effects were mild and reversible. Only one patient chose to cease treatment because of side effects. No prognostic factors were found in either the case history or in voiding chart data. Discussion: The present study, the first placebo-controlled trial, confirms that reboxetine is an evidence-based alternative to cardiotoxic antidepressant treatment in therapy-resistant enuresis. The fact that few patients achieved complete dryness may be due to the low dosage used. In our clinical practice we increase the dose to 8 mg when dryness is not achieved with the lower dose. Our experience is that this leaves more children with full response, but the evidence of this has yet to be shown. Conclusion: Reboxetine seems to be an alternative in the treatment of enuretic children who have not responded to standard treatment.
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| 22. |
- Lundmark, Elisabet
(författare)
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Therapy-resistant enuresis : In search of new therapies and prognostic markers
- 2019
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- A large minority of children with enuresis do not respond to treatment with either desmopressin or the enuresis alarm. Anticholinergics have not proven as successful as expected. The fourth evidence-based treatment of enuresis, the tricyclic antidepressant imipramine, is cardiotoxic when overdosed, which has led to diminished use. Since the long-term consequences of enuresis are potentially grave it is important that effective treatments of therapy-resistant enuresis are found.When investigating the enuretic child a full voiding-chart - in addition to the case history - is the method of choice. However, there is no robust evidence that daytime voiding chart data actually do predict nocturnal detrusor function.The aim of this thesis was to determine whether there is a role for the noradrenergic antidepressant reboxetine in the treatment of therapy-resistant enuresis, and whether anamnestic data and the voiding chart provides prognostic information regarding response to treatment with anticholinergics and antidepressants respectively in therapy-resistant patients.In a retrospective evaluation of 61 children who for humanitarian purposes had been treated with reboxetine 32(52%) responded to this treatment, 21 of them after desmopressin had been added. We then proceeded with a randomized placebo-controlled study with 18 patients, in which the reduction of wet nights was much better with either reboxetine in monotherapy or in combination with desmopressin than during the placebo period (p=0.002). However, no patient achieved complete dryness. No prognostic markers for therapy-response were found in either of these studies.In the randomized study we also sought to investigate whether reboxetine had any statistically significant effect on voiding-chart data. No such effect was found, but in respect to this secondary aim the sample size was too small. Nonetheless , this led to the speculation whether reboxetine exerts its antienuretic effect via modulation of arousal mechanisms.Prognostic markers were sought in a retrospective evaluation of 154 patients treated with anticholinergics or antidepressants, but few and inconsistent differences were found between the groups responding or not responding to the various treatment regimens, and this was true both for anamnestic and voiding chart data.In conclusion reboxetine seems to be an alternative in the treatment of enuretic children who have not responded to standard treatment, but further trials with higher doses and larger study populations are needed. The internationally recommended assessment of children with therapy-resistant enuresis does not seem to give the prognostic information intended.
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| 23. |
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| 24. |
- Läckgren, Göran, et al.
(författare)
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Endoscopic treatment of vesicoureteral reflux : current practice and the need formultifactorial assessment
- 2009
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Ingår i: Therapeutic Advances in Urology. - : SAGE Publications. - 1756-2880 .- 1756-2872. ; 1:3, s. 131-141
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Tidskriftsartikel (refereegranskat)abstract
- Vesicoureteral reflux (VUR) affects around 1% of all children. It carries an increased risk of febrile urinary-tract infections (UTIs) and is associated with impaired renal function. Antibiotic prophylaxis is an established approach to managing the condition, but it does not protect against UTI and encourages bacterial resistance. Ureteral re-implantation (open surgery) is a relatively traumatic procedure typically requiring hospitalization, and there is a risk of significant post-treatment complications. Endoscopic treatment with NASHA/Dx gel (Deflux) is minimally invasive, well tolerated and provides cure rates approaching those of open surgery: 8090% in several studies. It has also been shown to be effective in a variety of ‘complicated’ cases. Thus, endoscopic treatment is generally preferable to open surgery and long-term antibiotic prophylaxis. Non-treatment of VUR is being discussed as an alternative option, although this mainly appears suitable for children with low-grade reflux and normal kidneys. A new approach to managing VUR may be considered, with treatment decisions based not only on the grade of reflux but also on factors such as age, sex, renal scarring and bladder dysfunction. Open surgery would be reserved only for use in the 1015% of children notresponding to endoscopic treatment and those with severe ureteral anomalies.
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| 25. |
- Läckgren, Göran, 1942-, et al.
(författare)
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Endoscopic Treatment With Stabilized Nonanimal Hyaluronic Acid/Dextranomer Gel is Effective in Vesicoureteral Reflux Associated With Bladder Dysfunction
- 2007
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Ingår i: Journal of Urology. - : Ovid Technologies (Wolters Kluwer Health). - 0022-5347 .- 1527-3792. ; 177:3, s. 1124-1129
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: Endoscopic injection of stabilized nonanimal hyaluronic acid/dextranomer gel is an established treatment for vesicoureteral reflux in children. We performed a subgroup analysis to assess this treatment in reflux associated with bladder dysfunction. MATERIALS AND METHODS: Of 308 consecutive children treated endoscopically with stabilized nonanimal hyaluronic acid/dextranomer gel for dilating vesicoureteral reflux 54 were observed retrospectively to have bladder dysfunction. Initial followup consisted of voiding cystourethrogram at 3 and 12 months after injection, with positive response defined as reflux grade 0 or I. At 7 to 12 years following treatment patient charts were checked for urinary tract infections and bladder dysfunction, and a followup survey (postal questionnaire) was administered. RESULTS: A positive response to therapy (cure) was observed in 45 children (83%) after 1 to 3 endoscopic treatments. Concurrently, bladder dysfunction had resolved in 32 patients (59%). After the last stabilized nonanimal hyaluronic acid/dextranomer gel implantation 45 patients (83%) were free of urinary tract infections. Questionnaire results were similar to chart based findings. Stabilized nonanimal hyaluronic acid/dextranomer gel implantation was well tolerated, with no associated complications. CONCLUSIONS: Endoscopic treatment with stabilized nonanimal hyaluronic acid/dextranomer gel appears to be similarly effective in patients with vesicoureteral reflux with and without bladder dysfunction. These data indicate that bladder dysfunction should not be considered a contraindication to endoscopic treatment for reflux.
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