| 1. |
- Gotherstrom, Cecilia, et al.
(författare)
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Pre- and Postnatal Transplantation of Fetal Mesenchymal Stem Cells in Osteogenesis Imperfecta : A Two-Center Experience
- 2014
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Ingår i: Stem Cells Transnational Medicine. - : Oxford University Press (OUP). - 2157-6564 .- 2157-6580. ; 3:2, s. 255-264
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Tidskriftsartikel (refereegranskat)abstract
- Osteogenesis imperfecta (OI) can be recognized prenatally with ultrasound. Transplantation of mesenchymal stem cells (MSCs) has the potential to ameliorate skeletal damage. We report the clinical course of two patients with OI who received prenatal human fetal MSC (hfMSC) transplantation and postnatal boosting with same-donor MSCs. We have previously reported on prenatal transplantation for OI type III. This patient was retransplanted with 2.8 x 10(6) same-donor MSCs per kilogram at 8 years of age, resulting in low-level engraftment in bone and improved linear growth, mobility, and fracture incidence. An infant with an identical mutation who did not receive MSC therapy succumbed at 5 months despite postnatal bisphosphonate therapy. A second fetus with OI type IV was also transplanted with 30 x 10(6) hfMSCs per kilogram at 31 weeks of gestation and did not suffer any new fractures for the remainder of the pregnancy or during infancy. The patient followed her normal growth velocity until 13 months of age, at which time longitudinal length plateaued. A postnatal infusion of 10 x 10(6) MSCs per kilogram from the same donor was performed at 19 months of age, resulting in resumption of her growth trajectory. Neither patient demonstrated alloreactivity toward the donor hfMSCs or manifested any evidence of toxicities after transplantation. Our findings suggest that prenatal transplantation of allogeneic hfMSCs in OI appears safe and is of likely clinical benefit and that retransplantation with same-donor cells is feasible. However, the limited experience to date means that it is not possible to be conclusive and that further studies are required.
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| 2. |
- Johansson, Ann-Katrin, et al.
(författare)
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Eating disorders : knowledge, attitudes, management and clinical experience of Norwegian dentists
- 2015
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Ingår i: BMC Oral Health. - : BioMed Central (BMC). - 1472-6831. ; 15
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Tidskriftsartikel (refereegranskat)abstract
- Background: The purpose of this study was to investigate knowledge, attitudes and clinical experience with regard to patients with eating disorders (ED) among Norwegian dentists. Methods: In 2010, a questionnaire was sent to all dentists in Norway (N = 4282) comprising 33 questions related to demographics of the participating dentists, their knowledge of ED (general and oral health aspects), clinical experience, attitudes and perceived management preferences. Results: The participation rate was 40 % (47 % women and 53 % men). Their knowledge about ED was often retrieved from common media sources and the greater part of the participants reported they had seen very few patients with ED during their professional career. Female dentists reported superior knowledge about ED compared to males, but the former experienced greater difficulties to inform about the condition. Referrals of the patient to other health facilities were significantly more common among female compared to male dentists. The majority of dentists (76 %) reported a need of more education related to ED management. Conclusions: The Norwegian dentists in this study reported limited clinical experience and insufficient knowledge regarding ED. There is therefore a need to increase both undergraduate and continuing education in this field, which can improve preventive and management measures that a dentist can provide for ED patients.
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| 3. |
- Lindahl, Katarina, et al.
(författare)
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Genetic epidemiology, prevalence, and genotype-phenotype correlations in the Swedish population with osteogenesis imperfecta
- 2015
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Ingår i: European Journal of Human Genetics. - : Springer Science and Business Media LLC. - 1018-4813 .- 1476-5438. ; 23:8, s. 1042-1050
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Tidskriftsartikel (refereegranskat)abstract
- Osteogenesis imperfecta (OI) is a rare hereditary bone fragility disorder, caused by collagen I mutations in 90% of cases. There are no comprehensive genotype-phenotype studies on 4100 families outside North America, and no population-based studies determining the genetic epidemiology of OI. Here, detailed clinical phenotypes were recorded, and the COL1A1 and COL1A2 genes were analyzed in 164 Swedish OI families (223 individuals). Averages for bone mineral density (BMD), height and yearly fracture rate were calculated and related to OI and mutation type. N-terminal helical mutations in both the alpha 1-and alpha 2-chains were associated with the absence of dentinogenesis imperfecta (P<0.0001 vs 0.0049), while only those in the alpha 1-chain were associated with blue sclera (P = 0.0110). Comparing glycine with serine substitutions, alpha 1-alterations were associated with more severe phenotype (P = 0.0031). Individuals with type I OI caused by qualitative vs quantitative mutations were shorter (P < 0.0001), but did not differ considering fractures or BMD. The children in this cohort were estimated to represent >95% of the complete Swedish pediatric OI population. The prevalence of OI types I, III, and IV was 5.16, 0.89, and 1.35/100 000, respectively (7.40/100 000 overall), corresponding to what has been estimated but not unequivocally proven in any population. Collagen I mutation analysis was performed in the family of 97% of known cases, with causative mutations found in 87%. Qualitative mutations caused 32% of OI type I. The data reported here may be helpful to predict phenotype, and describes for the first time the genetic epidemiology in > 95% of an entire OI population.
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| 4. |
- Lindahl, Katarina, et al.
(författare)
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Homozygosity for CREB3L1 premature stop codon in first case of recessive osteogenesis imperfecta associated with OASIS-deficiency to survive infancy
- 2018
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Ingår i: Bone. - : Elsevier BV. - 8756-3282 .- 1873-2763. ; 114, s. 268-277
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Tidskriftsartikel (refereegranskat)abstract
- Background: Mutations of the endoplasmic reticulum (ER) stress transducer OASIS (encoded by CREB3L1), cause severe recessive osteogenesis imperfecta (OI) not compatible with surviving the neonatal period, as has been shown in two unrelated families through a whole gene deletion vs. a qualitative alteration of OASIS Heterozygous carriers in the described families have exhibited a mild phenotype. OASIS is a transcription factor highly expressed in osteoblasts, and OASIS(-/-) mice exhibit severe osteopenia and spontaneous fractures. Here, we expand the clinical spectrum by a detailed phenotypic characterization of the first case of OASIS-associated OI surviving the neonatal period, with heterozygous family members being unaffected.Methods: All OI-associated genes were sequenced. Primary human osteoblast-like cell (hOB) and fibroblast (FB) cultures were obtained for qPCR, and steady-state collagen biochemistry. FB, hOB and skin biopsies were ultrastructurally analyzed. Bone was analyzed by |mu CT, histomorphometry, quantitative backscattered electron imaging (qBEI), and Raman microspectroscopy.Results: The proband, a boy with severe OI, had blue sclera and tooth agenesis A homozygous CREB3L1 stop codon mutation was detected by sequencing, while several family members were heterozygotes Markedly low levels of CREB3L1 mRNA were confirmed by qPCR in hOBs (16%) and FB (21%), however, collagen I levels were only reduced in hOBs (5-10%) Electron microscopy of hOBs showed pronounced alterations, with numerous myelin figures and diminished RER vs. normal ultrastructure of FB. Bone histomorphometry and qBEI were similar to collagen I OI, with low trabecular thickness and mineral apposition rate, and increased bone matrix mineralization. Raman microspectroscopy revealed low level of glycosaminoglycans. Clinical response to lifelong bisphosphonate treatment was as expected in severe OI with steadily increasing bone mineral density, but despite this the boy suffered repeated childhood fractures.Conclusions: Deficiency of OASIS can cause severe OI compatible with surviving the neonatal period A marked decrease of collagen type I transcription was noted in bone tissue, but not in skin, and ultrastructure of hOBs was pathological. Results also suggested OASIS involvement in glycosaminoglycan secretion in bone.
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| 5. |
- Real, Francisco Gomez, et al.
(författare)
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The Association of Gum Bleeding with Respiratory Health in a Population Based Study from Northern Europe
- 2016
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- Background There is little knowledge about how oral and respiratory health is interrelated even though the mucosa of the oral cavity and airways constitutes a continuum and the exposures to these are partly similar. Aims To investigate whether gum bleeding is related to asthma, respiratory symptoms and self-reported COPD. Methods A postal questionnaire including questions about respiratory and oral health was sent to general population samples in seven Northern European centres. In 13,409 responders, gum bleeding when brushing teeth was reported always/often by 4% and sometimes by 20%. Logistic regressions accounted for age, smoking, educational level, centre and gender. Effects of BMI, cardio-metabolic diseases, early life factors, gastro-oesophageal reflux, dental hygiene, nasal congestion, and asthma medication were addressed. Results Gum bleeding always/often was significantly associated with >= 3 asthma symptoms (OR 2.58, 95% CI 2.10-3.18), asthma (1.62 [1.23-2.14]) and self-reported COPD (2.02 [1.283.18]). There was a dose-response relationship between respiratory outcomes and gum bleeding frequency (>= 3 symptoms: gum bleeding sometimes 1.42 [1.25-1.60], often/always 2.58 [2.10-3.18]), and there was no heterogeneity between centres (p(heterogeneity) = 0.49). None of the investigated risk factors explained the associations. The observed associations were significantly stronger among current smokers (p(interaction) = 0.004). Conclusions A consistent link between gum bleeding and obstructive airways disease was observed, not explained by common risk factors or metabolic factors. We speculate that oral pathogens might have unfavourable impact on the airways, and that the direct continuity of the mucosa of the oral cavity and the airways reflects a pathway that might provide novel opportunities for interventions.
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