| 1. |
- Burda, P, et al.
(författare)
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Characterization and review of MTHFD1 deficiency: four new patients, cellular delineation and response to folic and folinic acid treatment.
- 2015
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Ingår i: Journal of Inherited Metabolic Disease. - : Wiley. - 0141-8955 .- 1573-2665. ; 38:5, s. 863-872
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Tidskriftsartikel (refereegranskat)abstract
- In the folate cycle MTHFD1, encoded by MTHFD1, is a trifunctional enzyme containing 5,10-methylenetetrahydrofolate dehydrogenase, 5,10-methenyltetrahydrofolate cyclohydrolase and 10-formyltetrahydrofolate synthetase activity. To date, only one patient with MTHFD1 deficiency, presenting with hyperhomocysteinemia, megaloblastic anaemia, hemolytic uremic syndrome (HUS) and severe combined immunodeficiency, has been identified (Watkins et al J Med Genet 48:590-2, 2011). We now describe four additional patients from two different families. The second patient presented with hyperhomocysteinemia, megaloblastic anaemia, HUS, microangiopathy and retinopathy; all except the retinopathy resolved after treatment with hydroxocobalamin, betaine and folinic acid. The third patient developed megaloblastic anaemia, infection, autoimmune disease and moderate liver fibrosis but not hyperhomocysteinemia, and was successfully treated with a regime that included and was eventually reduced to folic acid. The other two, elder siblings of the third patient, died at 9 weeks of age with megaloblastic anaemia, infection and severe acidosis and had MTFHD1 deficiency diagnosed retrospectively. We identified a missense mutation (c.806C > T, p.Thr296Ile) and a splice site mutation (c.1674G > A) leading to exon skipping in the second patient, while the other three harboured a missense mutation (c.146C > T, p.Ser49Phe) and a premature stop mutation (c.673G > T, p.Glu225*), all of which were novel. Patient fibroblast studies revealed severely reduced methionine formation from [(14)C]-formate, which did not increase in cobalamin supplemented culture medium but was responsive to folic and folinic acid. These additional cases increase the clinical spectrum of this intriguing defect, provide in vitro evidence of disturbed methionine synthesis and substantiate the effectiveness of folic or folinic acid treatment.
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| 2. |
- Célind, Jimmy, et al.
(författare)
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Adherence to treatment guidelines for acute otitis media in children. The necessity of an effective strategy of guideline implementation
- 2014
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Ingår i: International Journal of Pediatric Otorhinolaryngology. - : Elsevier BV. - 0165-5876. ; 78:7, s. 1128-1132
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: Acute otitis media is the single diagnosis responsible for most prescriptions of antibiotics in Sweden and the USA. The treatment of acute otitis media has significant impact on child health, healthcare costs, and the development of anti-microbial resistance. In the Swedish national guidelines from the year 2000, watchful waiting was recommended for most children over 2 years of age. The aims of the present study were to assess the degree of adherence to acute otitis media guidelines at a busy pediatric emergency department of a university hospital and to determine whether an information campaign changed the result. Methods: Audit of 91 patient records before and 80 patient records after an information campaign consisting of an oral presentation, posting of flow charts, and sending of educational material to prescribing physicians. Four endpoints were studied: choosing to use antibiotics, choice of antibiotic, dosage of antibiotic, and duration of treatment. Results: Before the information campaign, adherence to guidelines was between 70% (dosage) and around 90% (duration). No significant change was seen after the information campaign. The endpoint choosing to use antibiotics showed a large divergence in adherence in children under 2 years (96%) compared to older children (39%). Conclusions: Overall adherence to recommendations was 70-90% but adherence to watchful waiting was poor. Information did not improve adherence, suggesting insufficient educational power or the existence of barriers other than lack of knowledge. Specific barriers should be identified, and implementation and follow-up should be part of producing guidelines in order to achieve the desired results. (C) 2014 Elsevier Ireland Ltd. All rights reserved.
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| 3. |
- Hjalmarson, Ola, 1941, et al.
(författare)
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Effect of antenatal corticosteroid treatment on lung function in full-term newborn infants.
- 2011
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Ingår i: Neonatology. - : S. Karger AG. - 1661-7819 .- 1661-7800. ; 100:1, s. 32-6
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Tidskriftsartikel (refereegranskat)abstract
- Background: Antenatal treatment of pregnant women with corticosteroids in order to stimulate surfactant production has been shown to be effective. However, lung structure is also affected by the treatment. Objective: We tested the hypothesis that changes within lung acini, induced by maternal corticosteroid treatment, persist during lung development. Methods: Twenty-two healthy infants, whose mothers were treated with up to three doses of betamethasone at 25-33 weeks of pregnancy because of preterm labour, but where labour terminated and the infants were born at term, were studied at term and compared to a group of 50 healthy newborn infants without prenatal treatment with corticosteroids. Gas-mixing efficiency was measured in terms of moment ratio with a nitrogen washout method together with functional residual capacity. Mechanical parameters were assessed with the single occlusion technique. Results: There were no signs of disturbed gas mixing or changed lung volume or mechanics in the treated group. Conclusion: The result contributes to an emerging body of evidence that antenatal treatment with corticosteroids does not permanently affect lung structure or function.
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| 4. |
- Hjalmarson, Ola, 1941, et al.
(författare)
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Lung function at term reflects severity of bronchopulmonary dysplasia
- 2005
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Ingår i: The Journal of pediatrics. - : Elsevier BV. - 0022-3476. ; 146:1, s. 86-90
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To test whether infants with bronchopulmonary dysplasia (BPD) express the same functional impairments at term as healthy, preterm infants, and whether clinical severity of BPD is qualitatively or quantitatively related. STUDY DESIGN: Prospective measurements on a consecutive sample of 50 infants with BPD and 19 healthy preterm controls in a university hospital. BPD infants were classified as "severe," "moderate," or "mild," according to their need for oxygen. A multiple-breath nitrogen wash-out method was used to assess functional residual capacity (FRC) and gas mixing efficiency. Mechanical variables were estimated by the occlusion test. RESULTS: Infants with severe BPD had lower FRC, less efficient gas mixing, and higher specific conductance than those with mild and moderate BPD, and the preterm controls. Mild and moderate BPD did not differ in any property from each other but differed from controls in the same variables. The elastic properties of the respiratory system appeared unaffected by BPD. CONCLUSIONS: The ventilatory impairments in BPD were of the same nature as in healthy preterm infants when compared with term infants, but their magnitude was related to the clinical severity of the BPD. Gas mixing efficiency together with FRC appears to be useful to assess lung development in BPD.
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| 5. |
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| 6. |
- Hjalmarson, Ola, 1941, et al.
(författare)
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Persisting hypoxaemia is an insufficient measure of adverse lung function in very immature infants.
- 2014
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Ingår i: Archives of disease in childhood. Fetal and neonatal edition. - : BMJ. - 1468-2052 .- 1359-2998. ; 99:4, s. F257-F262
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Tidskriftsartikel (refereegranskat)abstract
- Bronchopulmonary dysplasia (BPD), defined as protracted neonatal hypoxaemia, is considered a risk factor for respiratory disease in adulthood. The relationship between this diagnosis and the actual lung injury appearing in very immature infants is, however, unknown.
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| 7. |
- Hjalmarson, Ola, 1941, et al.
(författare)
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Spectrum of chronic lung disease in a population of newborns with extremely low gestational age.
- 2012
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Ingår i: Acta Paediatrica, International Journal of Paediatrics. - : Wiley. - 0803-5253 .- 1651-2227. ; 101:9, s. 912-918
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Tidskriftsartikel (refereegranskat)abstract
- Aims: To determine how the ability to oxygenate the blood develops after birth in infants of extremely low gestational age (ELGANs) and to find risk factors for chronic lung disease. Method: A prospective, population-based, cohort study was undertaken in one tertiary-care centre. The alveolar-arterial oxygen pressure difference (AaDO(2) ) was monitored. Results: Of 41 survivors, 21 had a period of normal lung function in the first week of life, after which oxygenation deteriorated. Low gestational age and low Apgar score at 5 min were found to be strong and independent predictors of AaDO(2) in the first month of life. Mechanical ventilation did not appear as a risk factor. Lung function at 36 weeks of gestation and duration of oxygen treatment could be better predicted by the severity of lung disease in the first month than by gestational age at birth. Conclusions: Difficulty in oxygenation was a general observation in ELGANs and not only a particular subset. Gestational age and Apgar score were independent predictors of the degree of difficulty over the first month of life. As oxygenation failure often developed after a few days, the process may be possible to treat or prevent once the pathogenesis is known.
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| 8. |
- Lagerkvist, Anna-Lena, 1956, et al.
(författare)
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Immediate changes in blood-gas tensions during chest physiotherapy with positive expiratory pressure and oscillating positive expiratory pressure in patients with cystic fibrosis.
- 2006
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Ingår i: Respiratory care. - 0020-1324. ; 51:10, s. 1154-61
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To assess and compare immediate effects of chest physiotherapy with positive expiratory pressure (PEP) versus oscillating PEP on transcutaneously measured blood-gas tensions in patients with cystic fibrosis. METHODS: Fifteen patients (mean age 12.5 y, range 6.9-21.5 y) participated. The treatments were randomized and performed on 2 separate occasions, 8 weeks apart. Spirometry was conducted before and after each treatment. We transcutaneously measured oxygen tension (P(tO2). RESULTS: There were no changes in spirometry values. During PEP, different trends in blood-gas tension were seen, and there were no consistent changes. During oscillating PEP, P(tO2) increased and P(tCO2) decreased. During oscillating PEP, P(tCO2) was lower and the intra-individual change in P(tCO2) was more pronounced than during PEP. The results obtained immediately after oscillating PEP showed a higher P(tO2) and a lower P(tCO2) than with PEP. CONCLUSION: PEP and oscillating PEP can both cause transitory effects on blood gases in patients with cystic fibrosis. However, oscillating PEP alters blood-gas tensions more than does PEP, and hyperventilation during oscillating PEP may reduce treatment time.
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| 9. |
- Ostergaard, Elsebet, et al.
(författare)
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A novel missense mutation in SUCLG1 associated with mitochondrial DNA depletion, encephalomyopathic form, with methylmalonic aciduria.
- 2010
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Ingår i: European journal of pediatrics. - : Springer Science and Business Media LLC. - 1432-1076 .- 0340-6199. ; 169:2, s. 201-5
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Tidskriftsartikel (refereegranskat)abstract
- Mitochondrial DNA depletion, encephalomyopathic form, with methylmalonic aciduria is associated with mutations in SUCLA2, the gene encoding a beta subunit of succinate-CoA ligase, where 17 patients have been reported. Mutations in SUCLG1, encoding the alpha subunit of the enzyme, have been reported in only one family, where a homozygous 2 bp deletion was associated with fatal infantile lactic acidosis. We here report a patient with a novel homozygous missense mutation in SUCLG1, whose phenotype is similar to that of patients with SUCLA2 mutations.
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| 10. |
- Sandberg, Kenneth, 1945, et al.
(författare)
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CPAP of 4 cm H(2)O Has No Short-Term Benefit at Term in Infants with BPD.
- 2012
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Ingår i: Neonatology. - : S. Karger AG. - 1661-7819 .- 1661-7800. ; 102:4, s. 282-286
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Tidskriftsartikel (refereegranskat)abstract
- Background: Lung development and function is compromised at term in infants with bronchopulmonary dysplasia (BPD), characterized by reduced functional residual capacity (FRC) and impaired gas-mixing efficiency in distal airways. Objective: To determine whether continuous positive airway pressure (CPAP) improves FRC, ventilation, distal airway function, and gas exchange in spontaneously breathing infants with BPD. Design/Methods: Twenty-one infants with BPD (median birth weight 0.72 kg (range 0.50-1.27) and median gestational age 26 weeks (range 23-28)) were studied before and after CPAP of 4 cm H(2)O was applied by a facemask system. A multiple-breath nitrogen washout method was used to assess FRC, ventilation, and gas-mixing efficiency. Moment analysis and lung clearance index was calculated from the nitrogen-decay curve for assessment of gas-mixing efficiency. Transcutaneous (Tc) PO(2)/PCO(2) was monitored during stable infant conditions before each washout test. Results: When CPAP was raised from 0 to 4 cm H(2)O, FRC increased significantly together with a significant increase in moment ratios (M(1)/M(0) and M(2)/M(0)). Tc PO(2) decreased significantly and the breathing pattern changed, with significantly reduced respiratory rate, minute ventilation, and alveolar ventilation. There was also an increase in tidal volume and dead space. Conclusions: CPAP of 4 cm H(2)O applied with a facemask at term to infants with BPD did not improve ventilation, gas-mixing efficiency in distal airways, or oxygenation despite an increase in FRC. We speculate that instead of promoting recruitment of unventilated lung volumes, increasing the end-expiratory pressure in infants with BPD may lead to an overexpansion of already ventilated parts of the lung, causing further compromise of lung function.
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