Neonatal treatment philosophy in Dutch and German NICUs: health-related quality of life in adulthood of VP/VLBW infants

Purpose

Although survival after very preterm birth (VP)/very low birth weight (VLBW) has improved, a significant number of VP/VLBW individuals develop physical and cognitive problems during their life course that may affect their health-related quality of life (HRQoL). We compared HRQoL in VP/VLBW cohorts from two countries: The Netherlands (n = 314) versus Germany (n = 260) and examined whether different neonatal treatment and rates of disability affect HRQoL in adulthood.

Method

To analyse whether cohorts differed in adult HRQoL, linear regression analyses were performed for three HRQoL outcomes assessed with the Health Utilities Index 3 (HUI3), the London Handicap Scale (LHS), and the WHO Quality of Life instrument (WHOQOL-BREF). Stepwise hierarchical linear regression was used to test whether neonatal physical health and treatment, social environment, and intelligence (IQ) were related to VP/VLBW adults’ HRQoL and cohort differences.

Results

Dutch VP/VLBW adults reported a significantly higher HRQoL on all three general HRQoL measures than German VP/VLBW adults (HUI3: .86 vs .83, p = .036; LHS: .93 vs. .90, p = .018; WHOQOL-BREF: 82.8 vs. 78.3, p < .001). Main predictor of cohort differences in all three HRQoL measures was adult IQ (p < .001).

Conclusions

Lower HRQoL in German versus Dutch adults was related to more cognitive impairment in German adults. Due to different policies, German VP/VLBW infants received more intensive treatment that may have affected their cognitive development. Our findings stress the importance of examining effects of different neonatal treatment policies for VP/VLBW adults’ life.

     

Protein studies in dysferlinopathy patients using llama-derived antibody fragments selected by phage display

Mutations in dysferlin, a member of the fer1-like protein family that plays a role in membrane integrity and repair, can give rise to a spectrum of neuromuscular disorders with phenotypic variability including limb-girdle muscular dystrophy 2B, Myoshi myopathy and distal anterior compartment myopathy. To improve the tools available for understanding the pathogenesis of the dysferlinopathies, we have established a large source of highly specific antibody reagents against dysferlin by selection of heavy-chain antibody fragments originating from a nonimmune llama-derived phage-display library. By utilizing different truncated forms of recombinant dysferlin for selection and diverse selection methodologies, antibody fragments with specificity for two different dysferlin domains could be identified. The selected llama antibody fragments are functional in Western blotting, immunofluorescence microscopy and immunoprecipitation applications. Using these antibody fragments, we found that calpain 3, which shows a secondary reduction in the dysferlinopathies, interacts with dysferlin.     

Optimisation of a host/vector system for heterologous gene expression by Hansenula polymorpha

Summary For the methylotrophic yeast, Hansenula polymorpha, expression vectors with different origins of replication have been constructed in order to analyse their influence on transformation and integration efficiency. The constructed plasmids are identical except for their origin of replication, which involve, respectively, that of the Saccharomyces cerevisiae 2-m plasmid and a H. polymorpha ARS sequence (HARS2). A plasmid with no origin of replication served as a control. The plasmids also contained the -galactosidase expression cassette, consisting of the Cyamopsis tetragonoloba -galactosidase gene, the H. polymorpha methanol oxidase promoter and terminator, and the S. cerevisiae invertase signal sequence. The transformation frequencies of the expression vectors containing the 2-m and the HARS2 origins of replication, and no origin of replication, were 2,50 and 15 per g of DNA respectively, which demonstrates the negative effect of the 2-m sequence on the transformation frequency. Autonomously replicating plasmids could be isolated from the transformants obtained with the plasmid containing either the 2-m or the HARS2 sequence. Integration of the 2-m based plasmid into the H. polymorpha genome could not be established using a standard procedure. This is in contrast with transformants containing a plasmid bearing the HARS2 sequence or else with no origin of replication, which shows that the 2-m sequence negatively influences the integration of the expression vector into the H. polymorpha genome. Integration of expression plasmids occurred in 50% of the analysed integrants on the homologous methanol oxidase locus, and tandem integration was favoured. The level of specific mRNA, and the expression of the -galactosidase protein by these integrants, was proportional to the number of integrated copies of the expression plasmid in the H. polymorpha genome.     

Trends in periodontal status and oral hygiene habits in Dutch adults between 1983 and 1995

In 1995, a dental survey, similar to one carried out in 1983, was performed among persons aged 25-54 in the city of 's-Hertogenbosch, the Netherlands. OBJECTIVE: To describe trends in adults periodontal health between 1983 and 1995. METHODS: The participants were interviewed at home and clinically examined in a dental van. RESULTS: Average scores for plaque, calculus, bleeding after probing and number of buccal root surfaces exposed to the oral cavity were lower in 1995 than in 1983. There was no significant change in the percentage of teeth with pocket depth of 3.5 mm or more between 1983 and 1995. No difference was found between frequency of toothbrushing in 1983 and 1995. CONCLUSION: The results suggest that the periodontal health of Dutch adults aged 25-54 years has improved since 1983.     

Effect of simvastatin in addition to chenodeoxycholic acid in patients with cerebrotendinous xanthomatosis

The effects of combination therapy with chenodeoxycholic acid (CDCA) and simvastatin on serum cholestanol, low-density lipoprotein (LDL) cholesterol, and lathosterol levels were investigated in seven adult patients with cerebrotendinous xanthomatosis (CTX) who were on long-term treatment with CDCA. The patients were treated with a combination of CDCA 750 mg daily and an increasing dose of simvastatin from 10 mg to 40 mg daily for a period of 6 months. We found a significant effect of this combination therapy compared with CDCA alone in terms of decreasing the serum cholestanol and LDL cholesterol levels, particularly with a daily dose of 40 mg simvastatin. The mean cholestanol level decreased from 9.27 micromol/L (baseline) to 6.69 micromol/L (40 mg simvastatin), while the mean LDL cholesterol level decreased from 5.08 mmol/L (baseline) to 3.04 mmol/L (40 mg simvastatin). No side effects were reported, and there were no effects on the clinical condition, cerebral magnetic resonance imaging (MRI), visual evoked potentials, and electroencephalographic features. We conclude that a combination of 750 mg CDCA and 40 mg simvastatin daily is effective to further reduce serum cholestanol, LDL cholesterol, and lathosterol in adult CTX patients treated with long-term CDCA. Whether this combination treatment will be effective for the long-term prevention of neurological deterioration and atherosclerosis remains to be established.     

Special dentistry assistance. An evaluation of the revised ruling 1990

Public Health insurance provision of dental care for patients with a physical, mental, dental or medical handicap has been reorganized in 1990. In order to evaluate this reorganization, general dental practitioners, dentists in hospital clinics or institutions for the handicapped as well as dentists employed as advisors to local health insurance authorities were interviewed. Results show that, until now, the reorganization has not resulted in an increase of seeking dental care by handicapped patients at the general dental practitioner's. The reorganization seems to have taken place in too much haste, thus not leading to the desired provision of dental care for handicapped patients.     

Skeletal Muscle Ultrasound: Correlation Between Fibrous Tissue and Echo Intensity

In this study, we examined the correlation between muscle ultrasound and muscle structure. Echo intensity (EI) of 14 muscles of two golden retriever muscular dystrophy dogs was correlated to the percentage interstitial fibrous tissue and fat in muscle biopsy. A significant correlation between interstitial fibrous tissue and EI was found (r = 0.87; p < 0.001). The separate influence of interstitial fat on muscle EI could not be established as only little fat was present. We conclude that fibrous tissue causes increased muscle EI. The high correlation between interstitial fibrous tissue and EI makes ultrasound a reliable method to determine severity of structural muscle changes. (E-mail: s.pillen@cukz.umcn.nl)     

Distal spinal muscular atrophy as a major feature in adult-onset ataxia telangiectasia

The authors report four adult-onset ataxia telangiectasia (AT) patients belonging to two families lacking pronounced cerebellar ataxia but displaying distal spinal muscular atrophy. AT was proven by genetic studies showing ATM mutations and a reduced level of ATM. ATM activity, as measured by phosphorylation of p53, was close to normal, indicating that the p53 response is not the only factor in preventing neural damage in anterior horn cells in AT.