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1.  Long-term effect of lifestyle intervention on adiposity, metabolic parameters, inflammation and physical fitness in obese children: a randomized controlled trial 
Nutrition & Diabetes  2011;1(10):e9-.
Background:
Behavioral lifestyle intervention, combined with parental involvement, is preferred over standard care or self-help in childhood obesity. The short-term results of such interventions are promising, but long-term follow-up results are equivocal.
Objective:
The objective of the present study was the short (3 months) and long-term (1 and 2 years follow-up) effect evaluation of a family-based multidisciplinary cognitive behavioral lifestyle intervention on markers of adiposity, metabolism, inflammation and physical fitness compared with standard care in children with obesity. Also the association between these outcome variables was determined.
Methods:
In this prospective longitudinal clinical trial, obese children were randomly assigned to a 3-month family-based cognitive behavioral multidisciplinary lifestyle treatment (n=40; body mass index-standard deviation score (BMI-SDS) 4.2±0.7; age; 13.3±2.0 years) or to a control group receiving an initial advice on physical activity and nutrition (n=39; BMI-SDS 4.3±0.6; age 13.1±1.9 years). Anthropometric data, physical fitness, metabolic parameters and inflammatory state were evaluated at baseline, after intervention (at 3 months) and at 1-year follow-up. At 2-year follow-up, anthropometric data and physical fitness were measured in the intervention group.
Results:
An intervention effect after 1 year was found for adiposity (P=0.02 for BMI-SDS, P=0.03 for waist circumference (WC)-SDS), physical fitness (absolute measured peak value of oxygen uptake (ml min−1), standardized for age and gender (VO2peak-SDS), P<0.01) and insulin resistance (HOMA-SDS, P=0.04). No significant intervention effect was found for serum lipid profile, high-sensitive C-reactive protein or for adiponectin. At 2-year follow-up, BMI-SDS in the intervention group (n=31) was 3.8±1.2 SDS, significantly less than at baseline (P=0.02).
Conclusion:
A positive 1-year follow-up treatment effect was found for adiposity, physical fitness and glucose homeostasis, but not for inflammatory markers. There was a significant long-term treatment effect on adiposity, although almost all children remained obese.
doi:10.1038/nutd.2011.5
PMCID: PMC3302141  PMID: 23455021
obesity; children; physical fitness; inflammation; insulin resistance
2.  Reducing access times for an endoscopy department by an iterative combination of computer simulation and Linear Programming 
Health Care Management Science  2009;13(1):17-26.
To reduce the access times of an endoscopy department, we developed an iterative combination of Discrete Event simulation and Integer Linear Programming. We developed the method in the Endoscopy Department of the Academic Medical Center in Amsterdam and compared different scenarios to reduce the access times for the department. The results show that by a more effective allocation of the current capacity, all procedure types will meet their corresponding performance targets in contrast to the current situation. This improvement can be accomplished without requiring additional equipment and staff. Currently, our recommendations are implemented.
doi:10.1007/s10729-009-9105-z
PMCID: PMC2819657  PMID: 20402279
Access time; Waiting lists; Diagnostic department; Gastroenterology; Discrete event simulation; Integer linear programming
3.  Nationwide age references for sitting height, leg length, and sitting height/height ratio, and their diagnostic value for disproportionate growth disorders 
Archives of Disease in Childhood  2005;90(8):807-812.
Aims: To obtain age references for sitting height (SH), leg length (LL), and SH/H ratio in the Netherlands; to evaluate how SH standard deviation score (SDS), LL SDS, SH/H SDS, and SH/LL SDS are related to height SDS; and to study the usefulness of height corrected SH/H cut-off lines to detect Marfan syndrome and hypochondroplasia.
Methods: Cross-sectional data on height and sitting height were collected from 14 500 children of Dutch origin in the age range 0–21 years. Reference SD charts were constructed by the LMS method. Correlations were analysed in three age groups. SH/H data from patients with Marfan syndrome and genetically confirmed hypochondroplasia were compared with height corrected SH/H references.
Results: A positive association was observed between H SDS, SH SDS, and LL SDS in all age groups. There was a negative correlation between SH/H SDS and height SDS. In short children with a height SDS <–2 SDS, a cut-off limit of +2.5 SD leads to a more acceptable percentage of false positive results. In exceptionally tall children, a cut-off limit of –2.2 SDS can be used. Alternatively, a nomogram of SH/H SDS versus H SDS can be helpful. The sensitivity of the height corrected cut-off lines for hypochondroplasia was 80% and for Marfan syndrome only 30%.
Conclusions: In exceptionally short or tall children, the dependency of the SH/H ratio (SDS) on height SDS has to be taken into consideration in the evaluation of body proportions. The sensitivity of the cut-off lines for hypochondroplasia is fair.
doi:10.1136/adc.2004.050799
PMCID: PMC1720514  PMID: 15863466
5.  Towards evidence based referral criteria for growth monitoring 
Archives of Disease in Childhood  2004;89(4):336-341.
Aims: To evaluate the performance of growth monitoring in detecting diseases. Turner's syndrome (TS) is taken as the target disease.
Methods: Case-control simulation study. Three archetypal screening rules are applied to longitudinal growth data comparing a group with TS versus a reference group from birth to the age of 10 years. Main outcome measures were sensitivity, specificity, and median referral age.
Results: Clear differences in performance of the rules were found. The best rule takes parental height into account. Combining rules could improve diagnostic accuracy.
Conclusion: Growth monitoring is useful to screen for TS. A combined rule that takes absolute height SDS, parental height, and deflection in height velocity into account is the best way to do this. Similar research is needed for other diseases, populations, and ages, and the results should be synthesised into evidence based referral criteria.
doi:10.1136/adc.2003.027839
PMCID: PMC1719884  PMID: 15033842
6.  Many referrals under Dutch short stature guidelines 
Archives of Disease in Childhood  2004;89(4):351-352.
doi:10.1136/adc.2003.038208
PMCID: PMC1719873  PMID: 15033845
7.  High dose growth hormone treatment induces acceleration of skeletal maturation and an earlier onset of puberty in children with idiopathic short stature 
Archives of Disease in Childhood  2002;87(3):215-220.
Background: Long term growth hormone (GH) treatment in children with idiopathic short stature (ISS) results in a relatively small mean gain in final height of 3–9 cm, which may not justify the cost of treatment. As it is unknown whether GH treatment during puberty adds to final height gain, we sought to improve the cost–benefit ratio, employing a study design with high dose GH treatment restricted to the prepubertal period.
Aims: To assess the effect of short term, high dose GH treatment before puberty on growth, bone maturation, and pubertal onset.
Methods: Five year results of a randomised controlled study are reported. Twenty six boys and nine girls were randomly assigned to a GH treatment group (n = 17) or a control group (n = 18). Inclusion criteria were: no signs of puberty, height less than -2 SDS, age 4–8 years for girls or 4–10 years for boys, GH concentration >10 µg/l after provocation, and normal body proportions. To assess GH responsiveness, children assigned to the GH treatment group received GH treatment for two periods of three months (1.5 IU/m2/day and 3.0 IU/m2/day), separated by three month washout periods, during the first year of study. High dose GH treatment (6.0 IU/m2/day) was then started and continued for at least two full years. When puberty occurred, GH treatment was discontinued at the end of a complete year's treatment (for example, three or four years of GH treatment).
Results: In response to at least two years on high dose GH treatment, mean (SD) height SDS for chronological age increased significantly in GH treated children from -2.6 (0.5) to -1.3 (0.5) after two years and -1.4 (0.5) SDS after five years of study. No changes in height SDS were observed in controls. A rapid rate of bone maturation of 3.6 years/2 years in treated children compared to 2 years/2 years in controls was observed in response to two years high dose GH treatment. Height SDS for bone age was not significantly different between groups during the study period. GH treated children entered into puberty at a significantly earlier age compared to controls.
Conclusions: High dose GH treatment before puberty accelerates bone age and induces an earlier onset of puberty. This may limit the potential therapeutic benefit of this regimen in ISS.
doi:10.1136/adc.87.3.215
PMCID: PMC1719235  PMID: 12193430
8.  Longitudinal analysis of growth and puberty in 21-hydroxylase deficiency patients 
Archives of Disease in Childhood  2002;87(2):139-144.
Aims: To evaluate growth from diagnosis until final height (FH) in 21-hydroxylase deficiency patients.
Methods: A retrospective longitudinal study was performed. Only patients treated with hydrocortisone and fludrocortisone (in case of salt wasting) were evaluated. This resulted in a sample of 34 (21 male, 13 female) salt wasting patients (SW) and 26 (13 male, 13 female) non-salt wasting patients (NSW). Auxological data were compared to recent Dutch reference values.
Results: In the first three months of life, the mean length SDS decreased to -1.50, probably because of the high average glucocorticoid dose (40 mg/m2/day). FH corrected for target height (FHcorrTH) was -1.25 and -1.27 SDS in females and males, respectively. Patients treated with salt supplements during the first year, had a better FHcorrTH (-0.83 SDS). In NSW patients, FHcorrTH was -0.96 and -1.51 SDS in females and males, respectively. In SW and NSW, age at onset of puberty was within normal limits, but bone age was advanced. Mean pubertal height gain was reduced in males. Body mass index was only increased in NSW females.
Conclusion: In SW, loss of final height potential might be a result of glucocorticoid excess in the first three months and sodium depletion during infancy. In NSW, loss of FH potential was caused by the delay in diagnosis. In SW and NSW, the advanced bone age at onset of puberty (undertreatment in prebertal years) resulted in loss of height gain during puberty. The effect of intensive sodium chloride support in early infancy should be examined prospectively. Neonatal screening is required if the height prognosis in NSW patients is to be improved.
doi:10.1136/adc.87.2.139
PMCID: PMC1719187  PMID: 12138066
9.  Adult height in patients with early onset of Crohn's disease 
Gut  2002;51(1):26-29.
Background: Growth impairment during childhood and adolescence is a common problem faced by patients with an early onset of Crohn's disease.
Aims: To establish how the final adult height is affected in patients with early onset of symptoms of Crohn's disease.
Methods: Information on height, parental height, and disease history was obtained from 135 patients with Crohn's disease who reached their adult height (men 22–40 years, women 18–40 years) using a questionnaire and by outpatient measurement of height where possible. Subsequently, adult heights were expressed as standard deviation scores, with and without correction for the expected target height.
Results: Patients with onset of disease before puberty were shorter compared with patients with onset in adulthood (p<0.01). This difference was not statistically significant when adult heights were corrected for parental height. Also, height standard deviation scores for those patients with onset of disease before puberty were significantly lower than those with onset of disease during puberty (p<0.05) but after correction for parental height the difference was not significant. The site of disease had no influence on adult height. Patients who had used corticosteroids during puberty were significantly shorter than patients who had not (p=0.005). This was also true when corrected for target height (p=0.007).
Conclusions: Although there was a trend indicating a deficit in adult height in patients with an early onset of Crohn's disease, once adjustment was made for parental height, this difference was not significant. Use of corticosteroids in puberty resulted in lower adult height.
PMCID: PMC1773272  PMID: 12077087
Crohn's disease; children; growth; target height
10.  Increase in sexually transmitted infections among homosexual men in Amsterdam in relation to HAART 
Sexually Transmitted Infections  2001;77(3):184-186.
Objectives: We investigated if a rise in rectal gonorrhoea and early syphilis among men who have sex with men (MSM) in Amsterdam coincided with the introduction of highly active antiretroviral therapies (HAART) in July 1996 and determined risk factors for these sexually transmitted infections (STI).
Methods: Subjects were patients of the STI clinic of the municipal health service in Amsterdam. Surveillance data (1994–9) represented consultations (n=11 240) of MSM (n=6103). For analyses we used logistic regression.
Results: Comparing the periods before and after the introduction of HAART, the infection rate for rectal gonorrhoea increased from 4% to 5.4% (p=.001) and for syphilis, from 0.5% to 0.8% (p = 0.050). Independent risk factors for rectal gonorrhoea (younger age, western nationality, and concurrent infection with another STI) and for early syphilis (non-western nationality and concurrent infection with rectal gonorrhoea) did not change after HAART became available. For rectal gonorrhoea, however, the infection rate increased only among men who had exclusively homosexual contacts (OR 1.38, p<0.01), compared with bisexual men. For early syphilis, the infection rate increased only among men of western nationality (OR 3.38, p<0.01) compared to men of non-western nationality.
Conclusions: Infection rates of rectal gonorrhoea and early syphilis increased, indicating a change in sexual behaviour, possibly as a result of the introduction of HAART. For now, it is important to find out how sexual behaviour is changing and to keep monitoring trends in STIs (including HIV) among MSM in Amsterdam.
Key Words: rectal gonorrhoea; syphilis; HAART; high risk sexual behaviour; MSM
doi:10.1136/sti.77.3.184
PMCID: PMC1744315  PMID: 11402225
11.  Body index measurements in 1996-7 compared with 1980 
Archives of Disease in Childhood  2000;82(2):107-112.
OBJECTIVES—To compare the distribution of body mass index (BMI) in a national representative study in The Netherlands in 1996-7 with that from a study in 1980.
METHODS—Cross sectional data on height, weight, and demographics of 14 500 boys and girls of Dutch origin, aged 0-21 years, were collected from 1996 to 1997. BMI references were derived using the LMS method. The 90th, 50th, and 10th BMI centiles of the 1980 study were used as baseline. Association of demographic variables with BMI-SDS was assessed by ANOVA.
RESULTS—BMI age reference charts were constructed. From 3 years of age onwards 14-22% of the children exceeded the 90th centile of 1980, 52-60% the 50th centile, and 92-95% the 10th centile. BMI was related to region, educational level of parents (negatively) and family size (negatively). The −0.9, +1.1, and +2.3 SD lines in 1996-7 corresponded to the adult cut off points of 20, 25,and 30 kg/m2 recommended by the World Health Organisation/European childhood obesity group.
CONCLUSION—BMI age references have increased in the past 17 years. Therefore, strategies to prevent obesity in childhood should be a priority in child public health.


doi:10.1136/adc.82.2.107
PMCID: PMC1718204  PMID: 10648362
12.  Spontaneous growth in idiopathic short stature. European Study Group. 
Archives of Disease in Childhood  1996;75(3):175-180.
Documenting the spontaneous growth pattern of children with idiopathic short stature (ISS) should be helpful in evaluating the effects of growth promoting treatments. Growth curves for children with ISS were constructed, based on 229 untreated children (145 boys and 84 girls) from nine European countries. The children were subdivided according to target range and onset of puberty, and the growth of these subgroups was evaluated from standard deviation scores (SDS). At birth, children with ISS were already shorter than normal (means; boys -0.8 SDS, girls -1.3 SDS). Height slowly decreased from -1.7 SDS at the age of 2 years to -2.7 SDS at the age of 16 years in boys and 13 years in girls. Final height was -1.5 SDS in boys and -1.6 SDS in girls (mean (SD): boys 164.8 (6.1) cm, girls 152.7 (5.3) cm)), which was 5-6 cm below their target height. The onset of puberty was delayed (boys 13.8 (1.3) years, girls 12.9 (1.1) years). Subclassification resulted in similar growth curves. These specific growth data may be more suitable for evaluating the effects of growth promoting treatments than population based references.
PMCID: PMC1511692  PMID: 8976652
13.  Modelling Bacterial Growth of Lactobacillus curvatus as a Function of Acidity and Temperature 
Models that describe the effect of acidity, temperature, and the combined effect of these variables on the growth parameters of Lactobacillus curvatus are developed and validated. Growth parameters (lag time, specific growth rate, and maximum population density) were calculated from growth data at different temperature-acidity combinations. Experiments were set up to assess the quantitative effects of temperature and acidity on the growth parameters rather than for parameter estimation solely. The effect of acidity is monitored at several constant temperature values. Models are set up and fitted to the data. The same procedure is used at constant acidity values to model the effect of temperature. For lag time, specific growth rate, and maximum population density, the effect of temperature could be multiplied with the effect of acidity to obtain combinatory models that describe the effect of both controlling factors on the growth parameters. Lag time measurements showed large deviations, and therefore the lag time models developed can only be used to estimate the order of magnitude of lag time.
PMCID: PMC1388487  PMID: 16535069
14.  Catch-up growth in early treated patients with growth hormone deficiency. Dutch Growth Hormone Working Group. 
Archives of Disease in Childhood  1995;72(5):427-431.
Catch-up growth of 26 children with growth hormone deficiency during four years of growth hormone treatment, which was started young (< 3 years), was compared with that of 16 children with coeliac disease on a gluten free diet. In children with growth hormone deficiency mean (SD) height SD score increased from -4.3 (1.8) to -1.9 (1.4) and in patients with coeliac disease from -1.8 (0.9) to -0.1 (0.8). Height SD score after four years correlated positively with injection frequency and height SD score at start of treatment in children with growth hormone deficiency. All patients with coeliac disease reached a height above -2 SD scores after four years, while the height of 26% of children with growth hormone deficiency on daily injections and of 86% of children on 2 or 4 injections/week was still below -2 SD scores. In patients with growth hormone deficiency on daily injections with an initial height SD score between -2 and -4 catch-up was similar to that of patients with coeliac disease with a comparable initial height deficit. Growth hormone deficient children with an initial height SD score < -4 did not reach full catch-up growth within four years. In conclusion, catch-up growth in early treated children with growth hormone deficiency over four years is adequate provided that daily injections are given and the initial height SD score is not less than -4.
PMCID: PMC1511086  PMID: 7618910
15.  Comparative effect of two doses of growth hormone for growth hormone deficiency. The Dutch Growth Hormone Working Group. 
The comparative effect and safety of 2 IU compared with 4 IU/m2/day of recombinant human growth hormone (rhGH) was studied in 38 growth hormone deficient children regarding the impact of several factors on short term (one year) and long term (three year) growth response. In 21 newly diagnosed patients, three years of rhGH treatment resulted in a significant increase of height velocity SD score, height SD score, and predicted adult height SD score, irrespective of rhGH dose. In 17 transfer patients (previously treated with 12 IU rhGH/m2/week) 4 IU/m2/day resulted in a significantly higher height velocity SD score and height SD score for chronological age than 2 IU/m2/day, while more of them reached their target range or showed a substantial height SD score increment. Height SD score for bone age and predicted adult height SD score only increased significantly with 4 IU rhGH. After one year of rhGH treatment, new patients showed significant negative correlation between delta height SD score with age and baseline insulin-like growth factor I (IGF-I) SD score, and positive correlation with rhGH dose. After three years of treatment, delta height SD score for chronological age was significantly, negatively correlated with age and baseline 'corrected' height SD score (height SD score for chronological age minus target height SD score). There was no significant correlation with rhGH dose. Prolonged treatment with either dose had no adverse effect on IGF-I concentrations, carbohydrate or lipid metabolism. As early age and divergence between height SD score and target height SD score seem more important for growth response than rhGH dose, it is recommended that treatment starts early with 2 IU rhGH/m(2)/day and the dose is doubled if growth is insufficient after several years of treatment.
PMCID: PMC1029904  PMID: 8067786
16.  Evaluation of Data Transformations and Validation of a Model for the Effect of Temperature on Bacterial Growth 
The temperature of chilled foods is an important variable for controlling microbial growth in a production and distribution chain. Therefore, it is essential to model growth as a function of temperature in order to predict the number of organisms as a function of temperature and time. This article deals with the correct variance-stabilizing transformation of the growth parameters A (asymptotic level), μ (specific growth rate), and λ (lag time). This is of importance for the regression analysis of the data. A previously gathered data set and model for the effect of temperature on the growth of Lactobacillus plantarum (M. H. Zwietering, J. T. de Koos, B. E. Hasenack, J. C. de Wit, and K. van 't Riet, Appl. Environ. Microbiol. 57:1094-1101, 1991) is extended with new data. With the total data set (original and new data), a variance-stabilizing transformation is selected in order to determine which transformation should precede fitting. No transformation for the asymptote data, a square root for the growth rate, and a logarithmic transformation for the lag time were found to be appropriate. After these transformations, no significant correlation was found between the variance and the magnitude of the variable. Model corrections were made and model parameters were estimated by using the original data. With the new data, the models were validated by comparing the lack of fit of the models with the measurement error, using an F test. The predictions of the models for μ and λ were adequate. The model for A showed a systematic deviation, and therefore a new model for A is proposed.
PMCID: PMC201289  PMID: 16349150
17.  Modeling of Bacterial Growth with Shifts in Temperature 
The temperature of chilled foods is an important variable for the shelf life of a product in a production and distribution chain. To predict the number of organisms as a function of temperature and time, it is essential to model the growth as a function of temperature. The temperature is often not constant in various stages of distribution. The objective of this research was to determine the effect of shifts in temperature. The suitability and usefulness of several models to describe the growth of Lactobacillus plantarum with fluctuating temperatures was evaluated. It can be assumed that temperature shifts within the lag phase can be handled by adding relative parts of the lag time to be completed and that temperature shifts within the exponential phase result in no lag phase. With these assumptions, the kinetic behavior of temperature shift experiments was reasonably well predicted, and this hypothesis was accepted statistically in 73% of the cases. Only shifts of temperature around the minimum temperature for growth showed very large deviations from the model prediction. The best results were obtained with the assumption that a temperature shift (within the lag phase as well as within the exponential phase) results in an additional lag phase. This hypothesis was accepted statistically in 93% of the cases. The length of the additional lag phase is one-fourth of the lag time normally found at the temperature after the shift.
PMCID: PMC201290  PMID: 16349151
18.  Prepubertal height velocity references over a wide age range. 
Archives of Disease in Childhood  1992;67(10):1277-1280.
In order to correct height velocities for the confounders age and sex, SD scores can be calculated using the mean and the SD of the height velocity in the normal population. However, current methods are inappropriate for prepubertal children in the age range in which puberty occurs, because reference groups then consist of a mixed prepubertal/pubertal population. The mathematical infancy-childhood-puberty (ICP) model opens up the possibility of dissecting the puberty component from the total growth curve. New references for height velocity for prepubertal children calculated over a 12 month interval up to the ages of 15.5 years (boys) and 13.5 years (girls) have been constructed on the basis of adaptations of the ICP model and the Swedish longitudinal growth study.
PMCID: PMC1793929  PMID: 1444528
19.  Growth of infants with neonatal growth hormone deficiency. 
Archives of Disease in Childhood  1992;67(7):920-924.
In view of contradictory reports on the growth hormone dependency of early postnatal growth we studied the growth curves of 15 infants with neonatal growth hormone deficiency. In seven infants the growth curve was parallel to the standards of the infancy-childhood-puberty (ICP) model (group 1), but in the remaining infants there was an immediate deviation of the growth curve (group 2). In this group the mean (SD) at 4 and 9 months of age was -3.3 (1.1) and -4.9 (1.4), respectively, when compared with the ICP model. The mean birth length in both groups was decreased and five out of 15 had a birth length of less than -2 SD. Serial measurements of the growth hormone response to provocation tests in two patients in group 2 showed decreasing concentrations, while four patients with documented complete growth hormone deficiency belonged to group 2. We conclude that growth hormone is needed for early infant growth and that the normal growth pattern in some infants with neonatal pituitary dysfunction is due to incomplete insufficiency.
PMCID: PMC1793852  PMID: 1519958
20.  Molecular cloning of the human DNA excision repair gene ERCC-6. 
Molecular and Cellular Biology  1990;10(11):5806-5813.
The UV-sensitive, nucleotide excision repair-deficient Chinese hamster mutant cell line UV61 was used to identify and clone a correcting human gene, ERCC-6. UV61, belonging to rodent complementation group 6, is only moderately UV sensitive in comparison with mutant lines in groups 1 to 5. It harbors a deficiency in the repair of UV-induced cyclobutane pyrimidine dimers but permits apparently normal repair of (6-4) photoproducts. Genomic (HeLa) DNA transfections of UV61 resulted, with a very low efficiency, in six primary and four secondary UV-resistant transformants having regained wild-type UV survival. Southern blot analysis revealed that five primary and only one secondary transformant retained human sequences. The latter line was used to clone the entire 115-kb human insert. Coinheritance analysis demonstrated that five of the other transformants harbored a 100-kb segment of the cloned human insert. Since it is extremely unlikely that six transformants all retain the same stretch of human DNA by coincidence, we conclude that the ERCC-6 gene resides within this region and probably covers most of it. The large size of the gene explains the extremely low transfection frequency and makes the gene one of the largest cloned by genomic DNA transfection. Four transformants did not retain the correcting ERCC-6 gene and presumably have reverted to the UV-resistant phenotype. One of these appeared to have amplified an endogenous, mutated CHO ERCC-6 allele, indicating that the UV61 mutation is leaky and can be overcome by gene amplification.
Images
PMCID: PMC361360  PMID: 2172786
21.  Molecular cloning and biological characterization of the human excision repair gene ERCC-3. 
Molecular and Cellular Biology  1990;10(6):2570-2581.
In this report we present the cloning, partial characterization, and preliminary studies of the biological activity of a human gene, designated ERCC-3, involved in early steps of the nucleotide excision repair pathway. The gene was cloned after genomic DNA transfection of human (HeLa) chromosomal DNA together with dominant marker pSV3gptH to the UV-sensitive, incision-defective Chinese hamster ovary (CHO) mutant 27-1. This mutant belongs to complementation group 3 of repair-deficient rodent mutants. After selection of UV-resistant primary and secondary 27-1 transformants, human sequences associated with the induced UV resistance were rescued in cosmids from the DNA of a secondary transformant by using a linked dominant marker copy and human repetitive DNA as probes. From coinheritance analysis of the ERCC-3 region in independent transformants, we deduce that the gene has a size of 35 to 45 kilobases, of which one essential segment has so far been refractory to cloning. Conserved unique human sequences hybridizing to a 3.0-kilobase mRNA were used to isolate apparently full-length cDNA clones. Upon transfection to 27-1 cells, the ERCC-3 cDNA, inserted in a mammalian expression vector, induced specific and (virtually) complete correction of the UV sensitivity and unscheduled DNA synthesis of mutants of complementation group 3 with very high efficiency. Mutant 27-1 is, unlike other mutants of complementation group 3, also very sensitive toward small alkylating agents. This unique property of the mutant is not corrected by introduction of the ERCC-3 cDNA, indicating that it may be caused by an independent second mutation in another repair function. By hybridization to DNA of a human x rodent hybrid cell panel, the ERCC-3 gene was assigned to chromosome 2, in agreement with data based on cell fusion (L. H. Thompson, A. V. Carrano, K. Sato, E. P. Salazar, B. F. White, S. A. Stewart, J. L. Minkler, and M. J. Siciliano, Somat. Cell. Mol. Genet. 13:539-551, 1987).
Images
PMCID: PMC360615  PMID: 2111438
22.  Methionyl human growth hormone in Turner's syndrome. 
Archives of Disease in Childhood  1988;63(10):1211-1217.
Sixteen girls with Turner's syndrome aged 7.9-15.2 years (bone ages 7.0-11.8 years) were given methionyl growth hormone (somatrem) 4 IU/m2 body surface daily, corresponding to 0.9 IU/kg/week. During one year of treatment their mean (SD) height velocity increased from 3.4 (0.9) to 7.2 (1.7) cm/year and height prediction from 148.2 (4.4) to 150.0 (4.4) cm. All the girls except one had a height velocity increment of more than 2 cm/year and these velocities are above the age references for girls with Turner's syndrome. The girl with a low growth response had antibodies against growth hormone with high binding capacity (3.7 U/l). The height velocity increment was inversely correlated with age and bone age, but this might be partly due to the somewhat higher dosage/m2 body surface and kg body weight that the younger patients were given because of the rounding off of the dose. The better results of our study compared with those of other workers who used similar dosages but did not give the drug as often suggest that giving it daily might have increased the growth response as it does in children deficient in growth hormone.
PMCID: PMC1779019  PMID: 3196048
23.  Who should get growth hormone? 
Archives of Disease in Childhood  1985;60(5):499-500.
PMCID: PMC1777330  PMID: 4015164
24.  Cross-contamination during the preparation of frozen chickens in the kitchen. 
The Journal of Hygiene  1979;83(1):27-32.
A study was made of the extent to which frozen broilers, contaminated with indicator organisms, can cause cross-contamination in the kitchen. In 60 kitchens a number of relevant objects were sampled during the preparation of contaminated frozen broilers. The results show that cross-contamination occurred in a high proportion of the kitchens examined. In many instances the indicator organism was still present on various objects even after rinsing, 'clearing' or washing up. In view of the possible risk of a cross-contamination with Salmonella spp. the importance of instructing food preparers is emphasized. No salmonellas could be found in the sinks of the 60 kitchens examined.
PMCID: PMC2130101  PMID: 379210

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