Reference data for jumping mechanography in healthy children and adolescents aged 6-18 years.

OBJECTIVES: To present gender-specific pediatric normative data on the main parameters of muscle function assessed using jumping mechanography. METHODS: The study population included 796 non-selected Caucasian children and adolescents (432 girls and 364 boys) aged 6-19 years recruited from 6 primary schools and 3 high schools. Maximum peak power (Pmax) was examined by a single two-legged jump, and maximum force (Fmax) was examined by a multiple one-legged hopping. All measurements were performed using a portable force platform (Leonardo Mechanograph, Novotec). Pmax, Pmax/mass, Fmax and Fmax/body weight were analyzed as the main outcome parameters. LMS method was used to generate age- and weight-specific reference smooth curves. RESULTS: Both Pmax and Fmax were strongly dependent on age and weight in both genders (all p<0.001). In prepubertal children, there was no intergender difference in Pmax or Fmax. Both parameters steadily increased in boys and plateaued in girls aged >13 years. Whereas Pmax/mass was more dependent on anthropometric parameters, Fmax/BW remained nearly constant with respect to age and weight. CONCLUSIONS: These reference data are intended to assist clinicians in the assessment of muscle function by jumping mechanography in pediatric patients.

Prepubertal girls with Turner syndrome and children with isolated SHOX deficiency have similar bone geometry at the radius.

CONTEXT: The low bone mineral density (BMD) and alterations in bone geometry observed in patients with Turner syndrome (TS) are likely caused by hypergonadotropic hypogonadism and/or by haploinsufficiency of the SHOX gene. OBJECTIVE: Our objective was to compare BMD, bone geometry, and strength at the radius between prepubertal girls with TS and children with isolated SHOX deficiency (SHOX-D) to test the hypothesis that the TS radial bone phenotype may be caused by SHOX-D. DESIGN AND SETTING: This comparative cross-sectional study was performed between March 2008 and May 2011 in 5 large centers for pediatric endocrinology. PATIENTS: Twenty-two girls with TS (mean age 10.3 years) and 10 children with SHOX-D (mean age 10.3 years) were assessed using peripheral quantitative computed tomography of the forearm. MAIN OUTCOMES: BMD, bone geometry, and strength at 4% and 65% sites of the radius were evaluated. RESULTS: Trabecular BMD was normal in TS (mean Z-score = -0.2 ± 1.1, P = .5) as well as SHOX-D patients (mean Z-score = 0.5 ± 1.5, P = .3). At the proximal radius, we observed increased total bone area (Z-scores = 0.9 ± 1.5, P = .013, and 1.5 ± 1.4, P = .001, for TS and SHOX-D patients, respectively) and thin cortex (Z-scores = -0.7 ± 1.2, P = 0.013, and -2.0 ± 1.2, P < .001, respectively) in both groups. Bone strength index was normal in TS as well as SHOX-D patients (Z-scores = 0.3 ± 1.0, P = .2, and 0.1 ± 1.3, P = .8, respectively). CONCLUSIONS: The similar bone geometry changes of the radius in TS and SHOX-D patients support the hypothesis that loss of 1 copy of SHOX is responsible for the radial bone phenotype associated with TS.

Bone geometry and volumetric bone density at the radius in patients with isolated SHOX deficiency.

UNLABELLED: The short stature homeobox-containing gene (SHOX) plays an important role in bone development and growth. We aimed to assess bone geometry and volumetric bone mineral density at the radius in patients with isolated SHOX deficiency and to relate these bone parameters to the severity of disproportion between the upper and the lower body segment. 17 patients with isolated SHOX deficiency (median age 12.3 yrs, range 6.7-37.2, 12 children and 5 adults) were examined by peripheral quantitative CT (pQCT) at the non-dominant forearm. Results were expressed as Z-scores using published reference data. Linear regression analyses were performed to describe associations between pQCT parameters and the severity of disproportion expressed as sitting height to standing subischial leg height ratio. Trabecular volumetric bone mineral density (vBMD) at the distal radius was normal, whereas cortical vBMD was decreased (mean Z-scores 0.34±1.5, n.s., and -2.2±2.2, p<0.001, respectively). Total bone cross-sectional area was enlarged at the diaphysis (2.1±1.2, p<0.001), while cortical bone cross-sectional area was normal (-0.51±1.4, n.s.). Consequently, cortical thickness was decreased (-1.2±1.3, p<0.01). The polar strength-strain index as a surrogate of long bone strength was normal (0.40±1.4, n.s.). We found no associations between pQCT parameters and the severity of disproportion. CONCLUSIONS: Patients with isolated SHOX deficiency are characterized by decreased cortical vBMD and cortical thickness and enlarged diaphysis. As similar changes have been described in girls with Turner syndrome, these findings suggest that haploinsufficiency of SHOX could cause characteristic skeletal anomalies at the radius.

Defect-diaphragmatic ratio: a new parameter for assessment of defect size in neonates with congenital diaphragmatic hernia.

AIM: The aim of our study is to introduce a new objective method of perioperative evaluation of the size of diaphragmatic defect to enable comparison of results among various centres and methods used for diaphragmatic reconstruction. MATERIALS AND METHODS: Prospective observational study of neonates with congenital diaphragmatic hernia (CDH) and respiratory distress within 24 h of birth operated on from January 2009 to December 2011. Weight, length, thoracic shape and the diameters of diaphragmatic defect were measured. To determine the relative size of the defect, a defect-diaphragmatic ratio (DDR = defect area:diaphragm area × 100) was calculated. The measured and calculated data were subsequently compared between Gore-Tex patch group (GT) and primary repair group (PR). Mann-Whitney U test was used for statistical analysis. RESULTS: Forty-seven patients with CDH were admitted during study period. The overall survival rate was 79 % (37/47). Preoperative stabilization was achieved in 85 % (40/47). Survival of operated neonates was 93 % (37/40). Diaphragmatic reconstruction with Gore-Tex patch was used in 7 neonates (17 %), and primary repair in 33 (83 %). Mortality in Gore-Tex group was 29 %; mortality in primary repair group was 3 %. Data of anthropometric measurement were complete in 34 children (5 GT and 29 PR). Significant differences were found between GT group and PR group in the size of diaphragmatic defect with the transverse and sagittal diameters of defect (48.0 ± 5.7 vs. 30.1 ± 5.9, P < 0.00061; 34.0 ± 12.5 vs. 16.0 ± 7.3, P < 0.0022) and DDR (18.29 ± 4.60 vs. 5.77 ± 3.28, P < 0.0005), respectively. CONCLUSION: The value of DDR as an objective criterion of the extent of diaphragmatic defect was confirmed by the close correlation between DDR and feasibility of primary repair in the study group. This objective assessment of defect size may improve comparing various surgical techniques and results of different centres, and thus facilitates sharing experience with management of neonates with CDH.

Boys with haemophilia have low trabecular bone mineral density and sarcopenia, but normal bone strength at the radius.

Although a decreased areal bone mineral density (BMD) has been reported in patients with haemophilia, data are lacking that would reflect the three-dimensional structure of the bone and the muscle-bone relationship. We aimed to assess volumetric BMD, bone geometry and muscle-bone phenotype in boys with haemophilia, and to describe the association between clinical characteristics of haemophilia and bone quality and structure. A cross-sectional study was conducted in 41 boys with haemophilia (mean age 12.4, range 6.6-19.8 years) using peripheral quantitative CT (pQCT) at the nondominant forearm. Results were transformed into Z-scores using previously published reference data. Significant differences were tested by one-sample t-test or sign test. Two-sample t-test and anova were used to compare results between subgroups of patients divided according to the severity of the disease, the fracture history and the number of joint and muscle bleedings. Boys with haemophilia had a decreased trabecular volumetric BMD (mean Z-score -0.5, P < 0.01), while their cortical volumetric BMD was increased (mean Z-score 0.4, P < 0.05). The volumetric bone mineral content and the bone geometry at the radial diaphysis were normal when adjusted for patients' shorter body height. Muscle area was decreased (mean Z-score -1.0, P < 0.001), irrespective of age. No association was observed of bone quality parameters and bone geometry with the disease severity, fracture history or number of bleedings. Bone strength measured at the diaphysis of the radius is not impaired in boys with haemophilia. The finding of the decreased trabecular bone density can be most likely attributed to their sarcopenia.

Large diaphragmatic defect: are skeletal deformities preventable?

PURPOSE: The aim of study was to compare growth, nutritional status and incidence of chest wall deformities and scoliosis in survivors of large congenital diaphragmatic hernia (CDH) defect (Gore-Tex patch reconstruction) with survivors with smaller defects and primary reconstruction. MATERIALS AND METHODS: An anthropometric study of 53 children who underwent CDH repair in neonatal period was carried out. Weight, height, and skin-fold thickness were measured, scoliosis and chest wall deformity were evaluated. Body mass index (BMI) and thoracic index (TI) were calculated using standard rules. The measured data were compared with national population standard with the use of standard deviation score (SDS). According to the type of diaphragmatic reconstruction, the patients were divided into two groups [Gore-Tex patch (10) versus primary repair (43)]. Student t test and Fisher exact tests were used for statistical analysis. RESULTS: Pectus excavatum was found in 25 (47%) patients, poor posture in 33% and significant scoliosis in 5%. Compared with the population norm, CDH children had a significantly lower body height SDS (mean -0.39, p < 0.05), weight SDS (mean -0.75, p < 0.001), BMI (mean SDS -0.68, p < 0.001) and lower TI (mean SDS -0.62, p < 0.01). Gore-Tex versus primary repair group significantly differed in incidence of pectus excavatum and BMI (PE: p = 0.027, BMI SDS: p = 0.016). A majority of anthropometric parameters (weight, height, thoracic index, and thorax circumference) and incidence of scoliosis and poor posture in children after Gore-Tex patch reconstruction did not significantly differ from children after primary repair. CONCLUSION: The differences in some anthropometric parameters (weight, BMI, and TI) and in the skeletal deformity suggest that the CDH not only disturbs normal lung growth, but also seems to have implications on some other aspects of somatic development. Whether these changes could be related to the type of diaphragmatic reconstruction or rather to the size of the defect remains uncertain.

[Psychomotor and cognitive development of children born after intracytoplasmic sperm injection]. / Psychomotorický a kognitivní vývoj detí narozených po mimotelním oplodnení metodou intracytoplazmatické injekce spermie.

OBJECTIVE: To analyse data on psychomotor and cognitive development of children born after intracytoplasmic sperm injection (ICSI). DESIGN: Open cross-section clinical study. SETTING: Institute for the Care of Mother and Child, Prague and Department of Paediatrics, Charles University, 2nd Medical School and University Hospital Motol, Prague. METHODS: In 133 children (75 boys and 58 girls) psychological examination was made at the age range 11 months - 8.5 years in the years 2004-2006. All children were born after intracytoplasmic sperm injection (ICSI). Psychomotor development of children aged from 11 months to 3.5 years was assessed using the Bayley Scales (BSID-II). In older children, Global Intelligence McCarthy Test was used. RESULTS: In our sample of ICSI-children, no significantly higher incidence of children delayed in mental (cognitive) as well as in motor development has been found as compared with the population norms. However, the results indicate a significantly lower average value of the Psychomotor Developmental Index (PDI) in the group of younger children as compared with the given norm (92.3 +/- 13.9 versus 100 +/- 15; p<0.01). In the group of older children, lower average value of the General Cognitive Index (GCI), as compared with corrected population norm has been found (105.1 +/- 14.7 versus 110 +/- 16; p<0.05). In the group of twins, a significantly higher number of mild developmental disorders was ascertained on the contrary in the group of singletons (64.7% versus 333%; p<0.01) in our older children conceived by ICSI. CONCLUSION: The results indicate only mild lowering of some performances in our ICSI-children: in motor domain in younger children, and in cognitive domain in older children. Children from multiple pregnancies are at greater developmental risk than singletons.

[Parental attitudes and socio-emotional development in children born after ICSI]. / Rodicovské postoje a socioemocní vývoj detí pocatých po ICSI.

OBJECTIVE: To analyze parental attitudes and socio-emotional development of children conceived by ICSI. DESIGN: Open cross-sectional study. SETTING: Department of Clinical Psychology, Thomayer University Hospital, Prague and Department of Paediatrics, Charles University, 2nd Medical School, University Hospital-Motol, Prague. METHODS: 133 children (75 boys, 58 girls) conceived by ICSI, age ranged from 11 months to 8.5 years were psychologically assessed between the years 2004-2006. Children's behavior was evaluated by 4 rating scales during the assessment. Parents answered questionnaires concerning children's temperament, behavioral problems (TBC) and the parental attitudes questionnaire (PARQ). RESULTS: Children's behavior during the psychological assessment was rated mostly as very good or good, although the children were often less communicative. Most of the children have mixed or easy temperament, a difficult type of temperament didn't report any of the parents. Most of the parents didn't describe significant behavioral problems in their children, in particular there were very few externalizing difficulties (opposition, aggression), but in 29.5% of the sample, there were found some social or emotional difficulties. We found surprisingly high frequency of milder forms of autism spectrum disorders and another social problems (social and other anxiety disorders) in the sample, other psychopathology was rare. Parental attitudes had a tendency to grater involvement with the child and high affection in relation with him. CONCLUSION: Socio-emotional development of ICSI children is good, although some have specific social difficulties, externalising problems were present only exceptionally. Parental attitudes toward ICSI children are positive, there is slight tendency to higher emotional involvement with the child.

[Children born after intracytoplasmic sperm injection (ICSI): factors of infertility, pregnancy complications, neonatal period and neonatal characteristics]. / Deti narozené po intracytoplazmatické injekci spermie: faktory neplodnosti, prubeh tehotenství a porodu, perinatální období.

OBJECTIVE: To analyze the type of infertility, pregnancy and neonatal outcome in children conceived after intracytoplasmic sperm injection (ICSI children). DESIGN: Prospective open cross-sectional clinical study. SETTING: University hospital and private IVF unit. METHODS: Type of infertility, pregnancy complications, neonatal period and neonatal characteristics were evaluated in 135 newborns conceived after ICSI from singleton and twin pregnancies and compared to general population. RESULTS: The percentage of twins was significantly higher after ICSI compared to general population (31% versus 1.7%; p<0.001) as well as the percentage of caesarean section deliveries (31% versus 17.8%; p<0.001). Some complication in neonatal period was found in 21.5% ICSI newborns (18 out of 42 twins and 12 out of 93 singletons; p< 0.001). Some complication during the course of pregnancy was found in 50.9% ICSI children. CONCLUSIONS: no differences in gestational age, birth weight and birth length were found when ICSI and spontaneously conceined (sc) singletons and ICSI and SC twins were compared. However, complications during the course of pregnancy and in the neonatal period were more frequent in ICSI conceived children.

[Birth defects, medical outcome and somatic development in children conceived after intracytoplasmic sperm injection (ICSI)]. / Vrozené vývojové vady, zdravotní stav a somatický vývoj detí narozených po intracytoplazmatické injekci spermie.

OBJECTIVE: To analyze the incidence of birth defects, medical outcome and somatic development in children conceived after intracytoplasmic sperm injection (ICSI). DESIGN: Prospective open cross-sectional clinical study. SETTING: University hospital and private IVF unit. METHODS: 135 Czech children (59 girls, 76 boys) from singleton and twin pregnancies conceived after ICSI (age 03-9.5 years; median 5.9) were assessed during the period 2004-2006. The incidence of birth defects, medical outcome and somatic development were evaluated and compared with data of general population and/or with control group matched for sex and age. RESULTS: Birth defects were found in 133% of ICSI children (compared to 4.6% in children after spontaneous conception; p<0.001). The general health of ICSI children did not differ significantly compared to general population. ICSI children required more surgery or hospitalization compared to general population data. There is high rate (69.6%) among ICSI children in the care of various specialised clinics. Body height and weight in ICSI children is in normal range and corresponds to their growth potential. Head circumference in ICSI children is larger compared to reference data (0.43 SD; p<0.001). CONCLUSIONS: No clinically important differences in somatic development between ICSI and general population of Czech children were found. Birth defects were more frequent in ICSI children. The overall general health in ICSI children seems satisfactory but ICSI children were more likely to need health care compared to general population.

[Hormonal suppression and sexual development in children with central precocious puberty in the first treatment cycle 12 weeks after injection of triptoreline 11.25 mg (Diphereline S. R. 11.25 mg): a pilot study]. / Hormonální suprese a pohlavní vývoj detí s centrální predcasnou pubertou v prvním lécebném cyklu 12 týdnu po injekci triptorelinu 11.25 mg (Diphereline S. R. 11.25 mg): pilotní studie.

OBJECTIVE: To evaluate hormonal suppression and pubertal development in children with central precocious puberty (CPP) after injection of triptoreline 11.25 mg (Diphereline S. R. 11.25 mg; Ipsen) in the first treatment cycle of 12 weeks. DESIGN: Pilot study. SETTING: Paediatric department, University Hospital Motol-Prague. METHODS: Serum levels of FSHmax and LHmax and basal levels of estradiol/testosterone were monitored in GnRH test before, 4, 8 and 12 weeks after triptoreline 11.25 mg injection in 3 girls and 2 boys with CPP (age 3.9-10.6 years) previously treated by triptoreline 3 mg every 4 weeks. Uterine and ovarian volume, hormonal cytology (vaginal smear), breast development and testicular volume were evaluated before and 12 weeks after triptoreline 11.25 mg injection. RESULTS: 8 weeks after triptoreline 11.25 mg, FSHmax in girls increased (2.3 IU/l vs. 1.7 IU/l before injection; median) without any other change in 12th week. In boys after initial decrease LHmax 12 weeks after injection rose to 1.7 IU/l (identical as LHmax before injection). Estradiol and testosterone levels were in prepubertal range. Pubertal development in girls did not progress, and testicular volume decreased in both boys (treated for CPP 0.3 and 0.7 years). CONCLUSIONS: Triptoreline 11.25 mg injection in 12 weeks interval can be considered as effective, useful and safe for therapy of CPP. The long-term follow-up will be necessary.

Association of tumour necrosis factor alpha variants with the CF pulmonary phenotype.

BACKGROUND: The pulmonary phenotype in patients with cystic fibrosis (CF), even in those with the same CF transmembrane conductance regulator (CFTR) genotype, is variable and must therefore be influenced by secondary genetic factors as well as environmental factors. Possible candidate genes that modulate the CF lung phenotype may include proinflammatory cytokines. One such protein is tumour necrosis factor alpha (TNFalpha), a member of the immune system. METHODS: Three polymorphic loci in the promoter (-851c/t, -308g/a, -238g/a) and one polymorphic locus in intron 1 (+691g ins/del) of the TNFalpha gene were typed by a single nucleotide primer extension assay in CF patients and healthy controls. Spirometric data and first age of infection with Pseudomonas aeruginosa were collected retrospectively from patients' medical records. RESULTS: An association was found between the TNFalpha +691g ins/del polymorphic locus and severity of CF lung disease. Patients heterozygous for +691g ins and +691g del were more likely to have better pulmonary function (mean (SD) forced expiratory volume in 1 second (FEV1) 79.7 (12.8)% predicted) than patients homozygous for +691g ins (mean (SD) FEV1 67.5 (23.0)% predicted; p = 0.008, mean difference 12.2%, 95% CI 3.5 to 21.0). Also, patients heterozygous for +691g ins and +691g del were more likely to have an older first age of infection with P aeruginosa (mean (SD) 11.4 (6.0) years) than patients homozygous for +691g ins (mean (SD) 8.3 (4.6) years; p = 0.018, mean difference 3.1 years, 95% CI 0.5 to 5.6). An association was also found with the -851c/t polymorphic locus. In the group of patients with more severe FEV1% predicted, a higher proportion of patients were homozygous for the -851c allele than in the other group of patients (p = 0.04, likelihood ratio chi2, odds ratio = 2.4). CONCLUSION: TNFalpha polymorphisms are associated with the severity of CF lung disease in Czech and Belgian patients with CF.

Czech dysplasia metatarsal type.

We report three further patients of the recently described new bone dysplasia-dominantly inherited pseudorheumatoid arthritis. The patients of this report have a similar clinical history, the same distinctive phenotype and almost identical radiographic findings. The only major difference is absence of weather dependent articular pain which characterized the family of the previous study. This report expands the clinical data of this bone dysplasia. All patients are Caucasians and originate from different parts of the Czech Republic. It seems that this disorder is quite a common constitutional bone disorder in this country. We propose the name of Czech Dysplasia Metatarsal Type for this unique disease.

3-M syndrome in two sisters.

3-M syndrome is a rare, autosomal recessive dwarfing syndrome characterized by prenatal growth restriction, facial dysmorphism and absence of both microcephaly and mental retardation. The term 3-M syndrome originates from the common initial of the first three authors of the first report. The diagnosis is established by a combination of clinical history, clinical examination and radiographic findings. The present report shows two sisters whose facial features were slightly different from those usually reported. In addition, they presented with small nails and abnormal dermatoglyphics. The present report expands the phenotypic spectrum of 3-M syndrome.

[Growth and development in untreated girls with slowly progressing idiopathic central or borderline-onset puberty]. / Rust a vývoj nelécených dívek s pomalou progresí idiopatické centrální predcasné nebo hranicne nastupující puberty.

OBJECTIVE: To analyse growth and development of girls with slowly progressive idiopathic precocious or early puberty. DESIGN: Long-term open clinical study. SETTING: Department of Obstetrics and Gynaecology, Second Faculty of Medicine, Charles University, Prague. METHODS: In 20 untreated girls with slowly progressive puberty starting at 6-9 years neurogenic aetiology was excluded. During follow-up period 4.7 +/- 2.2 (2-8.5) years (mean +/- SD; range), sexual development (Tanner criteria), age at menarche, menstrual cycle and auxological parameters were evaluated. RESULTS: 13 girls reached menarche at 11.1 +/- 0.9 years (3.7 +/- 1.1 years after the onset of puberty), earlier than in their mothers (12.9 +/- 1.1 years) and Czech standards (P < 0.05). Menstrual cycle 28 (24-29) days was regular in all 6 girls with gynaecological age > 2 years. In one girl microprolactinoma was diagnosed, therapy with bromocryptine started at the age 14.7 years (3.5 years after menarche). At the onset of follow-up, bone age (TW20) advancement was 1.8 +/- 1.4 years above the chronologic age. Initial prediction of final height (graphic method) was 162.3 +/- 5.5 cm vs final prediction 163.7 +/- 5.1 cm. Final height 162.2 +/- 5.7 cm achieved 7 girls vs target height 163.6 +/- 5.2 cm (NS). CONCLUSION: In untreated girls, menarche occurred later after the first signs of puberty than in normal population, menstrual cycle was regular. Height potential was preserved, final height corresponded with their target height. Not all girls with early and slowly progressive puberty should be treated. Therapy is necessary in organic aetiology, rapid progressive precocious puberty and impaired growth prognosis.

Insulin-like growth factor-I and insulin-like growth factor-binding protein-3 in cystic fibrosis: a positive effect of antibiotic therapy and hyperalimentation.

UNLABELLED: Patients with cystic fibrosis (CF) are underweight and growth retarded. This study tested the link between serum insulin-like growth factor-I (IGF-I) and insulin-like growth factor-binding protein-3 (IGFBP-3) levels and body height, nutritional status, pulmonary function tests and activity of inflammation in 92 subjects with CF (age 2.1-18.8 y). It also analysed the effect of short-term antibiotic treatment and hyperalimentation on IGF-I and IGFBP-3 levels in 33 subjects (age 3.6-33.7y) on 41 occasions. Both IGF-I (-1.19 +/- 0.17 SD) and IGFBP-3 levels (-0.66 +/- 0.12 SD; both p < 0.0001 vs 0) were decreased in cross-sectional measurements. Their standardized values were inversely proportional to age (IGF-I: r = -0.23, p = 0.03; IGFBP-3: r = -0.29, p = 0.005) and positively correlated with SDS of height (IGF-I: r = 0.40, p < 0.0001; IGFBP-3: r = 0.36, p = 0.0005) and of mid-arm circumference (IGF-I: r = 0.39, p = 0.0001; IGFBP-3: r = 0.38, p = 0.0002), and with pulmonary function tests. After a short-term course of intensive antibiotic therapy and hyperalimentation, IGF-I normalized (from -0.66 +/- 0.20 to 0.00 +/- 0.25 SD; p < 0.0001) and IGFBP-3 increased (from -0.78 +/- 0.15 to -0.53 +/- 0.16 SD; p = 0.002). IGFBP-3 correlated inversely with erythrocyte sedimentation rate (r = -0.40, p = 0.01). CONCLUSION: The levels of IGF-I and IGFBP-3 are markedly decreased in patients with CF and tend to normalise after a short course of antibiotic treatment and hyperalimentation.

Characterization of a novel 21-kb deletion, CFTRdele2,3(21 kb), in the CFTR gene: a cystic fibrosis mutation of Slavic origin common in Central and East Europe.

We report a large genomic deletion of the cystic fibrosis transmembrane conductance regulator (CFTR) gene, viz., a deletion that is frequently observed in Central and Eastern Europe. The mutation, termed CFTRdele2,3(21 kb), deletes 21,080 bp spanning introns 1-3 of the CFTR gene. Transcript analyses have revealed that this deletion results in the loss of exons 2 and 3 in epithelial CFTR mRNA, thereby producing a premature termination signal within exon 4. In order to develop a simple polymerase chain reaction assay for this allele, we defined the end-points of the deletion at the DNA sequence level. We next screened for this mutation in a representative set of European and European-derived populations. Some 197 CF patients, including seven homozygotes, bearing this mutation have been identified during the course of our study. Clinical evaluation of CFTRdele2,3(21 kb) homozygotes and a comparison of compound heterozygotes for deltaF508/CFTRdele2,3(21 kb) with pairwise-matched deltaF508 homozygotes indicate that this deletion represents a severe mutation associated with pancreatic insufficiency and early age at diagnosis. Current data show that the mutation is particularly common in Czech (6.4% of all CF chromosomes), Russian (5.2%), Belorussian (3.3%), Austrian (2.6%), German (1.5%), Polish (1.5%), Slovenian (1.5%), Ukrainian (1.2%), and Slovak patients (1.1%). It has also been found in Lithuania, Latvia, Macedonia and Greece and has sporadically been observed in Canada, USA, France, Spain, Turkey, and UK, but not in CF patients from Bulgaria, Croatia, Romania or Serbia. Haplotype analysis has identified the same extragenic CF-haplotype XV-2c/KM. 19 "A" and the same infrequent intragenic microsatellite haplotype 16-33-13 (IVS8CA-IVS 17bTA-IVS 17bCA) in all examined CFTRdele2,3(21 kb) chromosomes, suggesting a common origin for this deletion. We conclude that the 21-kb deletion is a frequent and severe CF mutation in populations of Eastern- and Western-Slavic descent.

[Effect of estrogens on final body height in girls with a constitutionally tall stature--risk or benefit?]. / Ovlivnení definitivní telesné výsky estrogeny u dívek s konstitucne vysokým vzrustem--rizika nebo prínos?

OBJECTIVE: Investigation of the effect of a long-term oestrogen treatment on the growth and development of children, elaboration of a theoretical model for remaining growth of girls on a long-term oestrogen therapy predicting reduction of the final height in girls with constitutionally tall stature, analysis of early and late side-effects of therapy. TYPE OF STUDY: Open clinical study. NAME AND PLACE OF DEPARTMENT: Endocrine out-patient clinic of the Second Paediatric Department and gynaecological out-patient clinic for children and adolescents of the Gynaecological-Obstetric Department, Second Medical School--Charles University and University Hospital Prague--Motol. METHOD: Elaboration of theoretical model for remaining growth of girls on a long-term oestrogen therapy was based on an analysis of the remaining growth of upper and lower body segment of healthy Czech girls. RESULTS: The extent of assumed reduction of the final height in girls with constitutionally tall stature treated with oestrogen declines with advancing age at the onset of treatment. The optimal age for the onset of treatment is between 10 and 11 years. CONCLUSION: Treatment can be recommended only in girls with growth prediction above 185 cm and serious psychological difficulties resulting from excessive height, always after careful analysis of the biological development and growth prediction. In every case it is necessary to evaluate the possible benefit of treatment in relation to potential risks. The greatest problem is according to the authors late onset and overrating of the therapeutic possibilities.

[Cystic fibrosis--a disease of adolescents and adults?]. / Cystická fibróza--nemoc dospívajících a dospelých?

BACKGROUND: Cystic fibrosis (CF) is no longer a childhood disease. Since the identification of the gene in 1989 research has made advances and changed views on the pathogenesis, diagnosis and treatment. The objective of the present work is to make doctors treating adult patients familiar with modern therapeutic methods and their value. METHODS AND RESULTS: In the CF Centre of the Faculty Hospital in Prague Motol 349 patients are followed up on a long-term basis, incl. 95 who died since 1985. Hundred and twenty six (36.1%) patients survived to the age of 18 years, of those 41 died and 85 patients live. Comparison of semilongitudinal data of a group of 83 patients born before 1975 whose treatment during childhood and puberty was inadequate and 196 patients born in 1976-90 treated by modern methods proved the great effect of treatment on the course and prognosis of the disease. The median age at death increased during from 12.2 years in 1985-90 to 18.8 years in 1991-1998 (p = 0.004). The nutritional status of adult patients is satisfactory in 40.4%, poor in 33.3% and marginal in 26.3%. A normal pulmonary function was recorded in 17.5%, 22.8% are severely affected, the majority of patients (59.7%) has values within 40 to 80% of normal levels. CONCLUSIONS: Modern intensive treatment improved the prognosis and quality of live in patients with CF. Critical deterioration of the clinical condition shifted to the threshold of adult age. It is therefore essential that doctors treating such patients should be familiar with this issue.