S6dation en endoscopie gastrointestinale p6diatrique DC BELLI, I. SPAHR-SCHOPFER, F.BALDERRAMA, A... more S6dation en endoscopie gastrointestinale p6diatrique DC BELLI, I. SPAHR-SCHOPFER, F.BALDERRAMA, A. CORBOZ, W. HABRE, J.-C. ROUGE H6pital des Enfants, Gen~ve (Suisse) Sedation during gastrointestinal endoscopy in paediatric patientts ... Saint-Maurice et coll. ...
Infections represent a significant threat in solid-organ recipients. However, a certain number of... more Infections represent a significant threat in solid-organ recipients. However, a certain number of infections can be prevented by immunizing patients before their transplantation. The aim of this study is to determine the level of immunity of children undergoing liver transplantation and to assess their capacity to maintain protective levels after surgery. Charts of 44 children transplanted with deceased donation livers between 1990 and 2002 at the Children's Hospital of Geneva were reviewed. Vaccine antibody responses were established pre- and post-transplantation. Only 43% of patients were up to date for diphtheria, tetanus, acellular pertussis, and polio vaccines at the pretransplantation visit, while 44% of children older than 12 months had received their required measles-mumps-rubella vaccines. Six of 44 children had received at least one dose of hepatitis B vaccine, while only two patients had received at least one dose of hepatitis A vaccine. After immunization, and one yr after transplantation, only 14 of 44 patients had detectable anti-HBs antibodies and seven of 18 had anti-HAV antibodies. Varicella antibodies were undetectable in 15 of 19 patients immunized prior to transplantation. This study highlights the need to enforce vaccination before transplantation, follow-up on vaccine- induced immunity, and adapt vaccination schedules after liver transplantation in children, especially for non-live vaccines, which are universally recommended in this population.
The Journal of Clinical Endocrinology & Metabolism, 1999
The objective of this study was to determine whether vitamin D supplementation of breast-fed infa... more The objective of this study was to determine whether vitamin D supplementation of breast-fed infants during the first year of life is associated with greater bone mineral content and/or areal bone mineral density (aBMD) in later childhood. The design was a retrospective cohort study. One hundred and six healthy prepubertal Caucasian girls (median age, 8 yr; range, 7-9 yr) were classified as vitamin D supplemented or unsupplemented during the first year of life on the basis of a questionnaire sent to participating families and their pediatricians. Bone area (square centimeters) and bone mineral content (grams) were determined by dual energy x-ray absorptiometry at six skeletal sites. Vitamin D receptor (VDR) 3'-gene polymorphisms (BsmI) were also determined. The supplemented (n = 91) and unsupplemented (n = 15) groups were similar in terms of season of birth, growth in the first year of life, age, anthropometric parameters, and calcium intake at time of dual energy x-ray absorptiometry. The supplemented group had higher aBMD at the level of radial metaphysis (mean +/- SEM, 0.301+/-0.003 vs. 0.283+/-0.008; P = 0.03), femoral neck (0.638+/-0.007 vs. 0.584+/-0.021; P = 0.01), and femoral trochanter (0.508+/-0.006 vs. 0.474+/-0.016; P = 0.04). At the lumbar spine level aBMD values were similar (0.626+/-0.006 vs. 0.598+/-0.019; P = 0.1). In a multiple regression model taking into account the effects of vitamin D supplementation, height, and VDR genotype on aBMD (dependent variable), femoral neck aBMD remained higher by 0.045 g/cm2 in the supplemented group (P = 0.02). Vitamin D supplementation in infancy was found to be associated with increased aBMD at specific skeletal sites later in childhood in prepubertal Caucasian girls.
Cholesteryl ester storage disease (CESD) and Wolman disease (WD) are both autosomal recessive dis... more Cholesteryl ester storage disease (CESD) and Wolman disease (WD) are both autosomal recessive disorders associated with reduced activity of lysosomal acid lipase (LAL), that leads to the tissue accumulation of cholesteryl esters in endosomes and lysosomes. WD is caused by genetic defects of LAL that leave no residual enzymatic activity, while in CESD patients a residual LAL activity can be identified. We have analyzed the LAL cDNA in three CESD patients from two nonrelated families and identified the mutations responsible for the disease. The associated genetic defects characterized revealed compound heterozygosity for a splice defect leading to skipping of exon 8, due to a G-->A transition at position -1 of the exon 8 splice donor site, and a point mutation leading to a Hisl08Pro change (CAT-->CCT) in two patients (siblings) with mild CESD phenotype. A further CESD patient was hemizygous for a His108-->Arg missense mutation (CAT-->CGT) in combination with a partial deletion of the LAL gene and was affected more severely. Expression of the LAL enzymes with the His108-->Pro and His108-->Arg mutation in insect cells revealed residual enzymatic activities of 4.6% versus 2.7%, respectively, compared with controls. Therefore, His108 seems to play a crucial role in folding or catalytic activity of the lysosomal acid lipase. This is the first description of two different, naturally occurring mutations involving the same amino acid residue in the lysosomal acid lipase in unrelated CESD patients. Moreover, our results demonstrate that the variable manifestation of CESD can be explained by mutation-dependent, variable inactivation of the LAL enzyme.
We report the rare association of Caroli disease (intrahepatic bile duct ectasia associated with ... more We report the rare association of Caroli disease (intrahepatic bile duct ectasia associated with congenital hepatic fibrosis), bilateral cystic renal dysplasia, situs inversus, postaxial polydactyly, and preauricular fistulas in a female child. She presented with end-stage renal disease at the age of 1 month, followed by a rapidly progressing hepatic fibrosis and dilatation of the intrahepatic bile ducts, leading to secondary biliary cirrhosis and portal hypertension. Combined liver-kidney transplantation was performed at the age of 4 years, with excellent outcome. DNA analysis showed a NPHP3 (coding nephrocystin-3) homozygote mutation, confirming that this malformation complex is a ciliopathy. This rare association required an exceptional therapeutic approach: combined simultaneous orthotopic liver and kidney transplantation in a situs inversus recipient. The long-term follow-up was excellent with a very good evolution of the renal and hepatic grafts and normalization of growth and weight. This malformation complex has an autosomal recessive inheritance with a 25% recurrence risk in each pregnancy.
S6dation en endoscopie gastrointestinale p6diatrique DC BELLI, I. SPAHR-SCHOPFER, F.BALDERRAMA, A... more S6dation en endoscopie gastrointestinale p6diatrique DC BELLI, I. SPAHR-SCHOPFER, F.BALDERRAMA, A. CORBOZ, W. HABRE, J.-C. ROUGE H6pital des Enfants, Gen~ve (Suisse) Sedation during gastrointestinal endoscopy in paediatric patientts ... Saint-Maurice et coll. ...
Infections represent a significant threat in solid-organ recipients. However, a certain number of... more Infections represent a significant threat in solid-organ recipients. However, a certain number of infections can be prevented by immunizing patients before their transplantation. The aim of this study is to determine the level of immunity of children undergoing liver transplantation and to assess their capacity to maintain protective levels after surgery. Charts of 44 children transplanted with deceased donation livers between 1990 and 2002 at the Children's Hospital of Geneva were reviewed. Vaccine antibody responses were established pre- and post-transplantation. Only 43% of patients were up to date for diphtheria, tetanus, acellular pertussis, and polio vaccines at the pretransplantation visit, while 44% of children older than 12 months had received their required measles-mumps-rubella vaccines. Six of 44 children had received at least one dose of hepatitis B vaccine, while only two patients had received at least one dose of hepatitis A vaccine. After immunization, and one yr after transplantation, only 14 of 44 patients had detectable anti-HBs antibodies and seven of 18 had anti-HAV antibodies. Varicella antibodies were undetectable in 15 of 19 patients immunized prior to transplantation. This study highlights the need to enforce vaccination before transplantation, follow-up on vaccine- induced immunity, and adapt vaccination schedules after liver transplantation in children, especially for non-live vaccines, which are universally recommended in this population.
The Journal of Clinical Endocrinology & Metabolism, 1999
The objective of this study was to determine whether vitamin D supplementation of breast-fed infa... more The objective of this study was to determine whether vitamin D supplementation of breast-fed infants during the first year of life is associated with greater bone mineral content and/or areal bone mineral density (aBMD) in later childhood. The design was a retrospective cohort study. One hundred and six healthy prepubertal Caucasian girls (median age, 8 yr; range, 7-9 yr) were classified as vitamin D supplemented or unsupplemented during the first year of life on the basis of a questionnaire sent to participating families and their pediatricians. Bone area (square centimeters) and bone mineral content (grams) were determined by dual energy x-ray absorptiometry at six skeletal sites. Vitamin D receptor (VDR) 3'-gene polymorphisms (BsmI) were also determined. The supplemented (n = 91) and unsupplemented (n = 15) groups were similar in terms of season of birth, growth in the first year of life, age, anthropometric parameters, and calcium intake at time of dual energy x-ray absorptiometry. The supplemented group had higher aBMD at the level of radial metaphysis (mean +/- SEM, 0.301+/-0.003 vs. 0.283+/-0.008; P = 0.03), femoral neck (0.638+/-0.007 vs. 0.584+/-0.021; P = 0.01), and femoral trochanter (0.508+/-0.006 vs. 0.474+/-0.016; P = 0.04). At the lumbar spine level aBMD values were similar (0.626+/-0.006 vs. 0.598+/-0.019; P = 0.1). In a multiple regression model taking into account the effects of vitamin D supplementation, height, and VDR genotype on aBMD (dependent variable), femoral neck aBMD remained higher by 0.045 g/cm2 in the supplemented group (P = 0.02). Vitamin D supplementation in infancy was found to be associated with increased aBMD at specific skeletal sites later in childhood in prepubertal Caucasian girls.
Cholesteryl ester storage disease (CESD) and Wolman disease (WD) are both autosomal recessive dis... more Cholesteryl ester storage disease (CESD) and Wolman disease (WD) are both autosomal recessive disorders associated with reduced activity of lysosomal acid lipase (LAL), that leads to the tissue accumulation of cholesteryl esters in endosomes and lysosomes. WD is caused by genetic defects of LAL that leave no residual enzymatic activity, while in CESD patients a residual LAL activity can be identified. We have analyzed the LAL cDNA in three CESD patients from two nonrelated families and identified the mutations responsible for the disease. The associated genetic defects characterized revealed compound heterozygosity for a splice defect leading to skipping of exon 8, due to a G-->A transition at position -1 of the exon 8 splice donor site, and a point mutation leading to a Hisl08Pro change (CAT-->CCT) in two patients (siblings) with mild CESD phenotype. A further CESD patient was hemizygous for a His108-->Arg missense mutation (CAT-->CGT) in combination with a partial deletion of the LAL gene and was affected more severely. Expression of the LAL enzymes with the His108-->Pro and His108-->Arg mutation in insect cells revealed residual enzymatic activities of 4.6% versus 2.7%, respectively, compared with controls. Therefore, His108 seems to play a crucial role in folding or catalytic activity of the lysosomal acid lipase. This is the first description of two different, naturally occurring mutations involving the same amino acid residue in the lysosomal acid lipase in unrelated CESD patients. Moreover, our results demonstrate that the variable manifestation of CESD can be explained by mutation-dependent, variable inactivation of the LAL enzyme.
We report the rare association of Caroli disease (intrahepatic bile duct ectasia associated with ... more We report the rare association of Caroli disease (intrahepatic bile duct ectasia associated with congenital hepatic fibrosis), bilateral cystic renal dysplasia, situs inversus, postaxial polydactyly, and preauricular fistulas in a female child. She presented with end-stage renal disease at the age of 1 month, followed by a rapidly progressing hepatic fibrosis and dilatation of the intrahepatic bile ducts, leading to secondary biliary cirrhosis and portal hypertension. Combined liver-kidney transplantation was performed at the age of 4 years, with excellent outcome. DNA analysis showed a NPHP3 (coding nephrocystin-3) homozygote mutation, confirming that this malformation complex is a ciliopathy. This rare association required an exceptional therapeutic approach: combined simultaneous orthotopic liver and kidney transplantation in a situs inversus recipient. The long-term follow-up was excellent with a very good evolution of the renal and hepatic grafts and normalization of growth and weight. This malformation complex has an autosomal recessive inheritance with a 25% recurrence risk in each pregnancy.
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Papers by Dominique Belli