Biomedical subjects

Christer Holmberg

Publications and source records attributed to Christer Holmberg.

41 records · Page 3Linked to original sources

PubMed2002

Neurodevelopmental outcome in high-risk patients after renal transplantation in early childhood.

Patient and graft survival rates of pediatric renal transplant recipients are currently excellent, but there are few reports regarding the long-term neurodevelopmental outcome after renal transplantation (Tx) in early childhood. Children with renal failure from infancy would be expected to have a less favorable developmental prognosis. We report the neurodevelopmental outcome in 33 school-age children transplanted between 1987 and 1995 when < 5 yr of age. We prospectively performed a neurological examination, magnetic resonance imaging (MRI) of the brain, electroencephalograms (EEGs), audiometry, and neuropsychological tests (NEPSY), and measured cognitive performance (WISC-R); we related these results to school performance and to retrospective risk factors prior to Tx. Twenty-six (79%) children attended normal school and 76% had normal motor performance. Six of the seven children attending a special school had brain infarcts on MRI. The EEG was abnormal in 11 (35%), and five (15%) received anti-convulsive treatment after Tx. Sensorineural hearing loss was documented in six patients. The mean intelligence quotient (IQ) was 87, and 6-24% showed impairment in neuropsychological tests. The children attending a special school had been more premature, but had not had a greater number of pre- or neonatal complications. They had experienced a greater number of hypertensive crises (p = 0.002) and seizures (p = 0.03), mainly during dialysis, but the number of septic infections and the mean serum aluminum levels were not significantly greater than in the children with normal school performance. In these previously lethal diseases, the overall neurodevelopmental outcome is reassuring. However, it is of crucial importance to further minimize the risk factors prior to Tx.

Audiometry↗

PubMed2002

The number of podocyte slit diaphragms is decreased in minimal change nephrotic syndrome.

The pathophysiology of proteinuria in acquired kidney diseases is mostly unknown. Recent findings in genetic renal diseases suggest that glomerular epithelial cells (podocytes) and the slit diaphragm connecting the podocyte foot processes play an important role in the development of proteinuria. In this work we systematically evaluated the podocyte slit pores by transmission electron microscopy in two important nephrotic diseases, minimal change nephrotic syndrome (MCNS) and membranous nephropathy (MN). As controls, we used kidneys with tubulointerstitial nephritis (TIN). Effacement of podocyte foot processes was evident in proteinuric kidneys. However, quite normal looking foot processes and slit pores with varying width were also observed. Careful analysis of slit pores revealed, that the proportion of the pores spanned by the linear image of slit diaphragm, was reduced by 39% in kidneys from MCNS patients (1265 pores analyzed) compared with TIN samples (902 pores analyzed, p = 0.0003). To enhance the detection rate of the slit diaphragms, the "empty" podocyte pores were further analyzed with tilting series from -45 to +45. This revealed the linear diaphragm image in 71% and 26% of the slits in TIN and MCNS kidneys, respectively (p = 0.0003). In contrast to findings in MCNS, no significant reduction of the slit diaphragms were seen in MN kidneys compared with the controls. The results suggest that MCNS is associated with disruption of glomerular slit diaphragms.

Adolescent↗

PubMed2002

Recombinant human growth hormone treatment, using two dose regimens in children with chronic renal failure--a report on linear growth and adverse effects.

The aim of this study was to study the efficiency and the adverse effects of 2 or 4 IU/m2/day of growth hormone (GH) in the first year and 4 IU/m2/day in the second. Of 29 growth-retarded children with chronic renal failure (CRF) (aged 3.4-15.1 years), 23 completed the first year of therapy, and 16 completed the second year. Height velocity SDS (HVSDS) increased in the first year in the low-dose group with 3.0, and 3.8 in the high-dose group. In the second year, HVSDS increased by 1.3 in the low-dose group and by 2.1 in high-dose group (p < 0.05). The IGF-I/IGFBP-3 ratio rose identically during the first year (p < 0.01). The retarded bone age did not advance inappropriately. The integrated insulin levels (AUC) increased significantly after 1 year of therapy in both groups. HbA1c, levels did not change. The number of adverse events was highest in the low-dose group, in which one patient developed overt insulin dependent diabetes mellitus. In conclusion, glucose metabolism should be monitored in children with CRF during rhGH-treatment. GH therapy in our patients resulted in a significant increase in height velocity with no inappropriate bone age progression and few serious adverse effects, all without relation to the dose of rhGH. The low start dose (2 IU/m2/ day) was of no advantage compared to the high dose.

Adolescent↗

PubMed2002

Genetic screening for maternal uniparental disomy of chromosome 7 in prenatal and postnatal growth retardation of unknown cause.

OBJECTIVE: Many short-statured children lack an etiologic explanation for their retarded growth. Recently, uniparental disomy (UPD), the inheritance of both chromosomes of a chromosome pair from only 1 parent, has been associated with short stature for many chromosomes. Silver-Russell syndrome (SRS) represents an extreme syndrome of intrauterine growth retardation (IUGR) and slight dysmorphic signs, and maternal UPD of human chromosome 7 (matUPD7) has been observed in approximately 10% of SRS cases. In addition, matUPD7 has been reported in patients with only slight dysmorphic features and prenatal or postnatal growth retardation. The objectives of this study were to study the role of matUPD7 in growth failure of unknown cause and in cases of SRS, and to evaluate the efficiency of genetic testing for matUPD7 as a diagnostic tool. METHODS: DNA samples were studied from 205 children, 92 girls and 113 boys, with short stature of unknown cause and their parents. The patient cohort included 39 cases of SRS, 91 patients with IUGR and subsequent postnatal short stature, and 75 patients with postnatal growth retardation only. MatUPD7 was screened for by genotyping DNA samples from the patient, mother, and father with 13 chromosome-7-specific polymorphic microsatellite markers. RESULTS: Six (3%) of 205 matUPD7 cases were observed exclusively among 39 (15%) SRS patients studied. Patients with IUGR and/or postnatal growth retardation and with dysmorphic features did not reveal cases of matUPD7. CONCLUSIONS: Our results indicate that matUPD7 cases are predominantly observed among patients meeting the criteria of SRS, and matUPD7 is not a common cause for growth retardation. Genetic screening for cases of matUPD7 among growth-retarded patients should be focused on patients with severe IUGR and features of SRS. In addition, matUPD7 screening is advisable in individuals with cystic fibrosis and other recessive disorders mapped to chromosome 7 who have unusually short stature.

Abnormalities, Multiple↗

PubMed2001

Expression of nephrin in pediatric kidney diseases.

Nephrin is a podocyte cell adhesion protein located at the slit diaphragm area of the kidney glomerulus. Mutations in the nephrin gene (NPHS1) lead to congenital nephrosis, suggesting that nephrin is essential for the glomerular filtration barrier. This prompted this study of the expression of nephrin in acquired pediatric kidney diseases using in situ hybridization and immunohistochemistry. In situ hybridization for nephrin mRNA was performed in biopsy samples from patients with proteinuria caused by minimal change nephrosis, focal segmental glomerulosclerosis, and membranous nephropathy. The expression of nephrin mRNA was evaluated by grading the signal intensity visually and by counting the number of grains in separate glomeruli. No significant difference was observed in these samples as compared with controls. Immunostaining for nephrin was performed using antibodies directed against extra- and intracellular parts of the molecule. Nephrin staining gave a linear pattern along the glomerular capillary loops. In minimal change nephrosis, focal segmental glomerulosclerosis, and membranous nephropathy, the distribution of nephrin was similar to that in controls. In proliferative forms of glomerulonephritides (Henoch-Schönlein nephritis, IgA nephropathy, postinfectious and membranoproliferative glomerulonephritis), crescents and sclerotic lesions were negative for nephrin, and mesangial proliferation led to a scattered and sparse staining pattern. The staining pattern of nephrin was compared to that of ZO-1, a component of the cytoplasmic face of the slit diaphragm. The distributions of these two proteins in capillary tufts were similar in all disease entities studied. In conclusion, immunohistochemistry and in situ hybridization did not reveal major alterations in the expression of nephrin in proteinuric kidney diseases in children. Further studies are needed for more precise evaluation of the role of nephrin in these diseases.

Animals↗