[Child in contemporary Croatian society]. / Dijete u suvremenome hrvatskom drustvu.

The symposium on the topic "Child in contemporary Croatian society", organized by Croatian Pediatric Society, Croatian Academy of Sciences and Arts, Ministry of health and social welfare and UNICEF Croatia Office, was held in Zagreb on December 12, 2009. The lecturers have shown important information on difficulties the children in Croatia are exposed to. Namely, diseases of the so called "new morbidity", which are becoming more and more frequent in the contemporary world, demand a new approach of work from all who participate in healthcare for children, including additional education. These diseases are not part of a practitioner's routine activity. Due to variety of problems children are exposed to, the approach can be only multidisciplinary. Basic national interest of every country (basic interest of every human society) should be to direct more attention and financial resources to the healthcare of children, which would ensure the existence and healthy future of the society. This approach requires a national consensus and clear political decision of all responsible official services.

Abnormal motoneuron migration, differentiation, and axon outgrowth in spinal muscular atrophy.

The role of heterotopic (migratory) motoneurons (HMN) in the pathogenesis of spinal muscular atrophy (SMA) is still controversial. We examined the occurrence and amount of HMN in spinal cord tissue from eight children with SMA (six with SMA-I and two with SMA-II). All affected subjects were carrying a homozygous deletion of exon 7 in the SMN1 gene. Unlike controls, virtually free from HMN, all SMA subjects showed a significant number of HMN at all levels of the spinal cord. Heterotopic neurons were hyperchromatic, located mostly in the ventral white matter and had no axon or dendrites. More than half of the HMN were very undifferentiated, as judged from their lack of immunoreactivity for NeuN and MAP2 proteins. Small numbers of more differentiated heterotopic neurons were also found in the dorsal and lateral white matter region. As confirmed by ultrastructural analysis, in situ end labeling (ISEL) and CD68 immunoreactivity, HMN in the ventral outflow were found to have no synapses, to activate microglial cells, and to eventually die by necrosis. An unbiased quantitative analysis showed a significant negative correlation between age of SMA subjects (a reflection of the clinical severity) and the number of HMN. Subjects who died at older ages had increased number of GFAP-positive astrocytes. Complementing our previous report on motoneuron apoptosis within the ventral horns in SMA, we now propose that abnormal migration, differentiation, and lack of axonal outgrowth may induce motoneuron apoptosis predominantly during early stages, whereas a slower necrosis-like cell death of displaced motoneurons which "escaped" apoptosis characterizes later stages of SMA.

[Long-term monitoring of children with focal segmental glomerulosclerosis and a transplanted kidney]. / Dugotrajno pracenje djece s fokalnom segmentalnom glomerulosklerozom i presadenim bubregom.

INTRODUCTION: Focal segmental glomerulosclerosis (FSGS) is an important cause of nephrotic syndrome and end-stage renal disease. Children with FSGS are at a risk of recurrence of disease following renal transplantation. The rate of recurrence has been estimated to range from 15% to 50%, having a potentially detrimental course towards the loss of renal function. The factors associated with an increased probability of recurrence are not well known. PATIENTS: The authors followed 8 pediatric patients (3 girls and 5 boys) with FSGS who had undergone renal transplantation (16% of all transplanted pediatric patients) over a long period (1982-2001). The mean age of the children at the time of disease onset was 4 years and 8 months (range: 2 months-12 years). Children were monitored from 10 months to 4 years before the first dialysis. On average, the first dialysis was performed at 7 years of age (range: 12 months-16 years). Time elapsed between the first dialysis and transplantation ranged from 1 to 3 years (mean 1.5 year), and mean age at transplantation was 8 years and 6 months (range: 4-18 years). The grafts were from 2 living-related and 6 cadaveric donors. Five recipients were immunosuppressed with cyclosporin A (CsA) -steroids-azathioprine (Aza), 2 with CsA-steroids-mycophenolate mofetil (MMF), and 1 with CsA-steroids regimen. Follow-up period after transplantation ranged from 2 to 15 years (mean time 7 years and 8 months). RESULTS: Creatinine values, proteinuria range and blood pressure were monitored every 3 months after transplantation, and were as follows: creatinine 41-386 mumol/l (mean value 153 mumol/l), proteinuria 0.01-3,14 g/l (mean 0.27 g/l, median 0.03 g/l), systolic blood pressure 90-140 mm Hg (mean 110 mm Hg), diastolic blood pressure 60-90 mm Hg (mean 80 mm Hg). Two patients developed hypertension grade I and III after renal transplantation. There were 5 (0.6 per patient) acute rejection episodes. Two grafts (25%) were rejected 5 and 9 years after transplantation, but recurrence of FSGS was not confirmed by renal biopsy. CONCLUSION: Due to the small sample size no firm conclusions about recurrence of FSGS could be made. However, the fact that none of 8 children developed recurrence of FSGS after renal transplantation speaks against the relatively high recurrence rates in our pediatric population.

[Primary cytomegalovirus infection after combined cadaveric transplantation of the liver and kidney]. / Primoinfekcija citomegalovirusom nakon kombinirane kadavericne transplantacije jetre i bubrega.

Seronegative transplant recipients are at a high risk of developing primary cytomegalovirus (CMV) infection. The D+/R--constellation produces a 60%-80% probability of CMV disease. In such cases CMV prophylaxis is justified. Presentation of a 12-year old boy who developed a primary CMV infection following A combined liver-kidney transplantation; evaluation of prophylactic options and review of some difficulties in the diagnosis of CMV infection. A cadaveric liver-kidney transplantation (Tx) was done in a 12-year old boy with ESRD due to type I primary hyperoxaluria. CMV status: D+, R-; number of mismatches: 5. PRA 0; kidney cold ischemia time (CIT): 13.54 h; liver CIT: 10.10 h; immediate diuresis; Immunosuppression protocol: anti IL-2 receptor antibodies, steroids, mycophenolate mofetil (MMF); cyclosporine introduced on day 6. Over the first week, daily hemodialyses were done in order to remove oxalate deposits. Kidney and liver biopsies: no ACR, no oxalate deposits. CMV prophylaxis with ganciclovir started on day 0. Routine serology and PCR for CMV follow-up showed: pp 65, IgM and IgG, CMV. DNA (Murex CMV. DNA Hybrid Capture test 2.0): negative over the first 3 months. Day 98: CMV pp 65 positive, IgM neg, DNA neg. Day 108: pp 65 neg, IgM positive, IgG neg. CMV. DNA positive (15 x 105 copies/ml). Clinical status: except for mild Cushing, liver tests and kidney function were normal. Ganciclovir was administered intravenously (i.v.) and after 14 days continued perorally. A few days later, leukopenia with severe neutropenia (neutrophil count: 400) and right otitis media developed. MMF and ganciclovir were withdrawn for a few days and reintroduced after WBC count reconstitution. We had no possibility to monitor MMF. Day 150 pp 65 neg, IgM still positive, IgG neg. No clinical signs of infection. Liver and kidney functions normal. After liver-kidney transplantation in a CMV high-risk pediatric patient (D+/R-), asymptomatic CMV primary infection developed. Although ganciclovir prophylaxis could not prevent the infection, it was mild and delayed. Due to bone marrow suppression, discontinuation of MMF and ganciclovir was necessary. Antigenemia assay pp 65 did not correlate very well with CMV viremia so it could not be recommended as a routine test. It should be used in combination with other CMV tests.