Andrzej Brodkiewicz

Thiopurine S-methyltransferase (TPMT) polymorphisms in children with acute lymphoblastic leukemia, and the need for reduction or cessation of 6-mercaptopurine doses during maintenance therapy: The Polish multicenter analysis†

6‐Mercaptopurine (6‐MP) is used for the treatment of pediatric acute lymphoblastic leukemia (ALL). Mutations in the TPMT gene may influence the efficacy and safety of 6‐MP treatment. This multicenter study investigated the association between TPMT genotype, 6‐MP dose adjustments, and the incidence of adverse effects in patients.

Serum selenium level and glutathione peroxidase activity in steroid-sensitive nephrotic syndrome

In our previous study the pattern of glutathione peroxidase (GPX) activity in the course of steroid–sensitive nephrotic syndrome (SSNS) in children suggested a defect in antioxidant defense. In the present report the serum selenium (Se) level, an essential component of GPX activity, was measured in a comparable group of children with SSNS at the same clinical stages at which GPX activity was determined in the previous study. Nephrotic children had normal serum Se levels during the edematous stage, at the end of prednisone treatment, and in remission. At the end of high-dose prednisone treatment, the serum Se level increased (P<0.01) simultaneously with enhanced activity of GPX. These results suggest that children with SSNS have a persistent defect in the antioxidant defense at the important stage of hydrogen peroxide and fatty acid hydroperoxide decomposition. This defect is transiently alleviated by high-dose prednisone treatment.

Treasure your exceptions: recent advances in molecular genetics of glomerular disease

The glomerular filtration barrier consists of endothelial cells, the glomerular basement membrane, and podocytes. The membrane is a highly crosslinked macromolecular meshwork composed of specific extracellular matrix proteins. The adjacent foot processes of podocytes are bridged along their basolateral surfaces by a slit diaphragm (a porous filter structure of nephrin molecules). Recent discoveries of mutations in the range of genes encoding proteins involved in the structure or function of the glomerular filtration barrier have provided new insights into mechanisms of glomerular diseases. In this review, we summarize recent progress in the elucidation of the genetic basis of some glomerulopathies in humans.

An insertion/deletion ACE polymorphism and kidney size in Polish full-term newborns

The number of nephrons is a multifactorial trait controlled by the interaction of environmental factors and genetic variants that influence the extent of branching nephrogenesis during foetal life. A correlation between renal mass and nephron number in newborns allows the use of the total kidney volume at birth as a surrogate for congenital nephron number. Since the renin–angiotensin system plays an important role in renal development we hypothesized that the common, functional insertion/deletion (I/D) polymorphism in the ACE gene might be responsible for the variation in kidney size amongst healthy individuals. We recruited 210 healthy Polish full-term newborns born to healthy women with uncomplicated pregnancies. The kidney volume was measured sonographically. Total kidney volume (TKV) was calculated as the sum of left kidney volume and right kidney volume. TKV was normalized to body surface area (TKV/BSA). The I and D alleles were identified using polymerase chain reaction. TKV/BSA in newborns carrying at least one insertion ACE allele was significantly reduced by approximately 8% as compared with homozygous newborns for the D allele (DD genotype) (105.1±23.6 vs. 114.2±28.2 cm3/m2, p<0.05). The results of this study suggest that I/D ACE polymorphism may account for subtle variation in kidney size at birth, which reflects congenital nephron endowment.

Highly effective unconventional management of aspergillosis of the left maxillary sinus in an 11-year-old girl with rhabdomyosarcoma embryonale of the frontal sinus.

Invasive fungal infections are common causes of death in children treated for malignancies, and therefore present an important and growing clinical problem. Fungal invasion usually affects immunocompromised patients, but increased incidences are also associated with intensification of antineoplastic therapy and increased numbers of organ and bone marrow transplantations. Fungal infections in parameningeal and cerebral locations carry high risks of treatment failure. We describe the case of an 11-year-old female patient with rhabdomyosarcoma embryonale of the frontal sinuses with metastases to the neck lymph nodes, treated according to the CWS 2002 protocol for high-risk patients. Left maxillary sinus aspergillosis was diagnosed during chemotherapy following radiotherapy, and 56 days after surgical excision of the tumour. No effect was achieved by use of amphotericin B. Further treatment included intravenous voriconazole at 6 mg per kg body weight every 12 h for 2 weeks, followed by oral voriconazole at 4 mg per kg body weight twice daily for 6 months. Simultaneous excision of necrotic tissues from the nasal cavity, ethmoid bone, maxillary sinus and frontal recess was performed. The sinus was kept open for 3 weeks to allow voriconazole lavage every 12 h for 3 weeks. This unconventional treatment resulted in eradication of sinus aspergillosis and allowed intensive chemotherapy to be continued with no recurrence of aspergillosis.

Evidence for the efficacy of immunotherapy in children with high-risk neuroblastoma.

Neuroblastoma is the most common extra-cranial malignancy of childhood, with the highest incidence in children younger than 4 years. The prognosis depends on many factors, such as age at diagnosis, stage of disease and molecular genetic subtype. More than 50% of children who present with the disease are deemed to have high-risk neuroblastoma. The standard therapy for children with high-risk neuroblastoma consists of intensive chemotherapy, surgery, radiotherapy, myeloablative consolidation with autologous haematopoietic stem cell rescue followed by the treatment of minimal residual disease with 13-cis-retinoic acid. Unfortunately, more than half of the patients relapse regardless of the treatment intensity. Combined therapy with monoclonal antibodies (anti-GD2), intravenous interleukin-2 (Il-2), intravenous granulocyte-macrophage colony-stimulating factor (GM-CSF) and oral 13-cis-retinoic acid have been proved to be effective in some randomised trials. A better understanding of the underlying immunological processes in therapy with anti-GD2 antibodies will allow its success to be evaluated more accurately and direct future endeavours. Nevertheless, the long-term benefit of this treatment approach needs to be established.

Ocena wielkości i funkcji nerek u dzieci z ostrą białaczką limfoblastyczną (OBL) po zakończeniu leczenia

Wstep Nerki są organem szczegolnie narazonym na upośledzenie ich funkcji oraz wystepowanie powiklan w czasie leczenia i po zakonczonym leczeniu ostrej bialaczki limfoblastycznej (OBL), ktore w sposob istotny mogą wplywac na komfort i dlugośc zycia pacjentow. Cel pracy Celem pracy byla ocena wielkości i funkcji nerek u dzieci, oraz określenie czynnikow mających wplyw na wystepowanie nieprawidlowości w ich funkcjonowaniu po zakonczonym leczeniu OBL za pomocą wybranych badan klinicznych, biochemicznych i obrazowych. Material i metody Badaniami objeto grupe 48 dzieci, w tym 29 (60%) chlopcow i 19 (40%) dziewczynek, w wieku 79–275 miesiecy (średnia 159 miesiecy; SD 49 miesiecy), u ktorych w latach 1989–2001 ustalono rozpoznanie OBL. Wyniki i wnioski Wykazano, ze stosowany program chemioterapii i czas obserwacji dluzszy niz 5 lat po zakonczenia leczenia w sposob istotny wplywaly na obnizenie wartości GFR, wystepowanie blizn w nerkach oraz zmniejszenie objetości i dlugości nerek. Dlatego konieczne wydaje sie objecie okresową opieką nefrologiczną pacjentow po zakonczeniu leczenia OBL.