Biomedical subjects
H Jalanko
Publications and source records attributed to H Jalanko.
Conversion from cyclosporine to Neoral in pediatric recipients for kidney, liver, and heart transplantation.
Explore the source record for details and available documents.
Congenital nephrotic syndrome.
Congenital nephrotic syndrome (CNS) can be caused by neonatal infections, renal diseases which exceptionally occur in early infancy and syndromes with a renal histology of DMS. The most common CNS is the Finnish-type (CNF), an autosomal recessively inherited disease characterized by intrauterine onset of massive proteinuria. The CNF gene has been localized to the long arm of chromosome 19, but the pathogenesis remains unclear. Forty-six CNF patients have been treated at our institution. The diagnosis was based on family history, severe proteinuria of intrauterine onset (serum albumin < 10 g/liter at presentation and urinary protein > 20 g/liter when serum albumin was corrected to > 15 g/liter), a large placenta (> 25% of birth wt), exclusion of other CNS-types and normal glomerular filtration rate during the first six months. Treatment included i.v. albumin substitution, optimal nutrition, thyroxine and anticoagulation. Forty-one patients had been nephrectomized bilaterally at a mean age of 1.2 years and after 3 to 25 months on peritoneal dialysis renal transplantation (Tx) had been performed on 34 who were a mean age of 2.2 years. Growth and development has been normal. Patient survival after Tx was 97%, graft survival 94%, 81% and 81% one, three and five years after Tx was (50% cadaver grafts). Mean GFR was 75 ml/min/1.73 m2 after three years, mean height SDS -1.42, and the nine oldest patients attend school in a normal class.
Liposomal amphotericin B prevents invasive fungal infections in liver transplant recipients. A randomized, placebo-controlled study.
Eighty-six consecutive liver transplant recipients were prospectively randomized in a double-blind, placebo-controlled antifungal prophylaxis study. Seventy-seven patients received 5 days of prophylaxis starting during the transplantation with either liposomal amphotericin B (AmBisome) 1 mg/kg/day or placebo. Among 40 AmBisome-treated patients, no invasive Candida infection was seen during the first month, compared with 5 invasive Candida albicans infections among 37 control patients (P < 0.05). Furthermore, 1 placebo patient experienced Aspergillus niger pneumonia. Thus, the overall incidence of invasive fungal infections was 0/40 (0%) in the AmBisome group versus 6/37 (16%) in the placebo group (P < 0.01). Patient survival at 30 days was 92% versus 94% for AmBisome- and placebo-treated patients, respectively. One patient experienced backache related to AmBisome infusion. Two patients had transient thrombocytopenia possibly caused by AmBisome treatment. AmBisome was otherwise well tolerated. The total cost for all antifungal drugs used in both groups was equal. However, prophylaxis with AmBisome was $5000 less expensive than treatment of proven invasive fungal infections among placebo patients.
Management of congenital nephrotic syndrome of the Finnish type.
Congenital nephrotic syndrome of the Finnish type (CNF) is a rare autosomal recessively inherited disease characterised by intrauterine onset of massive urinary loss of proteins, 90% of which is albumin. The CNF gene has been localised to the long arm of chromosome 19, but the pathogenesis remains unclear. Historically, all CNF patients died, usually within the first 6 months of life. Today, a normal life can be achieved for a child with CNF by correcting the protein deficiency and normalising nutrition. This is accomplished by early intravenous albumin supplementation, nutritional support, aggressive treatment of complications and early renal transplantation, after bilateral nephrectomy and peritoneal dialysis. In the present article current treatment strategies are reviewed, and our own experience with 43 CNF patients during the last 10 years is presented.
Resistance to activated protein C as an underlying cause of recurrent venous thrombosis during relapsing nephrotic syndrome.
A 16-year-old patient with relapsing nephrotic syndrome had three episodes of deep vein thrombosis after the age of 15 years. An autosomal inherited genetic abnormality of clotting factor V, resistance to activated protein C, was found. The clinical course showed that this resistance and the nephrotic syndrome potentiated each other as risk factors for deep vein thrombosis, and long-term anticoagulation was indicated.
Impaired response to hepatitis B vaccine in children receiving anticancer chemotherapy.
Serologic responses to hepatitis B vaccine were investigated in 197 pediatric cancer patients. The patients, ages 1 to 21 years, comprised 66 with solid tumors, 101 with hematologic malignancies and 30 with various benign conditions. Of them 51 were receiving cytotoxic chemotherapy and 114 had not received chemotherapy for 0.2 to 11 years. Three doses of plasma-derived hepatitis B vaccine (20 micrograms) were given at 0, 1 and 6 months; and antibody concentrations to hepatitis B surface antigen were determined at 3, 6 and 8 months. The geometric mean antibody concentration after 3 vaccine doses was 1076 mIU/ml in cancer patients receiving chemotherapy and 18,833 mIU/ml in cancer patients not receiving chemotherapy. The protective titer of antibody (> or = 10 mIU/ml) was reached after 3 doses of vaccine by 67% of patients receiving chemotherapy and by 97% of those not receiving chemotherapy. The patients being treated for solid tumors had weaker responses than those being treated for hematologic malignancies: after 3 vaccine doses no response was observed in 6 of 11 patients with solid tumors compared with 3 of 25 of patients with hematologic malignancies. Children receiving anticancer chemotherapy have essentially weaker responses to hepatitis B vaccine than children not receiving chemotherapy or those with benign conditions. This reflects the profound immunosuppression during chemotherapy. The effect of more intensive immunization schedules should be investigated.
Glomerular antigens in severe hereditary nephrosis.
In search of the basic defect and cell type responsible for the massive treatment-resistant proteinuria of congenital nephrotic syndrome of the Finnish type (CNF), we examined tissue samples of CNF kidneys using established antibody and lectin markers of various glomerular cell types. Markers of vascular endothelium (antibodies to factor VIII and a human homologue of podocalyxin (anti-PHM5) and UEA I lectin) showed no qualitative changes in the endothelial cells of glomeruli or peritubular areas in CNF as compared with controls. Markers of glomerular mesangial cells (antibodies to desmin, smooth muscle actin, RCA I lectin) revealed a secondary increase in mesangial reactivity reflecting the sclerosis and expansion of the mesangial areas in CNF. Markers of visceral epithelial cells (antibodies to a human homologue of podocalyxin, C3b receptor, vimentin, common lymphocytic leukemia antigen, gp44, and the WGA, LFA and, after neuraminidase treatment, PNA lectin) failed to show appreciable qualitative changes in CNF kidney samples. Interestingly, the alpha 2 beta 1 integrins appeared greatly reduced in all CNF samples studied, possibly explaining the mechanisms of CNF-associated proteinuria.
Glomerular anionic charge in congenital nephrotic syndrome of the Finnish type.
Decrease of the anionic charge of the glomerular basement membrane and especially the reduced amount of heparan sulphate proteoglycan in the lamina rara externa has been suggested to be the basic pathogenetic defect in congenital nephrotic syndrome. In the present study the anionic charge of glomeruli was examined in the congenital nephrotic syndrome of the Finnish type and in controls using cationic stains (polyethyleneimine, Ruthenium Red) in electron microscopy. Chondroitinase and heparinase treatments were used to characterize further the anionic elements detected. Scanning electron microscopy (SEM) was used in addition to transmission electron microscopy (TEM) to examine the tridimensional structure and secondary changes of podocytes in this syndrome. The number (mean +/- SD) of polyethyleneimine granules per 1 micron length of lamina rara externa of the glomerular basement membrane was 24.9 +/- 4.5 in control and 23.2 +/- 4.3 [corrected] in congenital nephrotic syndrome subjects. The Ruthenium Red staining pattern was closely similar in syndrome and control kidneys. The granules evident after staining with either cationic stain were seen after chondroitinase but not after heparinase treatment in control as well as in syndrome patient kidney samples. No denuded areas of basement membrane in 42 glomeruli from four syndrome patients were found in SEM. In conclusion, the amount of anionic sites in the lamina rara externa as detected by either cationic stain was comparable to controls. These results do not support the hypothesis of decreased anionic sites in the lamina rara externa of the glomerular basement membrane in congenital nephrotic syndrome of the Finnish type.
Renal allograft histology and correlation with function in children on triple therapy.
Histopathological findings of 13 LRD and 17 CAD renal allografts of paediatric recipients were prospectively semiquantitatively scored and correlated with clinical and functional parameters 18 and 36 months after transplantation. The most common findings at 18 months were diffuse interstitial fibrosis (incidence 57%), glomerular mesangial matrix increase (91%), arteriolar intimal proliferation (70%), and tubular atrophy (83%). Most changes were mild and most biopsies were scored normal or borderline (Banff classification). At 18 and at 36 months 30% of grafts showed mild chronic rejection (CR). Only two grafts showed grade II CR at 18 months and one graft grade III CR at 36 months. Progressive CR was not seen. Donor source or recipient age had no effect on graft histology. Vascular-interstitial cyclosporin (CsA) nephrotoxicity was not found. On the contrary, cumulative CsA dose (mg/kg/day) showed an inverse correlation with arteriolar intimal proliferation (P < 0.001). 51Cr-EDTA and lithium clearances showed inverse correlations with diffuse interstitial fibrosis and lymphocytosis. PAH clearance did not correlate with interstitial or vascular changes. The results indicate good prognosis in children on triple immunosuppression (with CsA administered in three doses/day to pre school children) regardless of donor source.
Functional and histopathological cyclosporine A nephrotoxicity in children after organ transplantation.
Explore the source record for details and available documents.
Prophylaxis with liposomal amphotericin B (AmBisome) prevents fungal infections in liver transplant recipients: long-term results of a randomized, placebo-controlled trial.
Explore the source record for details and available documents.
Cytomegalovirus DNA persists in various structures of liver allografts with chronic rejection.
Explore the source record for details and available documents.
[Antibodies as medication].
Explore the source record for details and available documents.
[Organ transplantation in children is a rational therapy].
Explore the source record for details and available documents.
[Why does renal insufficiency progress?].
Explore the source record for details and available documents.
Renal transplantation in children with emphasis on young patients.
We report the results of 41 consecutive renal transplantations performed on 39 children (median age 2.7 years). Twenty-six recipients were less than 5 years old. Twenty-one recipients (13 under the age of 5 years) received cadaver (CAD) grafts. All grafts except 2 were from adult donors and were placed extraperitoneally. Patients were on triple immunosuppression (cyclosporine plus azathioprine plus methylprednisolone). Mean follow-up time was 2.3 years. No vascular and only one ureteral complication was seen. Acute tubular necrosis occurred in 3 patients (7.3%). No grafts were lost due to acute rejection. Three-year patient survival and 1-year graft survival were 100%. The overall 3-year actuarial graft survival was 86%. Three-year survival of grafts from living-related donors (LRD) was 92% and that of CAD grafts 75%. In recipients younger than 5 years, 3-year LRD graft survival was '89% and CAD graft survival 73%. No significant differences in graft survival between recipients of different age groups or between LRD and CAD grafts were found. We conclude that results of renal transplantation in children under 5 years of age are comparable to those of older children, even using CAD grafts, when adult donors and triple immunosuppression are used.