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Biomedical subjects

H Jalanko

Publications and source records attributed to H Jalanko.

At least 73 records · Page 4Linked to original sources

Renal function and histopathologic changes in children after liver transplantation.

Up to 60% reduction of renal function has been reported after orthotopic liver transplantation (OLT) in patients receiving cyclosporine. We prospectively investigated renal function and histopathology in 16 children on triple immunosuppression therapy during 3 years after OLT. Cyclosporine was administered in 3 doses/day to preschool children. The median age at OLT was 5.4 years. Determinations of chromium 51-labeled ethylenediaminetetraacetic acid, p = aminohippuric acid, lithium, and sodium clearances, measurements of serum and urinary electrolytes, and urinary concentration tests were performed. Renal biopsy specimens were taken 18 and 36 months after transplantation. The mean glomerular filtration rate was 121.5 ml/min per 1.73 m2 before transplantation, 86.3 at discharge, and 119.4 36 months after OLT. Hyperuricemia, hyperkalemia, and reduced urinary concentrating capacity were common. Hyperkalemia occurred in 13% to 19% of the patients, only during the first 6 months. Hyperuricemia and reduced concentrating capacity occurred with incidences of 17% to 44% and 40% to 63%, respectively. Histopathologic changes were mild, and severe nephrotoxic effects of cyclosporine was not seen. However, tubular atrophy, mesangial matrix increase, and mesangial cell proliferation were common. We conclude that triple immunosuppression with cyclosporine administration, in three doses per day, to small children and careful renal follow-up ensure good renal function after OLT.

Adolescent↗

Recombinant human granulocyte-macrophage colony-stimulating factor in the treatment of febrile neutropenia: a double blind placebo-controlled study in children.

In a double blind study of 58 episodes of fever and profound neutropenia, children with cancer received either recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) or placebo, combined with identical antimicrobial therapy, i.e. imipenem, on admission. The criteria for discontinuation of therapy were identical. A difference was demonstrated both in the number of hospital days, totaling 252 days in the rhGM-CSF group and 354 in the placebo group, days receiving antibiotics (220 vs. 322), and in the resolution of neutropenia (4.5 days vs. 6.0 days; P < 0.05). The number of episodes requiring antimicrobial therapy for longer than 10 days was 5 of 28 (12%) in the rhGM-CSF group as opposed to 15 of 30 (50%) in the placebo group (P = 0.01). rhGM-CSF was well-tolerated. We conclude that rhGM-CSF was efficacious in accelerating myeloid recovery and reducing the length of hospitalization in febrile neutropenia.

Adolescent↗

Congenital nephrosis of the Finnish type (CNF): matrix components of the glomerular basement membranes and of cultured mesangial cells.

Congenital nephrosis of the Finnish type (CNF) is a hereditary renal disease of unknown aetiology manifested by massive proteinuria of the newborn and unresponsive to any treatment. In this study kidney samples and cultured glomerular mesangial cells from five patients with CNF were studied by indirect immunofluorescence microscopy for the presence and location of major basement membrane matrix (GBM) components. Histological changes of glomeruli ranging from mild thickening of basement membranes to total obliteration and sclerosis were seen. Notably, thickening of the subepithelial layer of Bowman's capsules was regularly seen along with hypercellularity at the juxtaglomerular areas. The matrix components studied (laminin, plasma- and cellular fibronectin, type IV collagen, including the NC-1, alpha-1 and alpha-3 chains, heparan sulphate proteoglycan (HSPG) core protein, thrombospondin) were characteristically seen within the glomeruli. Local thickenings alternating with total loss of epitopes along the GBM were seen, especially with anti-type IV collagen and anti-HSPG antibodies. Sera from CNF patients after transplantation failed to show antibodies against GBM structures in immunofluorescence microscopy, suggesting that no missing epitopes of GBM are introduced with the transplant kidney. Cultured mesangial cells of CNF glomeruli also showed continued in vitro production of the matrix components and their incorporation into the matrix underneath the cell layer.

Adult↗

Post-transplantation nephrosis in congenital nephrotic syndrome of the Finnish type.

Congenital nephrotic syndrome of the Finnish type (CNF) is an autosomal recessively inherited disease manifesting as massive proteinuria, edema and ascites in the neonatal period. The disease is believed to be limited to the kidneys and recurrences after renal transplantation have not been reported. At our center 29 transplantations have been performed on 28 CNF patients. One to 33 months after transplantation, seven grafts (24%) of six patients have developed a steroid-resistant nephrotic syndrome. The clinical data and renal histology of these patients were analyzed in order to elucidate the cause of the proteinuria. At the onset of six of the seven episodes of nephrosis, the patient had evidence of a preceding CMV- or EBV-infection and the remaining patient had sinusitis. Upon light and electron microscopy examination, endothelial swelling of the glomerular capillaries resembling transplant glomerulopathy (TG) was seen, but unlike TG, the glomerular basement membranes were normal. The response of proteinuria to steroid or cyclophosphamide therapy was poor, with total remission in only two patients and partial remission in one patient, all treated with methylprednisolone and cyclophosphamide immediately after the diagnosis. Four grafts have been lost. Our data show that CNF patients have an increased tendency for post-transplantation nephrosis.

Biopsy↗

Fever and neutropenia in children with cancer: diagnostic parameters at presentation.

We evaluated 91 episodes of fever in 46 profoundly neutropenic children with cancer, in a search for any symptom, sign or laboratory test that would serve to identify patients with septicemia and differentiate them from those in no immediate need of prompt antimicrobial therapy. Seventeen episodes (19%) were bacteremias, 59 (64%) were suspected septic infections, 9 (10%) were focal bacterial infections and 6 (7%) proved not to be bacterial infections. We were unable to detect any parameter, either on admission or after two days of antimicrobial therapy (except for blood culture findings), that would be helpful in differentiating bacteremia from an episode not of bacterial origin. We focused on serum levels of C reactive protein and found them unreliable on an individual level. Prompt institution of antimicrobial therapy at the occurrence of fever results in low mortality, but does not allow assignment of cases to different categories.

Adolescent↗

Fever and neutropenia: bacterial etiology revealed by serological methods.

In a prospective study, 91 episodes of fever in neutropenic children with cancer were evaluated. Fifteen episodes were septicemias, verified by a positive blood culture, 62 were fevers of unknown origin, 6 were focal infections and 8 were of other etiologies (i.e. drug fevers and viral infections). Serum antibody responses to bacteria were measured in paired sera by an enzyme immunoassay method. Bacterial infection was demonstrated serologically in 20% of documented septicemias, in 35% of fevers of unknown origin and occasionally in the other groups. Tests were available and found positive in the fever of unknown origin group for Staphylococcus aureus, Streptococcus pneumoniae, Haemophilus influenzae, Moraxella (Branhamella) catarrhalis and enterobacteria. Some had multiple etiology. In conclusion, bacterial serology is a promising method of identifying bacterial etiology in fever of otherwise unknown origin in neutropenic children with cancer.

Adolescent↗

Management of indwelling central venous catheters in pediatric cancer patients with fever and neutropenia.

This prospective study comprises 97 episodes of fever and neutropenia in children with cancer and central venous access. In 76% of episodes, patients had a Broviac-Hickman-like catheter, and in 24% a totally implanted venous access chamber system. The need for catheter removal during a febrile infection was 0.32/1000 catheter days, and the documented sepsis rate was 0.59/1000 catheter days. Our data indicate that 94% of episodes of fever and neutropenia in total, 78% of documented septicemias, and 97% of fevers of unknown origin were curable with broad-coverage antimicrobial therapy without removing the central venous line. Totally implanted chambers had a lower infection rate than catheters of Broviac-Hickman type.

Adolescent↗

The glycosaminoglycan content of renal basement membranes in the congenital nephrotic syndrome of the Finnish type.

A decrease in the concentration of heparan sulphate proteoglycan (HSPG) in the glomerular basement membrane (GBM) is supposed to cause the increased GBM permeability in the congenital nephrotic syndrome (CNS). Therefore, we analysed the glycosaminoglycan (GAG) content and composition of the GBM and tubular basement membrane (TBM) from 3 patients with CNS of the Finnish type (FCNS) and 16 control infants. The GAG content, determined by spectrophotometric assay after papain digestion, was not significantly different in FCNS patients compared with controls. In addition, the GAG composition was comparable in the two groups, with heparan sulphate (HS) constituting at least 75% of the total GAG content. The urinary GAG content (expressed as mg GAG/mmol creatinine) was age dependent, but similar in both groups. Indirect immunofluorescence studies on kidney tissue from normal human infants, using monoclonal or polyclonal antibodies against the core protein of human GBM HSPG, showed linear staining of almost all renal basement membranes. A monoclonal antibody directed against the HS chain of HSPG showed strong GBM and a weak TBM staining. Kidney tissue from three patients with FCNS displayed no discernible differences in the distribution or quality of staining with the same antibodies. These biochemical and immunohistochemical results are in contrast to the decrease in anionic sites (by polyethyleneimine staining) and the replacement of GBM HS by chondroitin sulphate, observed by others in CNS of the diffuse mesangial sclerosis type.

Basement Membrane↗

Cytokine and acute-phase reactant levels in serum of children with cancer admitted for fever and neutropenia.

Serum concentrations of tumor necrosis factor-alpha (TNF alpha), interleukin (IL)-1 beta, IL-6, and the acute-phase reactants C-reactive protein (CRP) and serum amyloid A (SAA) were measured on admission in 46 neutropenic children with cancer in 81 episodes of fever. The aim was to find out whether any of these variables would differentiate true bacteremia from fever due to other causes. In most episodes serum concentrations of TNF alpha and IL-1 beta were elevated. IL-6 was detectable in 68%, but the serum concentration was elevated in only 15%. SAA proved to be more sensitive than CRP for the early detection of bacteremia. However, not even SAA was sufficiently accurate at the individual level. We conclude that the cytokine and acute-phase protein levels found were related to the febrile response but did not correlate with documented bacterial etiology.

Acute-Phase Proteins↗

Tumour markers CA 19-9 and CA 50 in digestive tract malignancies.

CA 19-9 and CA 50 are tumour marker tests measuring the same carbohydrate structure, sialosyl-fucosyl-lactotetraose--that is, the sialylated Lewis blood group antigen. In addition, the C50 antibody reacts with sialosyl-lactotetraose, which may be expressed in small amounts in some carcinomas. In this study we compared these tests in sera from patients with benign and malignant digestive tract diseases. The sensitivity of the markers for different cancers was also compared at several specificity levels with patients with benign diseases as reference groups. Both markers showed a high sensitivity for pancreatic cancer (77% for CA 19-9; 69% for CA 50) and biliary cancer (88%). The figures in colorectal cancer were almost as high as those reported for CEA; 16-21% elevated values in Dukes A and B tumours and 44-47% in Dukes C and D tumours. The sensitivity for gastric cancer was 48% for both markers. CA 50 had a higher sensitivity for liver cancer (55%) than CA 19-9 (9%), but the proportion of elevated values in benign liver diseases was also higher (33% versus 15%, respectively). Overall, there was good correlation between the CA 19-9 and CA 50 levels, and the difference in sensitivity and specificity was marginal. In clinical practice the greatest value of CA 19-9 and CA 50 is in the diagnosis of pancreatic cancer.

Antigens, Tumor-Associated, Carbohydrate↗