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Biomedical subjects

R Palsson

Publications and source records attributed to R Palsson.

7 recordsLinked to original sources
PubMed2001

Clinical features and genotype of adenine phosphoribosyltransferase deficiency in iceland.

The purpose of this study was to characterize the clinical, diagnostic, and prognostic features of adenine phosphoribosyltransferase (APRT) deficiency in Icelandic patients, as well as determine their genotype. Medical records of all known patients in Iceland were reviewed. Urinalysis and polymerase chain reaction-based DNA mutation analysis were performed in all patients, siblings, and living parents of index cases. Twenty-three individuals homozygous for type I APRT deficiency were identified in 16 families from 1983 to 1998. There were 12 males and 11 females, and the median age at diagnosis was 37 years (range, 0.5 to 62 years). Seventeen patients were index cases and 6 patients were diagnosed during screening of first-degree relatives. Eighteen patients had symptomatic disease, 15 of whom experienced nephrolithiasis; 4 patients had mild to moderate renal insufficiency, 1 patient had advanced renal failure, and 1 patient died of uremic complications. Six patients experienced recurrent urinary tract infections and 3 infants had a history of reddish-brown diaper stains. Five patients were asymptomatic; 3 of these patients were diagnosed during routine urinalysis and 2 patients were identified during family screening. Urinary 2,8-dihydroxyadenine crystals were detected in all cases, except for the patient who died of end-stage renal failure. All 23 patients were homozygous for the same mutation (D65V) in the APRT gene. Allopurinol therapy successfully prevented further stone formation and significantly improved renal function in most patients with renal insufficiency. Our results suggest that APRT deficiency may be more common than previously recognized and can lead to severe renal failure if left untreated.

Acute Kidney Injury↗
PubMed2001

Genotype-phenotype interactions in Wilson's disease: insight from an Icelandic mutation.

Wilson's disease, an autosomal recessive disorder of copper transport, usually presents with symptoms from the liver or central nervous system. Rarely, the initial manifestation is fulminant hepatic failure. The abnormal gene (ATP7B) is located on chromosome 13q and encodes a copper-transporting ATPase. A large number of mutations have been reported. We describe a previously healthy 16-year-old girl who presented with fulminant hepatic failure. The girl died within 24 h of admission to a hospital from refractory shock. Autopsy revealed cirrhosis and widespread necrosis of the liver. The copper content of the liver was markedly increased (975 micrograms/g dry weight), strongly suggesting a diagnosis of Wilson's disease. Genetic studies revealed that the girl was homozygous for the mutation 2007 del7, which is the mutation found in all Wilson's disease patients previously identified in Iceland. This is the first known case of fulminant hepatic failure due to Wilson's disease in Iceland. Despite the same mutation, the clinical picture is vastly different from other Icelandic patients with Wilson's disease, who all presented with relatively late-onset neurological disease. This suggests that factors other than the specific mutation have significant impact on the phenotype of the disease.

Adolescent↗
PubMed1999

Regional citrate anticoagulation in continuous venovenous hemofiltration in critically ill patients with a high risk of bleeding.

BACKGROUND: Systemic heparinization is associated with a high rate of bleeding when used to maintain patency of the extracorporeal circuit during continuous renal replacement therapy (CRRT) in critically ill patients. Regional anticoagulation can be achieved with citrate, but previously described techniques are cumbersome and associated with metabolic complications. METHODS: We designed a simplified system for delivering regional citrate anticoagulation during continuous venovenous hemofiltration (CVVH). We evaluated filter life and hemorrhagic complications in the first 17 consecutive patients who received this therapy at our institution. Blood flow rate was set at 180 ml/min. Ultrafiltration rate was maintained at 2.0 liters/hr and citrate-based replacement fluid (trisodium citrate 13.3 mM, sodium chloride 100 mM, magnesium chloride 0.75 mM, dextrose 0.2%) was infused proximal to the filter to maintain the desired fluid balance. Calcium gluconate was infused through a separate line to maintain a serum-ionized calcium level of 1.0 to 1.1 mM. RESULTS: All patients were critically ill and required mechanical ventilation and vasopressor therapy. Systemic heparin anticoagulation was judged to be contraindicated in all of the patients. A total of 85 filters were used, of which 64 were lost because of clotting, with a mean life span of 29.5 +/- 17.9 hours. The remaining 21 filters were discontinued for other reasons. Control of fluid and electrolyte balance and azotemia was excellent (mean serum creatinine after 48 to 72 hr of treatment was 2.4 +/- 1.2 mg/dl). No bleeding episodes occurred. Two patients, one with septic shock and the other with fulminant hepatic failure, developed evidence for citrate toxicity without a significant alteration in clinical status. Nine patients survived (52.9%). CONCLUSION: Our simplified technique of regional anticoagulation with citrate is an effective and safe form of anticoagulation for CVVH in critically ill patients with a high risk of bleeding.

Adult↗
PubMed1998

Immunohistochemical study of actin binding protein (p55) in the human kidney.

BACKGROUND: In clinical transplantation, "passenger" dendritic cells (DCs) in the allograft have been thought to induce allograft rejection. However, the presence of DCs in the normal human kidney is controversial. Most reports have relied on the examination of MHC class I and II antigen expression in combination with DC morphology for identification of DCs. METHODS: The distribution of the p55 antigen (fascin), which is selectively expressed by human blood and lymphoid DCs, was investigated by immunohistochemistry. RESULTS: Our study demonstrates that p55-positive DCs are absent from the normal human kidney and CD1a- and S100-positive cells are absent or very rare. Furthermore, HLA-DR and factor VIII-related antigen show almost complete colocalization in capillaries. In contrast, all 16 kidney biopsies from patients with inflammatory processes demonstrated p55-positive DCs in the cellular infiltrates. CONCLUSIONS: These results suggest that DCs are not present or are very rare in normal renal tissues but may migrate into the renal interstitium with inflammatory changes.

Adult↗
PubMed1996

Characterization and cell distribution of polycystin, the product of autosomal dominant polycystic kidney disease gene 1.

BACKGROUND: In a majority of cases, autosomal dominant polycystic kidney disease (ADPKD) is caused by mutations within a putative open reading frame of the PKD1 gene. The encoded protein, polycystin, is predicted to span the plasma membrane several times and contains extracellular domains, suggestive of a role in cell adhesion. The cellular distribution and function of polycystin is not known. MATERIALS AND METHODS: We selected as immunogens two conserved 15 amino acid peptides: P1, located in a predicted extracellular region of polycystin, and P2, located in the C-terminal putative cytoplasmic tail. The anti-peptide antibodies from immunized rabbits were affinity purified on peptide-coupled resins and their specificity confirmed by their selective binding to recombinant polycystin fusion proteins. Western blotting and immunohistochemistry were used to characterize the size, tissue, and cell distribution of polycystin. RESULTS: A high-molecular mass protein (about 642 kD) was detected by Western blotting in rat brain tissue. A few additional bands, in the 100- to 400-kD range, probably representing tissue-specific variants and/or proteolytic fragments, were recognized in human and rat tissues. Polycystin was abundantly expressed in fetal kidney epithelia, where it displayed basolateral and apical membrane distribution in epithelial cells of the ureteric buds, collecting ducts, and glomeruli. In normal human adult kidney, polycystin was detected at moderate levels and in a cell surface-associated distribution in cortical collecting ducts and glomerular visceral epithelium. Expression of polycystin was significantly increased in cyst-lining epithelium in ADPKD kidneys, but was primarily intracellular. CONCLUSIONS: Polycystin appears to be a developmentally regulated and membrane-associated glycoprotein. Its intracellular localization in the cyst-lining epithelium of ADPKD kidneys suggests an abnormality in protein sorting in this disease.

Animals↗
PubMed1995

Inhibition of proteinase 3 by ANCA and its correlation with disease activity in Wegener's granulomatosis.

Detection of circulating antineutrophil cytoplasmic antibodies (ANCA) to the neutrophil serine proteinase, proteinase 3 (PR3), has proven valuable for the diagnosis of Wegener's granulomatosis (WG). However, the importance of these autoantibodies in the pathogenesis of WG remains unknown. It was recently reported that anti-PR3 autoantibodies (PR3-ANCA) from some patients with WG inhibit the proteolytic activity of PR3 and interfere with the inactivation of PR3 by the physiologic inhibitor, alpha 1-proteinase inhibitor (alpha 1-PI). We have studied the effect of PR3-ANCA on the enzymatic activity of PR3 and its correlation with disease activity in patients with WG. We purified IgG from 21 PR3-ANCA positive sera obtained from 17 patients with WG, and determined its effect on the esterolytic and proteolytic activity of purified human PR3 using Boc-Ala-O-Nitrophenyl ester and fluoresceinated-elastin as enzyme substrates. Controls included seven sera containing anti-MPO autoantibodies (MPO-ANCA) from patients with systemic vasculitis and seven ANCA-negative sera obtained from healthy individuals. We found that PR3-ANCA from 9 of the 17 patients significantly inhibited the activity of PR3. There was no correlation between the titers of PR3-ANCA and their inhibitory activity. For one extensively characterized autoantibody, the inhibition reached 70 to 95% at 20-fold molar excess of IgG to enzyme, with an apparent Kiapp of 56.5 microM. This inhibition was non-competitive in nature, and was additive to that produced by alpha 1-PI. A review of the clinical histories of the patients revealed a strong association between active WG and inhibitory autoantibodies.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies, Antineutrophil Cytoplasmic↗