Biomedical subjects

A Eddy

Publications and source records attributed to A Eddy.

18 recordsLinked to original sources

PubMed2001

Role of cellular infiltrates in response to proteinuria.

Tubulointerstitial injury caused by multiple insults, including significant proteinuria, results in interstitial inflammation. Evidence supports the hypothesis that interstitial inflammatory cells initially recruited in response to injury subsequently contribute to interstitial fibrosis. Experimental manipulations that decrease the number of interstitial macrophages (Mphis) preserve renal function. Mphis have the potential to secrete a large number of products, including some with fibrosis-promoting effects. Their most potent profibrotic effect may be the production of soluble fibrogenic factors, such as transforming growth factor-ss, endothelin-1, and tumor necrosis factor-alpha. These factors stimulate the synthesis of extracellular matrix proteins by neighboring myofibroblasts. Mphis may also release inhibitors of such matrix-degrading proteases as tissue inhibitor of metalloproteinase-1 and plasminogen activator inhibitor-1. Protease inhibitors have a role in renal scarring by impairing the process of matrix remodeling and degradation, which normally functions in parallel with matrix synthesis. It is predicted that therapeutic interventions that dampen the interstitial inflammatory response will attenuate the renal fibrogenic response, preserving normal renal architecture and function.

Animals↗

PubMed2000

Evaluation and management of proteinuria and nephrotic syndrome in children: recommendations from a pediatric nephrology panel established at the National Kidney Foundation conference on proteinuria, albuminuria, risk, assessment, detection, and elimination (PARADE).

OBJECTIVE: The development of this review article evolved from a National Kidney Foundation consensus conference on recent advances in the importance of evaluating and treating proteinuria. From this conference, a series of recommendations for the evaluation of adults with proteinuria was published. Because specific pediatric aspects of the problem were outside the scope of the original National Kidney Foundation publication, an ad hoc committee of 6 pediatric nephrologists who were active participants in the National Kidney Foundation conference was established to provide primary care physicians with a concise, up-to-date reference on this subject. METHODS: The recommendations that are given represent the consensus opinions of the authors. These are based on data from controlled studies in children when available, but many of the opinions are, by necessity, based on uncontrolled series in children or controlled trials performed in adults, because controlled trials in children have not been performed to evaluate many of the treatments described. RESULTS AND CONCLUSIONS: These recommendations are intended to provide primary care physicians with a useful reference when they are faced with a young child or teenager who presents with proteinuria, whether this is mild and asymptomatic or more severe, leading to nephrotic syndrome.

Child↗

PubMed1999

Tubulointerstitial nephritis and uveitis in children and adolescents. Four new cases and a review of the literature.

We identified 35 cases of tubulointerstitial nephritis and uveitis (TINU), 31 from a MEDLINE search (1966-1996) of the English literature and 4 from our hospital records (1988-1996). To meet the case definition, the patient had to be less than 18 years old and have TINU of unknown cause. Common presenting symptoms included fatigue, weight loss, fever, and abdominal pain. The uveitis was usually anterior and could occur at any time with respect to the onset of the renal disease. Common laboratory features included anemia, increased erythrocyte sedimentation rate, and decreased creatinine clearance. Most patients (33 of 35) had renal biopsies that commonly revealed an intense inflammatory interstitial infiltrate, glomerular sparing, and negative immunofluorescence studies. Of the 35 patients, 26 received systemic corticosteroid therapy (5 of 26 for eye disease); 22 had follow-up for at least 1 year; 13 of 35 patients had a recurrence of their uveitis. The outcome in all 35 cases was normal renal function with no documented visual loss. In conclusion, TINU is a unique syndrome with characteristic clinical features, laboratory changes, and renal biopsy results. Treatment is controversial, and the outcome in children, even if untreated, is excellent.

Adolescent↗

PubMed1999

Renal remodelling in dietary protein modified rat polycystic kidney disease.

Dietary protein restriction slows progression of the Han:SPRD-cy rat model of polycystic kidney disease. We undertook studies to examine the relative changes in interstitial and tubular pathology as a result of feeding an 8% casein (LP) diet to Han:SPRD-cy rats. Archival tissue from a previous study comparing LP and 20% casein (NP) diets was examined morphometrically after immunohistochemical or histochemical staining for apoptosis, proliferation antigens, interstitial fibrosis, and macrophage infiltration. Expression of common extracellular matrix genes was measured by Northern analysis. Animals fed LP diet demonstrated reduced tubular epithelial remodelling compared with animals fed NP diet by both proliferating cell nuclear antigen-positive cells (57.5 vs. 71.6 cells/mm epithelium, P=0.007) or apoptosis (31.2 vs. 35.6 cells/mm epithelium, P=0.006). Interstitial pathology demonstrated that LP feeding was associated with proportionately greater reductions in interstitial fibrosis (0.3 vs. 1.3 ml/kg body weight, P=0.003), interstitial cellularity (361 vs. 604 cells/high-power field, P=0.0002), and interstitial macrophages (67 vs. 149 cells/high-power field, P=0. 0002). Northern analysis only revealed significantly lower levels of monocyte chemoattractant protein mRNA (P=0.04) in animals fed the LP diet. Dietary protein restriction modifies both tubule and interstitium, with significant impact upon interstitial inflammation and fibrosis in the Han:SPRD-cy rat.

Animals↗

PubMed1998

Single photon emission computed tomography scanning in childhood systemic lupus erythematosus.

OBJECTIVE: To determine the role of central nervous system (CNS) perfusion scanning in detecting CNS disease in childhood onset systemic lupus erythematosus (SLE) and serial single photon emission computed tomography (SPECT) scans in monitoring CNS disease activity in childhood. METHODS: The charts of 108 patients with a confirmed or suspected diagnosis of SLE during the period February 1987 to June 1992 were reviewed. Twenty patients with a diagnosis of CNS SLE and 10 patients without CNS involvement had at least one SPECT scan. Patients were divided into (a) focal CNS SLE, when there were clinical manifestations that could be attributed to localized lesions of the CNS (6 patients); and (b) diffuse CNS SLE, when there was a global defect in CNS function including organic brain syndrome, psychosis, and depression (14 patients). If a patient had both diffuse and focal CNS disease that patient was designated as having diffuse disease. Forty-three patients with a diagnosis other than SLE comprised our non-SLE control group. RESULTS: SPECT scans were performed in 20 patients with acute CNS involvement. In patients with acute diffuse CNS disease, diffuse patchy areas of hypoperfusion were seen in 86% of patients at presentation of the CNS event. In the focal CNS disease subgroup, 33% of patients had an abnormal scan at CNS presentation. In these patients focal rather than diffuse abnormalities were seen. Eight patients with diffuse CNS SLE had at least one followup study at intervals ranging from 1 month to 3 years after initial scan. In 50% of these patients with diffuse CNS involvement, improvement in their abnormal scan correlated with clinical improvement, while in the other 50% clinical improvement was not associated with SPECT scan improvement. The most common abnormal SPECT scan pattern in patients with CNS SLE was one of widespread multiple small areas of decreased uptake at multiple sites, suggestive of generalized patchy hypoperfusion. Although SPECT scans were sensitive to the presence of CNS disease, the diffuse hypoperfusion was not specific for clinically detectable CNS involvement. In patients with SLE, a diffusely abnormal scan had a specificity of 69% and a likelihood ratio of 2.2 to correctly detect overt diffuse CNS disease. CONCLUSION: Although we found that SPECT scanning was a highly sensitive method, it was not a specific method in correctly diagnosing diffuse CNS SLE in children. However, the presence of an abnormal SPECT scan in SLE patients with no history of overt CNS SLE may suggest that subclinical CNS disease may be more common in children than previously suggested.

Adolescent↗

PubMed1996

Antiribosomal P antibodies in pediatric patients with systemic lupus erythematosus and psychosis.

OBJECTIVE: To study antibodies directed against ribosomal P proteins, a sensitive and specific marker of depression and psychosis in systemic lupus erythematosus (SLE), in pediatric patients with SLE. METHODS: One hundred six serum samples were obtained from 79 patients with SLE. Sixty age- and sex-matched control sera were obtained, and 12 samples were obtained from children with primary psychosis. Antibodies to recombinant ribosomal P (rRP) protein were detected using a standard enzyme-linked immunosorbent assay. RESULTS: All 12 children with non-SLE-associated psychosis had normal levels of anti-rRP antibodies. Elevated levels of anti-rRP were found in 11 of 64 pediatric SLE patients without a history of psychosis (17%). In the group of 13 SLE patients with psychosis, 5 (38%) had increased anti-rRP antibody levels during the time of acute psychosis, and which significantly decreased during remission. In addition, most of the SLE patients without a history of psychosis had a good correlation between anti-rRP antibody levels and disease activity. The patients with psychosis had significantly less renal involvement than the patients without a history of psychosis. This apparent protection from renal disease was not related to the presence or absence of either antiribosomal P or anti-DNA antibodies. CONCLUSION: Elevated serum levels of antibodies to ribosomal P protein can distinguish SLE-associated psychosis from primary psychosis of childhood. In SLE, elevated antiribosomal P antibody levels were not specific for psychosis. Serial assays were useful for monitoring the disease activity.

Antibodies, Anti-Idiotypic↗

PubMed1995

An immunological renal disease in transgenic mice that overexpress Fli-1, a member of the ets family of transcription factor genes.

The proto-oncogene Fli-1 is a member of the ets family of transcription factor genes. Its high expression in the thymus and spleen and the presence of DNA binding sites for Fli-1 in a number of lymphoid cell-specific gene suggest that Fli-1 is involved in the regulation of lymphopoiesis. Activation of the Fli-1 gene by either chromosomal translocation or viral insertion leads to Ewing's sarcoma in humans and erythroleukemia in mice, respectively. Thus, Fli-1 is normally involved in pathways involved in the regulation of cell growth and differentiation. We have generated H-2Kk-Fli-1 transgenic mice that overexpress Fli-1 in various mouse tissues, with the highest levels of Fli-1 protein in the thymus and spleen. These Fli-1 transgenic mice developed a high incidence of a progressive immunological renal disease and ultimately died of renal failure caused by tubulointerstitial nephritis and immune-complex glomerulonephritis. The incidences of renal disease correlated with the levels of Fli-1 protein in lymphoid tissues of transgenic lines. The hypergammaglobulinemia, splenomegaly, B-cell hyperplasia, accumulation of abnormal CD3+ B220+ T lymphoid cells and CD5+ B220+ B cells in peripheral lymphoid tissues, and detection of various autoantibodies in the sera of diseased Fli-1 transgenic mice suggested the involvement of an immune dysfunction in the pathogenesis of the renal disease. In addition, splenic B cells from transgenic mice exhibited increased proliferation and prolonged survival in vitro in response to mitogens. Taken together, these data suggest that overexpression or ectopic expression of Fli-1 perturbs normal lymphoid cell function and programmed cell death. Thus, H-2Kk-Fli-1 transgenic mice may serve as a murine model for autoimmune disease in humans, such as systemic lupus erythematosus.

Animals↗

PubMed1994

Evidence for the temporal processing of odor mixtures in humans.

The neural mechanisms underlying the perception of complex odor mixtures are largely unknown. The present study investigated the hypothesis that odorants in a mixture are processed and perceived in series. The results indicate that (i) odorants in mixtures are temporally processed with up to several hundred milliseconds separating individual components; (ii) 'fast' odorants are more likely to be a suppressor of 'slow' odorants than the reverse; and (iii) separation times can be altered by changing the concentrations of mixture components. These findings provide a new mechanism to account for the limited ability of humans to identify odorants in mixtures and for odor suppression.

Brain↗

PubMed1994

Perceptual characteristics of binary, trinary, and quaternary odor mixtures consisting of unpleasant constituents.

Among the most obnoxious stimuli that the population at large is exposed to during everyday life are odorous emissions from sewage treatment plants. Such emissions are complex and contain many different types of odorants that vary in quantity depending upon the contents and efficiency of treatment processes. Because little is known about how individual odorants in complex mixtures affect the perception of each other, it is difficult to develop mathematical models that can predict the pleasantness, strength, and quality characteristics of an emission at different distances from a source. In the present study, the interactions of the four major types of odorants emitted by treatment plants worldwide, namely, hydrogen sulphide, isovaleric acid, butanethiol, and skatole, were investigated by measuring the perceived intensity of individual odorants alone and in mixtures, and the overall perceived intensity, unpleasantness, and qualities of mixtures. In addition, models for predicting odor strength were investigated. The results indicated that (i) the perceived odor intensity (odor strength) of mixtures of the odorants was equal or greater than that of any of the individual constituents, but less than the sum of their intensities. However, as the number of components in a mixture increased, the intensity of the most dominant component provided a good approximation of the intensity of the mixture. (ii) The vector model of intensity summation also satisfactorily predicted the odor intensity of mixtures containing two, three, or four of the odorants investigated. (iii) In no instance was the intensity of one odorant enhanced by another, i.e., no synergistic interactions occurred; the greater the number of odorants in a mixture, the greater was the degree of suppression of the individual constituents. (iv) The greater the number of constituents in a mixture the more difficult it became to identify individual constituents. (v) Hydrogen sulphide was the least frequently suppressed constituent, and isovaleric acid and skatole were the most frequently suppressed constituents in mixtures. (vi) The unpleasantness of mixtures was usually greater than that of the individual constituents, indicating that models used for predicting complaint levels in communities affected by sewage odor and based on assumptions related to a single odorant, e.g., hydrogen sulphide, will underestimate the number of complaints. Even mixtures with low but above threshold concentrations of these odorants are likely to generate complaints.

Adult↗

PubMed1991

Quality control of radiotherapy during pelvic irradiation.

For 20 patients undergoing pelvic irradiation, various set-up methods were compared for accuracy of field placement. The overall incidence of errors on 294 fields checked was lower (p less than 0.001) than that in a previous study. A standard deviation of 1.5 mm for lateral placement accuracy was obtained.

Carcinoma↗

PubMed1990

Coagulation abnormalities in chronic peritoneal dialysis.

To determine whether children treated with chronic peritoneal dialysis have a hypercoagulable state, various coagulation and fibrinolytic factor concentrations or activities were measured in 17 children undergoing chronic peritoneal dialysis. The patients had significantly increased activities of factors VII and VIII, and increased concentrations of von Willebrand factor (vWF), fibrinogen, factor XIIIA and factor XIIIS compared to reference values (P less than 0.001 in each case). The activated partial thromboplastin time was prolonged (P less than 0.001) and the thrombin clotting time was decreased (P less than 0.05) in these children. The prothrombin time and activities of factors XII, XI, IX, X, V and II were not significantly different from control values. Protein C concentrations were similar to normal, but antithrombin III concentrations were increased (P less than 0.05). Within the fibrinolytic pathway, decreased concentrations of plasminogen were found (P less than 0.001) and the concentrations of alpha-2-antiplasmin were increased (P less than 0.001). The plasma albumin concentration was below 33 g/l in 13 of the 17 children. The duration of treatment with peritoneal dialysis was directly correlated with vWF concentrations (P less than 0.001) and inversely correlated with factor VII concentrations (P less than 0.01). Of these patients 2 have since had clinical thrombotic episodes. The coagulation abnormalities found may have a role in the occurrence of thrombosis complicating renal transplantation.

Adolescent↗

PubMed1990

A study by immunofluorescence microscopy of the NC1 domain of collagen type IV in glomerular basement membranes of two patients with hereditary nephritis.

The NC1 domain of the collagen type IV molecule, the major component of glomerular basement membranes (GBM), consists of dimers and 24 kilodalton (K), 26 K and 28 K monomers in man, and contains the Goodpasture antigen. Serum obtained from patients with Goodpasture's syndrome has been reported not to stain GBM of most male and some female patients with hereditary nephritis (HN) by immunofluorescence (IF) microscopy. In the present study, GBM seen on the renal biopsies of 2 patients (one male and one female) with HN were examined by IF to ascertain whether NC1 monomers were detectable. Three reagents were used: a plasmapheresis fluid (PPF) obtained from a patient who was treated for anti-GBM nephritis (human anti-GBM PPF); a commercial rabbit antibody against human NC1; and a rabbit antibody raised by us against dog NC1, which cross-reacted with human NC1. All 3 reagents detected NC1 determinants in GBM of normal human kidney by IF and reacted with human NC1 by a plate-binding radioimmunoassay (RIA). The human anti-GBM PPF bound to 28 K and 26 K monomer components of NC1 by Western blotting, the rabbit anti-human NC1 antibody bound to 26 K and 24 K monomers, while the rabbit anti-dog NC1 antibody bound only to the 26 K monomer. By IF, the human anti-GBM PPF did not stain GBM of the male patient with HN, but produced segmental staining of GBM (i.e., some GBM stained, while others did not) of the female patient. In contrast, the rabbit anti-NC1 antibodies produced global staining by IF of GBM of both patients. The absence of staining (i.e., global or segmental) seen with the human anti-GBM PPF implied that the 26 K and 28 K monomers of NC1 were either absent from GBM, or were present but altered structurally, leading to a diminution in their immunological reactivity. However, the positive staining observed with the rabbit anti-NC1 antibodies implied that the 26 K monomer was actually present in GBM. Hence, we postulate that the 26 K monomer of NC1 in GBM was structurally altered, and that the 28 K monomer was either absent, or present but altered. These findings suggest that there is an abnormality of more than one monomer of NC1 in GBM of patients with HN.

Basement Membrane↗

PubMed1989

Characterization of the NC1 domain of collagen type IV in glomerular basement membranes (GBM) and of antibodies to GBM in a patient with anti-GBM nephritis.

Anti-glomerular basement membrane (GBM) nephritis is associated with production of antibodies to the Goodpasture antigen (GPA) component of the NC1 domain of collagen type IV. We studied a patient with anti-GBM nephritis with regard to 1) reactivity of the anti-GBM antibodies in his serum, plasmapheresis fluid (PPF), and an eluate prepared from GBM of his nephrectomy specimen, and 2) electrophoretic and immunologic properties of the NC1 domain extracted by collagenase digestion from GBM of his nephrectomy specimen. Antibodies to different NC1 determinants in serum, PPF and eluate were detected by immunofluorescence of glomerular capillaries of normal kidney. In addition, the antibody in PPF, but not in the eluate, reacted strongly in a plate-binding radioimmunoassay with NC1 domain extracted from normal human GBM, and bound by Western blotting to both dimer (46 kD and 49 kD) and monomer (24 kD, 26 kD and 28 kD) components of the NC1 domain. Analysis of the NC1 domain in the patient's GBM by SDS-PAGE showed a number of abnormalities, including an absence of monomer bands. Moreover, there was diminished reactivity of the patient's NC1 domain by the radioimmunoassay and Western blotting, using his PPF and a rabbit anti-NC1 antiserum. These findings indicated that there were different types of antibodies to NC1 domain in PPF and eluate, associated with an abnormal NC1 domain in GBM. These results have allowed us to speculate on the pathogenesis of anti-GBM nephritis in this patient.

Anti-Glomerular Basement Membrane Disease↗

PubMed1987

Demonstration by light microscopy of cytomegalovirus on a renal biopsy of a renal allograft recipient: confirmation by immunohistochemistry and in situ hybridization.

A 14-year-old boy with end-stage renal failure secondary to reflux nephropathy received a renal transplant and was immunosuppressed with prednisone, azathioprine, and Minnesota antilymphoblast globulin, followed by cyclosporine A. A renal biopsy was performed 43 days post-transplantation because of fever and an elevated serum creatinine. The biopsy showed a mild interstitial lymphocytic infiltrate and immunosuppression was not changed. A second renal biopsy was performed 66 days after transplantation because of a persistent elevation of the serum creatinine following a cytomegalovirus (CMV) infection. CMV inclusions were seen by light microscopy (LM) in glomerular and peritubular capillary endothelial cells and tubular epithelial cells but no viral inclusions were present on the grids examined by electron microscopy (EM). However, the inclusions seen by LM were confirmed as CMV by immunohistochemistry, using polyclonal and monoclonal antibodies to CMV, and by in situ hybridization, using a biotinylated CMV DNA probe, emphasizing the usefulness of these techniques when studies by EM are not contributory.

Adolescent↗

PubMed1986

Cathartic-induced magnesium toxicity during overdose management.

A 39-year-old women was admitted to the hospital following a large ingestion of a tricyclic antidepressant. The administration of magnesium citrate in repeated doses with activated charcoal resulted in a striking increase in serum magnesium levels followed by acute neuromuscular deterioration and respiratory depression. The patient required dialysis for control of hypermagnesemia. Her clinical condition improved slowly without further complication and she was discharged to a rehabilitation center.

Adult↗

PubMed1985

Decreased plasma fibronectin levels in children with hemolytic-uremic syndrome.

Fibronectin is a normal plasma glycoprotein thought to have an important role in platelet aggregation and clot formation. Because of the participation of the coagulation system in hemolytic-uremic syndrome, the present study sought to determine if fibronectin plays a role in the pathogenesis of this disease. With this purpose in mind, plasma fibronectin levels were measured in 17 children with the clinical diagnosis of hemolytic-uremic syndrome and in 22 age-matched control subjects. Fibronectin levels were significantly depressed in 13 of 17 (76 percent) patients with hemolytic-uremic syndrome during the acute phase of their illness. The levels did not correlate with age, sex, serum creatinine level, platelet count, or hemoglobin concentration. Serial plasma samples were available in eight of these patients: fibronectin remained depressed from two to 10 days and then returned toward the normal range concomitant with increasing platelet counts and improvement in renal function. During remission, fibronectin levels were normal in all nine patients tested. To try to determine if fibronectin is deposited in the kidney during hemolytic-uremic syndrome, kidney biopsy specimens from six patients with hemolytic-uremic syndrome were examined by immunofluorescence for the presence of fibronectin, fibrinogen, and platelet antigens. Extensive deposition of all three antigens was demonstrated along the glomerular capillary wall in all biopsy specimens. In conclusion, plasma fibronectin levels are decreased during the acute phases of hemolytic-uremic syndrome in the majority of patients. Kidney biopsy findings suggest that fibronectin is intimately involved in the activation of the coagulation system in this disease and that decreased plasma fibronectin levels in hemolytic-uremic syndrome may be due, at least in part, to accelerated consumption of the protein at the sites of injury.

Adolescent↗

PubMed1984

The distribution of the CR3 receptor on human cells and tissue as revealed by a monoclonal antibody.

The mouse monoclonal antibody MN-41 has been characterized as an anti-human iC3b receptor (CR3) antibody on the basis of its ability to inhibit the binding of EC3bi indicator cells to monocytes and polymorphonuclear cells while having no effect on their Fc and C3b receptors. Use of this monoclonal antibody in indirect immunofluorescence studies with dual fluorochrome labels established the widespread distribution of CR3 in man--detected on 97% of circulating monocytes, 90% of granulocytes, 17% of T lymphocytes, and 28% of B lymphocytes while erythrocytes and platelets were negative. Isolated peritoneal macrophages were 90% positive while pulmonary macrophages were 83% positive. Monocytes in culture for 8 days were universally positive. Within tissues, CR3 reactive cells displayed unique topographical localization within the spleen, tonsil, and lymph nodes whereas numerically fewer positive cells were scattered within hepatic sinusoids, papillary dermis, medullary regions of the thymus, and submucosa of the small intestine. CR3 was not detected on Raji cells, glomerular epithelial cells, or placental stromal cells. Immunoprecipitation and electrophoretic separation of two glycoprotein bands of 150,000 and 95,000 Da suggest possible structural homology of CR3 in man and mouse (Mac-1 antigen).

Animals↗

PubMed1984

Renal allograft failure due to recurrent dense intramembranous deposit disease.

Dense intramembranous deposit disease (DIDD) almost universally recurs in renal allografts. However, the 29 previously reported cases suggest that recurrent DIDD rarely results in graft failure. We studied the clinical course and renal histology of the 6 patients with DIDD who have received renal allografts here since 1967. All patients had characteristic findings of DIDD in their native kidneys by light, immunofluorescence and electron microscopy. Seven grafts in 4 patients failed and histological evaluation showed that 5 of these allografts in 4 patients were lost due to recurrent disease. They all demonstrated marked mesangial proliferation with crescents but minimal acute interstitial or vascular changes of rejection. Patients with graft failure due to recurrent disease were male and developed recurrent nephrotic syndrome. The 2 patients with rapidly progressive glomerulonephritis (RPGN) in their native kidneys lost the transplanted kidney due to recurrent disease within 1 year. This study suggests that recurrence of DIDD in renal allografts is a more serious problem than previously appreciated, especially in patients with RPGN.

Adolescent↗