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Biomedical subjects

B Hartley

Publications and source records attributed to B Hartley.

At least 19 recordsLinked to original sources
PubMed1999

The Banff 97 working classification of renal allograft pathology.

BACKGROUND: Standardization of renal allograft biopsy interpretation is necessary to guide therapy and to establish an objective end point for clinical trials. This manuscript describes a classification, Banff 97, developed by investigators using the Banff Schema and the Collaborative Clinical Trials in Transplantation (CCTT) modification for diagnosis of renal allograft pathology. METHODS: Banff 97 grew from an international consensus discussion begun at Banff and continued via the Internet. This schema developed from (a) analysis of data using the Banff classification, (b) publication of and experience with the CCTT modification, (c) international conferences, and (d) data from recent studies on impact of vasculitis on transplant outcome. RESULTS: Semiquantitative lesion scoring continues to focus on tubulitis and arteritis but includes a minimum threshold for interstitial inflammation. Banff 97 defines "types" of acute/active rejection. Type I is tubulointerstitial rejection without arteritis. Type II is vascular rejection with intimal arteritis, and type III is severe rejection with transmural arterial changes. Biopsies with only mild inflammation are graded as "borderline/suspicious for rejection." Chronic/sclerosing allograft changes are graded based on severity of tubular atrophy and interstitial fibrosis. Antibody-mediated rejection, hyperacute or accelerated acute in presentation, is also categorized, as are other significant allograft findings. CONCLUSIONS: The Banff 97 working classification refines earlier schemas and represents input from two classifications most widely used in clinical rejection trials and in clinical practice worldwide. Major changes include the following: rejection with vasculitis is separated from tubulointerstitial rejection; severe rejection requires transmural changes in arteries; "borderline" rejection can only be interpreted in a clinical context; antibody-mediated rejection is further defined, and lesion scoring focuses on most severely involved structures. Criteria for specimen adequacy have also been modified. Banff 97 represents a significant refinement of allograft assessment, developed via international consensus discussions.

Acute Disease↗
PubMed1997

Low molecular weight protein excretion in glomerular disease: a comparative analysis.

We studied 23 children with steroid-sensitive nephrotic syndrome (SSNS), 21 children with steroid-resistant types of nephrotic syndrome and 32 children with other types of nephritis. Our controls were 43 apparently healthy children. We measured the urinary excretion of N-acetyl-beta-D-glucosaminidase (NAG) and the low molecular weight (LMW) protein beta 2-microglobulin (B2M), retinol-binding protein (RBP), alpha 1-microglobulin (A1M) and urine protein 1 (UP1). Results for B2M were considered only for a urine pH greater than 6.0. Comparisons were made with urine albumin excretion, glomerular filtration rate (GFR) and tubular abnormalities in selected renal biopsy samples. We found that abnormalities of LMW protein excretion occurred in between 50% (B2M) and 88% (UP1) of all subjects. In children with SSNS, A1M (r = 0.73), UP1 (r = 0.65) and NAG (r = 0.54) excretion were significantly correlated with albumin excretion, but not RBP or B2M excretion. Increased fractional excretion of A1M, B2M and UP1 and increased plasma A1M were demonstrated in 9 children with SSNS, suggesting competition for tubular reabsorption with albumin, most marked for UP1. In the steroid-resistant nephrotic and nephritic syndromes, correlation with albumin was found for all proteins. In these subjects, RBP (r = 0.37), B2M (r = 0.42) and A1M (r = 0.28) were inversely correlated with GFR, but not UP1, NAG or albumin. We found that RBP excretion was significantly greater in the presence of severe tubular abnormalities in 11 children with recent renal biopsies, but not A1M, UP1 or NAG. We conclude that LMW proteinuria is common in children with glomerular disease, and does not necessarily imply a poor prognosis. Factors other than histologically proven tubular abnormality may account for elevated LMW protein excretion. RBP is the LMW protein most closely associated with structural abnormality and least affected by increasing albuminuria.

Albuminuria↗
PubMed1997

Juvenile arthritis: a nursing perspective.

Juvenile arthritis is the fifth most common chronic illness in children. When a child is diagnosed with juvenile arthritis, the family must adjust in many ways in order to cope with the demands of this illness. This article provides an overview of the disease, presents the case history of two sisters with polyarticular arthritis, and discusses how nurses and other health team members can empower a family to manage more successfully with this disease and thereby enhance quality of life. Professional resources that aid families coping including educating the family about the disease, providing psychologic support, as well as knowledge and assistance for optimal physical functioning and maintaining energy reserves, and suggesting strategies to sustain self esteem, motivation and hope.

Adaptation, Psychological↗
PubMed1997

Expression of tissue type plasminogen activator and type 1 plasminogen activator inhibitor, and persistent fibrin deposition in chronic renal allograft failure.

Persistent fibrin deposition has been observed in kidneys undergoing chronic rejection, and has been suggested to contribute to the obliteration of the vasculature in these grafts. The mechanisms leading to it are not clear. Fibrinolysis, the process to remove fibrin in tissues, is initiated by tissue type plasminogen activator (tPA) and suppressed by type 1 plasminogen activator inhibitor (PAI-1). To investigate their roles in chronic rejection and fibrin deposition, we serially examined the expression of tPA and PAI-1 in an unmodified chronic rejection model, using a Fisher 344 to Lewis rat renal transplant, at 0, 2, 4, 6, 10, 12, 16 and 20 weeks post-transplantation (N = 4 rats/time point in each group). We also analyzed fibrin deposition and the development of chronic changes in the grafts. Our results show that tPA was up-regulated only in the acute phase of rejection (P < 0.05), whereas PAI-1 was induced and persistently expressed during the progressive phase of chronic rejection, together with persistent fibrin deposition in the grafts. Immunohistochemistry showed PAI-1 was mainly localized to the damaged/proliferative vascular intima. The results suggest that persistent induction of PAI-1 may be responsible for the continuance of fibrin deposition, which is associated with irreversible damage and chronic graft loss.

Animals↗
PubMed1997

Protection against anti-glomerular basement membrane (GBM)-mediated nephritis in C3- and C4-deficient mice.

Mice rendered completely deficient of the complement components C3 or C4 were used to determine the influence of complement activation in the heterologous phase of the anti-GBM disease model. In wild-type animals the disease is characterized by a neutrophil infiltrate, capillary thrombosis, proteinuria and C3 and C4 deposited within the glomerulus. The early infiltration of neutrophils into the glomeruli is greater in wild-type mice (2.8 +/- 0.3) compared with C3-deficient (1.4 +/- 0.2) and C4-deficient (1.2 +/- 0.003) mice. Deficiency also protects against the subsequent development of proteinuria (2.99 +/- 1.11 mg/24h, 0.059 mg/24h and 0.327 +/- 0.14 mg/24h in wild-type, C3-deficient and C4-deficient mice, respectively) and decreases glomerular capillary thrombosis in both C3- and C4-deficient mice. The degree of protection is greater in the C3-deficient than the C4-deficient animals, suggesting both classical and alternative pathway involvement. These studies support a critical role for complement in the development of anti-GBM disease. However, the protective effect of complement deficiency can be broken if the dose of nephritogenic antibody is increased.

Albuminuria↗
PubMed1997

The effect of OM-89 (Subreum) on the murine model of systemic lupus erythematosus MRL-lpr/lpr.

OM-89 (Subreum), an E. coli extract, is used clinically in the treatment of rheumatoid arthritis. In this study, the authors examined the effect of OM-89 on some aspects of SLE in the murine model MRL-lpr/lpr. Animals were given OM-89 orally at a dose of 400 mg/kg weight (40 mg active substance) 5 d a week from six weeks old. It was found that mice receiving the drug reached the point of 55% (6/11) survival at the age of 33 weeks compared with 27 weeks for the control group (54%; 7/13). There was a significant increase in the delay before developing alopecia in the treated group (P < 0.01). The increase in proteinuria in the control group was significantly higher than in the treated group (P < 0.03). In a second set of experiments sacrificing the animals at week 22, a significant decrease in anti-dsDNA auto-antibodies was also found in the treated group (P < 0.05), histopathologically a less severe tubular destruction in the kidney was observed in the treated group. It can be concluded that the oral treatment of OM-89 can significantly reduce the severity of SLE in this strain of mice. It can be postulated that the administration of the bacterial extract could modulate the immune response, modifying the Th1 and Th2 balance and inducing oral tolerance.

Administration, Oral↗
PubMed1996

Up-regulation of type 1 plasminogen activator inhibitor messenger RNA with thrombotic changes in renal grafts.

Small vessel thrombosis is a prominent feature in kidneys undergoing vascular rejection. Type I and type 2 plasminogen activator inhibitors (PAI-1 and PAI-2, respectively) are known to mediate thrombosis. To examine the potential role of PAI-1 and PAI-2 in the mediation of vascular injury, the relationship and the time course of gene expression of PAI-1 and PAI-2 with the thrombotic changes in renal grafts were investigated in an unmodified rejection model in rats. Orthotopic renal transplantation was performed from Lewis to dark agouti (DA) rats and from DA to DA isografts; untreated normal rat kidneys were used as controls. The rats were killed on days 1-9 posttransplantation (n=18 in each allograft and isograft group). The grafts were analyzed by histopathology, in situ mRNA hybridization and Northern blot methods. The results show that PAM mRNA was first detected at day 4, when the thrombotic changes in the grafts were first seen, and that this relationship persisted during the time course observed to day 9. There was no detectable PAI-1 mRNA in the control groups and no PAI-2 in either group. In situ hybridization showed that PAI-1 positive cells were predominantly located in the cortical interstitium, consistent with the distribution of interstitial microthrombi. These results provide experimental evidence that the thrombotic changes in rejecting allografts are associated with the up-regulation of PAI-1 in the donor tissue, whereas PAI-2, from our results, does not seem to influence these changes. The data are consistent with a role for PAI-1 in the pathogenesis of vascular rejection.

Animals↗
PubMed1994

Comparison of a monoclonal and polyclonal anti-idiotype against a human IgG anti-DNA antibody.

Over the last decade a number of idiotypes (Id) have been identified on monoclonal IgM anti-DNA antibodies which represent germ-line genes. This study describes two new idiotypes present on a monoclonal human IgG anti-DNA antibody, D5 derived from a patient with active SLE. The two idiotypes, designated D5-RId and D5-MId, are defined by a polyclonal and monoclonal anti-Id respectively. Both anti-Ids inhibited each other's binding to D5 in an ELISA and did not bind to human IgG. Using western blotting the D5-RId was located on the light chain whereas the D5-MId bound to conformational determinants; both idiotypes were close to or at the binding site for DNA. The anti-Id reagents were used in ELISAs to screen human sera and tissue samples for the presence of the D5-MId and the D5-RId. The upper limit of normal for sera in the D5-MId ELISA was much lower than the D5-RId ELISA indicating a greater degree of specificity in the former. The idiotypes were found only in the IgG fraction of the sera. About 30% of SLE patients had either the D5-MId or the D5-RId and 20% had elevated levels of both, showing a considerable overlap in the expression of the two idiotypes. This overlap was also observed in the other disease groups including patients with other autoimmune diseases, though the numbers of patients expressing the idiotypes were significantly lower than in the SLE group. The idiotypes were present on both DNA binding and non-DNA binding fractions of lupus sera. D5-MId was present in 6/10 renal lupus biopsies and only in 2/15 disease control renal biopsies in which immunoglobulin was deposited. D5-RId did not stain any sections. There is a close correlation between the presence of the D5-MId and D5-RId in SLE sera and the level of expression. It is evident that both idiotypes are associated with SLE and are markers of a population of IgG anti-DNA antibodies, the isotype associated with active disease. Since the idiotypes are not found on IgM antibodies they are likely to be generated by somatic mutation.

Animals↗
PubMed1994

Juvenile dermatomyositis: a Roy nursing perspective.

With current medical treatment, juvenile dermatomyositis (JDMS) is rarely fatal. However, for most families, it is a chronic illness that interrupts life for both the affected child and the rest of the family. This article provides an overview of the disease, presents a case history of a 9-year-old affected girl, and discusses nursing care using the Roy Adaptation Model and nursing diagnoses.

Adaptation, Psychological↗
PubMed1993

Endogenous complement C3 synthesis in immune complex nephritis.

Human renal epithelial and mesangial cells have been shown to synthesise complement C3 in culture, but the relevance of this finding to the development of complement-mediated nephritis is uncertain. We investigated C3 gene expression in tissue biopsies that showed three main categories of renal injury. By semiquantitative polymerase chain reaction, biopsies from patients with immune-complex glomerulonephritis and those with cell-mediated interstitial nephritis showed increased C3 expression (p < 0.05), but biopsies from patients with non-immune glomerular injury did not. These findings suggest that local C3 production is enhanced in immune-mediated nephritis and are consistent with the hypothesis that locally synthesised complement components are involved in the pathogenesis of tissue injury.

Complement C3c↗
PubMed1992

What makes red cells dysmorphic in glomerular haematuria?

Although red cell morphology has been used to localise the site of haematuria in the urinary tract, the cause of red cell deformity is still speculative. We have conducted experiments in vitro using venous red cells which indicate that hypochromia depends mainly upon sodium concentration and occurs when this falls below 75 mmol/l. We simulated the passage of red cells through the renal tubule by sequentially treating them with fluids of composition similar to those in different tubular segments, and produced anisocytosis and hypochromia but not the typical "bizarre deformity"--the hallmark of glomerular haematuria. We conclude that dual injury is required to produce the "typical" dysmorphic red cells in glomerular haematuria. First, mechanical damage caused by passage of red blood cells through the glomerular basement membrane followed by a second, osmotic, injury sustained by red cells during passage through the hypotonic tubular segment.

Basement Membrane↗