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Biomedical subjects

T J Neale

Publications and source records attributed to T J Neale.

At least 37 records · Page 2Linked to original sources

Diabetic end stage renal failure--the Wellington experience 1975-1988.

Since the late 1970s patients with diabetic nephropathy have formed an increasing proportion of new entrants to the Hospital renal dialysis and transplantation programme, reaching 28% for the three year period to December 1988. Between 1 January 1975 and 31 December 1988, 87 diabetic patients were accepted for treatment. Fifty-one per cent were European, predominantly type I diabetics. Maori (9% of the total reference population) accounted for a disproportionately high 47% due to an over-representation by type II diabetic patients (34 of 41 Maori). These findings cannot be explained by the higher prevalence in Maori of type II diabetes but appear to be due to a more prevalent and/or aggressive diabetic renal lesion in this group. On commencing treatment, nearly all patients had retinopathy and the majority had evidence of peripheral vascular disease, hypertension and neuropathy. CAPD was the initial mode of renal replacement therapy in 70% of patients. Overall patient survival was 77% at one year and 42% at three years, and survival on CAPD was 76% and 37% at one and three years, respectively. Patient survival on transplantation was 63% at one year and 58% at three years. Graft survival was 51% at one year and 46% at three years. Although the short term outlook for diabetic patients on renal replacement therapy is encouraging, longer term survival compared to non-diabetic patients is poor. Vascular disease is the major cause of death and an important factor in patient morbidity.

Adult↗

"Quality of life" for patients with end-stage renal failure.

The assessment of health status and quality of life among chronically ill patients is an area of current scientific interest. This paper considers the utility of a short but comprehensive instrument to assess the quality of life for end-stage renal failure patients. the Spitzer QL-Index was completed by 8 nurses for all patients in the Wellington region currently being treated with home hemodialysis (n = 58); hospital hemodialysis (n = 13); and continuous ambulatory peritoneal dialysis (n = 37). Results indicated that home hemodialysis patients achieve the highest quality of life in comparison to the other two treatment modalities. It is concluded that the QL-Index has some discriminative validity for this patient population, and its use may contribute to informed decision making by both patients and doctors.

Adaptation, Psychological↗

Acute pulmonary and renal injury after administration of heterologous anti-lung antibodies in the rat. Characterization of ultrastructural binding sites, basement membrane epitopes, and inflammatory mediation systems.

Male Sprague-Dawley rats developed acute lung and renal injury after administration of heterologous anti-lung antibody. Both organs demonstrated an increase in protein permeability after antibody binding to basement membrane (BM) antigens (lung permeability index 0.342 +/- 0.009 versus control 0.214 +/- 0.011: p less than 0.05. Urinary protein excretion 5.112 +/- 0.899 mg/hour versus control 0.402 +/- 0.008 mg/hour: p less than 0.01). The threshold value for the development of lung injury was 27.2 +/- 4.8 micrograms of antibody globulin/g of tissue (micrograms/gm). Immunoblot analysis probing with the anti-lung antibody revealed at least one common antigenic determinant (82 to 84 kilodaltons) bound within collagenase-solubilized pulmonary and glomerular BMs. Increasing doses of antibody produced hemorrhagic pneumonitis and diffuse alveolar damage. Immunofluorescence microscopy confirmed linear alveolar and glomerular BM antibody binding. Immunogold electron microscopy allowed precise identification, in intense linear patterns, of BM binding sites within lung and glomeruli. Functional lung injury was prevented by either leukocyte-depletion or complement-depletion (lung permeability index antibody-treated, complement-depleted 0.235 +/- 0.034: both p greater than 0.05 compared with controls). Injury mediation in this acute humoral model of lung damage is both complement- and leukocyte-dependent, as previously described for the renal component of heterologous anti-glomerular BM antibody-induced inflammatory disease.

Animals↗

Isolation and characterization of an unique kidney antigen of relevance in human renal disease.

Recently we described a monoclonal antibody, designated 7-5Q, with specificity for a human non-glomerular basement membrane capillary wall antigen. In order to purify and characterize the corresponding antigen for the development of sensitive ELISA techniques, applicable to the diagnosis and monitoring of renal disease, human kidney cortices were extracted with a variety of detergents. A double band of 98/105 kD was evident by immunoblotting in all preparations most notably with a Triton X-114 extract. The caprylic acid- and ammonium sulfate-purified monoclonal antibody 7-5Q was covalently bound to CNBr-activated Sepharose and detergent extracts were applied to this affinity material. A pure protein of 98/105 kD (double band on SDS-polyacrylamide gels) was eluted. Glycan typing with lectins revealed N-acetyl glucosamine-residues and amino acid analysis a relatively high content of acidic (31%) and hydrophobic (30%) amino acids, indicating that the antigen is an acidic, membrane-bound glycoprotein.

Amino Acids↗

Cyclosporin therapy for steroid resistant nephrotic focal glomerulosclerosis.

A young man with focal glomerulosclerosis and severe steroid resistant nephrotic syndrome was treated with oral cyclosporin for six months without histological evidence of drug induced nephrotoxicity. A marked and sustained partial remission of the degree of proteinuria one year following cessation of treatment was not accompanied by a deterioration in renal function. Cyclosporin may have a role, as yet not fully defined, in the treatment of steroid-resistant or dependent nephrotic syndrome.

Administration, Oral↗

Definition of glomerular antigens by monoclonal antibodies produced against a human glomerular membrane fraction.

Experimental animal models of glomerulonephritis (GN) produced by direct antibody binding to non-basement membrane glomerular capillary wall antigens do not to date have human parallels. To examine the potential for this form of humoral glomerular injury in man, we sought to define discrete human non-GBM glomerular antigenic targets using hybridoma technology. Mice were immunised intraperitoneally with 20-100 micrograms of a human glomerular membrane fraction (HGMF). Six fusions have yielded 12 stable reagents defined by positive glomerular indirect immunofluorescence (IF) and microELISA using HGMF as the screening antigen. Subclass analysis of ascitic McAbs indicated several IgG1, one IgG2b, and three IgM reagents. Distinctive IF patterns of reactivity with epithelial, endothelial or mesangial structures have been observed, with or without peritubular capillary, tubular basement membrane and vessel wall reactivity. Seven normal non-renal human organs and the kidneys of rat, rabbit and sheep have shown patterns characteristic of each individual McAb, restricted to human or with species cross reactivity. To partially characterise McAb-reactive antigens, detergent-solubilised renal cortex and collagenase-solubilised GBM (CS-GBM) extracts have been probed by immunoblot. A unique McAb 7-5Q, reactive with glomerular and tubular epithelial structures, binds major bands of approximately 107 KD and 93 KD in detergent solubilised cortex and a single band of similar size by immunoprecipitation (110 KD). 5-3A (a human-restricted linear-reacting McAb) binds bands of 20-200 KD (major band 58 KD) in CS-GBM. In conclusion, distinct species-restricted and more broadly disposed glomerular epitopes are definable in man by McAbs and are potential targets for humoral injury. Purification of these antigens will allow assay for circulating putative nephritogenic auto-antibody and potentially, McAbs may be useful in screening urine for evidence of occult structural renal disease.

Animals↗

Ischaemic necrosis of the glans penis: a complication of urethral catheterization in a diabetic man.

Ischaemic necrosis of the glans penis is rare. Diabetic patients commonly have small vessel disease which may affect the penis. We report the case of a man with extensive diabetic vascular disease, in whom partial penectomy was necessary for ischaemia of the glans penis, following urethral catheterization. The decision to use a urethral catheter in diabetics, particularly those with evidence of vascular disease, must be made with the knowledge that internal compression caused by the catheter may cause irreversible ischaemic changes. In such patients, a suprapubic catheter should be considered as an alternative.

Catheterization↗

Acute perirenal lymphocele formation 8 years after renal transplantation.

The majority of lymphoceles forming as a result of renal transplantation present or are detected within 6 months of surgery. A rare case of late presentation is reported, where the lymphocele developed 8 years after renal transplantation, due to leakage of lymph from the transplant kidney surface.

Adult↗

Rhodococcus equi: an emerging opportunistic pathogen?

Human infection with Rhodococcus equi is apparently rare with most published reports describing the development of lung abscesses in immunocompromised hosts. Of only 18 cases of infection previously recorded, four have recently occurred in patients with the acquired immune deficiency syndrome (AIDS). In Australasia, R. equi has frequently been isolated from soil and infected farm animals yet no human infections have been reported thus far. Three cases of R. equi infection have occurred in New Zealand and, collectively, they cover a wider spectrum of disease than that previously recognised. The natural history of R. equi infections, their clinical features and treatment are described in the light of our recent experience.

Acquired Immunodeficiency Syndrome↗

Localization of antiglomerular basement membrane-binding polyclonal antibodies in rat lung and kidney using post-embedding immunogold electron microscopy.

Post-embedding immunogold electron microscopy (IAuEM) techniques utilizing low-temperature embedding in Lowicryl K4m and LR White resin were used to localize the binding sites of two sheep anti-rat glomerular basement membrane polyclonal antibodies (P1 and P2) and a sheep anti-rat lung antigen antibody. P1 localization was bilaminar in a linear pattern along the subepithelial and particularly the subendothelial aspect of the glomerular basement membrane. P2 was bound diffusely throughout the lamina densa, even at supramaximal doses. The anti-lung antibody bound in an interrupted linear pattern throughout the lung basement membrane (alveolar and capillary), and showed an intense, diffuse binding to the glomerular basement membrane. IAuEM allowed definition of the precise basement membrane binding sites of these polyclonal reagents.

Animals↗

Participation of cell-mediated immunity in deposition of fibrin in glomerulonephritis.

Fibrin deposition is prominent in delayed-type hypersensitivity (DTH) reactions and is initiated by antigen-specific, T-lymphocyte-directed macrophage expression of human tissue factor (HTF). To examine the role of DTH in glomerular fibrin deposition, 10 fibrin-positive and 24 fibrin-negative biopsy specimens from patients with glomerulonephritis (GN) and samples from normal controls were studied with monoclonal antibodies against T cells, macrophages, and HTF. Fibrin-positive sections showed intense glomerular staining for HTF and significantly more T cells and macrophages than fibrin-negative specimens. All the essential elements of DTH reactions can therefore be simultaneously demonstrated within glomeruli from patients with fibrin-related GN. These findings suggest a role for cell mediated immunity in GN.

Adolescent↗

Tubular antigen-associated renal disease in New Zealand white rabbits. II. Investigation of mediators of glomerular injury: localization and characterization of the glomerular capillary wall antigen.

Mediation of the glomerular lesion and proteinuria produced by sheep antirabbit F x 1A globulin (SAFG) in rabbits was examined by prior treatment with cobra venom factor and nitrogen mustard. SAFG binding and proteinuria at 24 h were independent of complement or leucocytes but dose dependent. SAFG reacted by immunoblot with a wide range of antigens in deoxycholate extracts of rabbit glomeruli and autologous F x 1A including eight prominent shared bands of 29-128 kd. Immunogold electron microscopy has revealed the in vivo glomerular binding of SAFG as discrete, nonlinear and predominantly within the laminae rarae, in association with epithelial and particularly endothelial components of the glomerular capillary wall. In vitro binding was prominent on the endothelium. Proteinuria in this model is mediated by antibody without requirement for complement or leucocytes. The putative antigen(s) is/are associated with components of the glomerular capillary wall which share epitopes with autologous tubular F x 1A. This model is an example of an in situ immune complex glomerular nephritis and is distinct from the classical anti-F x 1A model, passive Heymann's nephritis in the rat.

Animals↗