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Biomedical subjects

R G Walker

Publications and source records attributed to R G Walker.

At least 55 records · Page 3Linked to original sources
PubMed1994

Tamm-Horsfall protein: are serum levels a marker for urinary tract obstruction?

Tamm-Horsfall protein (THP) has been found in the renal interstitium in patients with obstructive uropathy. The aim of this study was to investigate whether serum concentrations of THP could serve as a screening test for urinary tract obstruction. The presence of THP in normal human serum was confirmed by sodium dodecyl sulphate polyacrylamide gel electrophoresis and Western blotting. A specific enzyme immunoassay was then used to measure the serum concentration of THP. Serum THP concentrations were estimated in a cross-sectional study of a group of 23 patients who had technetium-99m-diethylene-triaminepenta-acetic acid (DTPA) nuclear urinary excretion studies to define urinary tract obstruction, and in longitudinal studies in 2 patients who developed acute bilateral ureteric obstruction following operations for ureteric reimplantation. The subjects with DTPA-proven urinary tract obstruction had higher concentrations of serum THP (n = 10, median = 43.9 ng/ml, range 10.4-152.1 ng/ml) than those who did not have obstruction (n = 13, median = 9.6 ng/ml, range 1.26-61.9 ng/ml). While this difference was significant (P < 0.01, Mann-Whitney U test), 6 of the 10 patients with obstruction had serum THP concentrations within the range of those patients without obstruction. The patients who developed acute bilateral ureteric obstruction both had increases in serum THP concentrations with obstruction and decreases in serum THP concentrations following relief of obstruction. These changes paralleled those in serum creatinine. The studies indicate that urinary tract obstruction results in increases in serum THP concentrations but these changes are not sufficient in magnitude to allow screening of children for urinary tract obstruction.

Adolescent↗
PubMed1994

The effect of growth hormone on growth and blood urea levels in children with chronic renal failure.

It has been claimed that low protein diets slow deterioration of chronic renal failure (CRF) by reducing renal solute load. The anabolic effect of recombinant human growth hormone (rhGH) also has potential to reduce renal solute load and thereby slow progression of renal failure. The aim of this study was to determine the effect of rhGH on growth, renal solute load and renal function in children with CRF. Seven prepubertal children, aged 2-14 years, with moderately severe CRF (creatinine clearance 7.7-23.4 mL/min per 1.73m2) were treated with daily subcutaneous rhGH, 1 U/kg per week for 10-12 months. As expected, mean height velocity standard deviation scores (SDS) increased, from -2.87 before treatment to +3.39 on rhGH, and mean height increased from -3.1 to -2.4 SDS. Serum urea concentrations decreased in most patients during the first month of growth hormone treatment from a mean of 20.0 +/- 7.7 mmol/L to 14.8 +/- 5.8 mmol/L (P = 0.006). The serum urea then returned to pretreatment levels over the next few months. In the 12 months before treatment with growth hormone, mean creatinine clearance decreased from 19.3 mL/min per 1.73 m2 to 16.7 mL/min per 1.73 m2. In the next 12 months on rhGH mean creatinine clearance decreased further to 13.5 mL/min per 1.73 m2. Therefore the rate of deterioration of renal function was unaffected during treatment with growth hormone. Initial treatment with rhGH is associated with decrease in serum urea concentrations in children with CRF, probably mediated by stimulation of anabolic incorporation of dietary nitrogen into body protein.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1994

Vasculopathy in cyclosporine-treated renal allografts: possible protection by diltiazem.

Morphometric quantitative analysis of the renal arterioles (arteriole wall thickness and overall vessel size) in renal biopsies from 21 cadaveric renal allograft recipients taken immediately prior to (0 months) and 3 months after transplantation was carried out using a computer-aided image analyzer. Patients (n = 10) who received standard therapy (cyclosporine, azathioprine and prednisolone) showed an increase in arteriole wall thickness at 3 months compared to 0 months (p < 0.01). Patients (n = 11) who received standard therapy and oral diltiazem (60 mg t.d.s.) showed no such change in the arteriole wall thickness between 0 and 3 months. As cyclosporine toxicity and/or chronic vascular rejection are associated with an increase in arteriole wall thickness, the differences observed in this study may imply a protective role for diltiazem on renal arterioles.

Adult↗
PubMed1993

The potential for elderly donors to increase renal transplantation rates in Australia.

OBJECTIVE: To estimate the potential increase in renal donation rates if elderly donors (those over 60 years of age) were considered. DESIGN: Patients dying from acute brain damage resulting from stroke were identified using the Royal Melbourne Hospital (RMH) Stroke Service Register. Their records were retrospectively analysed to assess their eligibility as potential renal donors. SETTING: One hundred and ninety-eight patients dying from acute brain damage caused by stroke at a large metropolitan teaching hospital (RMH), from May 1987 to December 1990 inclusive. PATIENT ASSESSMENT: Patients were considered "eligible", "ineligible" or "possibly eligible" (requiring further assessment) as donors according to existing strict criteria (see methods) but irrespective of age. RESULTS: Of 198 stroke patients dying of brain damage, 92 satisfied the criteria of eligibility for renal donation; 51 of these were over 60 years old, yet only one became a renal donor. CONCLUSION: There is good evidence that elderly donors are acceptable for renal transplantation, yet they are not being referred. The consideration of elderly stroke victims as renal donors could have a dramatic effect on decreasing transplant waiting lists, increasing recipient patient well-being, and reducing hospital costs.

Adult↗
PubMed1993

Calmodulin and calmodulin-binding proteins in hair bundles.

Calcium ion plays an important role in the hair cell's mechanoelectrical transduction process; in particular, Ca2+ controls adaptation to protracted mechanical stimuli. Because calmodulin is a ubiquitous intracellular receptor for Ca2+ and has been shown to accumulate at the tips of stereocilia, we determined its concentration and identified the proteins with which it interacts in the hair bundle. By performing quantitative immunoblot analysis on isolated bundles, we ascertained that the average concentration of calmodulin within each stereocilium is approximately 70 microM. Extraction experiments disclosed that, in the presence of 20 microM Ca2+, 50% of the calmodulin is bound to detergent-soluble receptors. To distinguish these receptors, we developed an assay that utilizes calmodulin crosslinked to alkaline phosphatase. This technique is approximately 100-fold more sensitive than calmodulin-binding assays that employ 125I- or biotin-labeled calmodulin. When used with chemiluminescence detection in a blot-overlay assay, the calmodulin-alkaline phosphatase conjugate identified hair-bundle proteins of molecular masses 25, 35, 145, 175, 240, and 350 kDa. We examined the subcellular distribution of these receptors; all but the 240-kDa molecule are soluble in a nonionic detergent. The relatively high concentration of calmodulin and the presence of several calmodulin-binding proteins provide evidence for a role of calmodulin in hair bundles.

Alkaline Phosphatase↗
PubMed1993

Kidney transplantation from living related donors: a 19-year experience.

OBJECTIVE: To determine the outcome of patients with end-stage chronic renal failure treated by live donor renal transplantation at the Royal Melbourne Hospital and Royal Children's Hospital between 1973 and 1991, during which time two distinct immunosuppressive regimens were used. DESIGN: Data about live donor renal transplant recipients were retrieved from the Australian and New Zealand Dialysis and Transplantation Association Registry, to which we have submitted data on all transplant recipients at six monthly intervals since the commencement of our dialysis and transplant programs. PATIENTS: Seventy-two patients with chronic renal failure who received live donor renal transplants during the 19 years from February 1973 to February 1992 were included. MAIN OUTCOME MEASURES: Patient survival, transplant survival, transplant function, change in prednisolone requirements, and duration of hospital stay. RESULTS: The first 32 patients were treated with immunosuppressive regimens based on combinations of prednisolone and azathioprine ("dual therapy"), while the next 40 patients were treated with combinations of cyclosporin, prednisolone and azathioprine ("triple therapy"). Survival of patients in each group five years after transplantation was 97%. Actuarial graft survival at 5, 10 and 15 years in the dual therapy group was 58%, 52% and 47%, compared with a 5-year actuarial graft survival in the triple therapy group of 96%. There was no statistically significant difference in renal transplant function between the two groups within the first 6 years after transplantation. Twelve of 26 patients (46%) treated initially with triple therapy were able to stop treatment with prednisolone within 12 months of transplantation. Median hospital stay was 12 (range, 6-35) days during the period 1973-1985 and 8 (range, 5-20) days for the 1985-1992 period. CONCLUSION: Live donor renal transplantation has provided a highly satisfactory means of treating patients with end-stage chronic renal failure in the short and long term. Our recent experience indicates that excellent patient and graft survival and adequate renal function can be achieved by treating live donor renal transplant recipients with a triple immunosuppressive regimen of low dose cyclosporin, prednisolone and azathioprine.

Adolescent↗
PubMed1993

Anti-neutrophil cytoplasmic antibody-associated glomerulonephritis in children.

Two cases of anti-neutrophil cytoplasmic antibody (ANCA)-associated necrotizing and crescentic glomerulonephritis are reported. A 12-year-old girl and a 10-year-old boy presented with polyarthritis, anaemia, haematuria, proteinuria, impaired renal function, anorexia, nausea, marked loss of weight and lethargy. The boy also had a vasculitic rash and anterior uveitis. Both children had diffuse cytoplasmic ANCA identified by indirect immunofluorescence and confirmed by specific enzyme-linked immunosorbent assay. Renal biopsies showed severe focal and segmental necrotizing glomerulonephritis with 100% crescents. They were treated with plasma exchange, prednisolone, cyclophosphamide and heparin. Within 1 month of commencing treatment, both had normal serum creatinine concentrations and ANCA was not detectable. Renal biopsies 6 weeks following commencement of treatment revealed quiescent disease, although up to 40% of glomeruli were sclerosed or had fibrous crescents. Following cessation of cyclophosphamide and heparin after 7 months and reduction in steroid dose, a biopsy at 10 months in the boy revealed quiescent disease, but the girl had recurrent disease associated with reappearance of a low titre of ANCA and small cellular crescents in 20% of the glomeruli. These cases reflect the potential usefulness of ANCA determination for categorizing paediatric patients, helping in the selection of therapy and as a possible marker of disease activity, similar to the experience in adults.

Antibodies, Antineutrophil Cytoplasmic↗
PubMed1993

A screening assay to simultaneously determine the presence and specificity of HLA anti-idiotypic antibodies.

HLA sensitization is generally associated with an increased risk of graft failure. However, in many cases, highly sensitized patients with a negative current serum crossmatch may be successfully transplanted despite the high levels of alloantibodies (Ab1) in their serum. Sensitized patients may be divided into two groups. The group with a high-risk of early graft failure produces a negative current serum crossmatch as a result of antibody attrition, but upon transplantation the reactivation of Ab1 by the donor organ results in graft failure. The low-risk group gives a negative current serum crossmatch due to the abrogation of Ab1 by anti-idiotypic antibodies (Ab2). This specific inhibition results in the protection of the graft and improved graft survival. In this paper we describe a screening method which enables large numbers of patients to be assessed for the presence of Ab2 in pretransplant sera, while simultaneously determining the specificities of these antibodies. The pretransplant assessment of sensitized patients for the presence of Ab2 would enable low-risk patients to be distinguished from high-risk patients, while information regarding Ab2 specificity would enable permissible mismatches to be considered. With this information at hand, the pretransplant waiting time for these patients may be greatly reduced. In our modification of the inhibition assay, selected dilutions of peak sera (P/n) were tested in the presence of either platelet absorbed current serum (P/n + Cabs) or an equal volume of fetal calf serum (P/n + FCS) as a dilution control.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies, Anti-Idiotypic↗
PubMed1993

Pyeloureterostomy in the management of renal allograft ureteral complications: an alternative technique.

Pyeloureterostomy is the standard procedure for reconstructing renal allograft ureteral complications. Most reports describe an end-to-end technique with or without native nephrectomy. An alternative is an end-to-side anastomosis, leaving the native ureter in continuity. We report our experience with the latter method. Since July 1983, 437 renal transplantations have been performed at our institution. End-to-side pyeloureterostomy has been used in 5 cases for urological reconstruction after renal transplantation following ureteral ischemic necrosis or stenosis. In 1 patient the native kidneys had been removed several years previously but in the remaining 4 the native kidneys were left in situ. There have been no significant complications following this procedure. We believe that by not significantly mobilizing, ligating or dividing the native ureter the chance of anastomotic breakdown due to ischemia may be decreased.

Adolescent↗
PubMed1993

Clinicopathologic associations of anti-endothelial cell antibodies in immunoglobulin A nephropathy and lupus nephritis.

Sera from 45 patients with lupus nephritis (LN), 63 patients with immunoglobulin A nephropathy (IgA N), and 71 glomerulonephritic controls (including 44 mesangial proliferative glomerulonephritis cases, 14 membranous glomerulonephritis cases, and 13 focal segmental glomerular sclerosis cases), and from 33 normal control subjects were tested by a cellular enzyme-linked immunoabsorbent assay for their anti-endothelial cell antibody (AECA) activity. Compared with normal controls, AECAs of the IgG subtype (AECA-IgG) were detected in LN (P < 0.001) and AECAs of the IgA subtype (AECA-IgA) were detected in both IgA N and LN (P = 0.018 and P < 0.001, respectively). Binding activity of AECA to endothelial cells was inhibited by endothelial cell lysate and fibroblast lysate but not by lymphocyte lysate, double stranded-DNA, or bovine serum albumin. Anti-endothelial cell antibody-positive sera also reacted with fibroblasts. In IgA N, associations were found between the presence of AECA and younger age (P = 0.036), proportion of crescents greater than 10% (P = 0.016), fibrin crescents (P = 0.016), and focal and segmental necrotizing lesions (P = 0.047). In LN, inverse associations were found between the presence of AECA and the duration of disease (P = 0.021), elevated serum creatinine levels (P = 0.020), decreased creatinine clearance (P = 0.043), and frequency of chronic renal failure (P = 0.036). Positive associations were observed between the presence of AECA and active lupus (P = 0.017), anti-nuclear antibodies (P = 0.015), and anti-DNA antibodies (P = 0.041). Our results suggest that AECA may be linked with the pathogenesis of LN and IgA N.

Adult↗
PubMed1993

Collagen studies in newborn rat kidneys with incomplete ureteric obstruction.

Collagen studies in newborn rats with incomplete ureteric obstruction were performed to describe and quantify changes in collagen deposition resulting from urinary tract obstruction at an early developmental age. Incomplete ureteric obstruction was created in three-day-old rats by placing the left ureter in a tunnel formed by the psoas muscle, and sham-operated controls underwent a laparotomy. The rats were sacrificed at 10, 17, 24 or 31 days. Collagen types I, III, IV, and V were localized by indirect immunofluorescence microscopy, the total collagen content of the kidney was quantitated using hydroxyproline analysis, and collagen types I and III were quantitated using cyanogen bromide (CNBr) peptide analysis. Increased immunofluorescent staining for all of the collagens was found in the diffusely widened medullary interstitium of the obstructed kidney, and more focally in the cortical interstitium. Collagen types I, III and V, but not collagen type IV, were also found in bands in the interstitium at the junction of the cortex with the medulla. Increased staining for collagen type IV was found in thickened and tortuous tubular basement membranes (TBM) of the obstructed kidneys. The total collagen content of the obstructed kidney was significantly increased compared to the amounts in both the contralateral kidneys and in the kidneys from sham-operated controls at 24 and 31 days of age (P < 0.01 in each case, Wilcoxon matched pairs rank sum test and Mann Whitney U-test, respectively). The amount of collagen in the kidneys correlated with the degree of hydronephrosis (Spearman correlation test, r = 0.78, P < 0.02). CNBr peptide analysis demonstrated that over 50% of the collagen in the normal neonatal rat kidney was collagen type I and approximately 25% was collagen type III. In the obstructed kidneys most of the collagen was also collagen type I and collagen type III, although the proportion of total collagen comprised by these collagen types was decreased compared with the controls. The amount of collagen type III in the contralateral kidneys was reduced compared to that in the controls. Thus, the neonatal renal response to obstruction resulted in increased amounts of a range of collagens in the interstitium and TBM, and the extent of this response was partially related to the degree of hydronephrosis.

Animals↗
PubMed1993

Diltiazem in renal allograft recipients receiving cyclosporine.

Of 113 cyclosporine-treated primary renal allograft recipients, 60 were randomized to receive standard therapy without diltiazem (ND) and 53 received standard therapy plus diltiazem (D). There was no difference in CsA blood levels between ND and D at all intervals between 3 and 24 months follow-up, yet the D group required 35% less CsA than the ND group (measured at 12 months). At all intervals to 24 months there was no difference in blood pressure, renal function (as measured by serum creatinine), or in the number of grafts lost between the 2 groups (ND, 4 lost; D, 3 lost). There was no significant difference in the total number of rejection episodes in the 2 groups (ND, 89 episodes; D, 71 episodes). However, the severity of rejection episodes was greater in the ND group as evidenced by a significant difference in the usage of OKT3 (ND, 17 courses; D, 8 courses of OKT3, P < 0.05). Of the biopsy-proven episodes of rejection, there were more episodes of vascular rejection in the ND group (ND, 14 episodes; D, 3 episodes, P = 0.005). The incidence of primary nonfunction was less in the D group (ND, 16 patients; D, 5 patients, P = 0.05). It was concluded that the use of diltiazem was associated with a markedly reduced requirement for CsA without any adverse effect on graft function or graft outcome. Diltiazem with CsA was associated with fewer episodes of primary nonfunction and less-severe rejection episodes and in particular fewer episodes of vascular rejection.

Adult↗
PubMed1993

Recent advances in the management of vesico-ureteric reflux.

Recent studies have demonstrated that both congenital hypoplasia and acquired scarring are involved in the parenchymal lesions associated with reflux nephropathy. Medical therapy can prevent symptomatic infection. While there is no proof that either medical or antireflux surgery prevents acquired scarring, paradoxically there is evidence that surgery adds no benefit to medical therapy, and that the results of medical therapy and surgical therapy are similar in children with isolated severe reflux. The group at most severe risk of renal scarring is infants and the effects of medical and surgical therapy in preventing acquired renal injury in this group have not been sufficiently investigated. On the basis of this information it has been our practice to maintain urine sterility using continuous antibiotic prophylaxis throughout infancy and early childhood. Following the development of reliable urine toilet habit and the ability to collect midstream urine specimens, antibiotics are given according to the frequency of urine infection, and weekly testing of morning urine with nitrite strips at home is used for early detection of infection and prevention of symptomatic infection. Antireflux surgery is mandatory for those children with complicated VUR (such as urinary tract obstruction) and should otherwise be reserved for those having persistent breakthrough infections in infancy and early childhood.

Adolescent↗
PubMed1993

Right atrial catheters: reliable, immediate and durable vascular access for haemodialysis and plasma exchange.

This paper prospectively evaluates 33 dual lumen, right atrial catheters inserted into either an external or internal jugular vein by open operation in 29 patients, of whom 15 required haemodialysis and 14 required temporary plasma exchange. The median (range) catheter survival in the haemodialysis and plasma exchange groups was 108 days (7-334 days) and 61 days (10-116 days), respectively. Life table analysis demonstrated that overall catheter survival was 58% at 200 days. The main causes of catheter failure were infection (four cases), poor flow (three cases) and accidental removal (one case). Another nine catheters were removed electively because of maturation of alternative methods of vascular access (five cases), completion of plasma exchange treatment (three cases), or successful renal transplantation (one case). Long-term silastic catheters, inserted into the right atrium via a jugular vein, have distinct advantages over temporary subclavian vein catheters and external arteriovenous (AV) shunts; this form of access is the method of choice for haemodialysis and plasma exchange patients who require immediate and short- to medium-term vascular access.

Adolescent↗
PubMed1993

Is the second phase of a biphasic defibrillation waveform the defibrillating phase?

Why some biphasic waveforms defibrillate with lower energies than monophasic waveforms of similar duration is unknown. One hypothesis is that the first phase of a biphasic waveform acts as a conditioning, hyperpolarizing prepulse to prepare for defibrillation by a second depolarizing phase. To test whether the second phase of a biphasic waveform is the defibrillating phase, three monophasic waveforms, an ascending ramp (A), a square wave (S), and a descending ramp (D), were compared to three biphasic waveforms with A, S, or D in the first phase (biphasic first phase) and three biphasic waveforms with A, S, or D in the second phase (biphasic second phase). Two defibrillation thresholds for each waveform were performed in 18 open chest pigs and mean defibrillation thresholds were compared. In nine pigs 16-msec monophasic and 16/16-msec biphasic waveforms were ranked by mean current and energy at defibrillation threshold. The ranks were the same for monophasic and biphasic second phase waveforms: for mean current A < S = D and for energy A < S < D. The ranks were different for the biphasic first phase waveforms: for mean current S < A = D and for energy S < A = D. Although ranks for the 16-msec monophasic waveforms matched those for the 16/16-msec biphasic second phase waveforms, the biphasic waveforms had higher mean currents and energies at defibrillation threshold. In nine pigs defibrillation thresholds for 6-msec monophasic and 6/6-msec biphasic waveforms were ranked. For mean current the ranks were monophasic: A < S = D; biphasic first phase: A = S = D; and biphasic second phase: S = D < A. For energy the ranks were monophasic: A = S < D; biphasic first phase: A = S = D; and biphasic second phase: S = D < A. Thus, ranks for the 6-msec monophasic waveforms differed from those for the 6/6-msec biphasic second phase waveforms. For 16/16-msec biphasic waveforms, less effective for defibrillation than corresponding 16-msec monophasic waveforms, these results support the hypothesis that the second phase of a biphasic waveform defibrillates since the defibrillation efficacy of a 16/16-msec biphasic waveform is related to the defibrillation efficacy of its second phase waveshape. However, for clinically useful 6/6-msec biphasic waveforms, more effective for defibrillation than 6-msec monophasic waveforms, the hypothesis is not supported because the ability of a 6/6-msec biphasic waveform to defibrillate is unrelated to the defibrillation efficacy of its second phase waveshape.

Animals↗
PubMed1993

Gingival hyperplasia in renal allograft recipients receiving cyclosporin-A and calcium antagonists.

Although it is established that the immunosuppressant cyclosporin-A (CsA) and calcium antagonists [Nifedipine (Nif) and Diltiazem (Dz)] can independently induce gingival enlargement, little has been documented on the significance of the salivary CsA levels and the combined effect of CsA and a calcium antagonist upon gingival tissues. In the present cross-sectional investigation, clinical periodontal parameters and the pharmacologic profiles of CsA, Nif, and Dz were determined for 66 renal transplant recipients. Subjects were divided into the following groups: Group (Gp) 1: CsA [n = 18]; Gp 2: CsA + Nif [n = 15]; Gp 3: CsA + Dz [n = 12] and a negative Control Gp 4: azathioprine [n = 21]. A gingival enlargement score was assessed for each patient from study models using a hyperplastic index (HI). Pharmacologic profiles included CsA whole blood and whole saliva levels as measured by fluorescence polarization immunoassay. The HI scores between Gp 1, 2 and 3 were not significantly different. However, when compared with controls (Gp 4), there was a significant difference in HI and all individual groups (Gp 1, 2, 3) (p < 0.05). Gingival hyperplasia was only weakly related to plaque and calculus but was unrelated to CsA dose (mg/kg/day), duration of CsA therapy (months), CsA blood or saliva levels (ng/ml), or the concurrent administration of a Nif or Dz. Gingival enlargement was found to occur in 49% of subjects who were either on CsA or CsA and a calcium antagonist. It is concluded that CsA alone or in combination with a calcium antagonist caused a significant increase in gingival enlargement compared with controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗