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Biomedical subjects

B G Murphy

Publications and source records attributed to B G Murphy.

14 recordsLinked to original sources
PubMed1998

Treatment of renal failure in idiopathic membranous nephropathy with azathioprine and prednisolone.

BACKGROUND: Progressive deterioration in renal function occurs in 20-50% of patients with idiopathic membranous nephropathy (IMN). Several treatment regimens have been used to reverse this with varying effect and toxicity. METHODS: Thirteen patients (10 males, 3 females, median age 56 years) with IMN and progressive renal failure were treated with oral prednisolone 20-60 mg/day and azathioprine 1.3-2.7 mg/kgBW/day. All patients were followed up for a minimum of 2 years with a median follow-up of 73 months (range 24-103 months). RESULTS: Ten patients responded to treatment with a fall in serum creatinine and renal function stabilized in the remainder. Two patients relapsed, one of whom responded to an increase in immunosuppression, the other is now on dialysis. Proteinuria has significantly reduced in 10 patients, and only four patients still have nephrotic-range proteinuria. Mean (+/- SE) peak pretreatment serum creatinine of 229 (+/- 161) mumol/l and urinary protein of 11.8 (+/- 1.8) g/24 have fallen to 163 (+/- 65) mumol/l and 3.25 (+/- 1.0) g/24 h after 12 months treatment (P < 0.005, Wilcoxon matched pairs test). Immunosuppressive treatment has been successfully withdrawn in four patients after intervals ranging from 12 to 60 months. Adverse effects, which occurred in 10 patients, have been mild and have not led to treatment withdrawal though dose reductions have been necessary in some patients. CONCLUSIONS: Oral prednisolone and low-dose azathioprine is an effective therapy for progressing renal failure due to IMN, and induces remission of nephrotic syndrome. Side-effects are less than other immunosuppressive regimens.

Adolescent↗
PubMed1997

Influence of immunosuppressive therapy on lipoprotein(a) and other lipoproteins following renal transplantation.

Coronary heart disease (CHD) is more common in patients with chronic renal failure and is a major cause of death after renal transplantation. Elevated serum levels of lipoprotein(a) (Lp(a)) are a known risk factor for CHD in the general population and levels have been reported to be increased in renal transplant recipients. It has been suggested that cyclosporin may elevate Lp(a) levels. We therefore measured the serum concentration of Lp(a) in 50 renal transplant recipients who were receiving cyclosporin alone as immunosuppressive therapy and 50 who were treated with azathioprine and prednisolone, but not cyclosporin. The patients attended two renal transplant centres, one where cyclosporin alone was used as immunosuppressive treatment when possible and another where many patients commenced on azathioprine and prednisolone remain on this medication rather than cyclosporin. Patients in each group were matched for age and sex, but the time since transplantation was greater in those not receiving cyclosporin. Transplant function, obesity and the underlying cause of renal disease were similar in both groups of patients. Median Lp(a) concentration in the cyclosporin monotherapy group was 32.0 (range <0.8-140.3) mg/dl and was significantly (p < 0.05) greater than that of the azathioprine and prednisolone group which was 18.3 (range <0.8-167.7) mg/dl. The serum high-density lipoprotein (HDL) cholesterol concentration, which was 1.24 +/- 0.39 mmol/l (mean +/- SD) in patients receiving cyclosporin, was significantly (p < 0.05) less than that of those treated with azathioprine and prednisolone in whom it was 1.41 +/- 0.40 mmol/l. The lower level in those on cyclosporin was due to a decrease in the HDL2 subfraction. Serum lipid and lipoprotein concentrations were otherwise similar in the two groups of patients. The serum level of Lp(a) after renal transplantation may be influenced by the choice of immunosuppressive therapy.

Adolescent↗
PubMed1995

Effect of immunosuppressive drug regime on cardiovascular risk profile following kidney transplantation.

We have previously studied cardiovascular risk markers apolipoprotein (a) (apo(a)) and plasma fibrinogen in 146 control, 60 haemodialysis (HD), 53 continuous ambulatory peritoneal dialysis (CAPD) and 66 renal transplant subjects. Fibrinogen concentration was higher in all 3 renal replacement groups compared to controls. Apo(a) was higher in the CAPD group only. We have now restudied those dialysis patients (24 HD, 16 CAPD) who have since undergone transplantation. Fibrinogen concentration remained elevated in CAPD patients (mean (SE) 3.9 (0.17) vs. 3.77 (0.20) grams/l) and increased in HD patients (2.88 (0.16) vs. 3.72 (0.13) grams/l, P < 0.0001). Apo(a) fell in both groups (CAPD, geometric mean 287 vs. 151 U/l, P = 0.008; HD, 230 vs. 179 U/l, P = 0.013). Fibrinogen concentration was higher in the recent group compared to the original group (3.74 (0.11) vs. 3.19 (0.12) grams/l, P = 0.001). None of the 66 original patients received cyclosporin (cyA) compared to 35 of the 40 in the present study. In this recent group, patients maintained on prednisolone and azathioprine alone had significantly lower fibrinogen levels than those receiving cyA. Furthermore, the fall in apo(a) was smaller (31% vs. 74%) and the increase in apolipoprotein B (apo B) greater (0.55 (0.15) vs. 0.18 (0.05) grams/l, P = 0.014) in cyA-treated patients. CyA may have an adverse effect on cardiovascular risk profile in renal transplant recipients.

Apolipoproteins A↗
PubMed1994

Increased renal allograft thrombosis in CAPD patients.

In a retrospective analysis of 202 renal transplant procedures in the years 1989-1992 we identified an excess of grafts lost from primary renovascular thrombosis in patients receiving continuous ambulatory peritoneal dialysis (CAPD) compared to haemodialysis (HD) patients (9 CAPD versus 0 HD, Chi-squared = 9.63; P < 0.01). All graft losses from thrombosis occurred within 16 days of surgery. Possible predisposing causes were identified in three patients. Donor age was greater in CAPD patients losing their kidneys from thrombosis compared to the overall CAPD group [mean (SD) years, 43.0(12.9) versus 29.1(15.8); P = 0.01] whereas no significant difference in haematocrit, platelet count, antibody status, cyclosporin use, peroperative hypotension, primary diagnosis, smoking, or diabetes mellitus was found. Data from the EDTA registry for 1990-91 show that graft loss from primary renovascular thrombosis in UK-treated patients was reported in 7.1% of CAPD recipients compared with 1.8% in haemodialysis. We suggest that CAPD patients are at greater risk of graft loss from renovascular thrombosis than HD patients and may require more intensive fluid and anticoagulant treatment in the perioperative period.

Adolescent↗
PubMed1993

Renal replacement therapy in multiple myeloma and systemic amyloidosis.

Renal failure frequently complicates both multiple myeloma and systemic amyloidosis. Renal replacement therapy (RRT) may be poorly tolerated and its role in such patients is not clearly defined. Of fifty patients (26 males and 24 females) referred to a single centre because of renal failure associated with multiple myeloma or systemic amyloidosis 37 progressed to end-stage renal failure and 30 of these patients received RRT. Nine patients have been treated by CAPD, 13 by haemodialysis, and 8 patients have required both forms of dialysis. Overall one year and two year survival rates were 66% and 57% respectively. The median duration on RRT was 7.5 months (range 1-96 months) with a 51% one year, and a 46% two year survival rate. Of 7 patients with amyloidosis who underwent renal transplantation, 3 died within 6 months of transplantation. Undiagnosed cardiac involvement contributed to this early mortality. We conclude that renal replacement therapy is appropriate for some patients with multiple myeloma and systemic amyloidosis who develop endstage renal failure. Careful assessment and selection of patients is necessary prior to renal transplantation.

Adolescent↗
PubMed1992

Increased serum apolipoprotein(a) in patients with chronic renal failure treated with continuous ambulatory peritoneal dialysis.

Patients with end-stage renal failure (ESRF) on renal replacement therapy are at significantly increased risk of cardiovascular disease. To determine whether altered concentrations of apolipoprotein(a) (apo(a)), the plasminogen-like protein moiety of the atherogenic particle lipoprotein(a), contributed to this increased risk, apo(a) concentrations were measured in 48 non-diabetic patients with ESRF treated by continuous ambulatory peritoneal dialysis (CAPD) therapy and compared with 65 controls. Apo(a) concentration was increased in CAPD patients compared to controls (geometric mean 419 units/l versus 137 units/l; ratio of means 3.06 (95% CI 1.95-4.80). We conclude that CAPD patients have increased apo(a) concentrations which may contribute to their increased risk of cardiovascular disease.

Adult↗
PubMed1988

Localization of a biologically important epitope on toxic-shock-syndrome toxin-1.

A monoclonal antibody, designated B-14, inhibits the nonspecific T lymphocyte mitogenicity of toxic-shock-syndrome toxin-1 (TSST-1), and the antibody binds to an internal cyanogen bromide (CNBr) fragment (Mr, 14,000) of the toxin. The epitope recognized by B-14 was further localized to include a decapeptide at the NH2-terminus of the CNBr fragment. The decapeptide inhibited the ELISA and western blot reactivity of B-14 with TSST-1, although it was approximately 10,000-fold less effective than the native toxin. The peptide also inhibited the capacity of B-14 to block TSST-1-induced mitogenicity. A conjugate, consisting of decapeptide4-ovalbumin, was used to hyperimmunize three rabbits. Serum from these rabbits reacted specifically with intact TSST-1 in ELISA and western blots and partially neutralized toxin mitogenicity; however, the serum did not prevent fever and enhancement of susceptibility to endotoxin shock typically seen in rabbits after administration of TSST-1.

Amino Acid Sequence↗
PubMed1983

Effect of a hydrostatic pleural pressure gradient on mechanical behavior of lung lobes.

Using 133Xe, the vertical distribution of regional volume (Vr) was measured in three regions of excised canine lobes both in air and when completely submerged in saline at 40, 60, 70, and 80% lobar vital capacity (VC). The estimated pleural pressure gradient, derived from values of Vr, distance between regions, and the lobar pressure-volume (PV) curve, underestimated the true gradient by 45%. Conversely, the gradient of Vr was substantially less than predicted. From the mean depth of each region below the waterline, pleural, and hence transpulmonary, pressure (PL) was computed. The values of Vr-PL for each region at 40, 60, and 80% lung volume (VL) were related to the lobar PV curve. Slopes of lines joining initial VL-PL points on the lobar PV curve to corresponding Vr-PL points in submerged lobes represent an effective regional compliance of a lobe undergoing deformation. With one exception this was less than the corresponding homogeneous compliance, indicating a stiffening of the lobe during deformation. Slopes of lines joining Vr-PL points of each region at the three lobar volumes represent effective regional compliance of a deformed lobe undergoing volume change. This was not significantly different from the homogeneous compliance. However, effective compliance can only be an approximate indicator of the forces required for a given volume change due to the inadequacy of PL to represent the unequal stress components induced by lobe deformation.

Animals↗
PubMed1980

Shrinkage of dog lobes during air-drying fixation.

Air-drying of canine lung lobes, distended at a constant pressure corresponding to 50% of lobar total lung capacity, resulted in a volume shrinkage of 35.8%. To examine associated changes in shape of the lobes, the shrinkage of three orthogonal directions (x, y, and z) was quantitated by measuring the change in length per unit length (strain; epsilon) of straight lines between pleural markers. Epsilon x = 0.14, epsilon y = 0.22, and epsilon z = 0.12. This inequality of strains indicated that moderate shape changes occurred. The direction of the largest strain component (epsilon y) corresponded to a direction normal to the largest projected surface area of the lobe.

Animals↗
PubMed1978

Models of the pressure-volume relationship of the human lung.

The static pressure-volume (PV) curve from TLC to RV of 11 human subjects was fitted by a hyperbolic-sigmoid model: P = k1/(VM--V)+k2/(Vm--V)+k3, where VM and Vm are the upper and lower asymptotes respectively, and k1, k2, k3 are shape constants. Least-squares nonlinear regression was used to evaluate the constants for the individual and mean data. Average SD of residuals was 0.57 cm H2O and average reduction of residual variance was 99.93%. In spite of substantial differences between PV curves, the latter can be modelled accurately. For the mean PV curve, values for VM, Vm and k1, k2, k3 were 110% VC, -4.34% VC, 260 cm H2O/% VC, 50.5 cm H2O/% VC and 3.13 cm H2O respectively. Unlike previously proposed models, the above includes data below FRC. It describes the truly linear portion of the PV curve at and above FRC. The lower inflection point is accomodated at different lung volumes. When used in a compartmental analysis of a homogeneous lung exposed to a constant pleural pressure gradient, it predicts sequential emptying of dependent and nondependent lung regions consistent with that observed experimentally.

Humans↗
PubMed1976

Stress at the pleural surface.

The transmission of forces between the visceral and parietal pleural is modelled as being mediated by two distinct pathways: (a) a contact pressure (Pcon) acting on an area of contact (Acon) and (2) a pleural liquid pressure (Pliq) acting on the area of liquid anfractuosities (Aliq). Summation of the forces yields a new equation relating pleural surface pressure (Ppl) to Pcon, Acon, Pliq, and Aliq. A complete solution of the equation is restricted by present limitations on measurement technology. However, assuming that the volume of pleural liquid is constant during tidal breathing, analysis of the model explains the findings that tidal swings in Pliq (deltaPliq) are sometimes greater than tidal swings in Ppl (deltaPpl). It also predicts that the influence of a change of lung elastic recoil on Pliq may be different in magnitude than its effect on Ppl. Therefore deltaPliq is not necessarily equivalent to deltaPpl.

Airway Resistance↗
PubMed1976

Influence of posture on flow dependence of distribution of inhaled 133Xe boli.

The second 100 ml of gas inspired at constant flow rates (V) from 0.1 to 2.5 l/s was tagged with 133Xe to determine the apicobasal bolus distribution ratio (VAlvA/VAlvB) for seven normal subjects in both the upright and supine postures. Gas was preferentially distributed to the base at low V. As V increased, redistribution to the apex occurred but was greater in the supine posture. As apicobasal time constant differences should be minimal in the supine posture, the greater flow dependence of bolus distribution suggests that the pressure swing was greater over apical zones than basal zones. Model studies indicate that the pressure differences (deltaPd) necessary to predict the measured VAlvA/VAlvB at all flow rates are less than 1.0 cmH2O. Such sensitivity of gas distribution to deltaPd at both low and high flow rates makes it appear relatively insensitive to regional compliance and resistance.

Adult↗