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C D Short

Publications and source records attributed to C D Short.

At least 37 records · Page 2Linked to original sources
PubMed1994

Transforming growth factor beta 1 in renal allograft recipients.

Transforming growth factor beta (TGF beta 1) is a prosclerotic cytokine implicated in several disease processes. Recent reports have demonstrated a role for TGF beta 1 in experimental models of glomerulonephritis, focusing attention on the relevance of TGF beta to renal fibrogenesis in human disease. The study reported here was designed to investigate whether circulating, active TGF beta 1 could be detected in renal allograft recipients, and whether plasma levels correlated with episodes of rejection, a process involving both inflammation and fibrosis. We have developed an ELISA assay for active TGF beta 1 using commercially available antibodies, and measured plasma levels in 43 healthy controls, 11 patients with membranous nephropathy (MN) and impaired renal function, 17 transplant recipients with stable renal function, 27 patients with acute cellular rejection, 7 patients with chronic vascular rejection, and 10 patients with acute tubular necrosis and/or cyclosporine toxicity. In the last three groups diagnoses were biopsy-proved, and all samples were collected at the time of biopsy. TGF beta 1 was also measured in urine samples from 8, 11, 0, 9, 4, and 7 individuals, respectively, from each group. TGF beta 1 was not detected in plasma from any of the healthy controls or any of the MN patients, (detection limit of assay 0.1 ng/ml). By comparison, it was significantly increased in all groups of transplant recipients (unpaired t test, P < 0.01), but there were no significant differences between the transplant groups. Plasma TGF beta 1 level did not correlate with renal function (estimated by either serum creatinine or reciprocal creatinine), kidney donor age, recipient age, time since transplantation, or cyclosporine plasma trough level. TGF beta 1 was found in every urine sample tested from healthy controls, with a range from 1 ng/ml to 35 ng/ml. Among the 20 transplant patient urines tested, 2 were negative, 18 were positive but within the range determined for the healthy controls. There were no significant differences between the groups.

Acute Disease↗
PubMed1994

Comparative mortality from cardiovascular disease in patients with chronic renal failure.

Patients with chronic renal failure show an excess mortality from cardiovascular disease (CVD). Over a 4-year period (1983-1986) we have prospectively studied 305 patients (177 men, 128 women) from a geographically constrained population entering a renal replacement therapy (RRT) programme. The development of new cardiovascular events and patient survival have been documented up to the end of 1990. We have determined the incidence of CVD amongst the patients compared to the general population of the region and assessed the predictive value for future cardiovascular events of risk factors present at the start of RRT. One hundred and fourteen patients experienced a new cardiovascular event. One hundred and fifteen patients died, 89 from CVD. Stratification by age and sex identified diabetes, previous coronary heart disease, and cardiomegaly to be significantly associated with an increased risk of a cardiovascular event, and diabetes, previous coronary heart disease, and accelerated hypertension to be significantly associated with an increased risk of cardiovascular death. Mortality from CVD was 10.1 times that of the corresponding general population, and was increased 44 times for patients with diabetes. Duration of RRT did not influence mortality rates. This excessive early mortality has significant implications for RRT programmes and further research is necessary to identify individuals at risk and the modifiable risk factors that could receive targeted interventional therapy.

Adolescent↗
PubMed1993

Serum lipoprotein (a) concentrations in patients undergoing continuous ambulatory peritoneal dialysis.

Lipoprotein (a) is a subspecies of low-density lipoprotein which possesses as part of its protein moiety a mutant form of plasminogen termed apolipoprotein (a), and which may be closely related to the risk of ischaemic heart disease and cerebral infarction. We have investigated the serum concentrations of lipoprotein (a) and other lipoproteins in 24 male patients on CAPD and compared them to healthy men (n = 100) and to age-matched healthy controls (n = 38). The most striking finding was a substantial elevation of serum lipoprotein (a) in CAPD patients in whom it was 46.9 (2.2-168) mg/dl (median and range) compared to 9.0 (< 0.6-87.4) mg/dl in healthy control group and 6.7 (< 0.6-84.2) mg/dl in age-matched controls (both P < 0.001). Patients, when compared to healthy men, also had significantly increased serum triglycerides (median and range, 1.94 (0.55-8.00) versus 1.24 (0.36-4.40) mmol/l; P < 0.001), very-low-density lipoprotein cholesterol (median and range, 0.98 (0.10-3.71) versus 0.46 (0.10-1.17) mmol/l; P < 0.001), and lower-high-density lipoprotein cholesterol (mean +/- 1 SD, 1.26 +/- 0.29 versus 1.35 +/- 0.31 mmol/l). Of these, however, only the difference in very-low-density lipoprotein cholesterol remained statistically significant (P < 0.001) in comparison to age-matched controls. The marked elevation of serum lipoprotein (a) in patients on CAPD may be due to increased hepatic synthesis as a consequence of the substantial amounts of plasma proteins lost in the dialysate. Elevated serum lipoprotein (a) concentrations in CAPD patients may contribute to their risk of coronary artery disease.

Adult↗
PubMed1993

Serum and urine IL-6 and TNF-alpha in renal transplant recipients with graft dysfunction.

The object of the study presented here was to test whether measurement of blood or urine IL-6 or TNF-alpha could discriminate between the most common causes of renal allograft dysfunction, thus avoiding a biopsy. We present data here in which serum and urine IL-6 and TNF-alpha levels were measured at the same time as a diagnostic renal biopsy was performed. TNF-alpha and IL-6 were measured by sandwich ELISA. Thirty patients had acute cellular rejection, 18 had acute tubular necrosis/CsA toxicity, and 9 had chronic vascular rejection. There was no difference in the levels of IL-6 measured in serum and urine among the three categories of graft dysfunction (t < 1.31; P > 0.20). A similar result with considerable overlap between the groups was seen with TNF-alpha (t < 0.78; P > 0.44). Stratifying the results according to the precise immunosuppressive therapy, CsA dose, body weight, CsA level, body temperature, serum creatinine, the number of previous rejection episodes, original cause of renal failure, or the time elapsed since the transplant did not alter the results. The ratio of serum IL-6 divided by trough CsA level was compared among the three groups and there was no significant difference among them (t < 1.79; P > 0.09). In the light of our results, we therefore suggest that previously published reports of the clinical value of serum and or urine IL-6 and or TNF-alpha in relatively small numbers of patients, not all of whom had been biopsied and in whom rigorous clinical and statistical criteria had not been met, should be viewed with caution.

Antibodies, Monoclonal↗
PubMed1993

Serum lipoprotein (a) in renal transplant recipients receiving cyclosporin monotherapy.

Coronary heart disease is more common in patients with chronic renal failure and is a major cause of death after renal transplantation. Elevated serum lipoprotein (a) (Lp(a)) is a known risk factor for coronary heart disease in the general population. We measured the serum concentration of Lp(a) in 58 renal transplant recipients (40 male, 18 female) on cyclosporin monotherapy, and in 58 age- and sex-matched controls. Serum Lp(a) was significantly elevated in the transplant patients with a median of 27.5 (range < 0.8-140.3) mg/dl compared to 7.6 (range < 0.8-87.4) mg/dl in controls (P < 0.001). Total serum cholesterol, low-density lipoprotein cholesterol, and total triglyceride concentrations were also significantly raised (P < 0.001) in the transplant recipients. The increased serum Lp(a) may contribute to the increased cardiovascular morbidity associated with renal transplantation.

Adult↗
PubMed1993

The temporal relationship between urinary C5b-9 and C3dg and clinical parameters in human membranous nephropathy.

We have previously reported that urinary excretion of the complement activation products C3dg and C5b-9 in human membranous nephropathy (MN) correlated with clinical outcome in a cross-sectional analysis. We report here the results of a retrospective longitudinal study of the temporal relationship between urinary C3dg and C5b-9 excretion and clinical parameters. A group of 23 adult patients with biopsy-proven MN were studied over a mean time period per patient of 3.5 years. Freshly voided urine samples were collected regularly; C3dg and C5b-9 were measured by ELISA (mean number of samples per patient = 13). During the period of the study, nine patients with declining renal function (group A) were treated with a standard steroid regimen. Serum creatinine had improved or stabilized in seven of these patients at the end of treatment. All nine patients were excreting C3dg and C5b-9 before treatment. Six other patients with declining renal function (group B) were not treated with steroids because of clinical contraindications. Serum creatinine continued to increase during the study in four of these six patients. C3dg and C5b-9 were present in the urine samples of these six patients on the majority of dates tested. Eight patients maintained stable renal function during the study (group C), either normal (6 patients) or impaired (2 patients). Of these patients, six were consistently negative for urinary C3dg and C5b-9 despite persistent proteinuria, and one patient who was initially positive became negative within 15 months, and remained negative for the rest of the study period. One patient was positive on one of 12 occasions tested. These results suggest that urinary complement activation products indicate ongoing active glomerular damage and may prove to be important determinants for the introduction and monitoring of therapy.

Complement Activation↗
PubMed1992

Urinary C3dg and C5b-9 indicate active immune disease in human membranous nephropathy.

We have measured complement activation markers, C3dg and C5b-9 in plasma and urine from patients with idiopathic membranous nephropathy and IgA nephropathy. There was no significant difference in levels of plasma C5b-9 between the patient groups. However, high plasma concentrations of C3dg were associated significantly with IgA nephropathy with 45% of patients having levels over 25 U/ml (P less than 0.001). High concentrations of urinary C3dg and C5b-9 were associated significantly with membranous nephropathy (43% and 43% of the patient group, respectively) compared to patients with IgA nephropathy (10% and 0%, respectively, P less than 0.001). In a retrospective analysis of 31 patients with membranous nephropathy, 66% of patients with high initial urinary C5b-9 showed an unstable clinical course compared to 18% of patients with initially absent or low C5b-9 (P less than 0.001). We suggest that high urinary C5b-9 identifies those patients with a membranous lesion which retains an active immunological component contributing to the pathology of progressive glomerular damage.

Adult↗
PubMed1992

Serum lipoprotein (a) in men with proteinuria due to idiopathic membranous nephropathy.

Patients with heavy proteinuria have an increased incidence of venous thrombosis and coronary heart disease (CHD). They also exhibit perturbations in lipoprotein metabolism. Lipoprotein (a) (Lp(a)) predisposes to CHD; it may also promote intravascular thrombosis since it contains apolipoprotein (a), which could act as a competitive inhibitor of plasminogen activation. We have measured the concentration of serum Lp(a) in 10 men with proteinuria due to idiopathic membranous nephropathy (IMN), in eight men with a similar diagnosis but who were in remission, and in 103 healthy men. Serum Lp(a) levels were significantly elevated in the men with active IMN, having a median value of 31.3 (range 3.2-75.0) mg/dl, whereas they were 8.4 (3.4-31.5) mg/dl in the patients in remission, which was similar to the value of 11.3 (< 0.8-87.4) mg/dl found in the healthy controls. Lp(a) is unique in containing an apolipoprotein which is a giant mutant of plasminogen and it is thus possible that the high circulating levels of Lp(a) contribute to the vascular morbidity associated with proteinuria by promoting thrombosis or atherogenesis or both.

Adult↗
PubMed1989

Fundus changes in mesangiocapillary glomerulonephritis type II: clinical and fluorescein angiographic findings.

Previously we have demonstrated a deposit in Bruch's membrane in a single case of mesangiocapillary glomerulonephritis type II. We studied a group of patients with this disease and described extensive clinical and fluorescein angiographic abnormalities, which were in marked contrast to the findings in a group of patients with other forms of glomerulonephritis. This finding contributes to our understanding of the pathophysiology of the complex of the retinal pigment epithelium, Bruch's membrane, and choriocapillaris.

Adult↗