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J F Medcalf

Publications and source records attributed to J F Medcalf.

7 recordsLinked to original sources

Role of diuretics in the preservation of residual renal function in patients on continuous ambulatory peritoneal dialysis.

BACKGROUND: Patients on continuous ambulatory peritoneal dialysis (CAPD) are dependent on residual renal function for solute and water clearances, and this declines with time on dialysis. Loop diuretics have been postulated to slow this decline. METHODS: Sixty-one patients new to dialysis were randomly assigned to either furosemide 250 mg every day or no furosemide at the time of CAPD training and were followed prospectively. Urine volume (UV), urea clearance (C(Urea)), and creatinine clearance on cimetidine (C(Cr)) were measured at randomization at six months and at one year. Patients underwent a standard four-hour peritoneum equilibrium test, and total body water was measured by bioelectrical impedance. Results were expressed on an intention-to-treat basis. RESULTS: UV, C(Cr), and C(Urea) were similar at randomization (1020 +/- 104 vs. 1040 +/- 130 mL/24 hours, 4.95 +/- 0.51 vs. 4.07 +/- 0.40 mL/min/1.73 m2, 0.91 +/- 0.09 vs. 0.84 +/- 0.08, diuretic vs. control). UV in the diuretic-treated group increased, whereas in the control group, it declined (+176 vs. -200 mL/24 hours at 6 months and +48.8 vs. -305 mL/24 hours at 1 year, P < 0.05). C(Cr) and C(Urea) declined at a constant rate and were unaffected by diuretic administration (0.12 +/- 0.05 vs. 0.071 +/- 0.04 mL/min/1.73 m2/month, 0.020 +/- 0.01 vs. 0.019 +/- 0.01 per month). Urinary sodium excretion increased in the diuretic group and declined in the control group (+0.72 +/- 0.85 vs. -2.56 +/- 1.31 mmol/24 hours/month, P = 0.04). Body weight rose in both groups (4.3 vs. 3.0 kg), but the percentage of total body weight rose in the control group and remained constant in the diuretic group (52 +/- 2.4 vs. 64 +/- 6.6%, P = 0.10). CONCLUSIONS: Long-term furosemide produces a significant increase in UV over 12 months when on CAPD and may result in clinically significant improvement in fluid balance. However, furosemide has no effect on preserving residual renal function.

Adult↗

Effects of glucose dialysate on extracellular matrix production by human peritoneal mesothelial cells (HPMC): the role of TGF-beta.

BACKGROUND: Dialysate glucose has been implicated in the loss of peritoneal membrane function seen in long-term CAPD patients. METHODS: In order to investigate this in vitro, human peritoneal mesothelial cells (HPMC) were cultured in a 50:50 mix of dialysis solution and M199 for 12 h. The dialysate was laboratory manufactured and designed to be identical in composition to PD4 (LAB). The final glucose concentration ranged between 5 and 40 mmol/l. Experiments were conducted in the presence and absence of an anti-transforming growth factor-beta (TGF-beta) antibody. Cell viability was measured by lactate dehydrogenase (LDH) release. Fibronectin (FN) and TGF-beta protein were measured by ELISA, and FN gene expression was measured by Northern analysis. Separately, the effects of recombinant TGF-beta(1) added to M199: dialysate at 5 mmol/l glucose were investigated. RESULTS: Forty millimoles per litre d-glucose LAB caused a decrease in cell viability, as evidenced by an increase in LDH release (6.0+/-1.3 vs 2.6+/-0.7%). This effect was dependent on osmolality. Forty millimoles per litre d-glucose LAB stimulated a 15.4+/-4.6% increase in FN, a 46.5+/-18.3% increase in TGF-beta protein (both P<0.05), and 1.4+/-0.09-fold increase in FN mRNA compared with 5 mmol/l d-glucose LAB. Exogenous TGF-beta 0-1 ng/ml induced a dose-dependent increase in FN protein (280+/-45% increase at TGF-beta 1 ng/ml, P<0.0001), and FN mRNA levels (10.0+/-1.8-fold at TGF-beta 1 ng/ml). The increase in FN in response to 40 mmol/l glucose was significantly reduced by anti-TGF-beta antibody to levels not different from control (93.8+/-6.6%, P<0.05 vs no Ab). CONCLUSIONS: These data suggest that the pro-fibrotic effect of glucose dialysate on HPMC is mediated through stimulation of TGF-beta, which promotes FN gene expression and protein production.

Antibodies↗

Haemodynamic responses to nonhypotensive central hypovolaemia induced by lower body negative pressure in men and women.

Haemodynamic responses to low levels of lower body negative pressure (LBNP) were investigated in two groups of healthy, normotensive volunteers (8 men and 8 women) during two repeated experimental runs on two occasions, the latter determined by the different phases of the menstrual cycle in the women. The data consisted of systolic blood pressure (SBP), diastolic blood pressure (DBP) and mean blood pressure (MBP), pulse rate (fc), forearm blood flow (FBF) and forearm vascular conductance (FC). The resting cardiovascular status was similar in men and women, except that women had a significantly higher fc than men. LBNP (1.3, 2.7 and 4 kPa) had no significant effect on any BP variable or on fc. However, FBF and FC were reduced at all levels of LBNP. Significant overshoots in FBF and FC were seen in all subjects following the release of LBNP of 2.7 and 4 kPa and, in most cases, after release of LBNP of 1.3 kPa. There were no significant gender differences in any of the responses to LBNP. Furthermore, none of the cardiovascular variables measured showed significant differences between the follicular and luteal phases of the menstrual cycle in women, either at rest or during exposure to LBNP, and the responses in the men on the two occasions were not different. These findings indicate that gender differences in responses to LBNP hypothesized previously are not apparent during and after exposure to low levels of LBNP.

Adult↗