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Biomedical subjects

C A Pollock

Publications and source records attributed to C A Pollock.

At least 19 recordsLinked to original sources

Tubular sodium handling and tubuloglomerular feedback in compensatory renal hypertrophy.

Tubular sodium handling and tubuloglomerular feedback (TGF) activity were assessed in established compensatory renal hypertrophy in Sprague Dawley rats. Hyperfiltration at the level of the single nephron was confirmed 4-6 weeks following a reduction in renal mass. TGF activity, determined as the difference between late proximal and early distal measurements of single-nephron glomerular filtration rate (SNGFR), was significantly increased in compensatory renal hypertrophy, being 7.8 +/- 1.0 vs 23.3 +/- 1.9 vs 25.5 +/- 2.6 nl/min (P for analysis of variance less than 0.05) following sham operation, unilateral nephrectomy, and 1 1/3 nephrectomy, respectively. Enhanced net tubular Na transport was also observed, with total Na reabsorption up to the late proximal site being 1.8 +/- 0.2 vs 2.7 +/- 0.1 vs 3.1 +/- 0.3 nmol/min (P less than 0.05), and to the early distal site being 3.4 +/- 0.5 vs 5.8 +/- 0.6 vs 7.9 +/- 0.8 nmol/min (P less than 0.05) in the three animal groups respectively. Comparison of proximal tubular length demonstrated a 71.9 +/- 8.1% increase in uninephrectomised vs sham-operated animals. This increase was proportionately greater than the increase in proximal Na reabsorption (50.0 +/- 4.0%) observed in the corresponding animal groups. Concurrent electron microprobe experiments in uninephrectomised and sham-operated animals demonstrated that the proximal tubular intracellular Na concentration was significantly lower following uninephrectomy (16.8 +/- 0.6 vs 18.9 +/- 0.5 mmol/kg wet weight, P less than 0.01), in association with evidence of reduced basolateral Na/K-ATPase activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Evidence for activation of tubuloglomerular feedback following nephrectomy in human subjects.

The intrarenal regulation of glomerular filtration rate (GFR) following a reduction in renal mass was evaluated in six normal subjects, studied before and 4 to 6 weeks after undergoing unilateral nephrectomy, performed for the purpose of living-related transplantation. The role of the tubuloglomerular feedback (TGF) system in regulating the final GFR on both occasions was assessed by determining the increase in GFR over baseline levels following blockade of TGF by a single dose of bumetanide, care being taken to replace sodium and water losses. Before donor nephrectomy, baseline GFR was 115 +/- 7 mL/min, which increased by 9.5% +/- 2.5% to 126 +/- 9 mL/min following the removal of TGF. Four to six weeks following donor nephrectomy, the baseline GFR was 83 +/- 8 mL/min, confirming significant hyperfiltration in the remaining kidney. After administration of bumetanide, the GFR increased by 15.6% +/- 3.1% to 96 +/- 9 mL/min. This greater fractional increase (P < 0.025) indicates an increase in tonic TGF activity in the uninephrectomized state compared with that demonstrated before nephrectomy. The results suggest that the hyperfiltration response following unilateral nephrectomy is limited by an appropriately activated TGF system. This phenomenon may be of importance in the maintenance of Na and water homeostasis, as well as limiting the pathological consequences that may result from, or be exacerbated by, an excessively high filtration rate in the remaining nephrons. Thus, dietary or therapeutic maneuvers that impair the TGF response may be best avoided following a reduction in renal mass.

Adult

Renal handling of endogenous lithium in experimental diabetes mellitus in the rat.

1. The usefulness of determining the renal handling of endogenous lithium as a marker of proximal tubular sodium reabsorption was assessed in streptozotocin induced diabetes mellitus in the Sprague-Dawley rat. 2. The clearance and fractional excretion of lithium were determined before and following the development of diabetes mellitus, and compared with measurements of proximal tubular reabsorption made directly using micropuncture techniques. Endogenous lithium was measured in order to avoid the toxic tubular effects of exogenously administered lithium salts. 3. Although a trend existed for a reduction in the fractional excretion of lithium in diabetic animals (1.8 +/- 0.3 vs 2.4 +/- 0.5%; P greater than 0.20), this did not reach statistical significance and did not accurately reflect the change in directly measured tubular Na reabsorption. 4. The decrease in proximal tubular Na reabsorption demonstrated in diabetic animals treated with phlorizin was not significantly reflected in the fractional lithium excretion, although again a corresponding trend was evident (1.9 +/- 0.8 vs 0.6 +/- 0.2%; P greater than 0.10. 5. In summary, the significant alterations in tubular Na handling in diabetes mellitus, previously demonstrated directly using micropuncture techniques, are not reflected in the renal handling of endogenous lithium. This indirect method is inadequate to assess proximal tubular Na transport in experimental diabetes mellitus.

Animals

Proximal tubular cell sodium concentration in early diabetic nephropathy assessed by electron microprobe analysis.

Electron microprobe X-ray analysis techniques were employed in order to assess the changes that occur in proximal tubular cell sodium concentration during the hyperfiltration phase of early diabetes mellitus induced by streptozotocin in Sprague Dawley rats. Intracellular rubidium accumulation following intravenous infusion of rubidium chloride was used as a marker of basolateral Na/K-ATPase activity. The diabetic animals studied had a significantly higher glomerular filtration rate compared with controls [1.44 +/- 0.07 vs. 1.00 +/- 0.07 ml min-1 (100 g body weight)-1; mean +/- SEM, P less than 0.001]. Intracellular Na concentration was significantly higher in diabetic animals (19.5 +/- 0.6 vs. 17.8 +/- 0.4 mmol/kg wet weight; P less than 0.01). Concurrent measurement of Rb demonstrated significantly higher intracellular accumulation in the proximal tubules of diabetic animals compared with control (7.9 +/- 0.5 vs. 5.5 +/- 0.5 mmol/kg wet weight; P less than 0.001). These results indicate that proximal tubular Na/K-ATPase activity is enhanced in the hyperfiltration phase of diabetes mellitus. Since, however, intracellular Na concentration is increased under these conditions, it may be inferred that apical Na entry into proximal tubular cells is stimulated beyond the rate of basal exit during the initial development of hyperfiltration. The reasons for these alterations in cellular Na transport are unclear but similar changes have been implicated in the pathogenesis of cell growth.

Animals

Tubular sodium handling and tubuloglomerular feedback in experimental diabetes mellitus.

Tubular Na handling and tubuloglomerular feedback (TGF) activity were assessed using micropuncture techniques during the hyperfiltration phase of streptozotocin-induced diabetes mellitus in Sprague-Dawley rats. Three animal groups were studied, designated as having severe diabetes [blood sugar level (BSL) 18-25 mmol/l], moderate diabetes (BSL 13-18 mmol/l) and control (BSL less than 10 mmol/l). Single-nephron glomerular filtration rate (SNGFR) measured at both late proximal (LP) and early distal (ED) sites was elevated in severe diabetes compared with both other groups. TGF activity, determined as the difference between LP and ED measurements of SNGFR, was significantly increased in severe diabetes (46.4 +/- 6.6 vs. 30.1 +/- 6.5 vs. 14.8 +/- 1.9 nl/min). Tubular Na transport was higher in severe diabetes compared with control, as demonstrated by a decrease in fractional delivery of Na to the LP (42.9 +/- 3.0 vs. 52.9 +/- 1.9%), as well as to the ED site (4.5 +/- 0.4 vs. 12.3 +/- 0.9%). Administration of phlorizin to severely diabetic animals resulted in a BSL comparable to that observed in moderate diabetes, and whole animal GFR, as well as SNGFR, TGF activity, and tubular Na handling were also similar to those found in moderate diabetes. Studies performed during mannitol infusion demonstrated that osmotic diuresis alone was not associated with the changes in TGF and tubular Na handling observed in the diabetic state. These data suggest that the hyperfiltration occurring in early diabetes is associated with enhanced proximal and loop resorption of Na independent of Na-glucose cotransport and osmotic diuresis. Activation of TGF serves to limit the rise in GFR, which results from factors as yet unrecognized in the diabetic state.

Animals

Total-body nitrogen by neutron activation in maintenance dialysis.

The nutritional status of 35 patients on continuous ambulatory peritoneal dialysis (CAPD) was assessed by the traditional methods of dietary history and anthropometric measurements, and was compared with simultaneous measurements of dietary protein intake (DPI) calculated from urea generation rate and total-body nitrogen (TBN) assessment by prompt neutron activation analysis (PNAA). DPI as determined by dietary recall was significantly higher than calculated DPI (1.04 +/- 0.42 v 0.84 +/- 0.28 g/kg/d; P less than 0.001). Anthropometric measurements did not differ significantly from the predicted normal values for sex, height, and age. However, PNAA measurements of TBN demonstrated significant nitrogen depletion, being 88.2% of normal for males (P less than 0.001) and 87.5% of normal for females (P less than 0.002); TBN correlated significantly with DPI calculated from urea generation rate (P less than 0.05). Assessment of these 35 patients 17.5 +/- 4.4 months later, demonstrated that patients who died or suffered serious morbidity requiring transfer from CAPD (n = 10) had significantly lower TBN than those who remained on CAPD or underwent successful renal transplantation (n = 25): 80.0% v 93.2% of normal (P less than 0.01). No difference in anthropometric measurements was observed between the two groups of patients. Eleven patients on maintenance home or satellite hemodialysis underwent identical dietary, anthropometric, and TBN assessments and results were similar to those obtained in the CAPD population, although no correlation with calculated DPI and TBN was observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Absorption

Hypertension due to renal artery stenosis in pregnancy--the use of angioplasty.

The use of transluminal percutaneous renal angioplasty for severe hypertension in the second trimester of pregnancy has not previously been reported. We describe its use in a 19-year-old female. The procedure resulted in a significant improvement in blood pressure control and allowed the pregnancy to proceed to term, resulting in the delivery of a normal female baby on the 90th percentile for weight. No morbidity to mother or fetus was observed as a result of diagnostic or therapeutic procedures. We conclude that pregnancy should not preclude making the diagnosis of renovascular hypertension as angioplasty may be a useful therapeutic option.

Adult

Afferent arteriolar C3 disease--a distinct pathological entity.

Afferent arteriolar C3 deposition was the sole histological abnormality in 79 and the major histological abnormality in an additional 39 of 959 renal biopsies performed over a 10-year period. Of these 79 patients, hematuria was the presenting symptom in 90%, with coincident loin pain in 49%. Urine microscopy of asymptomatic first-degree relatives revealed hematuria in 44% of children and siblings and 54% of parents, suggesting autosomal dominant inheritance. Arteriolar C3 deposition was confirmed by biopsy in four asymptomatic relatives with hematuria. Generalized thinning of glomerular basement membrane (less than 200 nm) was observed in five patients and focal thinning was observed in six patients with coincident afferent arteriolar C3 deposition. Seven other patients were identified as having generalized thinning of glomerular basement membrane in the absence of afferent arteriolar C3 deposition. Renal function was stable and similar in all groups studied over 37.9 +/- 23.7 months. No difference in clinical presentation or urinary abnormalities was evident between the groups. No arteriolar C3 deposition was evident in eight autopsy specimens with no known renal disease. It was concluded that afferent arteriolar C3 deposition is a marker of a distinct hereditary pathological entity, with differentiation from thin basement membrane disease not possible on clinical grounds. The medium- and long-term prognoses with respect to renal function are excellent.

Adolescent

Continuous ambulatory peritoneal dialysis. Eight years of experience at a single center.

One hundred and thirty-four patients using continuous ambulatory peritoneal dialysis (CAPD) for a mean time of 23.1 +/- 18.3 months (range, 1-76.6) from a single center are reviewed with respect to biochemistry, hematology, parameters of dialysis efficiency, nutrition, and the nature and frequency of complications. Cumulative patient survival was 90%, 86% and 75% at 1, 2 and 3 years, and survival of patients using this technique was 75%, 62% and 40% at corresponding time intervals with no difference demonstrated in diabetic patients or in those older than 50 years. Biochemical and hematologic parameters were well maintained with peritoneal creatinine clearance increasing and peritoneal protein loss remaining stable with ongoing CAPD. Loss of ultrafiltration, however, accounted for 17.7% of permanent transfers to alternative therapy. Low serum albumin and elevated serum triglyceride concentrations correlated with mortality, whereas low serum albumin, low cholesterol, and high phosphate levels correlated with morbidity as assessed by frequency of hospital admissions. Dietary protein intake assessed by urea generation rate was significantly lower than that estimated from a 24-hour dietary recall (0.82 vs. 1.02 g/kg/day, p less than 0.01) and with the exception of body mass index and serum albumin, anthropometric and visceral protein measurements showed few correlations with nutritional adequacy. Bacterial peritonitis remained the major complication, although fungal infections made a significant contribution to morbidity and mortality. Overall, CAPD is confirmed to be a satisfactory form of dialysis for all forms of end-stage renal failure and an integral part of any renal replacement program. However, nutritional adequacy and lowering of complication rates require further investigation.

Adolescent

Immunoglobulin abnormalities in renal transplant recipients.

Five renal transplant recipients were observed to have recurrent infections in association with low serum immunoglobulin levels. They have benefited from parenteral gamma globulin therapy. Following this observation, 110 renal transplant recipients were assessed; 46% had abnormal serum immunoglobulins with 4 patients identified as having monoclonal gammopathies, 8 polyclonal gammopathies, and 39 low levels of 1 or more immunoglobulins. Those with abnormal serum immunoglobulins had been immunosuppressed longer, but maintenance immunosuppression dosage was not different from those with normal immunoglobulins. Respiratory tract infection and skin cancer were more frequent in those with low immunoglobulin levels.

Adolescent

Peritoneal morphology on maintenance dialysis.

Thirty-eight peritoneal biopsies from 37 patients with normal renal function or with end-stage renal failure without replacement therapy or utilizing continuous ambulatory peritoneal dialysis (CAPD), haemodialysis (HD) or a functioning transplant were examined histologically. No abnormality in peritoneal membrane morphology was observed in uraemia in the absence of dialysis. Significant abnormalities of peritoneal membrane morphology were observed in association with CAPD, the predominant finding being the development of peritoneal fibrosis which had a deleterious effect on membrane function. Abnormal peritoneal morphology was less commonly observed in patients on maintenance HD and with functioning transplants but may have implications regarding the future use of CAPD in these patients.

Adult

Generalized lymphadenopathy in continuous ambulatory peritoneal dialysis patients associated with Staphylococcus epidermidis infection.

In patients utilizing continuous ambulatory peritoneal dialysis (CAPD), Staphylococcus epidermidis is the most prevalent organism isolated from peritoneal and exit site infections [1] although clinically significant systemic infection is unusual. We report 2 patients undergoing CAPD who developed generalized lymphadenopathy following peritonitis and exit site infection with S. epidermidis isolated from the excised lymph nodes. We conclude that catheter-related S. epidermidis infection may result in generalized lymphadenopathy due to dissemination of the infective focus.

Adult

Beta-2 microglobulin removal during continuous ambulatory peritoneal dialysis (CAPD).

Beta-2 microglobulin (B2M) handling in continuous ambulatory peritoneal dialysis (CAPD) was characterized in acute and chronic clinical studies. Average clearance rate was 0.7 mL/min and mean mass transfer coefficient, KoA, was calculated to be 0.95 cm2/min; these values are in the range expected from extrapolation of published data for other large solutes. In chronic studies with both anuric and oliguric populations, CAPD was shown to be much more effective than conventional hemodialysis in removing B2M and, in fact, CAPD removal rates were equivalent to those reported for high flux dialysis therapies. However, this greater extraction was not associated with any clinically significant reduction in circulating plasma concentrations. These trends remained valid in both the anuric and oliguric subsets of the study population.

Dialysis Solutions

Loss of ultrafiltration in continuous ambulatory peritoneal dialysis (CAPD).

Fifteen patients on long-term continuous ambulatory peritoneal dialysis (CAPD) were assessed with respect to net ultrafiltration capacity. Eight patients were defined as having good and seven as having poor ultrafiltration on the basis of net ultrafiltrate obtained/mmol glucose infused. Subsequently, dialysate was sampled at times 0, 1, 15, 30, 60, 90, 120, 180, and 240 min. No difference in residual volume was observed between the groups. A significantly greater decrease in dialysate sodium during the initial dialysis period in those patients with good as compared to those with poor ultrafiltration occurred, reflecting a greater transcapillary movement of electrolyte poor ultrafiltrate. In those with good ultrafiltration, glucose transfer was normal in five and rapid in three, suggesting the latter had low rates of lymphatic reabsorption. Five of seven patients with poor ultrafiltration had no fall in dialysate sodium in association with a high rate of glucose transfer, suggesting a low rate of transcapillary water movement and normal to high lymphatic absorption. Two patients with low ultrafiltration had an initial fall in dialysate sodium with a normal glucose transfer and thus net ultrafiltration is low due to elevated lymphatic reabsorption. We thus propose that the relative contribution of transcapillary water movement and lymphatic reabsorption can be determined by assessing net ultrafiltration and dialysate sodium concentration in conjunction with solute transfer.

Biological Transport

Lead intoxication in Sydney Harbour Bridge workers.

Thirty-eight Sydney Harbour Bridge workers were assessed for possible lead intoxication. Forty-seven per cent were found to have significant lead intoxication as assessed by calcium disodium edetate chelation (Ca EDTA) testing and were subsequently effectively and safely treated with Ca EDTA. The prevalence of neurological, constitutional, gastrointestinal and musculoskeletal symptoms was significantly greater in those with, than those without, lead toxicity. Although blood lead levels and, to a lesser extent, hematological parameters were of some use in diagnosis, they were not sufficiently sensitive and thus should not be used in screening workers at risk of lead intoxication. Ca EDTA testing remains the diagnostic method of choice. Patients exposed to lead dust and fumes, in whom symptoms of lead intoxication are present, should undergo such testing and if a positive result is obtained, then EDTA chelation therapy should be instituted.

Adult