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Biomedical subjects

J G Heaf

Publications and source records attributed to J G Heaf.

At least 19 recordsLinked to original sources
PubMed1995

Consistent absorption of cyclosporine from a microemulsion formulation assessed in stable renal transplant recipients over a one-year study period.

To evaluate the pharmacokinetic properties of the new microemulsion formulation of cyclosporine (Sandimmun Neoral), a double-blind, prospective study in stable renal transplant recipients was performed. The patients were randomized on a 4:1 basis either to receive Sandimmun Neoral (n = 45) or continue on regular Sandimmun (n = 12). Before randomization, a steady-state pharmacokinetic profile study was performed in all patients while they were still on regular Sandimmun. Pharmacokinetic assessments were then performed after 8 and 12 weeks and after 1 year. A milligram-to-milligram dose conversion was shown to be adequate to maintain the patients within a predefined target therapeutic window. Changes in pharmacokinetic parameters after conversion to Sandimmun Neoral were consistent with an increased rate and extent of cyclosporine absorption from the Neoral formulation. This was reflected by a shorter time to reach peak concentration and also by a mean increase in peak concentration by 67%, and an overall mean increase in drug exposure (area under the curve) by 34%. These findings were also confirmed 1 year after conversion. Furthermore, significantly reduced intraindividual variability in pharmacokinetic parameters was found, as well as improvements in the correlation between trough concentrations and area under the curve after conversion to Sandimmun Neoral. In conclusion, our results indicate an improved and consistent absorption of cyclosporine from the Neoral formulation, which should make clinical management easier and safer.

Absorption↗
PubMed1994

Osteocalcin: a non-invasive index of metabolic bone disease in patients treated by CAPD.

Serum osteocalcin has been found to correlate with bone formation. However, present literature gives only limited data on osteocalcin and bone histomorphometry in patients undergoing peritoneal dialysis. This study assessed serum osteocalcin, dialysate osteocalcin, peritoneal clearance of osteocalcin (Clp-osteocalcin) and mass transfer of osteocalcin (MTp-osteocalcin), and evaluated relationships between these values and bone histomorphometry. Eighteen patients were treated by continuous ambulatory peritoneal dialysis (CAPD). Bone biopsies, serum and dialysate osteocalcin, serum levels of parathyroid hormone, alkaline phosphatase, aluminum, phosphate, Ca2+ and vitamin D3 metabolites were measured at the start and in 10 of the patients a year later. Serum osteocalcin was found to be elevated. Osteocalcin was detected in the dialysate resulting in significant values of Clp-osteocalcin and MTp-osteocalcin. Serum and dialysate levels of osteocalcin correlated significantly (r = 0.66, P < 0.001) and like MTp-osteocalcin with serum levels of alkaline phosphatase and PTH. Histomorphometry showed that osteitis fibrosa was the predominant bone disease detected. Serum concentration of osteocalcin correlated with osteoid thickness, eroded and osteoclast surfaces, aluminum staining, and some of the bone dynamic parameters. Dialysate osteocalcin, MTp-osteocalcin, PTH and alkaline phosphatase correlated with practically the same histomorphometric parameters as serum osteocalcin. No correlations were seen between Clp-osteocalcin and any histomorphometric parameters. Serum osteocalcin was elevated above the normal range, and significant positive correlations between serum osteocalcin and bone formation parameters were found. Serum osteocalcin correlated with almost the same histomorphometric parameters as PTH. Thus, serum levels of PTH and osteocalcin gave additional information to one another as non-invasive parameters in this group of patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

[Analysis of phenprocoumon dose regulation based on measurement of coagulation factors II, VII and X].

One hundred anticoagulation treatment records were reviewed retrospectively using stepwise regression analysis to determine the influence of phenprocoumaron on the levels of coagulation factors 2, 7 and 10 (KF) measured relative to normal. The phenprocoumaron dose was expressed relative to the correct maintenance dose determined from the entire record ("overdose", OD measured in mg). Phenprocoumaron treatment influenced the KF over two days, approximately 50% on each day, the total change being -0.03 x OD. Continuous incorrect dosage resulted in KF change, equilibrating at a new level after about four weeks at -0.47 x OD. Similarly, continuous correct dosage in patients with a non-therapeutic FK resulted in equilibration within the therapeutic range after four weeks. For long-term treatment, the dosage was likely to be inaccurate under the following circumstances: 1) if the KF was outside the therapeutic range and moving away from it; 2) if the KF was inside the therapeutic range and the change was greater than 0.05. Algorithms for calculation of phenprocoumaron therapy are presented.

Adolescent↗
PubMed1992

Bisphosphonate kinetics in patients undergoing continuous ambulatory peritoneal dialysis: relations to dynamic bone histomorphometry, osteocalcin and parathyroid hormone.

In the evaluation of renal osteodystrophy bone biopsy is often performed. However, a reliable noninvasive test could be very useful, and recently the estimation of osseous tracer uptake as an index of bone formation has been introduced-the bone bisphosphonate clearance (BBC). The aim of the present investigation therefore was to compare BBC with parameters of bone histology, serum levels of osteocalcin, alkaline phosphatase, and parathyroid hormone in patients (n = 8) undergoing continuous ambulatory peritoneal dialysis (CAPD). No significant correlations were found between BBC values and the bone histomorphometrical variables measured. A positive correlation was seen between serum osteocalcin and resorption and active resorption surface (p < 0.05), as well as tetracycline-labelled surface, bone formation rate, surfaces, volume and tissue referents, respectively (p < 0.01). Furthermore, levels of alkaline phosphatase showed significant correlations to mineral appositional rate, tetracycline-labelled surface and bone formation rate, volume referent (p < 0.05). Values of parathyroid hormone were significantly correlated to resorption surface (p < 0.02), active resorption surface, mineral appositional rate and mineralization lag time (p < 0.05). In conclusion, BBC was of no use in patients treated with CAPD as a noninvasive test for evaluation of bone histomorphometry. However, osteocalcin correlated best with resorption and bone dynamics indices. Levels of alkaline phosphatase and parathyroid hormone were of a more limited value.

Adult↗
PubMed1991

[Hyperlipidemia in nephrotic syndrome].

Hyperlipidemia is common in patients with the nephrotic syndrome. The main cause is probably increased hepatic lipogenesis, a non-specific reaction to falling oncotic pressure secondary to hypoalbuminemia. Cardiovascular morbidity and mortality are increased in patients with the nephrotic syndrome, with the exception of patients with minimal change disease. It is not clear whether this is caused by the hypercholesterolemia or secondary to uremia or medical treatment. Experiments suggest that hypercholesterolemia may cause glomerulosclerosis, a common complication of the nephrotic syndrome. The hypercholesterolemia of the nephrotic syndrome can now be treated effectively with HMG coenzyme A reductase inhibitors.

Cardiovascular Diseases↗
PubMed1989

Vitamin D and vitamin-D-binding protein kinetics in patients treated with continuous ambulatory peritoneal dialysis (CAPD).

Serum and dialysate levels of 25-hydroxycholecalciferol (25-OHD3), 1,25 dihydroxycholecalciferol (1,25-(OH)2D3), and vitamin-D-binding protein (DBP) were measured in 14 patients undergoing continuous ambulatory peritoneal dialysis (CAPD). Serum levels of 25-OHD3 and DBP were within normal range (29.1 +/- 22.9 nmol/L and 5.9 +/- 1.1 mumol/L, respectively). Serum levels of 1,25-(OH)2D3 were subnormal in all (less than 16 pmol/L) but one. In 5 patients, dialysate concentrations of 25-OHD3 were 2.3 +/- 0.9 nmol/L, the rest had levels less than 1.0 nmol/L. Small quantities of 1,25-(OH)2D3 were found in the dialysate effluents. DBP could be detected in the dialysate in all patients (0.24 +/- 0.06 mumol/L). Mass transfer (MT) of 25-OHD3 and DBP were respectively -10.4 +/- 8.3 nmol/24 h and -1.46 +/- 0.46 0.46 mumol/24 h. Peritoneal clearances of 25-OHD3 and DBP were low (0.40 +/- 0.37 mL/min and 0.18 +/- 0.06 mL/min, respectively. We conclude that CAPD leads to losses of 25-OHD3 and DBP. However, the peritoneal loss of DBP is well compensated and does not result in serum deficiency. Serum 25-OHD3 levels did not correlate with time on CAPD.

Calcifediol↗
PubMed1989

Bone histology in CAPD patients: a comparison with hemodialysis and conservatively treated chronic uremics.

Thirteen patients treated with CAPD, 22 patients maintained on hemodialysis (HD) using aluminium-free water and matched for duration of treatment and 15 conservatively treated uremic patients (CONS) were evaluated by iliac bone biopsy to analyse the influence of CAPD on bone histomorphometry. CAPD patients were significantly (p less than 0.05) older (63.1 +/- 14.0, HD 52.7 +/- 13.3, CONS 53.3 +/- 11.7). Compared to HD the results were as follows: CAPD patients required significantly less aluminium to control hyperphosphatemia (0.16 vs. 0.49 g, p less than 0.005). They had a significantly lower incidence of symptomatic bone disease (p less than 0.05). Histomorphometry showed significantly lower osteoid volume (4.3 + 2.8% vs. 8.6 + 5.5%, p less than 0.05) and aluminium labelling intensity (0.15 vs. 1.0, p less than 0.05). Apart from bone mass indices, other histomorphometric variables showed an insignificantly more favourable trend in CAPD patients compared to HD. CONS patients had a significantly lower bone formation rate than CAPD (p less than 0.05), but otherwise no histomorphometric differences were observed. We conclude that CAPD patients require less aluminium therapy, have a lower risk of aluminium bone contamination, and may have a lower risk of developing uremic osteodystrophy.

Aluminum↗
PubMed1989

Aluminum concentrations in serum, dialysate, urine and bone among patients undergoing continuous ambulatory peritoneal dialysis (CAPD).

Aluminum (Al) concentration in serum, urine, and dialysate was estimated in 21 patients undergoing continuous ambulatory peritoneal dialysis (CAPD). In 12 of the patients bone Al concentration was measured as well. Mean serum Al level was 32.4 +/- 21.0 micrograms/l. The Al concentrations in the dialysate and urine were 9.1 +/- 4.1 micrograms/l and 52.5 +/- 47.3 micrograms/l, respectively. Bone Al concentration was 21.0 +/- 14.9 ppm and correlated significantly with concentrations of Al in serum (p less than 0.01) and dialysate (p less than 0.01). A mass transfer (MT) from the patients to the dialysate was observed in all patients (-44.0 +/- 28.8 micrograms/24 h). There was a highly significant correlation between peritoneal Al MT and serum Al (p less than 0.001), actual Al consumption (p less than 0.05) and bone Al concentration (p less than 0.005) supporting the existence of an overflow phenomenon. Despite very low Al levels in the dialysate, patients are at risk of elevated Al levels in the serum, dialysate, urine and bone because of consumption of Al-containing phosphate binders.

Adult↗
PubMed1988

Treatment of refractory cancer-associated hypercalcemia with aminohydroxypropylidene diphosphonate.

The case history is presented of a 45-year-old woman who was receiving chemotherapy for a pulmonary adenocarcinoma and who developed severe symptomatic hypercalcemia. Despite intensive treatment with fluids, loop diuretics, prednisone, calcitonin and repeated doses of mithramycin, she remained hypercalcemic. She was then treated with aminohydroxypropylidene diphosphonate (APD) with consequent rapid normalization of the serum calcium and disappearance of symptoms. We conclude that APD is a valuable supplement to the treatment of malignant hypercalcemia in that it may be effective when traditional therapies have failed.

Adenocarcinoma↗
PubMed1987

Noninvasive diagnosis of uremic osteodystrophy: uses and limitations.

45 bone biopsies from patients with chronic uremia were reviewed to define which noninvasive investigations were of value in predicting the histological diagnosis and to quantify the spectrum of uremic bone disease at a center that has consistently used an aluminum-free dialysis bath. 17 biopsies were taken postmortem. 15 patients received conservative treatment, the rest were on maintenance dialysis. 13 patients had symptomatic bone disease. Virtually all patients with a uremia duration greater than 3 years had uremic osteodystrophy. All patients with clinical bone disease, hypercalcemia or raised alkaline phosphatase activity had osteodystrophy, but the specific histology was not indicated. Greatly raised parathyroid levels suggested secondary hyperparathyroidism, but the test was only 100% specific when 20 times normal. Total aluminum consumption was highly indicative of bone aluminum concentration (p less than 0.0001) and aluminum-related osteomalacia (5 cases), suggesting that a considerable proportion of uremic bone disease is iatrogenic. Serum aluminum was of some use in the diagnosis of aluminum-related osteomalacia, but was not wholly reliable. Bone mineral content (BMC) using both forearm measurements and total body bone mineral levels (TBBM) were assessed in 32 patients and were found to be reduced in 12, with a preponderance of secondary hyperparathyroidism. BMC and TBBM were negatively correlated to resorbing surfaces and bone formation rate, suggesting that secondary hyperparathyroidism is the uremic bone disease that represents the greatest threat to bone mass. It is concluded that while noninvasive investigations give considerable information, reliable diagnosis requires the use of histological methods.

Adolescent↗
PubMed1987

The effect of oral aluminium salts on the bone of non-dialysed uremic patients.

12 patients with conservatively treated uremia were investigated using bone histomorphometry, bone aluminium concentration determination and total body bone mineral content (TBBM). The bone aluminum was raised in 10 patients and was significantly related to oral aluminium salt consumption (p less than 0.01). Two of four patients who had not received aluminium also had raised levels but the difference was not significant from nonuremic patients. The two patients with the highest levels had a mineralisation defect despite normal levels of 1,25-dihydroxyvitamin D. Three patients had significant bone loss of whom one had osteomalacia (OM) while two had secondary hyperparathyroidism (2HP). It is concluded that 1) aluminium salt consumption results in bone aluminium accumulation, and may contribute to the mineralisation defect; 2) uremic patients not treated ith aluminium salts may have slightly raised levels, but this seems not to be clinically important; 3) secondary hyperparathyroidism causes greater destruction of bone mass than other uremic bone diseases; 4) atomic absorption spectrometry is a more sensitive method for detecting aluminium bone deposition than histochemical methods.

Acetates↗
PubMed1986

Metabolic bone disease and aluminium contamination in 38 uremic patients. A bone histomorphometric study.

Iliac crest biopsies from 38 uremic patients, 26 hemodialysis, and 12 chronic uremics from a nephrology department with verified aluminium free dialysis water were investigated with histomorphometric method and aluminium-specific staining. For both the uremic and the dialysed group the results showed a high incidence of both metabolic bone disease (75%, 69% respectively) and aluminium contamination (25%, 62%).

Aluminum↗
PubMed1986

Bone aluminum deposition in maintenance dialysis patients treated with aluminium-free dialysate: role of aluminium hydroxide consumption.

Postmortem iliac crest biopsies were performed on 16 uremic patients. 3 had been treated conservatively while 13 had been entered into a maintenance dialysis program. The dialysate was treated by reverse osmosis for more than 10 years, and the aluminium concentration was consistently below the detection limit of 0.15 mol/l. 14 patients had been treated with aluminium hydroxide. Bone histomorphometry, aluminium labelling intensity, osteoid surface aluminium labelling extent (Al/OBI) and bone aluminium concentration were measured. 14 patients had significant bone aluminium deposition, including 2 who were not on dialysis of whom 1 had not received aluminium hydroxide. Bone aluminium concentration and labelling intensity were correlated to total aluminium hydroxide consumption (p less than 0.001, p less than 0.05) and present dose (p less than 0.01, p less than 0.01), while Al/OBI was not. The two patients with the highest aluminium concentrations had symptomatic osteomalacia, but 4 patients with significantly raised concentrations and mineralisation front labelling had secondary hyperparathyroidism. It is concluded that bone aluminium deposition occurs despite the use of aluminium-free dialysate and is associated with total and present aluminium hydroxide consumption; heavy aluminium deposition is associated with severe and symptomatic osteomalacia, but can also be observed in the presence of predominant hyperparathyroidism; aluminium deposition can occur in the absence of treatment with dialysis or aluminium hydroxide; bone aluminium concentration and labelling intensity are a better measure of bone deposition than Al/OBI.

Adolescent↗
PubMed1985

Albumin-induced changes in the electrocardiographic QRS complex.

The amplitude of the QRS wave of the electrocardiogram was correlated with conventional serum electrolyte concentrations in 94 nonhypertensive and 53 hypertensive patients. There was a highly significant correlation of QRS amplitude with serum albumin level in both groups. There was also significant correlation with serum calcium level in the nonhypertensive group, but this significance disappeared after correction for albumin. Changes in the serum albumin level during the hospital admission of the nonhypertensive patients were positively correlated with changes in QRS amplitude. Albumin infusion into 13 healthy persons resulted in significantly increased QRS amplitude, which was related to changes in serum albumin concentration. These results suggest that changes in serum protein concentration cause changes in QRS amplitude, possibly as a result of increased conductivity.

Adult↗
PubMed1984

Serum aluminium in haemodialysis patients: relation to osteodystrophy, encephalopathy and aluminium hydroxide consumption.

The serum aluminium concentration of 82 patients undergoing regular dialysis treatment in a large dialysis department was measured. Duration of known uraemia, total cumulative aluminium hydroxide consumption, present level of aluminium hydroxide consumption and chronic interstitial nephropathy as primary kidney pathology were all positively correlated to serum aluminium concentration. Serum aluminium concentration was positively correlated to the incidence of clinical osteodystrophy and negatively correlated to bone mineral content. There was, however, no correlation to parathyroid hormone concentration or parathyroidectomy. The highest serum aluminium concentration was accompanied by clinical dialysis encephalopathy. The centre uses reverse osmosis for water purification, and there has never been measurable aluminium contamination. On the basis of these findings it is concluded that: the source of aluminium in our patients is aluminium hydroxide consumption and not the dialysis water; aluminium plays no role in the development of osteitis fibrosa; the findings are consistent with the theory that hyperaluminaemia plays a role in the development of osteomalacia, and serum aluminium measurement may be useful in the diagnosis of dialysis encephalopathy.

Adolescent↗