Search PubMed⌕ Search

Biomedical subjects

J R Curtis

Publications and source records attributed to J R Curtis.

At least 91 records · Page 5Linked to original sources
PubMed1988

Relationship between ex vivo anti-proteinase (factor Xa and thrombin) assays and in vivo anticoagulant effect of very low molecular weight heparin, CY222.

There is uncertainty as to which activities of unfractionated heparin (UFH) and low MW heparin are responsible for their anticoagulant and antithrombotic properties. We have sought to answer this question by examining plasma samples taken during a recently conducted dose-finding study of the low MW heparin, CY222, in haemodialysis for chronic renal failure. In this study, in vivo anticoagulant effect was assessed by measurement of plasma FPA levels. UFH was administered as a dose of 5000 iu bolus + 1,500 iu/h maintenance infusion, while the effects of three doses of CY222 were studied (10,000, 15,000 and 20,000 Institute Choay anti-factor Xa u bolus, all with 1,500 Institute Choay anti-factor Xa u/h maintenance infusion). Anti-factor Xa levels were determined by chromogenic substrate assay. Anti-thrombin levels were determined by chromogenic substrate assay and by quantitation of catalysed thrombin-inhibitor complexes (using autoradiography). Analysis of the results indicate that plasma fibrinopeptide A (FPA) levels correlate with anti-factor Xa (r = -0.45) and anti-thrombin (substrate) (r = -0.63) levels of UFH, but only with the anti-factor Xa levels (r = -0.41) of CY222. These results suggest that the anti-factor Xa assay is currently the most suitable assay for monitoring low MW heparins such as CY222 in humans.

Anticoagulants↗
PubMed1988

Equivalent effective doses of heparin and low molecular weight heparin(oid)s in haemodialysis for chronic renal failure.

In an attempt to provide an objective means of comparing the anticoagulant action of heparin with those of newly developed low MW heparin-like anticoagulants we have utilized the fibrinpeptide A assay as a method of determining fibrin formation during haemodialysis. In vivo suppression of FPA levels by increasing doses of administered anticoagulant enables equivalent effective doses of anticoagulants to be determined without making prior assumptions about which ex vivo activities of these compounds are responsible. In this communication we summarize results of studies with heparin and three low MW heparin(oid)s.

Blood Coagulation↗
PubMed1988

Oxalate metabolism in end-stage renal disease: the effect of ascorbic acid and pyridoxine.

Oxalate metabolism was studied in ten patients with end-stage renal disease. No patient with primary hyperoxaluria was included in this study. Five patients were on regular haemodialysis and five patients were on chronic ambulatory peritoneal dialysis (CAPD). Oxalate metabolism was assessed by measurement of plasma oxalate concentration (POx), oxalate metabolic pool size (OxMP), tissue oxalate accumulation rate (TOxA), oxalate production rate (OxPR) and dialysis clearance of oxalate (DCOx). These observations were made on three separate occasions in each of the ten patients: initially when the patients were taking a routine ascorbic acid supplement of 100 mg per day; then after a period of 1 month with no ascorbic acid supplement; and then finally after a further period of 1 month's treatment with pyridoxine 800 mg daily. The values for POx, OxMP and TOxA were significantly increased in all ten patients and in the range observed in some patients with type I primary hyperoxaluria. There was no significant difference between immediate prehaemodialysis POx and the POx in the CAPD patients. The DCOx was very much greater during haemodialysis (mean 85 ml/min) than during CAPD (mean 8 ml/min). The acute fall in POx during haemodialysis was greater than 50% of the immediate pre-haemodialysis concentration. Ascorbic acid in a dose of 100 mg/day had no significant effect on the parameters of oxalate metabolism studied. Pyridoxine in a dose of 800 mg/day produced a significant fall in POx in both haemodialysis and CAPD patients.

Adult↗
PubMed1988

Neutropenia and plasma free radical reaction products during haemodialysis.

To determine whether haemodialysis produces an increase in free radical activity, plasma phospholipid plus free fatty acid (PL+FFA) octadeca-9,11-dienoic acid (18:2(9,11)) and plasma thiobarbituric acid reactivity (TBAR) were measured serially during dialysis with cuprophan and polycarbonate membranes. Plasma TBAR did not change significantly during dialysis with either membrane. There was however, an increase in PL + FFA 18:2(9,11) and in the molar ratio of 18:2(9,11) to its parent compound, linoleic acid (18:2(9,12)), with both membranes, although this was most significant with cuprophan membranes. The administration of heparin to normal controls without dialysis produces a comparable rise in PL + FFA 18:2(9,11). Haemodialysis with prostacyclin anticoagulation resulted in no significant change in PL+FFA 18:2(9,11). The data indicates that the increase in PL+FFA 18:2(9,11) during haemodialysis is due to a heparin-induced rise in FFA 18:2(9,11) and is not a consequence of increased free radical activity. In contrast to animal models of systemic complement activation, we were unable to demonstrate an increase in plasma free radical activity during haemodialysis. However, this does not preclude a role for free radicals, released by activated neutrophils, in the pathogenesis of pulmonary dysfunction during haemodialysis.

Agranulocytosis↗
PubMed1987

Aortic and mitral valve calcification in patients with end-stage renal disease.

The frequency and aetiology of aortic valve and mitral annular calcification was studied by echocardiography in 87 patients aged 35-70 on maintenance haemodialysis for a mean of 7.5 years (range 0.5-19). Aortic valve calcification (AVC) was found in 24 patients (28%) and mitral annular calcification (MAC) was found in 31 (36%). AVC was severe and produced aortic stenosis in 5 patients with a tricuspid aortic valve (mean age 51.6 years), which confirms that calcific aortic stenosis is a complication of chronic uraemia. MAC was associated with functional mitral stenosis in 1 patient. Premature AVC and MAC were associated with an increased calcium X phosphate product and long-term haemodialysis. There were no significant differences between those patients with aortic stenosis and those with AVC but no stenosis. Patients with AVC had an increased incidence of MAC and vascular calcification. Premature AVC and MAC is frequent in dialysis patients and appears to be related to abnormal calcium and phosphate metabolism and to increased mechanical stress on the valve cusps. In a small but important group of patients on long-term dialysis, premature valve calcification is severe and produces aortic stenosis, or less frequently, mitral stenosis.

Adult↗
PubMed1987

Is selenium deficiency the cause of uraemic cardiomyopathy?

We studied the relationship between serum selenium (Se) and left ventricular performance in 33 patients on maintenance haemodialysis. Low serum Se was frequent. However, there were no significant differences in echocardiographic indices of left ventricular function between patients with serum Se less than 0.9 umol/l and those with serum Se greater than 0.9 umol/l. We conclude that Se deficiency is not an important cause of cardiac failure in uraemia.

Adolescent↗
PubMed1987

Calcific aortic stenosis: a complication of chronic uraemia.

The incidence of aortic stenosis was studied in 174 consecutive patients aged less than 55 years at initiation of maintenance haemodialysis. Severe, calcific aortic stenosis developed in 6 patients a mean 9.7 years after starting haemodialysis (p = 0.0004 compared to population incidence). In 5 patients stenosis was due to severe premature calcification of a tricuspid aortic valve. Necropsy proven aortic valve calcification (with or without stenosis) was associated with an increased duration of haemodialysis, age greater than 35 years at starting dialysis and mitral annular calcification. There is an increased incidence of aortic stenosis in patients with chronic renal failure due to premature valvular calcification, which may be related to abnormal calcium and phosphate metabolism in uraemia.

Adult↗
PubMed1987

Increased free-radical activity during haemodialysis?

Free-radical activity was studied in patients on maintenance haemodialysis by measuring plasma octadeca-9, 11-dienoic acid (9,11-LA'), a diene-conjugated derivative of linoleic acid. Baseline values of 9,11-LA' (esterified as phospholipids and as free fatty acids) in 51 haemodialysis patients were similar to that of normal control subjects. However, during haemodialysis there was a highly significant (P less than 0.001) increase in 9,11-LA' in all 13 patients studied, which reached a peak 30 min after haemodialysis was started and then declined. The rise in plasma 9,11-LA' may be due to free radicals generated by activated neutrophils. Abnormal free-radical activity may be partly responsible for some haemodialysis-related complications, including pulmonary dysfunction in early haemodialysis.

Adult↗
PubMed1986

The anticoagulant effect of heparinoid Org 10172 during haemodialysis: an objective assessment.

The heparinoid of natural origin Org 10172 has anti-factor Xa activity but minimal anti-thrombin activity, and little effect upon broad spectrum assays such as the KCCT in vitro. Its anticoagulant effects have been compared to those of commercial heparin in 7 patients undergoing haemodialysis for chronic renal failure. Commercial heparin was administered in a dose (5,000 iu bolus + 1,500 iu/hour continuous iv infusion) previously shown to inhibit fibrin formation during haemodialysis. This produced mean anti-factor Xa levels in plasma between 0.7-1.0 iu/ml and largely suppressed fibrin formation for 5 h dialysis measured as mean FPA levels in plasma. Administration of Org 10172 as a bolus of 1,350 anti-factor Xa u or 2,000-2,400 anti-factor Xa u produced plasma anti-factor Xa levels of less than 0.5 u/ml and allowed fibrin clot and FPA generation during dialysis. Org 10172 administered as a bolus dose of 4,000-4,800 anti-factor Xa u produced mean anti-factor Xa levels of greater than 0.5 u/ml, allowed dialysis of 6 patients for 5 h and appreciably suppressed FPA generation during dialysis, with little effect on the KCCT. It is concluded that the anti-factor Xa activity of Org 10172 may reflect its ability to inhibit fibrin during dialysis and that single bolus injection of Org 10172 may be a useful alternative method of achieving anticoagulation.

Anticoagulants↗
PubMed1986

Serum ferritin in haemodialysis patients: is there a relationship to 'haemochromatosis alleles' HLA A3, B7, B14?

Serum ferritin levels were measured in 57 patients on maintenance haemodialysis to determine if patients who possessed 1 or more of the histocompatibility antigens associated with idiopathic haemochromatosis (HLA A3, B7 or B14) were at increased risk of iron overload. There was no significant difference in the mean serum ferritin levels between those patients with HLA A3, B7 or B14 (357.9 +/- 522.6 ng/1; n = 19) and those without these antigens (393.7 + 556.2 ng/1; n = 38). Iron overload in haemodialysis patients is not a histocompatibility-linked disorder.

Adolescent↗
PubMed1986

On the evaluation of heparin and low molecular weight heparin in haemodialysis for chronic renal failure.

Anticoagulation during haemodialysis for chronic renal failure can be assessed by measurement of plasma fibrinopeptide A (FPA) levels as an objective method of monitoring the initial step in fibrin formation, in conjunction with visual inspection of the dialyser circuit for fibrin clot deposition. Employing this approach, unfractionated commercial heparin administered as an intravenous bolus followed by an intravenous maintenance dose (5,000 IU + 1,500 IU/h) was found to suppress almost completely fibrin formation and deposition during prolonged dialysis. Comparison of a low molecular weight heparin, Kabi 2165, revealed that it can inhibit fibrin formation in the extracorporeal circulation, that this property is largely reflected in its anti-factor Xa activity in plasma, and that a useful and effective dose of Kabi 2165 for haemodialysis may be 4,000 anti-factor Xa U intravenous bolus + 750 anti-factor Xa U/h intravenous maintenance infusion. This dose only minimally alters the KCCT and corresponds to approximately 60% of that of unfractionated heparin, which may be important in the long-term use of heparin in these patients.

Biological Availability↗
PubMed1986

Haemodialysis with low MW heparin: dosage requirements for the elimination of extracorporeal fibrin formation.

We have performed a dose ranging study of a low MW heparin, Kabi 2165, during haemodialysis in humans (n = 16) and compared it to a dose of unfractionated commercial heparin that has already been shown to inhibit fibrin formation. Low MW heparin administered as 5000 or 10,000 anti-factor Xa units, s.c., half an hour prior to the initiation of dialysis was unable to prevent fibrin formation in the dialyser circuit. A single bolus injection of 5000 anti-factor Xa units of low MW heparin given i.v. inhibited fibrin formation, as determined by FPA generation, for up to 4 h and permitted dialysis for 6 h. Such a bolus injection may be useful for short frequent dialyses. Infusion of low MW heparin in the same dosage regimen as unfractionated heparin, 5000 anti-factor Xa units bolus plus 1500 anti-factor Xa units/h, resulted in a progressive rise in heparin, caused by its longer half-life of elimination from the circulation, and almost completely suppressed both FPA generation and fibrin clot formation for 6 h dialysis. From these studies we calculate that infusion of this low MW heparin at a dose of approximately 4000 anti-factor Xa units bolus plus 750 anti-factor Xa units/h should be a useful regimen that will be effective in suppressing fibrin formation during prolonged dialysis, and the plasma anti-factor Xa level of low MW heparin may reflect its ability to inhibit fibrin formation, although exactly comparable anti-factor Xa levels of unfractionated commercial heparin and low MW heparins may not have identical inhibitory effects.

Clinical Trials as Topic↗
PubMed1985

High-pressure liquid chromatography for isolation of clastogenic agents from urine.

Small columns of XAD-2 resin have been widely used to extract and concentrate mutagenic materials from urine. Using analytical HPLC and assays for clastogenicity with Chinese hamster ovary cells, we found that small columns of XAD-2 resin (1.5 ml bed volume) retain only a small percentage of organic material and undetectable amounts of genotoxic activity in urine samples. Increasing the size of the XAD resin bed resulted in better recoveries, but much organic material was still lost by overloading of the column. In contrast, when urine was acidified and chromatographed by preparative reversed-phase HPLC using large-bed-volume (500 ml) commercial columns, retention of hydrophobic organic material from urine was excellent. Subsequent stepwise elution of the column with increasing concentrations of acetone produce 3 fractions of organic material of increasing hydrophobicity. When urine from smokers was analysed, all 3 fractions contained material which was clastogenic to Chinese hamster ovary cells. The procedures developed are suggested as a new general purpose approach to the isolation of genotoxic materials from urine.

Animals↗