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Biomedical subjects

J Koutts

Publications and source records attributed to J Koutts.

At least 37 records · Page 2Linked to original sources

Deep vein thrombosis prophylaxis: a survey of current practice in Australia and New Zealand.

A survey of current practice for deep vein thrombosis (DVT) prophylaxis was undertaken in Australia and New Zealand. The most common indications for prophylaxis were a history of thrombo-embolism, the type and length of surgery and obesity. Prophylaxis was used in 65% of patients having hip surgery and in 39% undergoing knee surgery. In general surgery the corresponding rate was around 67% for colorectal surgery, hepatobiliary, upper gastrointestinal and major abdominal vascular surgery. Apart from open-heart cardiothoracic surgery (66%), use in other specialties was less than 50%. Physical methods (anti-embolism stockings, calf stimulation and calf compression devices) were most commonly used for prophylaxis (46%) with heparin being used by 40%. The main side effect reported with heparin was bleeding (18%). The estimated incidence of DVT and pulmonary embolus (PE) was 2.8 and 0.4% for general surgery, 2.7 and 0.7% for orthopaedic surgery and 6.6 and 1.3% for hip surgery. Intravenous heparin followed by oral anticoagulants was the most commonly used treatment for established DVT and nearly all respondents used intravenous heparin and oral anticoagulants for treatment of PE. Venography was the favoured objective test for diagnosing DVT. The principal reason for considering a change in prophylactic policy was the potential availability of an agent with increased efficacy and a reduced incidence of haemorrhagic complications.

Anticoagulants↗

Heparin-induced thrombocytopenia: laboratory investigation and confirmation of diagnosis.

We report here on the usefulness of the 14C-serotonin release assay for the laboratory confirmation of the clinical diagnosis of heparin-induced thrombocytopenia syndrome (HITS). Over the past 3 yrs, some 140 individual serum samples have been tested in our laboratory for heparin-associated anti-platelet activity ('heparin antibodies'). These included sera from 54 selected (4 positive, 50 negative) controls and a group of 86 patients where the test was requested on clinical grounds. Of 20 patients derived from within our institution, 7 out of 8 patients (88%) with good clinical probability of HITS were confirmed to have heparin platelet antibodies by the serotonin release assay. In contrast, only 2 out of 9 patients (22%) with a low clinical probability of HITS were shown to be positive by this procedure, as were 2 out of 3 patients (66%) deemed to have an 'intermediate' clinical probability of HITS. In addition, screening of 50 serum samples forming a 'negative-control non-HITS' group (either patients on heparin therapy without thrombocytopenia, patients with non-heparin associated thrombocytopenia [eg. ITP*, other drug related], or normal laboratory volunteers), consistently failed to display heparin associated anti-platelet activity by the 14C-serotonin release assay. In addition to the good specificity and sensitivity described above, the 14C-serotonin release assay was found to be nearly twice as sensitive when compared to the platelet aggregation procedure, and it is therefore a useful diagnostic test for the confirmation of clinically suspected HITS.

Blood Platelets↗

Development of a simple collagen based ELISA assay aids in the diagnosis of, and permits sensitive discrimination between type I and type II, von Willebrand's disease.

We have developed and evaluated an ELISA-based collagen binding assay (CBA) as an aid in the diagnosis and classification of von Willebrand's disease (vWD). The assay is simple to perform, and appears capable of differentiating Type II vWD from Type I vWD. Using plasma samples from both affected and non-affected patients, or from normal individuals, data obtained using the CBA were directly compared to data simultaneously derived from a standard von Willebrand factor antigen (protein; vWFAg) ELISA, and from a standard ristocetin cofactor (RCof) assay. Plasma derived from vWD patients (both Type I and Type II) showed overall reduced levels of vWF as detected by all three assays. Mean levels as a per cent of normal for vWFAg, CBA, RCof were 47.3, 60.7, 31.1 for Type I patients (n = 37), and 34.9, 1.6, 11.9 for Type II patients (n = 16) respectively. However despite the reduced vWF levels detected in Type I vWF binding values for both the CBA and vWFAg showed near comparability (i.e. vWFAg:CBA ratio generally less than or equal to 1.0). These ratio values were thus similar to those observed using plasma derived from either individual normal donors, or from non-vWD affected patients. On the other hand, plasma from Type II vWD affected patients showed markedly disparent values, with increased (greater than 8.0) vWFAg:CBA ratios coincident with virtually absent CBA binding in these patients. Thus, the CBA as reported here does appear to constitute a novel functional assay capable of detecting qualitative vWF differences in plasma of affected vWD patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Antigens↗

Ultrasound diagnosis of lower limb deep venous thrombosis.

Venous ultrasound imaging was compared with ascending contrast venography for the diagnosis of suspected deep vein thrombosis (DVT) in the femoral, popliteal and calf vein segments of 44 limbs in 44 patients. One femoral and one calf vein segment could not be imaged (1.5% of the segments examined), but during the same period venography failed in six patients because of an inability to cannulate a swollen limb. Ultrasound imaging compared with venography as a means of diagnosing DVT showed an overall sensitivity of 95% and a specificity of 92%. The sensitivity and specificity of ultrasound imaging for the diagnosis of both femoral and popliteal vein thromboses were 100% and 97%, respectively, and for calf vein thrombosis were 85% and 83%, respectively. This study supports the recommendation that ultrasound imaging is now the investigation of choice for the diagnosis of DVT provided that the scan is performed by an experienced vascular technologist. Ultrasound imaging may also define other pathological conditions presenting in the differential diagnosis of DVT, such as superficial thrombophlebitis and Baker's cyst.

Adult↗

Solvent extraction of test plasmas for improved recovery of lupus anticoagulant activity.

Phospholipid procoagulant material mainly derived from platelets interferes or "bypasses" the more specific tests for lupus anticoagulants. Such material in test plasmas can be inactivated with recovery of lupus anticoagulant activity by simple extraction with chloroform. This solvent treatment damages mainly factors VIII, V, VII and IX. Ether and various other solvents were less damaging to these clotting factors but not quite as effective as chloroform in the recovery of lupus anticoagulant activity.

Autoantibodies↗

Use of a simplified dilute Russell's viper venom time (DRVVT) confirms heterogeneity among 'lupus anticoagulants'.

A simplified dilute Russell's viper venom time (DRVVT) test--in which the venom, trace phospholipid and calcium were combined into a single reagent--was evaluated for the detection of lupus anticoagulants (LA) in 28 plasma samples containing non-specific circulating anticoagulants. In agreement with previous studies, the DRVVT was found to be insensitive to defects in contact and haemophilic factors and was only marginally affected by antibodies directed against factor VIII. Thus, the use of a DRVVT test in investigations of anticoagulants reduces the risk of confusing a haemorrhagic inhibitor of factor VIII with a non-haemorrhagic LA. In comparisons of sensitivity against activated partial thromboplastin time tests (APTT-Actin FSL and Organon-Teknika reagents) the simplified DRVVT was prolonged slightly more than the APTT in most of the test plasmas containing various non-specific circulating anticoagulants. Three anticoagulants affecting APTTs more than the DRVVT were found to be associated with anticardiolipin IgMs. APTT-prolonging anticoagulants, whether prolonging DRVVT tests or not, showed similar 'correction' of their APTTs by the addition of platelets or phospholipid. Thus, phospholipid-dependent or LA show heterogeneity. Those affecting only the APTT and not DRVVT should perhaps be classified differently.

Adult↗

Co-expression of haemopoietic antigens on vascular endothelial cells: a detailed phenotypic analysis.

Over 1000 monoclonal antibodies (MAB), previously characterized in terms of reactivity with various haemopoietic cells and including representatives from each of the currently known Clusters of Differentiation (CD), have now been evaluated by us for reactivity against human endothelial cells. In the current study, screening was performed on both fixed, and on non-fixed, endothelial cells derived and cultured from umbilical cord veins. Results indicate that endothelial cells co-express a wide variety of antigens that are otherwise characterized by expression on haemopoietic cells. The most intense and consistent degree of reactivity was seen using MAB to CD-9, CD-13, CD-29, CD-31, CD-44, CD-46, CD-51, CD-54 and CD-55, although reactivity was also observed using MAB belonging to CD-41, CD-47, CD-49, CD-61 and CD-71, in addition to a number of non-clustered MAB.

Antibodies, Monoclonal↗

Autologous bone marrow transplantation for acute myeloid leukaemia in remission: a preliminary report.

Autologous bone marrow transplantation, using unpurged cryopreserved autologous marrow, was performed on ten adult patients with acute myeloid leukaemia in remission. Seven patients were in first chemotherapy-induced remission of their disease, while three were in later remission. Patients ages ranged from 24 to 52 years, with a median of 38.5 years. Conditioning therapy consisted of oral busulphan 16 mg/kg over four days and intravenous cyclophosphamide 60 mg/kg on two days. Bone marrow cells were thawed and infused two days later. All patients showed signs of marrow engraftment, however this was delayed in comparison with patients receiving allogeneic transplants. All patients developed fever requiring antibiotic therapy and one patient died of overwhelming sepsis. Another patient died of hepatic veno-occlusive disease two months after transplant. Serious, but non-fatal, hepatic complications occurred in two other patients. One patient, transplanted in third remission, relapsed 16 months post-autograft. No other relapses have been seen, with one second remission patient remaining leukaemia-free at 24 months, and six first remission patients in continuing remission 11 to 23 (median 20) months post transplant. These encouraging results require confirmation in a randomised clinical trial comparing autologous marrow transplantation versus standard chemotherapy.

Adult↗

A case of thrombotic thrombocytopenic purpura following allogeneic bone marrow transplantation.

A case of thrombotic thrombocytopenic purpura (TTP) is reported in a 40-year-old man 6 months after allogeneic bone marrow transplantation for multiple myeloma. The features of TTP included microangiopathic haemolytic anaemia, severe thrombocytopenia, fluctuating neurological abnormalities, and progressive renal impairment. Despite treatment with anti-platelet agents, prostacyclin infusion, intensive immunosuppression and prolonged plasma exchange, the patient developed end-stage renal failure and is now on maintenance haemodialysis 18 months after the onset of TTP. Graft-versus-host disease and cytomegalovirus infection could not be implicated as aetiological factors, and cyclosporin medication had ceased 1 week before the clinical onset of his disease. The unusually intensive pre-transplant chemotherapy and radiotherapy protocol used in this patient appear to be most likely cause of the generalized endothelial damage resulting in TTP in this patient.

Adult↗

Aspirin and coronary heart disease. Clinical applications.

Aspirin, which is an effective anti-platelet agent, given in the low dosage of 60 to 100 mg per day appears to be beneficial for patients with a history of unstable angina, myocardial infarction, transient ischaemic attacks and stroke.

Aspirin↗

Endothelial cells and normal circulating haemopoietic cells share a number of surface antigens.

Human endothelial cells, cultured from umbilical cord veins, have been evaluated for expression of a large number of cell surface antigens with known haemopoietic, particularly myeloid, cell distribution. This was achieved by evaluating endothelial reactivity (using non-fixed cells) with groups of monoclonal antibodies (MAB) belonging to distinct Clusters of Differentiation (CD), as defined by the Third International Workshop on Leukocyte Differentiation Antigens (ILWS). Results indicate that many antigens known to be present on haemopoietic cells, including those on platelets, are co-expressed on endothelial cells. The most intense degree of reactivity was seen using MAB to CD-9 and CD-13, although significant reactivity was also observed using MAB to CD-31 and CD-32. Data also suggests weak binding to endothelial cells of MAB belonging to CD-14, CD-15 and CD-16. A number of unclustered MAB reactive with haemopoietic antigens can also be shown to bind to endothelial cells.

Antibodies, Monoclonal↗

Improved treatment results for lymphoblastic lymphoma in adolescents and adults using a doxorubicin-based (APO) protocol.

A multi-drug chemotherapy (APO) protocol incorporating doxorubicin was used to treat 12 patients (median age 19 years) with lymphoblastic lymphoma. The APO protocol consisted of intensive induction and consolidation phases, prophylactic CNS treatment, and 24 months of maintenance therapy. Eleven patients had an anterior mediastinal mass, while T cell markers were found on the lymphoma cells in eight of the nine cases tested. Two patients had initial CNS involvement, with one also having bone marrow replacement. Complete remission was obtained in all patients, with no deaths due to treatment toxicity. There have been four relapses, one in the patient with initial CNS and leukemic disease, two in abdominal sites, and in the mediastinum in one patient. With a median follow-up time of 30 months from diagnosis, 67% of patients remain alive in first remission. These results indicate that the APO protocol provides a highly effective approach to the management of this high grade lymphoma in adolescents and adults.

Adolescent↗

Autoimmune cardiolipin-binding antibodies in oral anticoagulant patients.

In a routine clinic of patients taking regular oral anticoagulant therapy (warfarin, n = 140) 14% were found to have elevated levels (greater than 4 SD above normal) of anticardiolipin antibody (ACA) assessed by a well standardised enzyme linked immunosorbent assay (ELISA). There was a higher incidence of raised ACA in patients being treated for thrombotic episodes (9/47 = 19%) than in cases with heart valve replacements (8/75 = 11%). Furthermore, the highest ACA titres were in younger patients with thromboses scheduled for short-term anticoagulant treatment. Borderline DNA binding studies, together with some positive ANA results, suggested autoimmune etiology in the minority of these cases. Lupus anticoagulant was strongly detectable in only one such patient. The ACA were predominantly IgG (14/17) and did not appear to compromise the conditions of patients while on anticoagulant therapy. Raised ACA may be a highly significant marker for an acquired prothrombotic state.

Administration, Oral↗

The neurotoxicity of high-dose cytosine arabinoside is age-related.

Fifteen patients with acute myeloid leukaemia were given a total of 17 courses of high-dose cytosine arabinoside (Ara-C). The median age of the patients was 37 years. Four patients developed severe irreversible neurotoxicity, three developed mild to moderate, reversible neurotoxicity, whereas eight patients had no toxicity. Of five patients over the age of 55 years given high dose Ara-C, four developed severe, irreversible neurotoxicity, but there were no severe episodes in nine patients aged 55 years or less. (P less than 0.01). At a dose of 3 g/m2 given intravenously every 12 hours for 3 days, three cases of severe irreversible neurotoxicity were noted in elderly patients. Neurotoxicity at this total dose has previously been considered unusual. Administration of high dose Ara-C at total doses of 18 g/m2 and over carries a risk of severe irreversible cerebellar toxicity that increases with age.

Activities of Daily Living↗

Simple immunochromometric assay for protein C activity.

Protein C binds readily from human plasma to antibody-coated wells, where it may be quantitated with an iodine 125-labeled antibody to protein C. Treatment with thrombin results in a small reduction in the protein C antigen detectable by this immunoradiometric assay (IRMA). However, activated protein C resulting from thrombin treatment and retained by the antibody on a solid phase may be detected by an overnight incubation with chromogenic substrates S-2366 or CBS 34.47. The immunochromometric assay (ICMA, analogous to IRMA) described uses a heterologous antibody to protein C, activation with relatively low concentrations of bovine thrombin, and quantitation by hydrolysis of chromogenic substrate in a convenient 96-well microtiter plate system. The correlation between IRMA and ICMA protein C results was found to be good with normal persons and patients with liver disease. Patients taking oral anticoagulants had reduced protein C antigen (IRMA) but even lower protein C by ICMA, indicating that inactive forms were present.

Animals↗