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Biomedical subjects

J Koutts

Publications and source records attributed to J Koutts.

At least 19 recordsLinked to original sources
PubMed1995

Aminopeptidase-N (CD13; gp 150): contrasting patterns of enzymatic activity in blood from patients with myeloid or lymphoid leukemia.

We have investigated the compartmentalization of aminopeptidase-N-like activity in various blood fractions obtained from patients with acute lymphoid (ALL) or myeloid (AML) leukemia. The primary difference appears not to be the absolute level of overall activity, but rather the relative proportions of the different forms of activity detected. Thus, despite similar levels of total aminopeptidase-N-like activity detected in cells from different leukemic groups, true aminopeptidase-N/CD13 activity was only detected in cells derived from AML patients. Even in these patients, however, most of the detected aminopeptidase-N-like activity ( > 80%) could not be attributed to aminopeptidase-N/CD13. In marked contrast, plasma from leukemic patients also contained substantial total aminopeptidase-N-like activity, of which (irrespective of leukemic group) most could be attributed to aminopeptidase-N/CD13. Whilst slightly higher levels of total activity were obtained in plasma from AML patients compared to ALL patients, there was no difference in the relative proportion attributable to aminopeptidase-N/CD13 (approximately 80% of total aminopeptidase-N-like activity). Evaluation of total aminopeptidase-N-like activity present in whole blood gave differential patterns, and whilst only a proportion (20-40% of total aminopeptidase-N-like activity) could be attributed to true aminopeptidase-N/CD13, blood from patients with CD13+ AML showed the greatest activity so attributable. In total, our results outline the complexities of peptidase activities present within blood of leukemic individuals, and may, in part, explain the variability of previous studies attempting to associate prognostic features with phenotypic expression of CD13.

Antibodies, Blocking↗
PubMed1994

von Willebrand's disease: use of collagen binding assay provides potential improvement to laboratory monitoring of desmopressin (DDAVP) therapy.

This report describes studies investigating the use of a collagen binding assay to improve the laboratory monitoring of desmopressin (DDAVP) therapy in patients with von Willebrand's disease (vWD). We evaluated the response of seven patients with vWD (four type I, three type IIA) to DDAVP, administered using a standard protocol, by assessing levels of von Willebrand factor (vWF) and factor VIII, as well as performing skin bleeding times (SBT) prior to, and at sequential time points following, DDAVP administration. The study employed the following assays: von Willebrand factor antigen assay (vWF:Ag; determined by ELISA); a novel functionally based collagen binding assay (CBA; determined by ELISA); ristocetin cofactor assay (RCof; determined by platelet aggregometry); von Willebrand factor multimer analysis (using SDS-agarose gels); factor VIII coagulant (FVIIIC; determined by clotting assay); and factor VIII antigen (FVIIICAG; determined by ELISA). All patients showed an initial incremental increase in vWF/FVIII levels using all assays above, and some showed some correction in SBT. Although the absolute levels of vWF/FVIII antigen or activity varied between patients, the CBA was found to provide consistently the greatest proportional incremental increases (i.e., -fold) compared to baseline (pre-DDAVP) levels. Accordingly, we consistently observed an increase in the CBA to vWF:Ag ratio for all patients evaluated. This supplements previous findings that have suggested a unique ability of our CBA procedure to bind preferentially to higher molecular weight (i.e., more functionally active) forms of vWF. We therefore propose that the use of the above test combination (e.g., vWF:Ag plus CBA) may provide the basis for more accurate estimation of a patient's functional responsiveness to DDAVP therapy in future studies.

Biopolymers↗
PubMed1994

The Western Sydney Stroke Risk in the Elderly Study. A 5-year prospective study.

Aging of the Australian population, as in other developed nations, will ensure that stroke remains one of the most important causes of death and disability. The Stroke Risk in the Elderly (SITE) study aims to measure prospectively the independent contribution of dietary, sociodemographic, blood lipid, blood pressure, and hemostatic factors to risk of stroke and other cardiovascular outcomes. The target population included all independently living men and women aged 65 years and over, residents in several retirement villages in western metropolitan Sydney, New South Wales, Australia. The study cohort consists of 225 men and 787 women, selected as a convenience sample from all eligible residents in the local government areas (LGAs) adjacent to Westmead Hospital. Participants attended a baseline session to complete dietary, life-style, medical, and sociodemographic questionnaires. Anthropomorphic variables and blood pressure were measured. Blood was taken for measurement of serum lipid, glucose, and hemostatic factors. Questionnaire results were compared with an age/sex-stratified, randomly selected sample drawn from the community (in the same LGAs), in order to quantify potential sampling and selection biases. The study cohort will be followed for a minimum of 5 years. The attendance rate of eligible residents for a baseline medical, dietary, life-style, and sociodemographic assessment was 72% for males and 69% for females. The study cohort was older, better educated, less ethnically diverse, and among women, less likely to have ever been married compared to people aged over 65 years in the comparison group. The baseline results suggest that hemostatic factors may be of importance in assessing risk of cardiovascular disease, (CVD), particularly in older men.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗
PubMed1994

Hodgkins disease: clinical and radiological prognostic factors in a laparotomy series.

From July 1979 to June 1988, 62 patients managed at Westmead Hospital underwent a staging laparotomy (LAP) for Hodgkins disease. Fifty-four patients were clinical stage (CS) I or II and eight were CS III. The sensitivities of the imaging modalities of computed tomography (CT), Gallium and bipedal lymphangiogram (LAG) were assessed for their predictive value for abdominal disease in patients who underwent a LAP. The most sensitive combination for predicting a negative laparotomy (78%) was a negative abdominal CT and a negative Gallium scan. Upstaging occurred in two of 16 Stage I patients (13%) and nine of 38 Stage II patients (24%). Of the 11 patients upstaged, the spleen was involved in 10 (91%). Factors which predicted for upstaging in a univariate analysis were: age greater than 40 years (P = 0.02), mixed cellularity or lymphocyte depleted histology (P = 0.02), and more than three sites involved above the diaphragm (P = 0.008). In a multivariate analysis, the only significant predictor was the number of sites of involvement (P = 0.007). Two subgroups who had a low probability of upstaging were favourable histology patients with up to two sites of involvement (0%) and females with up to two sites of involvement (0%). We conclude that abdominal imaging is associated with a high false-negative rate, particularly for CS II disease.

Abdomen↗
PubMed1993

Familial hypobetalipoproteinaemia: a rare presentation to the lipid clinic.

OBJECTIVE: To report a case of familial hypobetalipoproteinaemia in a woman who presented after the incidental finding of marked hypocholesterolaemia during laboratory tests. CLINICAL FEATURES: An asymptomatic 37-year-old Lebanese woman presented to the lipid clinic with a serum total cholesterol concentration of 1.1 mmol/L, high density lipoprotein (HDL) cholesterol of 1.0 mmol/L, and triglycerides of 0.28 mmol/L. No secondary cause for the hypocholesterolaemia was established. INVESTIGATION AND OUTCOME: Her serum apolipoprotein B (apo B) levels were markedly reduced at 0.07 g/L. Except for one daughter (IV-4), all other family members including her husband (her first cousin) had apo B levels about 25% of normal. Daughter IV-4 had undetectable apo B levels. Family studies confirmed an autosomal dominant pattern of inheritance consistent with familial hypobetalipoproteinaemia. CONCLUSION: Familial hypobetalipoproteinaemia is a rare condition that should be considered in the differential diagnosis of hypocholesterolaemia. Absence of clinical features, autosomal dominant pattern of inheritance, and reduced apo B levels suggest the diagnosis.

Adolescent↗
PubMed1993

von Willebrand's disease: laboratory investigation using an improved functional assay for von Willebrand factor.

This report details extensive studies investigating an improved screening procedure for the laboratory confirmation of clinically suspected von Willebrand's disease (vWD). Over the past two years, over 400 plasma samples, comprising samples derived from both normal individuals (n = 112) and from patients undergoing investigation on clinical grounds, underwent analysis in this screening procedure, comprising three distinct assays: a standard ELISA assay for von Willebrand Factor (vWF) antigen levels (vWF:Ag), a standard ristocetin cofactor (R Cof) assay, and a functional collagen based ELISA assay for vWF ('CBA'). Normal individual plasma samples yielded normal reference values (mean +/- 2SD) approximating 50-200% (vWF:Ag, R Cof) or 50-250% (CBA). In order to permit comparative analysis, and based upon derived assay values, and subsequent multimer analysis, patient samples were either deemed to derive from persons unlikely to suffer vWD ('non-vWD' patient group) or those potentially suffering vWD. The latter group was further separated into subgroups based upon the likelihood, and probable subtype of vWD. In conjunction with the vWF:Ag assay, the CBA provides the basis by which an effective predictor system (likelihood and probable subtype of vWD) can be offered on the basis of preliminary screening procedures. To date, there has been no overlap in vWF:Ag to CBA ratios (vWF:CBA) between patients yielding Type II vWD like multimer patterns and those yielding Type I vWD, or normal, multimer patterns. Thus, high vWF:CBA (i.e. > or = 3.0) would suggest a Type II, or pseudo, -vWD like defect, whereas low vWF:CBA (< or = 2.5) would likely derive from either normal individuals, or persons suffering from Type I vWD.(ABSTRACT TRUNCATED AT 250 WORDS)

Enzyme-Linked Immunosorbent Assay↗
PubMed1992

Thymic hyperplasia associated with Hodgkin disease and thyrotoxicosis.

A 19-year-old woman had a residual gallium-sequestering mediastinal mass after treatment for Hodgkin disease. Coincidentally, she also had hyperthyroidism. The initial concern was that the mass was residual Hodgkin disease. Thymic hyperplasia has been described in association with both these conditions. The mass disappeared after treatment of her hyperthyroidism.

Adult↗
PubMed1992

Platelet aggregation and coronary heart disease risk factor variation in Australian populations with different coronary heart disease mortality.

In a cross-sectional analytic study, we examined the differences in coronary heart disease (CHD) risk factors, including coagulation factors and platelet aggregation, among males from southern European countries and those of Anglo-Celtic descent who had widely different CHD standardized mortality ratios. The participants included 169 men aged 40 to 49 years, 27% of whom were born in southern European countries. The subjects had no history of heart disease and no other clinical conditions, or were not taking medications known to affect hemostasis. Data obtained included their medical history and CHD-related risk behaviors, blood pressure, height, weight, abdominal and pelvic circumference, and coagulation, fibrinolysis, platelet activity, lipids, and lipoproteins profiles. There were significant differences between the two groups in the prevalence of a positive family history, mean apolipoprotein A1 levels, and platelet aggregation responses to ADP. Other established risk factors, including coagulation factor levels, were not significantly different.

Adenosine Diphosphate↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1991

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↗
PubMed1990

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↗
PubMed1990

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↗
PubMed1990

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↗
PubMed1990

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↗
PubMed1990

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↗
PubMed1990

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↗