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Biomedical subjects

O S Roath

Publications and source records attributed to O S Roath.

At least 19 recordsLinked to original sources
PubMed1997

Prospective randomized placebo-controlled trial of aprotinin for elective aortic reconstruction.

BACKGROUND: The serine protease antagonist, aprotinin, reduces perioperative blood loss in cardiac surgery and orthotopic liver transplantation. A pilot study suggested that the drug may also reduce bleeding during infrarenal aortic replacement; the aim was to confirm or refute this observation with a prospective, randomized, double-blind, placebo-controlled trial. METHODS: Some 136 patients were randomized to receive either aprotinin, given as a loading dose of 2 x 10(6) kallikrein inactivator (KI) units followed by 0.5 x 10(6) KI units/h or equal volumes of 0.9 per cent saline. After 80 patients had been randomized the infusion dose was doubled to ensure that plasma levels were similar to those seen in successful cardiac studies. Blood loss, coagulation and haematological parameters were recorded throughout surgery and for 7 days afterwards. Blood was transfused to maintain the haemoglobin level at 100 g/l. RESULTS: Four patients were withdrawn after randomization when found at laparotomy to be unsuitable for the planned reconstruction. The 30-day mortality rate was 4.5 per cent, with no excess complications in either group. Blood loss collected on swabs was reduced from 480 ml in placebo-treated patients to 379 ml with aprotinin (P = 0.014). Blood loss into suction drains in the first 24 h after operation was reduced from 295 to 205 ml in aprotinin-treated patients (P = 0.002). However, no significant reduction was found in intraoperative or total blood loss, or transfusion requirement. CONCLUSION: The small reduction in blood loss in patients treated with aprotinin demonstrated in this study does not support its use in routine elective aortic surgery.

Aged↗
PubMed1996

High purity, recovery, and selection of human blood cells with a novel high gradient magnetic separator.

The selective isolation of cell subpopulations from previously cryopreserved human blood mononuclear cells was achieved magnetically using a novel, well-characterized conical funnel filter containing a variety of ordered wire arrays. Tetrameric antibody complexes targeted against the CD8 antigen were used to bind colloidal superparamagnetic dextran-iron particles to the desired cells with very low nonspecific binding. The novel design of the filter was such that the retention of cells at zero magnetic field was on average 0.9%. After two successive magnetic separations, an average purity of 98% was obtained for the desired labeled cells. A third separation gave > 99% purity. Purity was affected by the unlabeled cells, which expressed high intercellular adhesion (0.5% of the total cells). The ultimate recovery of the labeled cells was limited by the degree of nonmagnetic labeling of the cells expressing very low levels of targeted antigen. Recoveries could be as low as 78%, depending on the donor. The separation system described was believed suitable for difficult large-scale separations, that is, cells expressing the CD34 antigen.

Blood Preservation↗
PubMed1995

Hyperfibrinolysis during intracranial surgery: effect of high dose aprotinin.

A patient undergoing intracranial surgery developed disseminated intravascular coagulation with life threatening peroperative bleeding. Thromboelastography established the diagnosis of hyperfibrinolysis, usually a fatal complication of a neurosurgical operation. With the administration of a high dose regimen of aprotinin (Trasylol) the haemorrhage was controlled and the hyperfibrinolytic state reversed. Evaluation of blood samples from the jugular bulb suggested that there was a pronounced local release of tissue plasminogen activator into the circulation.

Aged↗
PubMed1993

Positive selection of human blood cells using improved high gradient magnetic separation filters.

High gradient magnetic separators (HGMS) create magnetic field gradients that can be used to attract much smaller and less magnetic particles than those required for conventional magnetic separation techniques. As a result cells can be labeled with submicron magnetic particles and still be separated using an HGMS filter. Typically, HGMS filters consist of random arrays of wire such as stainless steel wool. Wire elements arranged regularly in a filter should allow more efficient separation of cells. Filters were constructed containing ordered wire arrays composed of 430 series stainless steel wire mesh with wire diameters of 50, 100, or 150 microns. The ability of these filters to separate T cells from peripheral blood mononuclear cell suspensions was tested and found superior to random arrays of 302 series stainless steel wire (Thomas et al, 1992). Target cells recognized by OKT5 monoclonal antibody were cross-linked to dextran-iron particles of approximately 20 nm in diameter. Separation conditions were optimized and after one passage through the filter 88% of the OKT5+ cells were recovered in the enriched fraction with 85% purity (%OKT5+). Multiple passages (3 times) could achieve 99% purity with 68% recovery. Variations in separation flow rate had a large effect on the balance between purity and recovery. Optimum separation efficiencies were achieved only when > 10(8) cells were processed. The primarily cause of nonspecific entrapment of CD8- cells was not nonspecific magnetic labeling of cells but the physical (nonmagnetic) characteristics of the filter/filter chamber.

Adult↗
PubMed1992

Effect of aprotinin on neutrophil function after major vascular surgery.

High-dose aprotinin reduces blood loss and blood transfusion requirements during liver transplantation and cardiac and vascular surgery. The mechanism of the haemostatic effect of aprotinin is unclear. A general effect on the anti-inflammatory response may be involved. Because leucocyte activation is part of this process, white cell function was measured in patients undergoing aortic surgery who received high-dose aprotinin therapy (n = 10) and was compared with the results from controls who did not (n = 10). The test group received an intravenous bolus (2 x 10(6) kallikrein inhibitor units) of aprotinin after induction of anaesthesia followed by continuous infusion (0.5 x 10(6) kallikrein inhibitor units/h) until the end of the operation. Blood samples were obtained before operation, immediately after surgery, and 1 and 7 days after operation. Aprotinin maintained significantly better postoperative white cell function as measured by bipolar shape formation (P less than 0.001), unstimulated nitroblue tetrazolium (NBT) reduction (P less than 0.001) and chemotaxis (P less than 0.001). Endotoxin-stimulated NBT reduction was similar in both groups, indicating that neutrophils from treated individuals retained the capacity to respond to oxidative stimuli. Aortic surgery activates neutrophils in vivo, as reflected by impaired chemotaxis and increased superoxide production. Aprotinin protects the cells against this potentially deleterious effect without affecting their ability to respond when provoked. Whether this affects leucocyte interaction with coagulation pathways and contributes to the reduction in blood loss remains to be determined.

Aged↗
PubMed1992

Tissue procoagulant activity may be important in sustaining metastatic tumour growth.

There is strong evidence for an association between the haemostatic system and malignancy. Thus, cancer may adversely affect the host coagulation system while the haemostatic system may play a role in the development of both primary and metastatic tumours. Metastatic growth is not dependent simply on haemodynamic factors, and properties of both the tumour cell and host organ are important determinants of the site of metastatic growth. Previous studies have demonstrated that some organs are preferred sites for metastasis while others are less preferred or resistant. We have measured the procoagulant activity (PCA) of normal rat and human tissues and correlated the results with the previously reported ability of these organs to support metastatic tumour growth. In addition, we determined changes in PCA in rat tissues during oral anticoagulant therapy, and following colonic anastomosis and partial hepatectomy, procedures which are known to affect experimental metastasis. In both rat and human studies, organs which are preferred sites for metastasis had significantly higher PCA than non-preferred organs (P less than 0.001). The PCA of adrenal, lung and colon was significantly reduced by administration of warfarin (P less than 0.001). PCA was significantly (P less than 0.001) increased in both colonic anastomoses and regenerating liver and followed a time course similar to that of the enhanced tumour growth usually seen in these situations. Although the exact source of the procoagulant activity remains to be determined, the results suggest that there is a broad correlation between tissue PCA and the ability of a tissue to support metastatic tumour growth.

Anastomosis, Surgical↗
PubMed1992

Urinary tissue factor levels in transitional cell carcinoma of the bladder.

Production of procoagulant activity by host and tumour cells may be increased in patients with cancer. Using a simple chromogenic assay, we have determined urinary tissue factor (TF) levels in patients presenting with transitional cell carcinoma of the bladder (TCC, n = 63), normal controls (n = 20) and patients with benign prostatic hypertrophy (BPH, n = 35). In addition, a separate cohort of patients undergoing endoscopic surveillance for superficial bladder cancer were studied to determine whether there was any difference in levels in those with recurrent disease compared to those with normal cystoscopies. Urinary TF activity was higher in TCC compared to controls (p less than 0.001) and patients with BPH (p less than 0.05). In patients undergoing check cystoscopy, those with recurrent disease (n = 32) had higher levels (p less than 0.01) than those with normal examinations (n = 21). It is concluded that urinary TF levels are elevated in bladder cancer and that this reflects disease activity in those at risk of recurrent superficial disease.

Carcinoma, Transitional Cell↗
PubMed1991

Subjective and objective assessment of enalapril in primary Raynaud's phenomenon.

1. The efficacy and acceptability of enalapril were assessed in a double-blind, randomised, placebo controlled cross-over study in 21 patients with primary Raynaud's phenomenon. 2. Skin temperature was assessed by thermocouples in response to a 15 degrees C cold water challenge as an index of digital blood flow. 3. Following enalapril there were no significant changes in the number and severity of Raynaud's attacks, and no subjective benefit from treatment as measured by visual analogue scales, 5 point rating scales, and skin temperature response to cold challenge when compared with placebo. 4. Enalapril in a dose of 20 mg daily is ineffective in the management of primary Raynaud's phenomenon.

Adult↗
PubMed1990

Urinary tissue factor activity in colorectal disease.

Procoagulant activity (PCA) in normal urine has been recognized for over 50 years. Although tissue factor (TF) is produced by certain tumours, and is increased in both tumour-associated macrophages and blood monocytes, the possibility that it might also be increased in urine has not been studied in patients with cancer. We have measured urinary PCA in hospital controls without inflammatory or neoplastic disease (n = 79), in patients with rheumatoid arthritis (n = 8), inflammatory bowel disease (n = 19), colorectal cancer (n = 70) and in patients undergoing colonoscopy (n = 50). Urinary PCA was higher (P less than 0.001) in patients with colorectal cancer and inflammatory bowel disease than controls or patients with rheumatoid arthritis. Fourteen (88 per cent) out of 16 colonoscopy patients subsequently found to have carcinoma or inflammatory bowel disease had levels above the control upper quartile, compared with 8 (24 per cent) out of 34 with normal colonoscopy (P less than 0.001). TF inhibitors confirmed the nature of the PCA and Western blotting studies indicated a urinary TF molecular weight of approximately 38,000. These studies provide further evidence of abnormal haemostasis in malignancy and suggest that determination of urinary TF may provide a useful screening test in patients undergoing colonoscopy.

Arthritis, Rheumatoid↗
PubMed1990

The use of aprotinin in thrombocytopenic patients: a preliminary evaluation.

Previous studies have shown that high dose aprotinin successfully reduces blood loss in patients undergoing cardiac or vascular surgery, but the use of this approach to reduce bleeding associated with thrombocytopenia has not been studied. We report the results of high dose aprotinin treatment in five patients with thrombocytopenia of differing aetiology. Aprotinin was effective in controlling bleeding in all five patients, some of whom would otherwise have had a poor prognosis. These results suggest that this agent may have a role in the supportive treatment of thrombocytopenia and point to the need for controlled trials of high dose aprotinin treatment in such individuals.

Adult↗
PubMed1989

Vibrotactile sensation and response to nifedipine dose titration in primary Raynaud's phenomenon.

The clinical response to two doses of sustained-release nifedipine was assessed during a double-blind, randomized, placebo-controlled trial in 22 patients with primary Raynaud's phenomenon. Nifedipine at doses of 20 mg and 40 mg daily reduced the mean number of attacks by 40% compared with placebo with no significant differences between the two doses in the number of attacks or their severity. Unwanted effects were more common and more persistent with the higher dose of nifedipine. Fingertip vibrotactile thresholds measured at 31.5 and 125 Hz were unchanged by treatment with nifedipine. There was, however, a correlation between the pretreatment threshold at 125 Hz and the response to treatment with nifedipine, the most favorable responses occurring in patients with the lowest thresholds.

Adolescent↗
PubMed1988

Factor X-activating activity in normal and malignant colorectal tissue.

The factor X-activating activity (FXAA) of homogenates from human colorectal tumours and corresponding normal colonic mucosa from the same patients was assessed with a specific chromogenic substrate technique. FXAA was detected in all normal and tumour tissue tested, but was significantly higher in tumour tissue. The procoagulant activity was inhibited by DFP, but was unaffected by iodoacetamide and mercuric chloride. FXAA was largely abolished by prior incubation of both normal and tumour tissue homogenates with a rabbit anti-human factor VII serum, but was greatly enhanced by the addition of purified factor VII. FXAA was partially adsorbed on to aluminium hydroxide and almost completely abolished by treatment with barium citrate. It is concluded that the FXAA of both normal and malignant colorectal tissue is the result of tissue factor-factor VII interaction.

Adsorption↗
PubMed1988

The effect of nisoldipine on whole blood platelet aggregation in patients with Raynaud's phenomenon.

1. Whole blood platelet aggregation was measured by electrical impedance in 28 controls and 28 patients with primary Raynaud's phenomenon. 2. The patients were entered into a double-blind, placebo-controlled cross-over trial of the calcium antagonist nisoldipine, in which they received, in random order, three, 4 week treatments with placebo and nisoldipine (5 and 10 mg day-1). 3. Platelet aggregation responses to two concentrations (5.0 and 0.5 micrograms ml-1) of collagen were determined before treatment and at the end of each treatment phase. 4. There were no differences in aggregation response to either collagen concentration between controls and patients with primary Raynaud's phenomenon, or between placebo and active treatment phases. 5. These data do not support the suggestion that nisoldipine has a significant anti-platelet effect.

Adult↗
PubMed1987

Factor X-activating activity in patients with colorectal carcinoma.

The ability of malignant tissue from 50 patients with colorectal carcinoma to activate blood coagulation factor X directly was compared with samples of adjacent, macroscopically normal colonic mucosa from the same patients, and tissue from four patients with non-malignant bowel disease. The resected tissue was homogenized and incubated with purified factor X and calcium ions. The subsequent generation of activated factor X was measured spectrophotometrically with a chromogenic substrate. Results were expressed as absorbance units, and as the ratio of tumour and normal activities. Factor X-activating activity (FXAA) was present in all normal and malignant tissues tested. FXAA was significantly greater (P less than 0.001) in the tumour homogenates than in the uninvolved tissue. The tumour:normal ratio was significantly (greater than 1.2) elevated in 38 patients (76 per cent). FXAA was not correlated with the degree of differentiation of the tumour, the Dukes' classification of the disease or the exact site of the tumour. There was no difference between the FXAA content of non-involved tissue from the colorectal cancer group and colonic mucosa from patients with non-malignant bowel disease. It is concluded that colorectal carcinomas contain significantly more FXAA than adjacent, non-malignant colonic mucosa from the same subject, but there is no direct evidence for a relationship between procoagulant levels and the extent of malignancy in these patients.

Adenocarcinoma↗
PubMed1986

Clinical and rheological effects of nifedipine in Raynaud's phenomenon.

Thirty-four patients with Raynaud's phenomenon, 28 primary and six secondary, were entered into a double-blind placebo controlled, randomized cross-over trial of nifedipine treatment. Nifedipine was given as a 20 mg biphasic release formulation twice daily. Twenty-nine patients completed the study, during which the mean number of attacks was reduced by 25% during nifedipine treatment (P less than 0.001). Twenty patients scored nifedipine higher than placebo on a five point rating scale (P less than 0.001). Unwanted effects were experienced by 26 patients during active treatment, resulting in withdrawal from the study in five. Red cell deformability and fibrinogen concentrations were not altered by nifedipine.

Adolescent↗