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Biomedical subjects

J L Francis

Publications and source records attributed to J L Francis.

At least 19 recordsLinked to original sources
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↗
PubMed1992

The effect of Warfarin and factor VII on tissue procoagulant activity and pulmonary seeding.

Peri-tumour fibrin is a consistent feature of tumour stroma and is deposited shortly after tumour cell inoculation. Since there are several ways in which fibrin may be beneficial to tumour growth, it is possible that the ability of normal or malignant tissue to generate fibrin may influence metastasis. Many normal tissues and tumour cells possess a procoagulant activity that is due to a complex of tissue factor and factor VII. We have measured this tissue procoagulant activity in normal rats, rats stabilised on Warfarin and similarly anticoagulated animals injected with factor VII. The effect of Warfarin and factor VII administration on pulmonary seeding following injection of MC28 fibrosarcoma cells was also assessed. Procoagulant activity in adrenal, lung and colon was significantly reduced by Warfarin (P less than 0.001). Administration of factor VII significantly increased lung and adrenal tissue procoagulant activity in anticoagulated rats (P less than 0.02). Warfarinised rats had significantly slower primary tumour growth (P less than 0.001) and fewer lung deposits than control animals (P less than 0.001). Injection of factor VII restored pulmonary seeding to control levels (P less than 0.001). Warfarin did not affect the ability of the cells to adhere in vitro and did not reduce the number of tumour cells physically trapped in the lungs after intravenous injection. It is concluded that the procoagulant activity of normal tissues may influence their ability to support tumour growth and that the antimetastatic effect of Warfarin may be at least partly due to a reduction in the availability of the factor VII required for this activity.

Adrenal Glands↗
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

Principles of interfacing computers to medical equipment.

Table 3 shows a comparison of the interface standards considered. RS232 has the advantages of availability, flexibility and low cost. Variants on the standard overcome its limitations in data-rate and distance. The Centronics parallel standard is available on most personal computers and is particularly suitable for high data-rates over short distances. Other PC standards such as SCSI are special-purpose interfaces and therefore more difficult to use. GPIB is a robust and well-specified standard often used for the control of laboratory instruments.

Analog-Digital Conversion↗
PubMed1989

Whole blood procoagulant activity in breast and colorectal cancer.

Whole blood procoagulant activity was determined by measuring the recalcification time of citrated blood, with and without the addition of bacterial endotoxin, in patients with breast cancer (n = 39), colorectal cancer (n = 20), benign breast disease (n = 15), benign colorectal disease (n = 11), normal volunteers (n = 15) and inpatients with non-malignant disease (n = 22). The median clotting times of those samples incubated with endotoxin were significantly shorter in the patients with breast and colorectal cancer compared with normal controls. Furthermore, significant differences between the median clotting times of stimulated and unstimulated samples within each subject group were observed only in the two cancer groups. There was no correlation between whole blood procoagulant activity and absolute monocyte counts, with histological staging or with plasma concentrations of plasma fibrinopeptide A. The results suggest that blood from patients with cancer is more sensitive to endotoxin stimulation than that from normal or benign controls, but that in its present form the technique cannot be used to distinguish between malignant and non-malignant disease.

Adult↗
PubMed1989

Haemostasis and cancer.

Patients with cancer have an increased incidence of thromboembolic disease and haemostatic abnormalities, and there is considerable evidence that the haemostatic system is involved in the growth and spread of malignant disease. Anti-haemostatic agents have given promising results in the treatment of experimental tumours, and several clinical trials in humans have been initiated. The formation of fibrin around the tumour may be a particularly important factor in malignant dissemination. The precise mechanisms of peri-tumour fibrin deposition remain to be elucidated, but may involve alterations in local vascular permeability and the presence of tumour and/or macrophage procoagulants. In addition to their role in fibrin formation, haemostatic components may also be involved in neovascularisation and angiogenesis.

Blood Coagulation↗
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↗
PubMed1987

Nisoldipine in primary Raynaud's phenomenon.

The efficacy and tolerability of the dihydropyridine derivative nisoldipine was assessed in 36 patients with primary Raynaud's phenomenon. Nisoldipine was given at doses of 5 mg and 10 mg daily for one month each in a placebo controlled double-blind cross-over trial. There was no subjective improvement in symptoms or changes in resting finger blood flow, platelet aggregability or red cell deformability after nisoldipine. The incidence of unwanted effects was similar to that previously described with nifedipine, suggesting that plasma concentrations of nisoldipine were sufficient to cause pharmacodynamic effects. Nisoldipine, in contrast to nifedipine is ineffective in the treatment of primary Raynaud's phenomen when given in a dose of up to 10 mg/day.

Adult↗