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Biomedical subjects

C D Forbes

Publications and source records attributed to C D Forbes.

At least 19 recordsLinked to original sources
PubMed1992

Dipyridamole increases human red blood cell deformability.

An automated filtration technique has been used to investigate the effect of dipyridamole (DP) on red blood cell deformability in patients identified as having rigid red cells. They were patients on haemodialysis (HD) for chronic renal failure (n = 18), patients with peripheral vascular disease (PVD, n = 23) and controls (hospital outpatients, n = 33). Leucocytes and platelets were removed from heparinised blood by filtration through Imugard wool. Washed red cell suspensions in buffer at 5% haematocrit, without or with 5 microM DP, were filtered through Nuclepore Hemafil Membranes with 4.7 microns pores. The initial steady state relative filtration pressure (iRFP) was used to assess cell deformability. A low iRFP value reflects increased deformability and vice versa. The mean iRFP values were 0.33, 0.393 and 0.403 for controls, PVD and HD patients respectively, indicating that the red cells in the two groups of patients were significantly more rigid. DP reduced the iRFP to 0.266, 0.278 and 0.263 for controls, PVD and HD patients respectively. The results suggest that DP may be beneficial when red cell rigidity contributes to impaired microvascular perfusion.

Adult↗
PubMed1992

Assessment of blood compatibility of haemodialysis membranes using a miniature flat sheet dialyser.

Available pre-clinical techniques of assessing severity of untoward reaction by blood following contact with haemodialysis membranes do not account for the effects of dialysate and flow characteristics in the observed blood changes. A miniature flat sheet dialyser that considered these effects was prepared and tested in both in-vitro and ex-vivo circuits. Changes in platelets and leucocytes in heparinised human blood in-vitro tests did not distinguish regenerated cellulose (Cuprophan 150PM) membrane from a synthetic membrane, a copolymer of acrylonitrile and sodium methyl sulphonate (AN69S). Ex-vivo tests using rats showed more marked leucocyte (41.3%) and platelet (43.1%) depletion by Cuprophan 150PM than AN69S after 90 minutes of dialysis. Leucocyte and platelet loss due to AN69S were 26.9% and 13.4% respectively. In addition, Cuprophan 150PM membranes exhibited high affinity for leucocytes and platelets in both in-vitro and ex-vivo tests compared to AN69S membranes which were primarily covered with erythrocytes. Application of simulated in-use techniques in preclinical evaluation of blood compatibility membranes that are used in extra-corporeal treatment are recommended.

Acrylic Resins↗
PubMed1991

Relationships of plasma viscosity, coagulation and fibrinolysis to coronary risk factors and angina.

Plasma viscosity, molecular markers of activated coagulation and fibrinolysis (fibrinopeptides A and B beta 15-42), coagulation factors (fibrinogen and factor VII) and antiplasmins were measured in 529 men aged 35-54 years and related to new angina pectoris (n = 117) and to coronary risk factors in controls without angina (n = 412). Five major risk factors (cigarette-smoking, blood pressure, cholesterol, triglyceride and body mass index) were each associated with increases in plasma viscosity, coagulation factors, and imbalance of coagulation over fibrinolysis (increased ratio of fibrinopeptide A/fibrinopeptide B beta 15-42). Increased viscosity and fibrinogen in smokers were partly reversed in ex-smokers, but the imbalance of coagulation and fibrinolysis persisted. Cholesterol and triglyceride were also associated with increased antiplasmin activity. In men with angina, only fibrinogen was elevated compared to controls. We suggest that increased plasma viscosity and an imbalance of coagulation over fibrinolysis may be mechanisms by which known risk factors promote arterial thrombosis, but are not present in stable angina.

Adult↗
PubMed1991

B cell dysfunction in haemophilia in the absence and presence of HIV-1 infection.

56 haemophiliacs selected on the basis of HIV-1 antibody status, liver disease grade and mean annual dose of clotting factor concentrate used were studied. Spontaneous and stimulated IgG and IgM production in vitro were measured. HIV-1 infection was associated with increased spontaneous immunoglobulin production and an impaired response to pokeweed mitogen and Staph Aureus protein A. Implying a shift in the proportions of partially and fully activated B cells. In the absence of HIV-1 infection there was a shift to a greater proportion of partially activated B cells in patients with severe liver disease. The remainder had in vitro immunoglobulin production comparable to controls. B cell abnormalities occur early in the course of HIV-1 infection. Liver disease and not clotting factor concentrate treatment cause B cell abnormalities in the absence of HIV-1 infection in haemophilia.

Adolescent↗
PubMed1991

Effect of dipyridamole alone and in combination with aspirin on whole blood platelet aggregation, PGI2 generation, and red cell deformability ex vivo in man.

STUDY OBJECTIVE: The aim was to investigate the effects of dipyridamole, aspirin, and a combination of dipyridamole plus aspirin on platelet aggregation in whole blood, PGI2 generation, and red cell deformability ex vivo. SUBJECTS: were 16 male volunteers, aged 22-39 years, mean age, 26.6 years. DESIGN: This was a randomised, double blind, placebo controlled trial. The volunteer received each of the following treatments 10 days apart: dipyridamole 200 mg; aspirin 300 mg; dipyridamole 200 mg plus aspirin 300 mg; matched placebos. MEASUREMENTS AND MAIN RESULTS: Blood was taken for platelet function tests, PGI2 metabolite assay, and red cell deformability before and 2 h after the trial dose was taken. Platelet aggregation was quantified by measuring the fall in single platelet count after stimulation with 2 micrograms.ml-1 collagen or 50 nM platelet activating factor (PAF), or by rollermixing aliquots of blood to initiate spontaneous aggregation. The platelet function tests were completed at 37 degrees C within 10 min of venepuncture. The stable metabolite of PGI2, 6-keto PGF1 alpha, was measured in serum. There was inhibition of spontaneous platelet aggregation by dipyridamole (p less than 0.004), aspirin (p less than 0.005), and the combination of dipyridamole plus aspirin (p less than 0.0001) as compared with placebo. PAF induced platelet aggregation was inhibited by dipyridamole (p less than 0.002) and the combination of dipyridamole plus aspirin (p less than 0.0001) but aspirin alone had no inhibitory effect. Collagen induced platelet aggregation was inhibited by all three treatments: dipyridamole (p less than 0.06), aspirin (p less than 0.0001), and the combination of dipyridamole plus aspirin (p less than 0.0001). PGI2 generation was markedly inhibited by aspirin (p less than 0.0001) and the combination doses (p less than 0.0001) but was unaffected by dipyridamole alone. Of the three active treatments, only dipyridamole alone significantly (p less than 0.001) increased red cell deformability; there was a modest decrease in red cell deformability with aspirin. CONCLUSIONS: The results with PAF support the view that dipyridamole inhibits platelet activation by more than one mechanism; the effect on collagen induced and spontaneous platelet aggregation suggests that the effect of the combination doses is additive and that on red cell deformability the synergy is negative.

6-Ketoprostaglandin F1 alpha↗
PubMed1991

Haemorrhagic problems in obstetrics and gynaecology in patients with congenital coagulopathies.

OBJECTIVE: To review the obstetric and gynaecological problems in women with congenital coagulopathies. DESIGN: Retrospective review. SETTING: Regional Adult Haemophilia Unit, Glasgow Royal Infirmary. SUBJECTS: All women in contact with the Unit over a period of 30 years, comprising eight with von Willebrand's disease, 18 obligate carriers of haemophilia A and five obligate carriers of Christmas disease. Each woman was interviewed and details of their obstetric and gynaecological histories were obtained and their case records were reviewed. MAIN OUTCOME MEASURES: Haemostatic changes associated with pregnancy and gynaecological problems. RESULTS: In 14 pregnancies in seven patients with von Willebrand's disease, there were four primary and four secondary post-partum haemorrhages and a large perineal haematoma complicating an episiotomy. These problems arose despite the endogenous rise in factor VIIIc seen with pregnancy. All women seen with von Willebrand's disease complained of menorrhagia and had been referred to gynaecologists. Treatment included danazol, tranexamic acid and the contraceptive pill. Diagnostic curettage resulted in severe haemorrhage in one woman and two women with pelvic pain and dyspareunia were found to have spontaneous broad ligament haematomas, one requiring surgery. In 43 pregnancies in obligate carriers of haemophilia A and Christmas disease there were five post-partum haemorrhages and a large perineal haematoma. CONCLUSION: In von Willebrand's disease it should be noted that adequate laboratory correction of factor VIIIc levels does not ensure clinical haemostasis; hence platelet function should also be measured. Patients with congenital coagulopathies pose particular problems for the obstetrician and gynaecologist and should be managed in close association with the local haemophilia centre.

Blood Coagulation Disorders↗
PubMed1991

Retrospective cohort mortality study of workers at an aircraft maintenance facility. I. Epidemiological results.

A retrospective cohort study of 14,457 workers at an aircraft maintenance facility was undertaken to evaluate mortality associated with exposures in their workplace. The purpose was to determine whether working with solvents, particularly trichloroethylene, posed any excess risk of mortality. The study group consisted of all civilian employees who worked for at least one year at Hill Air Force Base, Utah, between 1 January 1952 and 31 December 1956. Work histories were obtained from records at the National Personnel Records Centre, St. Louis, Missouri, and the cohort was followed up for ascertainment of vital state until 31 December 1982. Observed deaths among white people were compared with the expected number of deaths, based on the Utah white population, and adjusted for age, sex, and calendar period. Significant deficits occurred for mortality from all causes (SMR 92, 95% confidence interval (95% CI) 90-95), all malignant neoplasms (SMR 90, 95% CI 83-97), ischaemic heart disease (SMR 93, 95% CI 88-98), non-malignant respiratory disease (SMR 87, 95% CI 76-98), and accidents (SMR 61, 95% CI 52-70). Mortality was raised for multiple myeloma (MM) in white women (SMR 236, 95% CI 87-514), non-Hodgkin's lymphoma (NHL) in white women (SMR 212, 95% CI 102-390), and cancer of the biliary passages and liver in white men dying after 1980 (SMR 358, 95% CI 116-836). Detailed analysis of the 6929 employees occupationally exposed to trichloroethylene, the most widely used solvent at the base during the 1950s and 1960s, did not show any significant or persuasive association between several measures of exposure to trichloroethylene and any excess of cancer. Women employed in departments in which fabric cleaning and parachute repair operations were performed had more deaths than expected from MM and NHL. The inconsistent mortality patterns by sex, multiple and overlapping exposures, and small numbers made it difficult to ascribe these excesses to any particular substance. Hypothesis generating results are presented by a variety of exposures for causes of death not showing excesses in the overall cohort.

Aircraft↗
PubMed1991

Retrospective cohort mortality study of workers at an aircraft maintenance facility. II. Exposures and their assessment.

Methods are presented that were used for assessing exposures in a cohort mortality study of 15,000 employees who held 150,000 jobs at an Air Force base from 1939 to 1982. Standardisation of the word order and spelling of the job titles identified 43,000 unique job title organisation combinations. Walkthrough surveys were conducted, long term employees were interviewed, and available industrial hygiene data were collected to evaluate historic exposures. Because of difficulties linking air monitoring data and use of specific chemicals to the departments identified in the work histories, position descriptions were used to identify the tasks in each job. From knowledge of the tasks and the chemicals used in those tasks the presence or absence of 23 chemicals or groups of chemicals were designated for each job organisation combination. Also, estimates of levels of exposure were made for trichloroethylene and for mixed solvents, a category comprising several solvents including trichloroethylene, Stoddard solvent, carbon tetrachloride, JP4 gasoline, freon, alcohols, 1,1,1-trichloroethane, acetone, toluene, methyl ethyl ketone, methylene chloride, o-dichlorobenzene, perchloroethylene, chloroform, styrene, and xylene.

Aircraft↗
PubMed1990

Self- and other-awareness of the risk of HIV/AIDS in people with haemophilia and implications for behavioural change.

Many people with haemophilia have been infected by HIV through the contamination of blood products they need for treatment of their bleeding. This study explored the perceptions of people with haemophilia of their own and others' risk of HIV/AIDS and their beliefs about others' perceptions of HIV/AIDS. The results have shown that many patients are not willing to disclose the existence of their haemophilia to certain categories of people and have a firm view of who should and should not know about their HIV antibody status. The patients' beliefs of others' perceptions of HIV and AIDS are associated with (a) their perceptions of risk for themselves and others and (b) with behavioural change to prevent the spread of HIV.

Adolescent↗
PubMed1990

HIV-1 infection in haemophilia.

Guidelines have been prepared by the National Hemophilia Foundation, USA, for treating patients with haemophilia, these are: 1. General recommendations. The risks of withholding treatment far outweigh risks of treatment. Patients should however be educated to use appropriate clotting factor doses to minimize overuse and contain costs. 2. Factor VIIIC-deficient patients. DDAVP should be used whenever possible by patients with mild or moderate factor VIIIC deficiency. When feasible, an alternative to concentrates may be the use of cryo-precipitate prepared from one well-screened donor or from a small number of such donors. (a) Prevention of hepatitis. Hepatitis B vaccination is essential for uninfected patients. Preliminary data suggest that products that are pasteurized, solvent/detergent-treated or monoclonal antibody-purified are at a reduced risk of transmitting hepatitis viruses. (b) Prevention of HIV-1. Concentrates pasteurized, treated with solvent/detergent, purified with monoclonal antibody, heated in suspension with organic solvents, or dry heat-treated for long periods are preferred. These products carry a substantially reduced risk of transmitting HIV-1. 3. Factor IX deficiency. For patients with severe deficiency the use of virus-inactivated Factor IX concentrate is recommended. For mild to moderate patients when feasible an alternative would be fresh, frozen plasma prepared from one well-screened and repeatedly-tested donor or from a small number of such donors. In the past few years, significant progress has been made in understanding the nature of the defect in haemophilia both at the molecular and structural levels, such a foundation is necessary for definitive treatments in the future. For now, however, the dark side of replacement therapy must be accepted along with its benefits.

Factor IX↗
PubMed1990

Daily living problems of people with haemophilia and HIV infection: implications for counselling.

The advent of AIDS not only signifies the emergence of a new disease that affects hitherto healthy members of the general population but also highlights many unresolved problems of people with haemophilia, a life-long genetic disorder of blood clotting. Although HIV infection and the threat of AIDS has been a tragedy for people with haemophilia, the reported study shows that in spite of recent technological advancement in treatment, problems caused by haemophilia as such are still devastating for some severely affected patients. The ability of people with haemophilia to cope with their daily living problems such as chronic and acute pain, stress in the family, difficulties with unemployment and social relationships affects their response to HIV/AIDS. These facts have important implications for their rehabilitation and counselling and raise questions about coping with HIV/AIDS for other risk groups.

Acquired Immunodeficiency Syndrome↗
PubMed1990

Capacity to produce interleukin 2 is impaired in haemophilia in the absence and presence of HIV 1 infection.

Capacity to produce interleukin-2 (IL-2) was measured in haemophiliacs from a well-defined treated cohort. Patients were selected on the basis of HIV-1 antibody status, mean annual dose of clotting factor and liver disease severity. T-cell subsets and peripheral blood mononuclear cell proliferation to Mycobacterium tuberculosis purified protein derivative (PPD) were also measured. Haemophiliacs had reduced IL-2 production, independent of HIV-1 antibody status, mean annual dose of clotting factor concentrate used and liver disease severity. In HIV-1 antibody positive patients reduced levels correlated with PPD proliferative responses (r = 0.6, P = 0.04) and CD8 + ve (r = 0.5, P = 0.05) but not CD4 + ve cell numbers (r = 0.3, P = 0.2). No such correlations were seen in HIV-1 antibody negative patients. Reduced IL-2 production in HIV-1 antibody negative haemophiliacs was due to a qualitative defect. In HIV-1 positive patients a qualitative defect in T lymphocytes that selectively proliferate in response to PPD was observed. CD4 + ve cell numbers were reduced in HIV-1 positive patients.

Adult↗
PubMed1990

Further evidence that the residual vWf:Ag in porcine FVIII:C induces human platelet aggregation.

Porcine or bovine factor VIII concentrates (FVIII:C) have been used during the past 3 decades to control bleeding in patients who have developed antibodies to human factor VIII. Since current preparations of animal FVIII:C are not known to transmit infectious agents such as hepatitis or human immunodeficiency virus, they are of potential therapeutic interest. A purified porcine FVIII:C (Hyate:C) is now widely used as an alternative to human FVIII:C in patients with inhibitor. Unlike earlier preparations of porcine FVIII:C, thrombocytopaenia is rare with the current preparation. Nonetheless, it causes the aggregation of human platelets in vitro. Our aim was to identify precisely the plasma factor which induces platelet aggregation. The effects of commercial porcine FVIII:C, porcine fibrinogen, porcine fibronectin and the corresponding preparations from human origin on platelet aggregation were studied. Platelet aggregation was quantified by measuring the fall in single platelet count in human whole blood. Of these preparations, only porcine FVIII:C (0.1-1 U/ml) and porcine fibrinogen (80-600 micrograms/ml) induced a fall in single platelet count of up to 85% due to aggregation. The extent of aggregation was directly proportional to the amount (0.007-0.1 U/ml test aliquot) of residual von Willebrand factor antigen (vWf:Ag) in the preparations. A monoclonal antibody to vWf:Ag inhibited the aggregation. We believe that the aggregation of human platelets induced in vitro by porcine FVIII:C is mediated by vWf:Ag which also may be responsible for thrombocytopaenia reported following administration of porcine FVIII:C in vivo.

Animals↗