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Biomedical subjects

C D Forbes

Publications and source records attributed to C D Forbes.

At least 55 records · Page 3Linked to original sources
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↗
PubMed1989

Dipyridamole inhibits red cell-induced platelet activation.

We have recently shown that red blood cells can induce spontaneous platelet aggregation (SPA) in whole blood ex vivo, which could be inhibited by dipyridamole. Since this drug, at therapeutic doses is not an effective inhibitor of platelet aggregation in platelet rich plasma, the inhibition of platelet interaction with the red cell was thought to be the mechanism of its action. Values for the percentage fall in the single platelet count due to SPA in whole blood after 3 and 6 min rollermixing were: control 15 +/- 2.2 and 42 +/- 2.9; 6 microM dipyridamole 6 +/- 1.1 (P less than 0.001) and 31 +/- 2.6 (P less than 0.01); 12 microM dipyridamole 2 +/- 0.9 (P less than 0.0005) and 22 +/- 2.3 (P less than 0.0005) (mean +/- SEM, n = 10). Electron microscopic observation revealed that the aggregation involves an initial platelet adhesion to the red blood cell; the adherent platelets then become activated and serve as foci for the growing aggregates. Dipyridamole appeared to inhibit the initial platelet adhesion to the red cell (the principal trigger mechanism for SPA) which may mimic the initiation of thrombosis in some situations in vivo. The inhibitory effect of dipyridamole on the platelet-red cell interaction suggests that this drug has antithrombotic potential in situations where red blood cells have a trigger role in platelet activation and may explain why the drug has been more effective in some situations than in others.

Adult↗
PubMed1989

Free radical pathology in chronic arterial disease.

The generation of toxic oxygen metabolites is more usually associated with inflammation. However, pathological free radical reactions can cause tissue damage by adversely affecting prostacyclin (PGI2) synthesis allowing initiation of coagulation. We have assessed changes in the red cell defence to toxic oxygen metabolite generation, viz measurement of glutathione concentration (GSH) and superoxide dismutase activity (SOD). GSH and SOD were measured in 20 patients with peripheral arterial disease, 22 patients with vasculitis, and 11 patients with angina, and compared to 17 matched controls. The 53 subjects with arterial disease had significantly lower SOD levels: in contrast GSH levels were significantly higher. Extracellularly plasma thiol levels (PSH) were low and caeruloplasmin (Cp) levels were high. We suggest that free radical pathology exists not only in inflammatory vascular disease but also in atherosclerosis.

Angina Pectoris↗
PubMed1989

Platelet aggregation inhibitory effects of the new positive inotropic agents pimobendan and UD CG 212 in whole blood.

A method is described for studying platelet function in human whole blood immediately after venepuncture in order to evaluate the antithrombotic potential of new pharmacological agents. In this method, platelet aggregation is quantified by measuring the fall in single platelet count, by using a whole blood platelet counter. We have investigated the platelet aggregation inhibitory effects of the new positive inotropic agents pimobendan and UD CG 212 (reported to be Ca++ sensitisers and phosphodiesterase inhibitors), alone and in combination with dipyridamole. Venous blood was drawn directly into prewarmed (37 degrees C) plastic syringes containing anticoagulants (3.2% trisodium citrate solution) plus a platelet aggregation inhibitor. Spontaneous platelet aggregation (SPA) was studied by roller mixing aliquots of blood in the collecting syringes for 6 min at 37 degrees C. Collagen induced platelet aggregation was studied by incubating aliquots of blood with 1 microgram/ml collagen on a shaking water bath for 3 min. In the absence of an inhibitor, there was a 50% fall in single platelet count due to SPA and a 65% fall was induced by collagen. Both SPA and collagen induced aggregation responses were inhibited by pimobendan (0.5-10 microM) and UD CG 212 (0.5-10 microM), in a dose dependent manner. A combination of 10 microM dipyridamole with 2 microM pimobendan or UD CG 212 was markedly a more effective inhibitor of platelet aggregation than a high dose of either inhibitor alone. It is suggested that the present method is simple and rapid, with minimal sample processing, and therefore the results may be protected from serious artifacts.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

Histometric studies on cellular infiltrates of tuberculin tests in patients with haemophilia.

The number of microanatomical location of CD4 and CD8 lymphocytes, of cells bearing receptors for I12 and transferrin, and of monocyte/macrophages in the dermis at the site of a tuberculin test were measured in 13 patients with haemophilia (10 seronegative and three seropositive for human immunodeficiency virus (HIV]. The overall density of lymphocytes in the perivascular and diffuse parts of the infiltrate was similar to that reported in other groups of subjects without evidence of immunosuppression. The CD4:CD8 ratio of the infiltrating lymphocytes throughout the section showed an inverse relation with clotting factor consumption. There was no significant change in the CD4:CD8 ratio in the diffuse infiltrate at various levels into the dermis in tuberculin reactions in patients with haemophilia, unlike healthy controls and other groups with no evidence of immunosuppression, who have previously been shown to have increasing CD4:CD8 ratio with increasing depth into the dermis. The number of cells bearing receptors for I12 and transferrin and of monocyte/macrophages was related to total lymphocyte density in the infiltrate. There was no evidence of serious impairment of the cell mediated response to a long term recall antigen, but the relatively low preponderance of CD4 lymphocytes in the diffuse infiltrate, particularly in the deeper dermis, may be the earliest indicator of impending immunosuppression.

CD4-Positive T-Lymphocytes↗
PubMed1989

Comparison of the effect of aspirin and choline magnesium trisalicylate on thromboxane biosynthesis in human platelets: role of the acetyl moiety.

Parameters of platelet thromboxane biosynthesis were measured 24 h after ingestion of equivalent salicylate doses (500 mg) of aspirin (ASA) and choline magnesium trisalicylate (CMT), a non-acetylated salicylate. In random order, 10 healthy volunteers received these drugs on 2 separate days, 2 weeks apart. While ASA significantly prolonged bleeding time, and decreased plasma thromboxane generation and serum thromboxane B2 levels, CMT failed to produce such effects. Thus CMT, which lacks an acetyl moiety in its structure, has no inhibitory effect on platelet thromboxane biosynthesis, and may therefore be considered safer than ASA for therapeutic use, when inhibition of platelet function can be hazardous.

Adult↗
PubMed1988

Haemostatic effects of ketorolac with and without concomitant heparin in normal volunteers.

Ketorolac is a potent cyclo-oxygenase inhibitor used for the treatment of postoperative pain. It is known to have anti-platelet properties. The aim of this study was to determine the effect of ketorolac on haemostasis both alone and in combination with low dose heparin in 12 healthy male volunteers. Each volunteer received the following drug combinations in a double blind, placebo controlled, cross over manner: ketorolac placebo/heparin placebo, ketorolac active/heparin placebo, ketorolac active/heparin active and ketorolac placebo/heparin active. Ketorolac significantly prolonged bleeding time, inhibited platelet aggregation to arachidonic acid and collagen and platelet thromboxane production. Heparin had no effect on bleeding time or platelet function, but significantly prolonged the kaolin cephalin clotting time and increased anti-Xa levels. Ketorolac had no effect on the kaolin cephalin clotting time or anti-Xa levels and no interaction was found between ketorolac and heparin in any of the investigations. The prolongation of bleeding time seen with ketorolac is unlikely, to be of any major clinical significance as almost all subjects remained within the normal range; however, it should be used with caution in subjects with haemostatic problems.

Adult↗
PubMed1988

Mechanisms of joint damage in an experimental model of hemophilic arthritis.

Autologous whole blood was injected into the knee joints of rabbits 3 times each week for 12 weeks. The resulting destructive arthritis showed macroscopic and microscopic changes similar to those described in hemophilic arthritis in humans. Immunofluorescence studies indicated that a specific immune response is probably not involved in the pathogenesis of hemophilic arthritis. Detailed histopathologic examinations of knee joints in both the early and the late phase of arthritis revealed an obvious synovial and cartilage iron load, in the absence of inflammatory changes. The implications of these findings in the pathogenesis of destructive cartilage changes are discussed.

Animals↗
PubMed1988

A double blind randomised placebo controlled trial of hexopal in primary Raynaud's disease.

The peripheral vasospastic symptoms associated with Raynaud's disease continue to be an unsolved clinical problem. Hexopal (Hexanicotinate inositol) has shown promise in uncontrolled studies and its use in patients with Raynaud's disease may reduce such vasospasm. This study examines the effects of 4 g/day of Hexopal or placebo, during cold weather, in 23 patients with primary Raynaud's disease. The Hexopal group felt subjectively better and had demonstrably shorter and fewer attacks of vasospasm during the trial period. Serum biochemistry and rheology was not significantly different between the two groups. Although the mechanism of action remains unclear Hexopal is safe and is effective in reducing the vasospasm of primary Raynaud's disease during the winter months.

Clinical Trials as Topic↗