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Biomedical subjects

C D Forbes

Publications and source records attributed to C D Forbes.

At least 127 records · Page 7Linked to original sources
PubMed1985

Double-blind trial of CL115,347, a transdermally absorbed prostaglandin E2 analogue, in treatment of Raynaud's phenomenon.

CL115,347 (Cyanamid International) is a stable transdermally absorbed prostaglandin E2 analogue said to have an antiplatelet vasodilatory effect. In a trial of this drug in Raynaud's phenomenon 15 patients were given 1 mg CL115,347/day transdermally for 6 weeks and 14 were given a placebo. The treated group had fewer and shorter spasm attacks and better healing of ulcers as assessed on a visual analogue scale. Blood supply as measured by cold challenge plethysmography ('Medimatic SP2') was also improved by CL115,347, as were hand temperatures. The treated group also had a significant rise in platelet count, but initial decreases in platelet aggregation were not maintained up to the end of the study.

Administration, Topical↗
PubMed1985

Further studies on the role of red blood cells in spontaneous platelet aggregation.

The influence of red blood cells on platelet aggregation has recently been a subject of considerable interest. We have studied the effect of red cells on spontaneously formed platelet aggregates in rotating vials at 37 degrees C. Platelet aggregation was quantified by measuring the fall in number of single platelets with a whole blood platelet counter. Autologous packed red cells, platelet rich plasma and platelet free plasma were used to reconstitute aliquots of blood with constant platelet count but 0-60% haematocrit (Hct). The fall in platelet count was minimal at zero Hct, increased markedly with the Hct in the anaemic range and less markedly in the normal to polycythaemic ranges of Hct. Scanning electron microscopic observation of whole blood showed the presence of small platelet aggregates after about 3 mins rotation and very large aggregates after about 12 mins. ADP from red cells has been implicated in triggering platelet aggregation in whole blood. Whether aggregates are formed as a result of ADP leaking from the red cells or by their jostling physical action on the platelets is discussed. The marked effect of the red cells on spontaneous platelet aggregation however, justifies the manipulation of the Hct as a useful therapeutic option in the control of thrombotic and bleeding tendencies.

Adult↗
PubMed1985

Plasma beta-thromboglobulin, fibrinopeptide A and B beta 15-42 antigen in relation to postoperative DVT, malignancy and stanozolol treatment.

Plasma levels of betathromboglobulin (BTG), fibrinopeptide A (FPA) and B beta 15-42 fragment, indices of platelet release, thrombin generation and plasmin activity respectively, were measured in 32 high risk patients during a double blind study of a single dose of the anabolic steroid stanozolol (50 mg IM) in the prevention of DVT after major gastro-intestinal surgery. The prevalence of malignancy and the incidence of DVT (125I fibrinogen scan) were similar in the two treatment groups. On the first postoperative day, BTG, FPA and B beta 15-42 levels were increased in most patients. Plasma BTG levels were significantly increased on the first post-operative day in patients who developed a DVT (n = 14) compared to those patients who did not (n = 18). A significant increase in FPA levels was found in the DVT group, 7 days after surgery. On the morning before surgery, plasma B beta 15-42 levels were significantly increased in patients who developed a DVT. In patients undergoing surgery for early malignancy (n = 17), we observed a pre-operative increase in FPA levels when compared to patients without malignancy. At post-operative day 7, B beta 15-42 levels were significantly increased in patients who received stanozolol (n = 15), when compared to the placebo group, suggesting that intramuscular stanozolol increases fibrinolysis in vivo.

Beta-Globulins↗
PubMed1985

Development of a radioimmunoassay for the measurement of prostacyclin metabolites in unextracted plasma.

Levels of plasma 6-keto-prostaglandin F1 alpha (6-keto-PGF 1 alpha) measured in normal subjects by radioimmunoassay show wide variation. In an attempt to develop a sensitive, specific and reproducible assay for the measurement of the circulating metabolites of prostacyclin (PGI2) we examined the different variables involved in radioimmunoassay such as choice of buffer; incubation time and temperature; amount of radioisotope tracer added and the separation method. The method described gives good reproducibility and shows good correlation with in vivo and in vitro doses of PGI2.

6-Ketoprostaglandin F1 alpha↗
PubMed1985

Increased prostacyclin metabolites and decreased red cell deformability in patients with systemic sclerosis and Raynauds syndrome.

Patients with systemic sclerosis (SS) often suffer from Raynaud's Syndrome (RS). As prostacyclin (PGI2) is of benefit in the treatment of RS in SS, we have measured endogenous stable metabolites of PGI2 (PGI2m) in 42 patients with Raynaud's Phenomenon (RP) of varying aetiology (15 SS patients, 15 patients with Raynaud's Disease (RD) but no other symptoms, and 12 other RS patients with probable connective tissue disorder). Results were compared with 15 matched controls. Since abnormally rigid red blood cells (RBC) may occur in SS, we also measured RBC deformability (filtration technique). Results show that the SS group have significantly elevated PGI2m levels compared to patients with RD alone and normal controls. In addition, SS patients have more rigid RBC. If all 42 patients with RS were analysed, a significant correlation between PGF and RBC filtration was obtained. The cells of SS patients are resistant to the effects of PGI2 and it would appear that as a compensatory mechanism, production of PGI2 is increased. Treatment with exogenous PGI2 may overcome this resistance and improve microcirculatory flow. The more rigid RBC in SS may also be related to the increased endogenous PGI2. These results may have important clinical implications and allow new therapeutic approaches.

6-Ketoprostaglandin F1 alpha↗
PubMed1985

Inhibition of thromboxane and prostacyclin production in whole blood by adrenoceptor antagonists.

There is increasing evidence implicating thromboxane A2 (TxA2) in vascular disease. Adrenergic blocking agents have been used with success in the secondary prevention of myocardial infarction. The aim of this study was to determine whether adrenergic blocking agents had any effect on the production of TxA2 and prostacyclin (PGI2) from whole blood in vitro. Fresh whole blood without anticoagulant was placed in glass tubes containing either drug or vehicle, the latter acting as control, and allowed to clot at 37 degrees C for 30 minutes. The serum PGI2 metabolites (PGI2M) and TxB2 (the stable hydration product of TxA2) were determined by radioimmunoassay. Labetalol, pindolol and propranolol all inhibited both PGI2M and TxB2 production in a dose dependent manner, while atenolol had no effect. Labetalol was the most potent significantly inhibiting TxB2 production at a drug concentration compatible with that found in-vivo. This inhibitory effect on TxB2 production may be of benefit in the treatment of vascular disease.

Adrenergic alpha-Antagonists↗
PubMed1985

The effect of a prostacyclin analogue (Iloprost) on skin temperature.

Skin temperature was measured in the forearms of 8 healthy volunteers to study the effect of transdermal application of a stable prostacyclin analogue (Iloprost). Local skin temperature was significantly increased 24 hours and 48 hours after application of the drug when compared with an area of control skin. The effect had worn off by 72 hours. At a dose of 25 micrograms there were no systemic effects of vasodilatation or antiplatelet behaviour, but when the dose was increased to 75 micrograms there was a decreased rate of platelet aggregation for 24 hours. Histology of a skin biopsy suggested that the increase in skin temperature was due to vasodilatation and not acute inflammatory reaction. The results of this pilot study suggest that transdermal application of Iloprost is a suitable vehicle for administration of the drug and a prospective randomised trial is proposed for patients with Raynaud's Syndrome.

Administration, Topical↗
PubMed1985

Radio-isotopic joint scans in haemophilic arthritis.

The majority of severe haemophiliacs will develop a crippling arthritis consequent upon recurrent haemarthroses although the pathogenic mechanism remains unclear. We have carried out technetium-99 pertechnetate joint scans in the elbows, knees and ankles of 23 haemophilic patients and compared the isotope uptake of the 15 patients with clinical and radiological evidence of arthritis to that of eight patients without arthritis, to 13 age-matched healthy male controls, and to 10 age-matched males with active rheumatoid arthritis. Isotope uptake into the knee joints was significantly higher in haemophilic arthritis than in controls, haemophiliacs without arthritis, and patients with rheumatoid arthritis [median percentage uptake of administered technetium (Tc) dose X 10(3) in right knee = 9.4, 6.2, 6.4 and 6.6, respectively]: and the differences from haemophilic arthritis were all significant (p less than 0.01, Mann-Whitney U test). Similar differences were seen in the elbows and ankles. Increased Tc uptake correlated strongly with frequency of haemarthrosis, pain, synovitis, range of movement and radiological changes in knees and elbows, but poorly with the lesser changes seen in the ankles. These results would support the theory that haemophilic arthritis amongst the inflammatory arthropathies and that scanning is an appropriate technique for following progression of joint disease.

Ankle Joint↗
PubMed1985

Platelet sensitivity to a prostacyclin analogue in systemic sclerosis.

Vascular prostacyclin (PGI2) regulates platelet function and blood flow. In systemic sclerosis (SS) there is increased platelet aggregation (PA) but no information is available on the platelet/PGI2 relationship. We evaluated platelet sensitivity to a PGI2 analogue ZK36374 in 17 SS patients and 18 controls. The percentage (%) inhibition of PA was measured at two doses of ZK36374 with saline giving the 100% baseline. In the SS group 2 ng ZK36374 produced a percentage inhibition of 19 + 14 compared to a control value of 60 + 21, and 3 ng a percentage inhibition of 47 + 21 in the SS group and 82 + 20 in the controls. In 11 SS patients treated with either prostaglandin E or nifedipine the sensitivity approached normal. These data suggest that SS platelets are less sensitive to the inhibitory effect of PGI2 on PA. This may contribute to the vascular lesions of SS. Other cells are resistant to the effects of PGI2 and our findings support this picture of cellular resistance.

Adult↗
PubMed1985

Immunoreactive prostacyclin and thromboxane metabolites in normal pregnancy and the puerperium.

Prostacyclin and thromboxane have been implicated in the pathophysiology of several disorders of pregnancy, but there is little information on concentrations of these prostaglandins in normal pregnancy. The aim of our study was to determine the range of values throughout normal pregnancy and the puerperium and to compare this with concentrations in normal non-pregnant women. Measurement was by radioimmunoassay of prostacyclin and thromboxane metabolites. We observed a significant difference in prostacyclin metabolites in the first trimester, (mean 19.9, SEM 0.96 pg/ml) compared with the normal non-pregnant group (mean 15.9, SEM 0.68 pg/ml). There were no significant differences between values in the normal non-pregnant group and those in the second and third trimester or postnatally. The increase in prostacyclin in the first trimester may be associated with placentation and physiological vasodilation, and insensitivity to angiotensin II seen in early pregnancy. We noted a significant reduction in thromboxane metabolites in the second (mean 133, SEM 14.9 pg/ml) and third (mean 123, SEM 10.7 pg/ml) trimesters and the puerperium (mean 119, SEM 6.3 pg/ml) compared with the values in the normal non-pregnant group (mean 142, SEM 4.9 pg/ml). This may be due to increased platelet stability or decreased thromboxane synthesis.

Epoprostenol↗