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Biomedical subjects

C D Forbes

Publications and source records attributed to C D Forbes.

At least 145 records · Page 8Linked to original sources

Application of an intragenic genomic probe to genetic counselling for haemophilia B in the west of Scotland.

Total ascertainment revealed 28 families with haemophilia B in the west of Scotland (prevalence 1/26 870 males). In 12 of these families more than one person was affected and 26 living obligate carriers were identified and tested. Of these, 42% were heterozygous for a DNA polymorphism recognised by a factor IX genomic probe. No recombination was observed in 11 phase known and four phase unknown informative meioses. Definitive genetic counselling was possible for 14 of 42 females at risk, 11 could not be traced, in 10 the probe was not informative, and in seven paternal absence prevented interpretation. Linkage disequilibrium was apparent for this restriction fragment length polymorphism and haemophilia B in the west of Scotland.

DNA↗

Evaluation of euglobulin methods for the study of blood fibrinolytic activity: results for patients with rheumatoid arthritis and in the postoperative period.

Euglobulin fractionation is a frequently employed pretreatment of plasma for the determination of fibrinolytic activity. The fractionation procedure suffers from possible in vitro artifacts, e.g., variable precipitation of C1-inactivator. This is illustrated by the following two situations. It is shown that increased amounts of C1-inactivator not related to an increased plasma concentration are present in euglobulin fractions in cases of classic rheumatoid arthritis. Similarly, postoperatively, a disproportional increase in C1-inactivator in euglobulin fractions occurs. In both cases, an artificially reduced fibrinolytic activity is recorded due to increased inhibition by C1-inactivator. This is circumvented and recognized by adding sodium flufenamate or C1s-esterase to euglobulin fractions to uniformly eliminate C1-inactivator. Two specific assays for tissue-type plasminogen activator activity in euglobulin fractions (as C1-inactivator-resistant activator activity and a parabolic rate assay on a synthetic substrate) correlate excellently (r = 0.8728; p less than 0.001; n = 108). The first mentioned is corrected for variable endogenous C1-inactivator; the latter assay is found to be insensitive to inhibition by C1-inactivator. It is concluded that with euglobulin methods a misinterpretation of blood fibrinolytic activity is possible in rheumatoid arthritis patients. In the postoperative period, the fibrinolytic shutdown concerns tissue-type plasminogen activator activity; the pattern of the shutdown can be misjudged in using traditional euglobulin methods.

Abdomen↗

Non-steroidal anti-inflammatory drugs in haemophilic arthritis. A clinical and laboratory study.

Non-steroidal anti-inflammatory drugs are theoretically contra-indicated in the haemophilias but might be useful for those patients with chronic arthritic pain, as long-term strong analgesics are also undesirable. We carried out studies of platelet function and coagulation in 8 normal controls and 7 haemophiliacs while they were taking sequentially benoxaprofen and salsalate. No significant alterations in platelet function, bleeding time or coagulation occurred with either drug. In a subsequent double-blind controlled clinical trial using ibuprofen and placebo 8 of 9 patients had a significant reduction in pain score whilst using ibuprofen without significant change in the frequency of bleeds or the amount of concentrate used. Laboratory measures of coagulation also failed to reveal any adverse effect of the active drug. Non-steroidal anti-inflammatory drugs may be beneficial and may be used with caution in haemophilia.

Adult↗

The effect of fibrinolytic stimulation by stanozolol on postoperative pulmonary complications.

Platelet aggregation in the lungs is common following abdominal surgery and may contribute to postoperative hypoxaemia. The hypothesis that an anabolic steroid, stanozolol, by preventing fibrinolytic shutdown, would prevent postoperative hypoxaemia was tested. Fifty patients undergoing abdominal surgery were randomly allocated to receive either placebo or stanozolol. Despite preventing fibrinolytic shutdown in most patients, the use of stanozolol did not influence the extent of postoperative hypoxaemia or the incidence of postoperative pulmonary complications. These results suggest that fibrinolysis does not play a significant part in the pathogenesis of postoperative pulmonary dysfunction.

Adult↗

AIDS--again.

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Acquired Immunodeficiency Syndrome↗

Haematocrit in patients attending a hypertension clinic.

In view of recent interest in the relationship of haematocrit and blood viscosity to hypertension and vascular disease, we have analysed retrospectively the relationship of haematocrit to blood pressure, vascular complications and other variables in 2,381 patients referred to the Glasgow Blood Pressure Clinic. Haematocrit correlated negatively with age and systolic pressure in men, and positively with age and systolic pressure in females. Positive correlations were found in both sexes between haematocrit and serum alanine aminotransferase (possibly due to mutual correlation with alcohol); and between haematocrit and overweight (Quetelet Index) but not obesity (Ponderal Index). Increased haematocrit was also associated with cigarette smoking; and with history of angina, myocardial infarction and intermittent claudication in females. No correlation was observed between haematocrit and history of stroke. These findings suggest that prospective studies of haematocrit in hypertensives may be of interest.

Adult↗

Serum oestradiol and ischaemic heart disease--relationship with myocardial infarction but not coronary atheroma or haemostasis.

Elevated oestradiol (E2) levels may be a risk factor for ischaemic heart disease in men, although the mechanisms for the elevation of oestrogen and for its adverse effects remain unclear. We have studied 100 Caucasian males undergoing elective coronary angiography for ischaemic chest pain and measured serum oestradiol, a profile of haemostatic tests, extent of coronary artery disease and evidence of previous myocardial infarction in order to assess any relationships which could explain the effect of elevated serum oestradiol levels. Levels were significantly higher in men with a history of myocardial infarction compared to those without (p less than 0.01), but were unrelated to the extent of coronary disease or to the haemostatic tests. These results suggest that the association of oestradiol with coronary events relates to myocardial infarction, not to atherogenesis, and is not due to any currently measurable alterations of haemostasis. Current beta-adrenoceptor blocker treatment was associated with lower oestradiol and thromboxane B2 concentrations (both, p = 0.06). These incidental findings suggest that further studies of the effects of beta-blockade on oestradiol and thromboxane metabolism are indicated.

Adrenergic beta-Antagonists↗

Abnormal haemostasis and blood viscosity in malignant hypertension.

We have previously shown abnormalities of haemostasis suggestive of intravascular coagulation in patients with malignant hypertension, a condition associated with retinopathy and renal fibrin deposition. To determine whether such abnormalities are specific to malignant hypertension, we have measured several haemostatic and haemorheological variables in 18 patients with malignant hypertension (Group 1), 18 matched healthy controls (Group 2), and 18 patients with non-malignant hypertension (Group 3) matched for renal pathology, blood pressure and serum creatinine with Group 1. Both Groups 1 and 3 had increased mean levels of fibrinogen, factor VIIIc, beta-thromboglobulin, plasma viscosity and blood viscosity (corrected for haematocrit); and decreased mean levels of haematocrit, antithrombin III and platelet count. Mean levels of fast antiplasmin and alpha2-macroglobulin were elevated in Group 1 but not in Group 3. We conclude that most blood abnormalities are not specific to malignant hypertension; are also present in patients with non-malignant hypertension who have similar levels of blood pressure and renal damage; and might result from renal damage as well as promoting further renal damage by enhancing fibrin deposition. However increased levels of fibrinolytic inhibitors in malignant hypertension merit further investigation in relation to removal of renal fibrin.

Adult↗

HTLV-III seropositivity in European haemophiliacs exposed to Factor VIII concentrate imported from the USA.

77 Scottish haemophiliacs and 22 Danish haemophiliacs were serologically tested for antibodies to human T-cell leukaemia virus III (HTLV-III). Since 1979 the Scottish patients had been treated largely with factor VIII concentrate produced in Scotland, whereas all but 2 of the Danish patients had received both locally prepared concentrate and commercial concentrate made from US donor material. 15.6% of Scottish and 59.1% of Danish haemophiliacs were antibody positive (p less than 0.001). None of 11 haemophiliacs not treated in the period 1979-84 was seropositive. 2 (6.7%) of 30 subjects who had been treated with locally produced concentrate only were antibody positive, compared with 23 (39.7%) of 58 subjects who had been treated with commercial concentrate. Among 52 users of both commercially and locally produced factor VIII concentrate, seropositivity was directly correlated with the consumption of commercial concentrate (p less than 0.001) but not locally produced material. These data indicate that European haemophiliacs were exposed to HTLV-III via some factor VIII concentrates obtained from the USA.

Adolescent↗

AIDS and hepatitis B.

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Acquired Immunodeficiency Syndrome↗