The white blood cell and plasma fibrinogen in thrombotic stroke. A significant correlation.

OBJECTIVES: Thrombotic stroke is a common disorder with considerable mortality and morbidity. Risk factors for stroke include cigarette smoking, hypertension and hyperlipidaemia and these have been linked to abnormalities of haemorrheology and coagulation such as increased fibrinogen. Other haemorrheological abnormalities have also been documented. These include an elevation in the white blood cell (WBC) count. The aim of our study was to evaluate plasma fibrinogen, WBC aggregation and the release of free radicals in thrombotic stroke. EXPERIMENTAL DESIGN: Thirty-four patients with thrombotic stroke were enrolled in the study. The data were compared to 58 matched controls. SETTING: This study was carried out in Ninewells Hospital, Dundee on patients previously admitted to the medical wards with acute stroke. MEASURES: Plasma fibrinogen, WBC aggregation and plasma malondialdehyde (MDA) were measured in this study. RESULTS: As expected, the stroke patients have a significantly higher fibrinogen level (4.3+/-1.2 g/dl versus 3.1+/-0.6, p<0.001). WBC aggregation is also increased in the patient group (47.5+/-10.4% versus 42.7+/-10.6, p=0.036), as is plasma MDA (8.6+/-2.0 micromol/l versus 7.1+/-1.07, p<0.001). The factor VIII von Willebrand factor antigen measured as a marker as vascular damage was also significantly higher in the patient group (251+/-87% versus 182+/-64, p<0.001). There was also a statistically significant correlation between fibrinogen level and WBC aggregation, and fibrinogen and MDA. These are both statistically significant p=0.012 and p<0.001 respectively. CONCLUSIONS: We believe our study suggests that enhanced WBC aggregation/adhesion with release of free radicals may be another mechanism whereby fibrinogen exerts its known detrimental effect in stroke development. This may allow planning of therapeutic strategies as yet undeveloped.

Genetic and acquired predisposing factors and treatment of osteoporosis in thalassaemia major.

We have previously shown a high incidence of osteopenia and osteoporosis in patients with thalassaemia major. These bone changes, were more severe in males than females, in those with diabetes mellitus and with hypogonadal-hypogonadism. Our recent studies concern the relationship of erythroid activity, assessed by serum transferrin receptors as an overall measure of anaemia, to osteoporosis. Serum transferrin receptor levels correlated with the mean pre-transfusion haemoglobin level, but there was no correlation with the incidence of osteopenia and osteoporosis. As osteoporosis has a strong genetic component we have also studied the COLIA1 and COLIA2 genes which code for the major protein of bone (type 1 collagen). Studies by others have shown in non-thalassaemic patients that a polymorphism G-->T or TT in a regulatory region of COLIA1 at the recognition site for transcription factor Sp1 is associated with the presence of osteoporosis. Our studies suggest that Sp1 polymorphism is not specific to any one ethnic group; the polymorphism occurs more commonly in females (female to male ratio 2:1). In male thalassaemia major patients the presence of the Sp1 mutation was associated with more severe osteoporosis of the spine and the hip compared with female patients. There is failure of improvement in spinal osteoporosis with bisphosphonate therapy (intravenous Pamidronate) in male patients with the Sp1 mutation.

Matching services to needs in the health care of elderly people.

This paper is based on the results of a postal enquiry to health care professionals working in the care of elderly people in a Scottish Health Board. Responses fall into three main categories. The first refers to issues of process, where lack of information or delays in response create problems. Second, there are problems of scarcity, with both lack of provision and pressures on existing provision. Third, the responses relate to the impact of constrained choices, which are the consequences of that scarcity: either people are sent to existing services because of a lack of alternatives, or people cannot be referred on appropriately because of the lack of alternatives. The process of referral is, then, affected directly by the options that are available. In the process, compromises have to be made, and this produces mismatches between needs and services.

Perceived mismatches between needs and services in the health care of elderly people.

A postal enquiry to professionals involved in service delivery points to a number of problems in the process of referring elderly people appropriately. These problems related to lack of choice and constrained options, rather than mis-referral through inadequate assessment.

Abnormal plasma fibrinolysis in patients with rheumatoid arthritis and impaired endothelial fibrinolytic response in those complicated by vasculitis.

OBJECTIVES: (a) To assess plasma fibrinolytic parameters in patients with rheumatoid arthritis (RA) and to determine whether there are differences between patients with RA alone and those with RA complicated by vasculitis. (b) To determine if patients with RA respond differently to venous occlusion compared with normal subjects and to assess whether such a response differs in patients with RA alone and those with rheumatoid vasculitis. (c) To determine the extent of vascular damage in patients with rheumatoid vasculitis and if this correlates with the levels of plasma fibrinolytic parameters. METHODS: Sixty three patients with RA (38 had RA only and 25 had evidence of rheumatoid vasculitis) were recruited. Plasma levels of tissue plasminogen activator antigen (t-PA Ag), plasminogen activator inhibitor (PAI) activity, and factor VIII von Willebrand factor (vWF) were measured before and 10 minutes after venous occlusion. RESULTS: Patients with RA, with or without rheumatoid vasculitis, had higher baseline PAI levels than control subjects. The difference was statistically significant for patients with RA alone but was not statistically significant for patients with rheumatoid vasculitis. After venous occlusion, t-PA Ag levels increased significantly in normal subjects and patients with RA alone, but not in patients with rheumatoid vasculitis. Plasma levels of vWF were significantly higher in patients with rheumatoid vasculitis than in normal subjects and those with RA alone. In patients with RA alone, baseline vWF correlated positively with t-PA Ag levels, whereas a negative correlation was found between these two parameters in patients with rheumatoid vasculitis. A negative correlation between vWF and t-PA Ag levels after venous occlusion was also found in patients with rheumatoid vasculitis. CONCLUSIONS: Patients with rheumatoid vasculitis showed evidence of vascular damage with increased levels of vWF and impaired t-PA Ag release after venous occlusion, a useful measurement of endothelial reserve to remove fibrin. This may be of pathophysiological importance in the development of vasculitis in these patients.

A classification of acute leukaemia for the 1990s.

The need for reproducibility in the classification of acute leukaemia has made it necessary to incorporate information derived from new techniques which have become essential for the study of these disorders. In addition to classic morphology and cytochemistry (FAB proposals), it is necessary to add immunology and cytogenetics (MIC proposals), as well as to investigate further the biological and diagnostic significance of molecular events. As a result of these investigations a new group of leukaemias merit recognition as distinct entities. These include three types of ALL with specific chromosome abnormalities, namely, i) t (9;22), ii) t (4;11) and iii) t (1;19) and four subtypes of AML, i) with minimal differentiation or AML-M0, ii) with basophilic precursors or M2Baso, iii) AML (M4/M5) with t (8;16) and iv) AML with trilineage myelodysplasia. Biphenotypic acute leukaemia constitutes also a distinct entity with features of ALL and AML and represents a malignancy probably affecting multipotent stem cells. We propose an objective evaluation system for biphenotypic leukaemias based on a score in which the various lineage markers are graded according to their known specificity.

The influence of cardiac staffing resources on permanent cardiac pacemaker implantation rates.

In Tayside region, from 1976 to 1986, the number of permanent pacemakers implanted per year more than doubled, with the increase particularly marked over the latter five years. In order to determine the factor(s) which had caused this increase in implantation rates, a retrospective analysis of patients undergoing pacemaker implantation during the period 1981-1986 was undertaken. No change in the number of elderly in the population, age of patients, mode of referral, waiting time before insertion or clinical indications for pacing was observed to account for this change. The advent of ambulatory ECG monitoring may have contributed to this increase, but the appointment of an extra cardiologist in Tayside in 1982 was believed to have been more important. These results suggest that the number of pacemakers implanted in a region is highly dependent on the number of cardiological staff in that region available for their insertion.