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Biomedical subjects

F E Preston

Publications and source records attributed to F E Preston.

At least 163 records · Page 9Linked to original sources
PubMed1988

Acquired dysfibrinogenaemia masquerading as disseminated intravascular coagulation in acute pancreatitis.

Acquired dysfibrinogenaemia as the cause of coagulation abnormalities occurred in a case of acute pancreatitis. Initial coagulation studies showed a prolonged thrombin time and increased concentrations of serum fibrinogen/fibrin degradation products and plasma D-dimer. Further studies on purified fibrinogen showed evidence of degradation of the C-terminal ends of the A-alpha chains, which, it is suggested, resulted from the action of circulating pancreatic proteases. Fibrin polymerisation was thus shown to be impaired, which explains the prolongation of the thrombin time. There was a temporal relation between increased amylase activities and the prolonged thrombin time, both of which returned to normal three weeks after admission. Acquired dysfibrinogenaemia may be an underrecognized phenomenon in acute pancreatitis and may lead to misinterpretation of coagulation test abnormalities.

Acute Disease↗
PubMed1987

Hypothyroidism as a cause of acquired von Willebrand's disease.

Three patients with bleeding tendency who met the criteria for type 1 von Willebrand's disease are described. In two patients, hypothyroidism was suspected and confirmed at presentation, and in the third hypothyroidism became apparent 4 years later. In all three, the history and clinical course after treatment with thyroxine indicated acquired von Willebrand's disease secondary to hypothyroidism. The possibility of hypothyroidism should be considered in patients presenting with von Willebrand's disease.

Adolescent↗
PubMed1987

Lack of effect of a 24-hour infusion of iloprost in intermittent claudication.

24 hour infusion of iloprost was compared with placebo infusion in 19 patients with stable intermittent claudication using a double blind, balanced crossover design. Despite significant inhibition of platelet aggregation to ADP and collagen (p less than 0.001) and the typical cardiovascular and gastrointestinal side effects, there was no significant effect on treadmill exercise times at any time up to 6 weeks after infusion. The 95% confidence limits indicated that an improvement of more than 25% was unlikely to occur. No significant changes in B thromboglobulin, platelet aggregate ratio, bleeding time, whole blood viscosity and euglobulin clot lysis time were demonstrated.

Aged↗
PubMed1987

Changes in the factor VIII complex in diabetic ketoacidosis: evidence of endothelial cell damage?

Factor VIII-related antigen and von Willebrand factor are synthesised by and released from vascular endothelium. Acute increases in the plasma concentration of these proteins may reflect endothelial cell damage. We have thus measured the plasma concentration of factor VIII-related antigen and von Willebrand factor, together with procoagulant factor VIII, during the course of acute diabetic ketoacidosis in seven patients. In addition, evidence for qualitative changes in the factor VIII complex was sought. Plasma factor VIII-related antigen and von Willebrand factor were markedly increased (plasma factor VIII-related antigen at presentation, median 2.75 U/ml; von Willebrand factor 2.95 U/ml) and returned toward normal with clinical and biochemical resolution (plasma factor VIII-related antigen at clinical recovery, median 1.80 U/ml; von Willebrand factor 2.05 U/ml). Plasma procoagulant factor VIII followed a similar pattern, but levels were less elevated (plasma procoagulant factor VIII, at presentation, median 1.6 U/ml; at clinical recovery, 1.2 U/ml). Crossed immunoelectrophoresis and sodium dodecyl sulphate-acrylamide electrophoresis with autoradiographic identification of multimeric structure revealed no evidence of structurally abnormal factor VIII-related antigen in diabetic ketoacidosis. However, an extra peak on crossed immunoelectrophoresis ("pre-peak") was a feature in the acute phase ketoacidotic plasma in six subjects, and may represent aggregated factor VIII. Changes in plasma factor VIII are a feature of diabetic ketoacidosis and, whilst not specific to this condition, may be the result of endothelial cell damage.

Adult↗
PubMed1987

Cortical and vascular prostaglandin synthesis during renal allograft rejection in the rat.

Alterations in local prostacyclin and thromboxane synthesis could mediate the changes in vascular perfusion and platelet deposition in acutely rejecting renal allografts and prostaglandin E2 (PGE2) has been implicated in the regulation of the immune response. 6-Keto-prostaglandin F1 alpha (6 KetoPGF1 alpha), thromboxane B2 (TxB2) (the stable degradation products of prostacyclin and thromboxane A2 [TxA2], respectively) and PGE2 were measured in incubates of cortical slices taken from rat renal allografts or isografts one to seven days after transplantation. 6 KetoPGF1 alpha and TxB2 synthesis was also measured in incubates of blood vessels supplying and transplanted with the kidney in these animals. During the phase of cellular rejection (3-5 days), TxB2 synthesis was selectively elevated in allografted renal cortex, renal artery, renal vein, and abdominal aorta in comparison with isografted tissues. There was also a small but significant rise in cortical PGE2 synthesis at this time, but vascular and cortical 6 KetoPGF1 alpha production remained unchanged. Renal infarction, occurring 7 days after transplantation, was accompanied by a nonspecific rise in the synthesis of all three prostaglandins by renal cortical slices. Increased tissue TxA2 synthesis may contribute to local thrombosis and decreased graft perfusion during acute rejection, thereby potentiating graft destruction.

6-Ketoprostaglandin F1 alpha↗
PubMed1987

Reduced risk of non-A, non-B hepatitis after a first exposure to 'wet heated' factor VIII concentrate.

The risk of post-infusion non-A, non-B hepatitis (NANBH) in patients receiving a first exposure to unheated or conventionally 'dry heated' factor VIII concentrates approaches 100%, implying invariable contamination of these products. Amongst 18 patients who received a first treatment with a 'wet heated' commercial concentrate, five (28%) developed asymptomatic NANBH, suggesting a more efficient inactivation of NANB agent(s) by this process. 2/9 (22%) of the batches of concentrate used in the study were implicated in NANBH transmission. One of those two batches, responsible for NANBH in four patients, had been prepared from a plasma pool containing an unusually large proportion of donations with high alanine aminotransferase (ALT) levels. A resulting high level of viral contamination in this batch may have been sufficient to override the effects of the sterilization process. All patients remained anti-HIV seronegative at 17-28 months of follow-up.

Adolescent↗
PubMed1987

A new familial 'giant platelet syndrome' with structural, metabolic and functional abnormalities of platelets due to a primary megakaryocyte defect.

We have investigated platelet morphology, function and biochemistry in a family affected by dominantly inherited congenital thrombocytopenia with giant platelets. A defect of aggregation was defined with evidence of disturbed fatty acid distribution in platelet membrane phospholipids and impaired arachidonic acid mobilization. Release of 5-hydroxytryptamine was normal. Platelet ultrastructure was grossly abnormal and volume analysis revealed small as well as giant forms. Bone marrow megakaryocytes were morphologically abnormal and the distribution of mean nuclear ploidy atypical, suggesting the production of abnormal platelets due to a primary megakaryocyte disorder. The features of this condition are distinct from those previously described in familial thrombocytopenia and constitute a new "giant platelet syndrome". The qualitative and quantitative platelet defects may be secondary to a disturbance of megakaryocyte cytoplasmic fragmentation.

Adult↗
PubMed1987

Demonstration of abnormal factor VIII multimers in acquired von Willebrand's disease associated with a circulating inhibitor.

We have studied the factor VIII multimeric structure in four patients with acquired von Willebrand's disease associated with a circulating inhibitor to the factor VIII complex. In three of the four patients tested, the high and medium molecular weights bands were absent when assessed by sodium dodecyl sulphate-agarose electrophoresis. Plasma from the fourth patient contained all the factor VIII multimeric forms, although the high molecular weight bands were markedly decreased in concentration. Intravenous infusion of 1-deamino-(8-D-arginine)-vasopressin (DDAVP) resulted in the appearance of a full complement of multimers in the plasma of the two patients tested. This response was, however, transient and a return to pre-infusion multimeric composition occurred within 2-4 h. In the patients studied, an inhibitor to the factor VIII complex has induced an acquired variant von Willebrand's disease which transiently corrects after the infusion of DDAVP.

Deamino Arginine Vasopressin↗
PubMed1987

Potential value of vintristine-adriamycin-dexamethasone combination chemotherapy (VAD) in refractory and rapidly progressive myeloma.

10 patients with myeloma refractory to alkylating agents were treated with either 4-d pulses of high-dose dexamethasone therapy, or 4-d pulsed high-dose dexamethasone in combination with 4-d continuous infusions of vincristine and adriamycin (VAD). 8 patients were evaluated after a median duration of treatment of 2.3 courses (range 1 to 4). 6 of the 8 evaluable patients achieved reduction in serum and/or urine paraprotein levels with a mean reduction in serum paraprotein of 74.1%. There was a concomitant improvement in wellbeing in these responding patients. 2 evaluable patients failed to show biochemical or clinical response (1 treated with VAD, 1 high-dose dexamethasone). 2 patients currently survive 390 d and 180 d, respectively, on continuing therapy. 8 patients died with a mean duration of survival of 99 d (range 10 to 246 d). We conclude that the use of VAD chemotherapy in patients with refractory myeloma confers both a worthwhile remission of disease symptoms and biochemical evidence of disease regression, and that trials of VAD as primary treatment for myeloma are indicated.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1987

Treatment of the hypercalcaemia of malignancy with intravenous clodronate.

We studied the effects of intravenous clodronate (100-300 mg daily for 3-10 days) in 27 episodes of hypercalcaemia due to malignancy. Comparisons were also made between responses in patients with haematological malignancies and those with solid tumours. Following extracellular volume expansion, clodronate induced a significant decrease in serum calcium within 2 days of the start of treatment which was maximal at 7 days. This was associated with a decrease in bone resorption as judged by decreases in urinary excretion of hydroxyproline and calcium. Hypercalcaemia recurred 5-7 days after stopping treatment. Patients with solid tumours had higher pretreatment serum calcium values than those with haematological malignancies despite comparable values for fasting urinary excretion of calcium suggesting that renal tubular reabsorption of calcium was more markedly increased in patients with solid tumours. No difference was observed in the final calcium values between patients with solid tumours and haematological malignancies except in those patients in whom renal tubular reabsorption of calcium was markedly increased before treatment. We conclude that intravenous clodronate provides a safe and effective treatment of hypercalcaemia due to a wide range of tumour types provided that increased bone resorption contributes significantly to the hypercalcaemia. When increased renal reabsorption of calcium is the predominant mechanism for the maintenance of hypercalcaemia, the response to clodronate is incomplete.

Adult↗
PubMed1987

Predictive markers of chronic liver disease in hemophilia.

In an attempt to predict progressive liver damage in hemophiliac patients by noninvasive means, we conducted a retrospective analysis of clinical and laboratory data from 44 liver biopsies taken from 35 hemophiliac patients. This showed that serum IgG was normal in patients with chronic persistent hepatitis (CPH) but significantly elevated in those with chronic active hepatitis (CAH) or cirrhosis (CIR) (P less than .001). Relationships were less significant between liver histology and IgM (P less than .01), IgA (P less than .05), and globulin (P less than .05). This was unaffected by human immunodeficiency virus (HIV) antibody status in asymptomatic individuals. Although patients with progressive liver disease were also older than those with CPH (P less than .001), the immunoglobulin abnormalities were independent of this. Neither clinical examination nor liver biochemistry at the time of biopsy were of significant diagnostic value. Our results indicate that in the absence of AIDS an elevated IgG level is a reliable indicator of progressive hemophilic liver disease.

Adolescent↗
PubMed1986

Changes in plasma osteocalcin concentration following treatment with stanozolol.

Treatment of healthy, adult, human volunteers with stanozolol, 5 mg twice daily, for six weeks caused a marked elevation in circulating levels of osteocalcin. Plasma osteocalcin concentrations did not fall to pretreatment values for a period in excess of four weeks after the cessation of treatment but remained similar to levels whilst on treatment. At the same time, as the rise in plasma osteocalcin was seen, plasma alkaline phosphatase activity fell; however, in this case, a return to pretreatment levels occurred within four weeks of treatment ending. These data demonstrate that stanozolol has a detectable effect on the plasma concentration of a protein thought to be a marker of osteoblast activity, and that this effect continues for a period after treatment has been discontinued.

Adult↗
PubMed1986

Abnormal vitamin K metabolism in the presence of normal clotting factor activity in factory workers exposed to 4-hydroxycoumarins.

The case histories of two patients exposed to the novel anticoagulants brodifacoum and difenacoum are reported. Abnormal vitamin K1 metabolism, as indicated by elevated vitamin K1 2,3-epoxide plasma concentrations after i.v. administration of vitamin K1, could be detected for more than 18 months after exposure to the anticoagulants. There was a marked prolongation of prothrombin time (greater than 50 s) in both cases, at the time of exposure. However, subsequent haematological investigations (prothrombin time and vitamin K-dependent clotting factor activity) have been shown to be normal in both cases for at least 18 months. These cases confirm the long-acting nature of brodifacoum and difenacoum and present an apparent dissociation between the effect of coumarin anticoagulants on vitamin K1 metabolism and clotting factor activity.

4-Hydroxycoumarins↗
PubMed1986

Evidence against a platelet cyclooxygenase defect in uraemic subjects on chronic haemodialysis.

Defective platelet thromboxane synthesis has been described in uraemia and attributed to a 'functional cyclooxygenase defect'. We have studied platelet aggregation and generation of immunoreactive thromboxane B2 (TXB2) in 11 subjects on a chronic haemodialysis programme. The platelet function abnormality of uraemia was confirmed, maximal aggregation in response to collagen (2 and 4 micrograms/ml) and sodium arachidonate (1.5 and 3.0 mM) being significantly depressed. However, increased platelet aggregation in response to sodium arachidonate 0.75 mM was noted. Due to the reduced haematocrit, the platelet concentration in platelet-rich plasma (PRP) of uraemic subjects was significantly lower than that of controls; when TXB2 generation in PRP adjusted to 200 X 10(9) platelets/l was assessed, no evidence for a defect of cyclooxygenase was found, although reduced synthesis of TXB2 in response to thrombin was noted. Furthermore, increased thromboxane generation by uraemic PRP in response to sodium arachidonate 0.75 mM was detected. We conclude that the mild platelet abnormality in uraemic subjects treated by haemodialysis is not explained by a 'functional cyclooxygenase defect', although an abnormality of thrombin-induced thromboxane synthesis may be present. Furthermore, the tendency to increased aggregation and thromboxane synthesis in response to a low concentration of arachidonic acid may contribute to the thrombotic tendency which is also described in such subjects.

Adult↗