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Biomedical subjects

C R Hay

Publications and source records attributed to C R Hay.

At least 19 recordsLinked to original sources
PubMed1992

The role of venom haemorrhagin in spontaneous bleeding in Bothrops jararaca envenoming. Butantan Institute Antivenom Study Group.

Thirty-eight patients bitten by Bothrops jararaca were investigated. Twenty-six had signs of local or systemic haemorrhage. Twenty-two of these had incoagulable blood, and these patients were found to have low fibrinogen levels (mean 0.17 +/- 0.03 g/l), thrombocytopenia, very high thrombin-antithrombin III complex (850 +/- 184 micrograms/l) and D-dimer (170 +/- 44 micrograms/ml) antigen levels. Serum venom haemorrhagin levels were significantly higher in patients with clinical signs of haemorrhage (36.4 +/- 6.4 ng/ml) than those without (11.7 +/- 3.7 ng/ml; p less than 0.002). Twelve out of 13 patients with thrombocytopenia were bleeding. High levels of thrombomodulin (22.3 +/- 1.5 ng/ml) and haemorrhagin (35.7 +/- 7.7 ng/ml) were detected in these 12 patients, suggesting vascular endothelial damage. Haemorrhagin levels also correlated inversely with platelet count in these patients. It was concluded that thrombocytopenia is one of the main causes of bleeding in B. jararaca victims, possibly as a result of venom haemorrhagin activity.

Adolescent↗
PubMed1992

Coagulation abnormalities and ivermectin.

Prothrombin ratios were measured 13-16 days after treatment in 148 subjects from Sierra Leone taking part in a double-blind placebo-controlled trial of ivermectin. Prolonged prothrombin ratios were observed more frequently in the ivermectin group, although this difference was not significant and no patients suffered bleeding complications. Further investigation of these patients failed to reveal any abnormality of liver function, although factor VII and II levels were reduced in most affected individuals, suggesting interference with vitamin K metabolism. Ivermectin has a minimal effect on coagulation and concern about mass treatment for this reason appears to be unjustified.

Adolescent↗
PubMed1991

Innovative use of porcine factor VIII:C for immune tolerance induction.

Of all nonhemophilic patients with acquired factor VIII:C (FVIII:C) inhibitors, as many as 87% suffer from hemorrhagic complications, and approximately 22% die as a result. Immunosuppressive therapy reduces or eradicates the inhibitor in 50-80% of patients, but a significant proportion remain refractory to such treatment and have a continued need for replacement therapy to manage bleeding complications. The possibility that porcine FVIII:C might fulfill this role has not been thoroughly investigated although limited data are available for patients with congenital hemophilia, which may offer some guidance. We recently reported the successful treatment with porcine FVIII:C over 2-8.5 years in five congenital hemophilia patients with high-level inhibitors initially lacking measurable cross-reactivity to porcine FVIII:C. One of four patients who developed transient, specific antiporcine inhibitors became refractory to treatment. Three further patients' antibodies demonstrated as much as 30% cross-reactivity but tolerated porcine FVIII:C therapy on demand for 18-24 months, with good clinical effect and no significant anamnesis or other untoward reactions. All five of these patients with non-cross-reacting antibodies began therapy with porcine FVIII:C and eventually lost their original inhibitors against human FVIII:C during treatment with the porcine factor. Surprisingly, when human FVIII:C was then reintroduced in three patients there was no recurrence of inhibitor activity during 3-4 subsequent years. This finding suggests that porcine FVIII:C, when administered over some interval to congenitally hemophilic patients, can induce a state of specific immune-tolerance to the human factor. On the other hand, porcine FVIII:C therapy may not suppress acquired inhibitors in nonhemophiliacs, since there is no evidence that administration of human FVIII:C causes immune-tolerance in this group. Porcine FVIII:C can be administered safely for a period of years. Anamnestic responses are unusual in acquired hemophilia, and only 20% of patients develop specific antiporcine antibodies. Porcine FVIII:C may play an important part in the long-term management of inhibitors in either congenital or acquired hemophilia.

Autoantibodies↗
PubMed1991

Coagulopathy and haemorrhage in human victims of Bothrops jararaca envenoming in Brazil.

Thirty-four patients envenomed by Bothrops jararaca in Brazil were studied. Of these, 20 (59%) had incoagulable blood associated with local and/or systemic bleeding and 10 of the 20 were thrombocytopenic. Among 14 patients with coagulable blood, 6 (43%) had bleeding symptoms and 3 (21%) were thrombocytopenic. High levels of von Willebrand factor (vWF), plasminogen activator inhibitor type 1 (PAI-1) and tissue type plasminogen activator (t-PA) antigens were also recorded in some patients with systemic bleeding with or without incoagulable blood. These substances may have been released from endothelial cells. Admission serum venom antigen levels were similar in both groups. The study indicated that systemic haemorrhage may occur in patients with coagulable blood and thrombocytopenia and that coagulopathy is not therefore the primary cause of haemorrhage.

Adolescent↗
PubMed1991

Anticardiolipin antibodies in leptospirosis.

The clinical course and serology of 16 cases of leptospirosis in an area with an unusually high endemic infection rate were studied to gain further insight into the pathology of the secondary immune phase that is typical of the disease. IgG anticardiolipin antibody concentrations were measured by immunoassay and found to be increased in eight serologically confirmed cases with severe complicated disease, compared with eight patients with relatively uncomplicated leptospirosis who had IgG anticardiolipin concentrations within the control reference range. This previously unreported association suggests that leptospira may induce vascular endothelial injury in severe cases and expose crypt antigens or induce conformational change of cell surface phospholipids. Leptospirosis may provide a model for an infective origin of some cases of the antiphospholipid syndrome.

Autoantibodies↗
PubMed1990

Induction of immune tolerance in patients with hemophilia A and inhibitors treated with porcine VIIIC by home therapy.

Home therapy with porcine factor VIIIC was safe and effective when administered to five hemophilic patients over periods of 8 1/2, 6, 4, 3 1/2, and 2 years. No significant transfusion reactions occurred. Before treatment with porcine factor VIIIC, all five had high-level, high-responding anti-human VIIIC inhibitors initially lacking anti-porcine factor VIIIC activity. Although specific anti-porcine VIIIC inhibitors arose in all patients, these were generally transient, and only one patient became refractory to treatment. We believe that porcine factor VIIIC is the treatment of choice in patients whose inhibitors do not cross-react. All five patients lost their original anti-human VIIIC inhibitors after starting treatment with porcine VIIIC, permitting the reintroduction of human VIIIC in three of them. There has been no recurrence of anti-human VIIIC inhibitor activity during 2 to 3 years of regular treatment with human VIIIC in these patients. This suggests that tolerance to human VIIIC has arisen as a result of treatment with porcine VIIIC. Porcine VIIIC may have a role in the desensitization of some factor VIIIC inhibitor patients.

Adolescent↗
PubMed1990

VIM-D salvage chemotherapy in Hodgkin's disease.

A total of 15 patients with relapsed or resistant Hodgkin's disease were treated with a combination of etoposide (VP16), ifosfamide, mitozantrone and dexamethasone (VIM-D). The regime was well tolerated, the only major toxicity being myelosuppression. Complete remissions (CRs) were obtained in 4 patients and were maintained for 2, 4, 10 and 14 months. 10 subjects subsequently received an autologous bone marrow transplant with high-dose chemotherapy (ABMT). Previous exposure to VIM-D did not appear to predict for or prejudice the response to subsequent ABMT.

Adult↗
PubMed1990

Inhibition of lymphocyte IL2-receptor expression by factor VIII concentrate: a possible cause of immunosuppression in haemophiliacs.

Factor VIII concentrate inhibits T-cell function in vitro and in vivo. The mechanisms underlying the phenomenon were investigated. Factor VIII concentrate has a direct effect on lymphocytes, uninfluenced by haemophilic monocyte dysfunction, since it inhibited lymphocyte transformation with phorbol myristate acetate, a reaction unaffected by monocyte depletion. Inhibition of lymphocyte transformation by factor VIII concentrate is not corrected by the addition of exogenous IL2, suggesting that it does not inhibit lymphocyte function by suppression of IL2 secretion alone. Factor VIII concentrate causes profound inhibition of IL2-receptor expression (CD25); with an 89% reduction in CD25-positive CD4 cells and a 50% reduction in CD25-antigen molecules per cell. CD8 lymphocytes are similarly affected. Smaller reductions in CD71 and HLA-DR expression are also observed. Down modulation of CD25-antigen may explain the reduced IL2 secretion observed by others, and may be an important cause of immunodeficiency in HIV-seronegative haemophiliacs.

Antigens, CD↗
PubMed1988

The relationship between inhibition of vitamin K1 2,3-epoxide reductase and reduction of clotting factor activity with warfarin.

1 The effect of low dose steady state warfarin (0.2 mg and 1 mg daily) on clotting factor activity and vitamin K1 metabolism was studied in seven healthy volunteers. 2 Steady state plasma warfarin concentrations were 41-99 ng ml-1 for the 0.2 mg dose and 157-292 ng ml-1 for the 1 mg dose. 3 There was a significant prolongation of the mean prothrombin time (0.9 s) after 1 mg warfarin daily, but no significant change in prothrombin time after 0.2 mg warfarin daily. There was no significant change in individual clotting factor activity (II, VII, IX or X) with either dose of warfarin. 4 Following the administration of a pharmacological dose of vitamin K1 (10 mg), all seven volunteers had detectable levels of vitamin K1 2,3-epoxide with both doses of warfarin (Cpmax 31-409 ng ml-1). 5 Both the Cpmax and the AUC for vitamin K1 2,3-epoxide were significantly greater on 1 mg of warfarin daily than 0.2 mg daily (P less than 0.01). 6 The apparent dissociation between inhibition of vitamin K1 2,3-epoxide reductase and reduction of clotting factor activity, produced by warfarin, may reflect the insensitivity of functional clotting factor assays to a small reduction in clotting factor concentration.

Blood Coagulation Factors↗
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

Granular common acute lymphoblastic leukaemia in adults: a morphological study.

2 cases of acute lymphoblastic leukaemia characterised by the presence of cytoplasmic inclusions morphologically similar to azurophil granules are described. Azurophil granulation of blasts is one of the cardinal features which differentiate acute myeloid from acute lymphoblastic leukaemia. Although such granulation of lymphoblasts has caused diagnostic confusion in the past, we found that the granules could be distinguished from myeloid azurophil granules both morphologically and by their characteristic cytochemical staining reactions. They were negative for peroxidase/sudan black and chloroacetate esterase, but gave coarse scattered granular positivity for both acid phosphatase and alpha-naphthyl acetate esterase. Both the electron microscopic appearance of the granules and their cytochemical staining reactions suggested that they were lysosomes. Granular ALL does not appear to be associated with any morphological subtype or karyotype; but is strongly associated with the common ALL phenotype. Its prognostic significance remains uncertain. It occurs more frequently than the small number of previous reports might suggest and, given the potential for misdiagnosis, should be more widely recognised.

Adult↗
PubMed1987

Atypical bullous pyoderma gangrenosum associated with myeloid malignancies.

Atypical bullous pyoderma gangrenosum was diagnosed during the course of a myeloid malignancy in three patients. One patient had chronic myeloid leukaemia, one acute myeloid leukaemia, and the third, refractory anaemia with excess of blasts. This atypical form of pyoderma gangrenosum has been specifically associated with myeloid malignancies. The atypical appearance of the skin lesions and the clinical context in which they arose caused the true diagnosis to be delayed in all cases. Treatment with steroids was associated with rapid healing of the skin lesion. The histopathological changes in the skin biopsy specimens from these cases were non-specific, and although the histology was considered to be atypical of pyoderma gangrenosum in one case, the unusual features could be attributed to the patient's neutropenia. (Skin biopsy was performed to exclude other specific pathology). Atypical bullous pyoderma gangrenosum is an uncommon association of the myeloid malignancies. It may remain unrecognised and should be considered more often.

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↗