Studies on the frequency of heparin-associated thrombocytopenia.
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Animals↗
Biomedical subjects
C J Carter
Publications and source records attributed to C J Carter.
Increased alanine aminotransferase activity in the Huntington's disease putamen.
The activities of both mitochondrial and cytosolic forms of alanine aminotransferase are markedly increased in Huntington's disease putamen autopsy samples. This increase was not observed in rats with kainic acid lesions of the striatum, and suggests a considerable alteration of glutamate and pyruvate metabolism as a feature of Huntington's disease.
Alanine Transaminase↗
Clinical usefulness of testing for a heparin-dependent platelet-aggregating factor in patients with suspected heparin-associated thrombocytopenia.
It is important to confirm the diagnosis of heparin-associated thrombocytopenia, because discontinuation of heparin requires the institution of other antithrombotic therapy. Reports describing a heparin-dependent platelet-aggregating factor in the serum of patients with heparin-associated thrombocytopenia suggest the potential for a specific diagnostic test. No study has evaluated the diagnostic usefulness of testing for this factor, and we tested for a heparin-dependent platelet-aggregating factor in sera from (1) 14 patients with heparin-associated thrombocytopenia, (2) 14 nonthrombocytopenic controls given heparin, (3) 16 patients with consumptive thrombocytopenic disorders not associated with heparin, and (4) 13 healthy laboratory personnel. Coded serum samples plus varying concentrations of heparin (final concentration 0.01, 0.1, 1.0, and 5 U/ml) plus platelets from healthy individuals were incubated together, and aggregation was measured. Positive results (greater than 20% aggregation) occurred in (1) five of 14 patients with heparin-associated thrombocytopenia, (2) 0 of 16 consumptive thrombocytopenic controls not given heparin therapy, (3) one of 14 nonthrombocytopenic controls given heparin, and (4) one of 13 healthy controls, giving a sensitivity of 36% and specificities of 100%, 93%, and 92%, respectively. No unique clinical or laboratory feature distinguished those patients with heparin-associated thrombocytopenia with positive aggregation results from those patients with heparin-associated thrombocytopenia with negative results. Fourteen of the 16 patients (86%) with heparin-associated thrombocytopenia had elevated levels of platelet-associated IgG; however, the test was also positive in 67% of the 16 patients with other consumptive (and probably immune) thrombocytopenic disorders not associated with heparin administration.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
The relationship among platelet-associated IgG, platelet lifespan, and reticuloendothelial cell function.
Platelet-associated IgG (PAIgG) has been reported to be elevated in nonthrombocytopenic patients who have a normal platelet lifespan. This has been interpreted as indicating that PAIgG is a nonspecific finding in these patients and not a determinant of platelet survival. It is important to recognize that the reticuloendothelial (RE) system plays an important role in the clearance of antibody-sensitized cells. In this study, we related the level of PAIgG and the platelet lifespan to the RE function in patients with: (A) idiopathic thrombocytopenic purpura (ITP), and (B) five patients with elevated levels of PAIgG yet normal or near-normal platelet counts. RE function was assessed by measuring the clearance of autologous chromium-labeled red cells sensitized with a precise amount of alloantibody (2,000-3,600 molecules of IgG/cell). Eight patients with immune thrombocytopenia had significantly shortened platelet survivals (less than 2-113 hr). In contrast, the five patients with elevated PAIgG, yet normal or near-normal platelet counts, all had normal autologous platelet survivals (186-222 hr). These patients also had significantly impaired clearance of IgG-sensitized red cells, with an average of 85% of the infused red cells remaining in the circulation at 60 min (normal 42% +/- 14%, n = 10). In this study, every patient with elevated PAIgG and normal RE function had a shortened platelet lifespan. Those patients with elevated PAIgG and impaired RE function did not invariably have a shortened platelet lifespan. The observation that the PAIgG is elevated in some patients whose platelet survival is normal does not indicate that PAIgG is not biologically relevant. It indicates that these patients may have RE blockade and do not clear IgG-sensitized cells.
Blood Platelets↗
The effect of aspirin on the size of the hemostatic plug.
The prolongation of the bleeding time by aspirin is presumably due to interfering with platelet function. Direct quantitative studies evaluating the effects of aspirin on the platelet component of the hemostatic plug have not been described. We measured blood loss from a standard ear injury in rabbits after treatment with either 5 mg or 200 mg/kg of aspirin (ASA) or sodium salicylate (SA), and related this observation to the number of platelets incorporated into the hemostatic plug. The high dose of aspirin was chosen since this dose inhibits PGI2 biosynthesis. Both doses of aspirin but not salicylate caused a significant increase on blood loss from the treated ear compared to the control (ASA 5 mg/kg, 0.012 +/- 0.009 ml, (m +/- SE), n = 44, p = 0.03; ASA 200 mg/kg, 0.02 +/- 0.007 ml, n = 17, p less than 0.05). Both doses of aspirin also caused a significant increase in the number of platelets incorporated into the hemostatic plug when compared to the SA treated animals (ASA 5 mg/kg, 3.52 +/- 0.34 X 10(6) platelets per incision, (m +/- SE), n = 59; SA 5 mg/kg, 1.9 +/- 0.15 X 10(6) platelets per incision, n = 54, p less than 0.001; ASA 200 mg/kg, 3.19 +/- 0.54 X 10(6) platelets per incision, n = 22; SA 200 mg/kg, 1.5 +/- 0.26 X 10(6) platelets per incision, n = 23, p less than 0.001). This study suggests that following aspirin administration hemostasis is achieved by the incorporation of a greater number of platelets into the platelet plug.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Glutamine synthetase and fructose-1, 6-diphosphatase activity in the putamen of control and Huntington's disease brain post mortem.
There is a linear negative correlation between the activities of glutamine synthetase and fructose-1, 6-diphosphatase in normal Human putamen autopsy samples, and also in the Huntington's disease putamen. However, glutamine synthetase activity is reduced in choreic brain samples, while fructose-1, 6-diphosphatase activity is normal. The ratio of fructose-1, 6-diphosphatase to glutamine synthetase is therefore increased in Huntington's disease. The products of the two reactions, glutamine and fructose-6-phosphate, are the starting substrates for glycolipid and glycoprotein biosynthesis, via the glutamine:fructose-6-phosphate aminotransferase catalysed formation of glucoseamine-6-phosphate. The alternative metabolic route of fructose-6-phosphate leads to glycogen. The availability of glutamine, and the activity of glutamine synthetase may control fructose-6-phosphate metabolism, and the increased ratio of fructose-1,6-diphosphatase to glutamine synthetase in Huntington's disease may explain the accumulation of glycogen, and the reduction in ganglioside levels reported in this state.
Fructose-Bisphosphatase↗
The diagnosis of acute, recurrent, deep-vein thrombosis: a diagnostic challenge.
Recurrent venous thrombosis presents a diagnostic challenge. Venography, impedance plethysmography and fibrinogen leg scanning all have potential limitations, and their role in this context has not been evaluated. We performed a prospective cohort study evaluating impedance plethysmography and leg scanning, plus venography, using outcome on long-term follow-up as the end point in 270 patients with clinically suspected recurrent deep-vein thrombosis. Anticoagulant treatment was withheld in the 181 patients negative by noninvasive testing and was given in patients positive by impedance plethysmography if leg scanning was positive or if intraluminal filling defects were detected by venography. The validity of this approach was tested by long-term follow-up. Three of 181 patients (1.7%) negative by noninvasive testing had a recurrence, compared with 18 of 89 (20%) with positive findings (p less than 0.001). Our objective diagnostic approach has high clinical utility; an objective rationale for withholding or giving treatment was established in 95% of patients.
Acute Disease↗
Pulmonary angiography, ventilation lung scanning, and venography for clinically suspected pulmonary embolism with abnormal perfusion lung scan.
Inherent contradictions in current diagnostic recommendations for pulmonary embolism have created considerable confusion and controversy. To resolve these contradictions, we did a prospective study of ventilation-perfusion scanning, pulmonary angiography, and venography in consecutive patients with clinically suspected pulmonary embolism and abnormal perfusion scans. Ventilation scanning increased the probability of pulmonary embolism in patients with large perfusion defects and ventilation mismatch, but a ventilation-perfusion match was not helpful in ruling out pulmonary embolism. Small perfusion defects with mismatch had neither sufficiently high nor low probability to be of diagnostic value. The observed frequency of proximal vein thrombosis (19% to 51%) and its association with the range of ventilation-perfusion defects have important implications for management of pulmonary embolism. Pulmonary angiography is required in combination with venography in most patients with perfusion abnormalities because the probability of pulmonary embolism is neither sufficiently high nor low to confirm or exclude pulmonary embolism.
Adolescent↗
Discordance between the anti-Xa activity and the antithrombotic activity in an ultra-low molecular weight heparin fraction.
The relationship between the in vivo antithrombotic effect of heparin and ex vivo anti-Xa activity has been investigated using an animal thrombosis model. Three low molecular weight heparins were compared with the standard heparin from which they were fractionated. All four heparins showed a dose-dependent antithrombotic effect enabling the relative antithrombotic and anti-Xa activities to be compared over a dosage range. A correlation between ex vivo anti-Xa heparin levels and antithrombotic effect was demonstrated for the standard (MW 16,000), intermediate (MW 7,600) and low (MW 4,600) molecular weight heparins but not for the ultra-low molecular weight (MW 3,000) fraction. The lack of relationship between anti-Xa activity and inhibition of thrombosis for the very low molecular weight fraction indicates that a very high anti-Xa activity (measured in vitro or ex vivo) is not always predictive of in vivo antithrombotic efficacy. These findings suggest that other properties of low molecular weight heparins contribute to their antithrombotic effectiveness.
Animals↗
Comparison of the in vivo hemorrhagic and antithrombotic effects of a low antithrombin-III affinity heparin fraction.
Antithrombin III (ATIII) affinity chromatography of commercial grade heparin yields fractions of high and low affinity for ATIII. In vitro, the high affinity fraction accounts for most of the anticoagulant effect while there is evidence that the low affinity material interferes with platelet function. We have studied the relative antithrombotic and hemorrhagic effects of low affinity heparin. The low affinity heparin fraction, specific activity 43 USP units/mg, was compared with standard heparin (150 USP units/mg) in rabbit experimental models. A residual 12.5% by weight of this low affinity heparin showed high affinity for ATIII. Inhibition of thrombosis in a stasis-hypercoagulability model was directly related to the weight (mg) of high affinity material in each of the heparins. In the bleeding model, when similar weights (mg) of high affinity material were infused, significantly more bleeding was demonstrated with the low affinity fraction which contained a 5-fold excess by weight of low affinity material. We have demonstrated that a low affinity heparin depleted of in vitro anticoagulant and in vivo antithrombotic activity significantly contributes to hemorrhage.
Animals↗
Glutamine synthetase activity in Huntington's disease.
Glutamine synthetase activity was measured in seven brain areas post-mortem from control patients, and those with Huntington's disease. The activity of the enzyme was reduced in the frontal and temporal cortex, putamen and cerebellum, but not in the hippocampus, thalamus or olivary nucleus. The results do not suggest a generalised deficiency of glutamine synthetase in Huntington's disease. However, as this enzyme is localised to astrocytic cells, the reduction in activity in areas of neuronal devastation, where the ration of astrocytes to neurones is increased, may reflect a greater functional deficit. The enzyme plays a crucial role in cerebral ammonia assimilation and its inhibition in laboratory animals is known to produce neuronal toxicity. A reduction in its activity in Huntington's disease may well contribute to the neuronal pathology in certain areas.
Ammonia↗
Ribosome structure, maturation of ribosomal RNA and drug sensitivity in temperature-sensitive mutants of Saccharomyces cerevisiae.
Selected strains of Saccharomyces cerevisiae were mutagenized with nitrosoguanidine and temperature-sensitive mutants isolated. These mutants were screened by two-dimensional gel-electrophoresis for the presence of ribosomal proteins with altered mobility relative to parental preparations. Electrophoretic changes were detected in three mutants designated ts205, ts212 and ts417, with the alterations apparently the same in the three cases. All three mutants were more sensitive than were their parents to the antibiotics G418, hygromycin B and MDMP. Mutant ts212 has an abnormal distribution of native ribosomal subunits and appears to be defective in its assembly of the smaller subparticle.
Electrophoresis, Polyacrylamide Gel↗
Topographical distribution of possible glutamatergic pathways from the frontal cortex to the striatum and substantia nigra in rats.
The topographical distribution of putative glutamatergic projections from the frontal cortex to the striatum and substantia nigra has been examined by measuring the high-affinity uptake of [14C]glutamate in synaptosomal preparations from rat anterior or posterior striatum and substantia nigra after a series of focal kainic acid lesions of the medial prefrontal cortex. The recorded changes in glutamate uptake suggest that the corticonigral glutamatergic projection arises from the rostral medial prefrontal areas, more caudal cortical areas projecting in turn to the anterior and posterior striatum.
Animals↗
Alpha feta (alpha FP) monitoring of response to adriamycin in hepatoblastoma.
While emphasizing the potential of chemotherapy (particularly adriamycin) in the treatment of hepatoblastoma, Andrassy et al., omit mention of the importance of serial serum alpha FP measurements in determining response and in early detection of recurrence. Serum alpha FP was elevated (range 5,000-1,800,000 micrograms/l) in 10 of 11 children with hepatoblastoma seen at our hospital between 1970 and 1980 and is, as others have emphasized, a potentially useful "marker" for this tumor. We report here the details of one patient in whom alpha FP monitoring was crucial to early detection of pulmonary metastases; complete response to adriamycin was subsequently documented.
Carcinoma, Hepatocellular↗
Disseminated intravascular coagulation: the application and utility of diagnostic tests.
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Animals↗
A prospective study of the usefulness of the measurement of platelet-associated IgG for the diagnosis of idiopathic thrombocytopenic purpura.
The measurement of platelet-associated IgG (PAIgG) is a potentially useful diagnostic test for idiopathic thrombocytopenia purpura (ITP). However, the restricted application of PAIgG measurements to thrombocytopenic populations primarily comprised of ITP patients will artificially enhance its diagnosis specificity. For this reason, we performed a prospective study in which the results of a sensitive technique for quantitating PAIgG were related to the cause of the thrombocytopenia. Over a 1-yr period, clinicians were invited to submit patient blood samples encompassing as wide a spectrum of thrombocytopenic disorders as possible for PAIgG measurements. The physician was then contacted and requested to indicate the likeliest cause for the thrombocytopenia. The PAIgG was elevated in only 24 of 254 samples obtained from nonthrombocytopenic patients. In contrast, 134 (79%) of the 169 thrombocytopenic patients had elevated PAIgG results, and the increased levels were apparent in all diagnostic categories. The sensitivity of the PAIgG test for clinically diagnosed idiopathic thrombocytopenic purpura was 91% and the specificity was 27%. The positive predictive value for a raised PAIgG as a diagnostic test for ITP in a thrombocytopenic patient was only 46%, while the negative predictive value was 82%. This study indicates that the presence of increased PAIgG provides little additional information in the diagnosis of ITP. This study also suggests that immune mechanisms may mediate many more thrombocytopenic disorders than have been previously thought likely.
Blood Platelets↗
The diagnostic value of the fibrinogen/fibrin fragment E antigen assay in clinically suspected deep vein thrombosis.
We have evaluated the fibrinogen/fibrin fragment E antigen assay as a diagnostic test in patients with clinically suspected venous thrombosis by comparing the results of this assay with venography in 272 patients. The result of the fragment E antigen assay was elevated in 79 of 80 patients with positive venograms for recent venous thrombosis (sensitivity 99%) and within the normal range in 161 of 192 patients with normal venograms (specificity 84%). The fragment E assay was also evaluated in 130 medical and surgical controls without evidence of venous thrombosis by leg scanning and the test was found to be relatively nonspecific. However, in the patient group under study, a correct clinical diagnosis of no thrombosis, based on a normal fragment E result, was made in 161 of 162 cases (negative predictive value of 99%). Therefore, a normal test result effectively excludes a diagnosis of venous thrombosis in clinically symptomatic patients. The assay, as currently performed, is technically demanding and takes 24 hr to complete. Therefore, it will have to be simplified before it can be applied to clinical practice.
Adolescent↗
Sex related differences in platelet function: the effect of aspirin.
There is evidence from clinical studies and animal experiments that aspirin has a greater antithrombotic activity in males compared to females. We investigated platelet function in vitro and in vivo in rabbits before and after the administration of a dose of aspirin (5 mg/kg) which inhibited collagen stimulated thromboxane B2 generation. Infusion of collagen into untreated animals resulted in a 38 +/- 4% (m +/- SE, n = 13) decrease in platelet count (assessed by whole blood radioactivity) in the male animals, and a 27 +/- 3% (m +/- SE, n = 13) in the female animals. Pretreatment with aspirin resulted in a significant inhibitory effect in the male but not the female animals (p less than 0.05). The male animals had significantly greater thromboxane B2 generation in vivo than did the female animals following an equal dose of collagen (males, 2.64 +/- 0.7 ng/ml thromboxane B2, n = 14; females, 1.67 +/- 0.4 ng/ml thromboxane B2, n = 15, p less than 0.05). In contrast no sex related difference in the inhibitory effect of aspirin on maximal collagen induced aggregation was found when platelets were studied in vitro. The greater reactivity of male patients in vivo may be accounted for by the observed increase in thromboxane B2 generation. This might also explain the greater thrombotic tendency of males, and the observed difference in the antithrombotic effect of aspirin in males and females.
Animals↗