Autoimmune vasculitis and aortic stenosis in aspirin-induced asthma (AIA).
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Aortic Valve Stenosis↗
Biomedical subjects
J Musial
Publications and source records attributed to J Musial.
Anticardiolipin, anti-beta(2)-glycoprotein I, antiprothrombin antibodies, and lupus anticoagulant in patients with systemic lupus erythematosus with a history of thrombosis.
OBJECTIVE: To determine the clinical importance of anticardiolipin (aCL), anti-beta(2)-glycoprotein I (a beta(2)-GPI), antiprothrombin (aPT), and lupus anticoagulant (LAC) antibodies in patients with systemic lupus erythematosis (SLE) with and without a history of thrombosis. METHODS: We studied 100 patients with SLE (32 with a history of thrombosis), 27 patients with a lupus-like disease (9 with a history of thrombosis), and 41 healthy volunteers, IgG and IgM aCL, antibodies to the protein cofactors (a beta(2)-GPI and aPT) were determined by ELISA. Eighty-six of 127 patients were also tested for LAC. RESULTS: IgG aCL and LAC were associated with thrombosis but sensitivity (63 and 61%) and specificity (66 and 66%, respectively) of these tests were low. IgG and IgM a beta(2)-GPI were, respectively, 85 and 86% specific for a thrombotic history, but sensitivity was very low (32 and 29%). High IgG aCL were associated with the presence of a beta(2)-GPI and were 85% specific for thrombosis. There was no significant association between IgG or IgM aPT and thrombosis. CONCLUSION: Only high levels of IgG aCL and presence of LAC and/or a beta(2)-GPI are relevant in defining a thrombotic subset of patients with SLE. Longitudinal prospective studies are needed to investigate the predictive value of the different antiphospholipid and protein cofactor antibodies.
Adult↗
Inhibition of thrombin generation by aspirin is blunted in hypercholesterolemia.
Recent evidence indicates that aspirin inhibits thrombin generation in clotting blood. We noticed that this effect was less pronounced in patients with hypercholesterolemia. The aim of the study was to prove this observation. The effects of aspirin on thrombin generation were evaluated in (1) 46 healthy volunteers, 2 hours after ingestion of a single, 500-mg dose and (2) 28 survivors of myocardial infarction who took 300 mg aspirin/d for 2 weeks. In both populations, two well-matched subgroups were distinguished, using a serum cholesterol level of 6.2 mmol/L (240 mg/dL) and an LDL cholesterol level of 4.0 mmol/L (155 mg/dL) as borderline. Thrombin generation was monitored ex vivo in blood emerging from a skin microvasculature injury and additionally, in a single-dose study in vitro in recalcified plasma. Aspirin depressed thrombin generation in the group of subjects with serum cholesterol < 6.2 mmol/L and LDL cholesterol < 4.0 mmol/L but not in the group with high blood cholesterol levels. Inhibitory effects of aspirin were more pronounced after the 2-week treatment than after a single dose. There was a significant correlation between total serum cholesterol or LDL cholesterol and total amount of thrombin generated after aspirin treatment. In subjects with high blood cholesterol levels, thrombin generation was not affected by aspirin. Blunting of aspirin action in hypercholesterolemia might be explained by (1) alterations in platelet lipid-protein matrix that render their membrane proteins less accessible for acetylation by aspirin and (2) changes in composition and structure of plasma lipoproteins that diminish the chance of aspirin to interact with prothrombin.
Adult↗
Autoimmune phenomena in bronchial asthma with special reference to aspirin intolerance.
We assessed the autoimmune status of 185 adult patients with bronchial asthma and 46 healthy subjects of similar sex and age. The patients were divided into groups with: (1) aspirin-induced asthma (AIA) (n = 80); (2) intrinsic asthma with good aspirin tolerance (n = 46); and (3) atopic asthma (n = 59). Antinuclear antibodies (ANA) at a titer of > or = 1:40 were present in the serum of 55% of the patients with AIA, 41% of those with intrinsic asthma, 39% of those with atopic asthma, and 11% of the healthy subjects, with the difference between each patient group and the healthy subjects being statistically significant (p < 0.05). The fluorescence staining pattern of ANA on Hep-2 cells was mainly speckled, but the precise antigen specificity of the antibodies could not be identified with reference sera against extractable nuclear antigens. None of the subjects exhibited anti-double stranded deoxyribonucleic acid (anti-ds-DNA) or anti-neurtrophil cytoplasmic antibodies (ANCA). Positive ANA were associated with signs of complement activation, the presence of rheumatoid factor, and circulating immune complexes. Clinical signs of autoimmunity, evidenced by rheumatic symptoms, cold sensitivity, and Raynaud's phenomenon, were more common among the patients who tested positively for ANA. The assessment of autoimmunity may help in better characterizing patients with asthma and understanding various symptoms of the disease. Any causal relationship between asthma and autoimmunity remains to be established.
Adolescent↗
The dual diagnosis of attention-deficit/hyperactivity disorder and substance abuse: case reports and literature review.
BACKGROUND: It is now recognized that attention-deficit/hyperactivity disorder (ADHD) may persist into adulthood. A number of studies have found an association between ADHD and substance abuse. This article describes three adult patients with both ADHD and substance abuse who were treated successfully with psychostimulants. A review of the relevant literature is included. METHOD: The patients were drawn from a university-based referral center for adults with ADHD. Evaluations for ADHD and substance abuse were completed. Medical therapy and follow-up were completed by the first author. RESULTS: All of the patients responded to psychostimulants and have remained abstinent from alcohol and other drugs for the past 2 to 3 years. CONCLUSION: This case series and review of the literature suggest that specific treatment for ADHD with psychostimulants is feasible in patients who also have substance abuse. Future studies should evaluate the prevalence of this "dual diagnosis" and the efficacy of differing management strategies.
Adult↗
Humoral immunosuppression in men exposed to polycyclic aromatic hydrocarbons and related carcinogens in polluted environments.
We evaluated humoral immunity by measuring IgG, IgA, IgM, and IgE concentrations in 274 male workers in an iron foundry in Cracow, Poland. There were two groups: 199 coke oven workers and 76 cold-rolling mill workers. The groups were similar with respect to age, length of work (average 15 years), and smoking habits. Exposure to polycyclic aromatic hydrocarbons (PAHs), assessed by personal and area monitoring, ranged from 0.2 to 50 micrograms/m3 benzo[a]pyrene in coke plant workers and was of 3-5 magnitudes higher than in the cold-rolling mill employees. Comparison of the two groups revealed a marked depression of mean serum IgG and IgA in coke oven workers (p < 0.001, Student's unpaired t-test). In the same subjects, serum IgM had a tendency to decrease, whereas serum IgE showed a trend toward higher values. Thus, workers exposed chronically to complex mixtures of air pollutants, composed primarily of PAHs, develop immunosuppression. It remains to be established whether the immunosuppression described here is related to the frequent development of lung cancer reported in coke plant employees. Workers exposed chronically to PAHs should have serum immunoglobulins monitored regularly.
Adult↗
Lipid peroxidation, vitamin E, and cardiovascular disease.
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Animals↗
Inhibition of platelet adhesion to surfaces of extracorporeal circuits by disintegrins. RGD-containing peptides from viper venoms.
Previous studies indicate that exposure of fibrinogen receptors associated with glycoprotein IIb/IIIa complex contributes to platelet loss during cardiopulmonary bypass. Recently, we isolated a number of RGD (Arg-Gly-Asp)-containing, low molecular weight, cysteine-rich peptides from viper venoms. These peptides, which we propose to call "disintegrins," block platelet-fibrinogen interaction and platelet aggregation. We compared the effect of RGDS (Arg-Gly-Asp-Ser) and four disintegrins (echistatin, flavoridin, albolabrin, and bitistatin) on platelet behavior in a membrane oxygenator. During simulated extracorporeal circulation for 2 hours, platelet count decreased to about 30% of initial values. Addition of echistatin (60-200 nM), albolabrin (60-200 nM), bitistatin (60 nM), and flavoridin (45 nM) significantly inhibited platelet loss in the circuit. RGDS (33 microM) did not show any significant inhibitory effect. ADP-induced platelet aggregation was inhibited in samples of platelet-rich plasma taken from the circuits containing disintegrins. However, echistatin appeared to be a more potent inhibitor of platelet aggregation, whereas albolabrin and flavoridin interfered more selectively with platelet loss from the circuit. Echistatin prevented the accumulation of glycoprotein IIIa on the surface of the circuit. Echistatin (60-200 nM), flavoridin (45 nM), bitistatin (60 nM), and albolabrin (200 nM) significantly inhibited the loss of beta-thromboglobulin from platelets into circulating plasma. Electron microscopy studies demonstrated shape change but not degranulation in platelets circulating in the presence of 200 nM echistatin. On the other hand, this peptide (up to 1,000 nM) did not prevent loss of alpha granules and beta-thromboglobulin from thrombin-stimulated platelets, although it prevented their aggregation. In conclusion, disintegrins protect platelets in the circuit by preventing their adhesion to surfaces and, therefore, preventing fragmentation of adhered platelets under the shear stress of flowing blood. This study indicates that disintegrins may be potential candidates for platelet protection during cardiopulmonary bypass.
Amino Acid Sequence↗
Bleeding time and PAF-acether-induced platelet aggregation in atopy.
In a double-blind cross-over study 20 mg of aspirin or placebo were administered to 18 patients with respiratory atopy without eczema and to 12 healthy controls. Mean bleeding time before administration of either aspirin or placebo was on average about 1 min. longer in atopics than in the controls, and this difference was significant (p 0.05). Atopics' platelets also aggregated less well in response to arachidonic acid in comparison to controls. On the contrary, no difference in platelet aggregability was detected in response to either PAF-acether alone or to combination of subthreshold, synergistic concentrations of PAF-acether and collagen. Aspirin at a dose used did not affect either bleeding time or platelet aggregability. Thus, in respiratory atopy there exists a moderate hemostatic imbalance, the reason of which remains to be established.
Adult↗
Quantitation of platelet preservation with prostanoids during simulated bypass.
Extensive blood-synthetic surface interactions during cardiopulmonary bypass produce adverse platelet alterations that can contribute to excessive blood loss following open cardiac surgery. These platelet alterations can be reduced by temporary inhibition of platelet function. In order to define further an optimal method of platelet inhibition during blood-synthetic surface contact, we quantitated platelet functional and structural alterations that occur during simulated extracorporeal circulation (SEC) despite platelet inhibition with Iloprost (ZK) or PGE1. Five-hundred milliliters of fresh heparinized human blood were recirculated for 2 hr in a circuit consisting of silicone rubber components and a spiral coil membrane oxygenator. When blood was recirculated for 2 hr without drug, platelet counts fell significantly to 46 +/- 7% (mean +/- SEM) of initial levels (P less than 0.01); mean platelet volume decreased from 6.90 +/- 0.25 micron3 to 6.05 +/- 0.33 micron3 (P less than 0.01); platelet dispersion increased from 1.73 +/- 0.02 to 2.14 +/- 0.09 (P less than 0.01) and platelets no longer aggregated in response to epinephrine or thrombin. In contrast, when blood was recirculated with either ZK (0.003 microM) or PGE1 (0.3 microM), platelet counts were significantly preserved when compared to blood recirculated without drug (82 +/- 5% and 89 +/- 7%, respectively; P less than 0.01); mean platelet volume did not change; and dispersion only increased from 1.74 +/- 0.02 to 1.85 +/- 0.04 (P less than 0.05). However, following gel filtration, platelets recirculated with PGE1 always responded less than platelets merely incubated with PGE1 when challenged with either epinephrine (50 vs 75%, P less than 0.05) or thrombin (37 vs 65%, P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
Adenosine Diphosphate↗
Fibrinogen receptors in platelet adhesion to surfaces of extracorporeal circuit.
The role of platelet fibrinogen receptors and platelet-protein interaction in platelet consumption during simulated cardiopulmonary bypass was investigated. In five recirculation experiments, with whole blood, the platelet count fell to 13% of initial values and in two experiments, with blood from patients with Bernard-Soulier syndrome, to 3% of normal values. However, in three experiments with blood from the patients with Glanzmann's thrombasthenia, the platelet count decreased to 69% of initial values. The extent of platelet consumption in normal blood was diminished to only 72% by addition of 0.5 microM prostaglandin E1 (PGE1) (5 experiments) and to 80% by precoating surfaces of the circuit with 2.5% human albumin (5 experiments). beta-Thromboglobulin antigen (beta TG) loss from platelets was associated with thrombocytopenia. The extent of beta TG loss was significantly reduced by the addition of PGE1 to blood or precoating surfaces with albumin. Proteins adsorbed on the surface of the circuit exposed to normal blood were removed with 0.5% Triton X-100. Some of these proteins were identified to be glycoprotein IIIa (GPIIIa) (3.4-4.3 micrograms/ml), beta TG (1.0-1.6 micrograms/ml), and fibrinogen (1.9-3.7 micrograms/ml). The amount of GPIIIa recovered in the Triton X-100 eluates correlated with the number of platelets lost during recirculation. These studies indicate that exposure of fibrinogen receptors associated with GPIIb-GPIIIa complex contributes to platelet consumption during cardiopulmonary bypass.
Blood Platelets↗
Effects of prostanoids on generation of superoxide ions by human neutrophils.
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Granulocytes↗
Evaluation of surface-bound heparin and platelet inhibition in a centrifugal pump left ventricular assist system.
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Aged↗
Loss of fibrinogen receptors from the platelet surface during simulated extracorporeal circulation.
In vitro recirculation of fresh human heparinized blood in an extracorporeal circuit with a membrane oxygenator decreased fibrinogen-induced platelet aggregation and diminished the number of fibrinogen receptors and glycoprotein IIb/IIIa (GPIIb/GPIIIa) antigenic sites on the platelet surface. In seven experiments, the mean +/- SD Km value for fibrinogen (i.e., molar concentration of fibrinogen required to cause 50% of the maximal rate of aggregation) was 1.58 X 10(-7) mol/L +/- 0.68 X 10(-7) mol/L. After recirculation, this value increased to 3.8 X 10(-7) mol/L +/- 1.94 X 10(-7) mol/L (P less than or equal to 0.025). The maximal aggregation rate of chymotrypsin-treated platelets decreased by 40% after 2 hours of recirculation (P less than or equal to 0.025). The number of fibrinogen receptors on platelets, which were treated with chymotrypsin after a recirculation, decreased from 41,370 +/- 24,000 to 13,230 +/- 10,230/platelet under the same conditions (P less than or equal to 0.025). The number of antigenic sites for monoclonal antibody reacting with GPIIb/GPIIIa complex of adenosine diphosphate-stimulated platelets decreased from 34,200 +/- 5,940 to 19,500 +/- 9,680/platelet after recirculation (P less than or equal to 0.025). Prostaglandin E1 (0.3 mumol/L) in the perfusion circuit preserved the ability of platelets to react with fibrinogen. In conclusion, the loss of fibrinogen receptors from the surface of platelet membranes results from the interaction of platelets with the surfaces of perfusion circuits.
Adenosine Diphosphate↗
Loss of platelet alpha 2-adrenergic receptors during simulated extracorporeal circulation: prevention with prostaglandin E1.
Cardiopulmonary bypass prolongs bleeding time and increases postoperative blood loss. During in vitro recirculation in an extracorporeal circuit containing a membrane oxygenator and primed with fresh heparinized human blood, we previously observed thrombocytopenia, impaired platelet aggregation, and depletion of granular contents, all of which were prevented with prostaglandin E1 (PGE1). To investigate these changes further, we studied the number and affinity of platelet alpha 2-adrenergic receptors by measuring the binding of 3H-yohimbine. Before recirculation, we found 235 +/- 28 alpha 2-adrenergic receptors per platelet, a Kd of 3.37 +/- 0.78 nmol/L, complete aggregation with 1.04 mumol/L epinephrine, and a platelet count of 281,000 +/- 33,000 microliters-1. After 2 minutes of recirculation, 9.44 mumol/L epinephrine was required to produce complete aggregation, and the platelet count was 104,000 +/- 22,000 microliters-1 (44% of control). The number of binding sites significantly decreased to 139 +/- 16 per platelet, but the affinity did not change (Kd = 3.78 +/- 0.44 nmol/L). After 2 hours of recirculation, the platelet count had increased to 123,000 +/- 21,000 microliters-1. However, epinephrine did not induce platelet aggregation even at 100 mumol/L. Moreover, alpha 2-adrenergic binding sites were not detectable, and affinity for yohimbine could not be calculated. Two minutes after PGE1 0.3 mumol/L was added to the circuit, platelet numbers, response to epinephrine, alpha 2-adrenergic binding sites per platelet, and affinity for yohimbine were not significantly different from control values. At 2 hours, the number of alpha 2-adrenergic sites was not significantly changed from control, but the affinity of yohimbine for platelets was significantly decreased 2.5-fold.(ABSTRACT TRUNCATED AT 250 WORDS)
Alprostadil↗
Prostacyclin and the fibrinolytic system in ischemic vascular disease.
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Adult↗
Role of kidney in the catabolic clearance of human platelet antiheparin proteins from rat circulation.
UNLABELLED: Stimulated platelets release at least two antiheparin proteins: platelet factor 4 (PF4) and low affinity platelet factor 4 (LA-PF4) from which beta-thromboglobulin (beta TG) is derived. We have found previously marked elevation of LA-PF4/beta TG antigen in platelet poor plasma of patients with chronic renal failure, whereas levels of PF4 remained normal. Therefore, we examined the role of the kidneys in the metabolic clearance of LA-PF4/beta TG and PF4. The supernates of aggregates of thrombin-stimulated human platelets were injected into sham operated control rats, nephrectomized rats, and into rats with acute ureteral ligation. The disappearance of human LA-PF4/beta TG antigen and PF4 in rat plasma determined by specific radioimmunoassays followed biphasic exponential curves. The half-lives (t1/2) for the fast and slow components of LA-PF4 in control rats were 6.4 and 68.4 min. Nephrectomy significantly increased these times to 9.7 and 144 min, while ureteral ligation resulted in no significant change. Comparison of the level of LA-PF4/beta TG antigen and of creatinine in aorta and in renal vein showed 25%-30% extraction of these compounds by the kidney. Less than 0.1% of the total LA-PF4 antigen injected was recovered in the urine of control rats. In contrast to these results, the clearance of PF4 was not affected by nephrectomy. IN CONCLUSION: (1) functional renal tissue is necessary for normal clearance of LA-PF4/beta TG, but renal excretion does not play a major role in its elimination suggesting that the protein is catabolized by the kidney; and (2) catabolic clearance of PF4 does not depend on functioning kidney tissue.
Animals↗
Observer variation in lower limb venography.
Three radiologists examined 34 venograms (68 limbs) performed supine without fluoroscopy for evidence of thrombosis. At 11 major veins in each limb they stated whether thrombus was "absent," "doubtful," "presumed" or "definite" or expressed " "no opinion." Data were analyzed by using the kappa statistic, which corrects for chance agreement. Results were compared with those from a previous study in which two of the observers assessed venograms performed under fluoroscopic control with the patient semi-erect. In the present study observers expressed "no opinion" much more often, particularly for anterior tibial and iliac veins. With these examinations excluded, the extent of observer variation was similar in the two studies, disagreement about the presence of thrombus occurring in about 10% of examinations. The frequency with which the diagnosis of thrombus remains in doubt severely limits the value of venography performed supine without fluoroscopy. Fluoroscopically-controlled examinations in the semi-erect position are preferable.
Humans↗