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Biomedical subjects

J D Sweeney

Publications and source records attributed to J D Sweeney.

At least 55 records · Page 3Linked to original sources

Hemostatic effects of salsalate in normal subjects and patients with hemophilia A.

Salsalate in a non-acetylated salicylate with activity as an antirheumatic agent. The hemostatic effects of this agent were studied in twelve healthy subjects and nine patients with hemophilia A. Healthy subjects showed no change in bleeding time, platelet aggregation response to adenosine diphosphate (ADP) or collagen, or adenosine triphosphate (ATP) release in response to arachidonic acid as measured in an impedance whole blood lumi-aggregometer. The patients with hemophilia A showed no bleeding time prolongation nor an effect on ADP or collagen induced platelet aggregation in platelet rich plasma. It is concluded that this agent may be useful in the treatment of arthritis in patients with hereditary coagulation disorders.

Arthritis↗

von Willebrand factor in head and neck cancer.

Laboratory abnormalities in blood coagulation factors are common in patients with cancer but the significance is unknown. Twenty-eight patients with head and neck cancer were studied at the time of diagnosis. Twenty-five were advanced-stage (III or IV) patients. Levels of clotting factors, antithrombin III, and plasminogen were normal. Levels of von Willebrand factor (vWF), both antigenic and functional (ristocetin cofactor), were elevated. This group of patients were followed for a minimum of 41 months (median, 48 months). Fifteen patients died within the follow-up period. von Willebrand factor levels were significantly higher in these 15 than the 13 survivors. Extreme elevation of ristocetin cofactor (greater than 300 U/dl) was seen in six of the 15 patients who died and in none of the survivors. Plasma vWF is elevated in head and neck cancer and the level measured at the time of diagnosis may have prognostic and potentially therapeutic implications.

Blood Coagulation↗

The RIIIS/J inbred mouse strain as a model for von Willebrand disease.

Mice of the RIIIS/J inbred strain have prolonged bleeding times (greater than 15 minutes) after experimental injury when compared with normal C57BL/6J mice (1.8 minutes) and other strains of mice. The prolonged bleeding time was accompanied by normal platelet counts. Platelet aggregation with collagen and agglutination with ristocetin were not significantly altered in RIIIS/J mice. Also, platelets from RIIIS/J mice had normal serotonin content and normal numbers of dense granules by electron microscopy. Thus, the bleeding abnormality is not due to platelet storage pool deficiency as has been found in several other mouse mutants. The activated partial thromboplastin time (APTT) which plasma from RIIIS/J mice was prolonged compared with normal mice, and factor VIII:C activity and von Willebrand antigen levels were one half to one third that of normal mouse plasma. Factor XI activity was also significantly deficient (levels at 42% to 64% of normal). Plasma of RIIIS/J mice contained the full complement of multimers of von Willebrand factor, although each multimer was lower in concentration compared with that in normal mice. Platelet alpha-granule von Willebrand antigen levels were similar to those of normal mice. The prolonged bleeding time of RIIIS/J mice was corrected by treatment with desmopressin. Heterozygous C57BL/6J x RIIIS/J F1 animals had low plasma von Willebrand antigen levels like the RIIIS/J parent and had variable bleeding times. Inheritance of the bleeding tendency was as an incomplete dominant, autosomal trait. These data indicate the RIIIS/J strain is a suitable animal model for type IA von Willebrand disease.

Animals↗

von Willebrand's variant (type II Buffalo). Thrombocytopenia after desmopressin but absence of in vitro hypersensitivity to ristocetin.

Von Willebrand's disease is categorized into types and subtypes based on multimeric analysis of plasma von Willebrand's factor. Such categorization is of value because both the mode of inheritance and the choice of therapeutic material differ between subtypes. The Type IIB variant is characterized by hypersensitivity in vitro to ristocetin and thrombocytopenia after administration of desmopressin (DDAVP). Hypersensitivity to ristocetin has also been described in Type I variants but without thrombocytopenia after DDAVP. This report describes a new Type II variant characterized by the converse situation, absence of hypersensitivity to ristocetin in vitro but transient thrombocytopenia after intravenous administration of DDAVP.

Deamino Arginine Vasopressin↗

Ristocetin-induced platelet aggregate formation and adherence to the probe of an impedance aggregometer.

The examination of the interaction between ristocetin and platelets generally is performed in an optical aggregometer where aggregate formation is detected by a change in turbidity. Ristocetin also will induce conductivity changes in an impedance aggregometer with either fresh whole blood or fresh platelet-rich plasma due to aggregate attachment to the electrical probe. Formaldehyde-fixed platelets, however, do not attach, and although fresh platelets agglutinate at extremes of pH, probe adhesion does not occur unless the pH is within a certain range. Incubation of platelet preparations with neuraminidase, colchicine, or cytochalasin-b affects neither aggregate formation nor probe adherence. Incubation of platelet preparations with a fibronectin tetrapeptide inhibitor eliminates aggregate formation in response to collagen but is without effect on ristocetin-induced attachment of aggregates to the impedance probe. It is suggested that the ability of platelet aggregates to attach to an impedance probe in response to ristocetin is dependent on additional aspects of the functional integrity of platelet preparations and that these changes required for probe adherence may have in vivo significance.

Blood Platelets↗

A nerve cuff technique for selective excitation of peripheral nerve trunk regions.

Numerical modeling and experimental testing of a nerve cuff technique for selective stimulation of superficial peripheral nerve trunk regions is presented. Two basic electrode configurations ("snug" cuff monopolar and tripolar longitudinally aligned dots) have been considered. In addition, the feasibility of "steering" excitation into superficial nerve trunk regions using subthreshold levels of current flow from an electrode dot located on the opposite side of the nerve has been tested. Modeling objectives were to solve for the electric field that would be generated within a representative nerve trunk by each electrode configuration; and to use a simple nerve cable model to predict the effectiveness of each configuration in producing localized excitation. In three acute experiments on cat sciatic nerve the objective was to characterize the effectiveness of each electrode configuration in selectively activating only the medial gastrocnemius muscle. Modeling and experimentation both suggest that longitudinally aligned tripolar dot electrodes on the surface of a nerve trunk, and bounded by a layer of insulation (such as a nerve cuff), will restrict excitation to superficial nerve trunk regions more successfully than will monopolar dot electrodes. Excitation "steering" will improve the spatial selectivity of both monopolar and tripolar electrode configurations.

Animals↗

Hyperzincuria and hypozincemia in patients treated with cisplatin.

The effect of cis-diamminedichloroplatinum (DDP) on plasma and urinary zinc was studied in fifteen patients with squamous cell carcinoma. A decrease in plasma zinc accompanied by an increase in urinary zinc excretion was observed. Pretreatment plasma or urinary zinc did not correlate with tumor size or site, nor was there a correlation between changes in these measurements and a response to therapy. The enhanced excretion of urinary zinc may be related to a decrease in amino acid resorption in the proximal tubule. It is concluded that DDP administration may result in hyperzincuria and could potentially precipitate a symptomatic zinc deficiency state.

Carcinoma, Squamous Cell↗

Whole blood aggregation in von Willebrand disease.

Platelet function testing in von Willebrand disease is generally performed in platelet rich plasma using an optical system. The characteristic abnormality is an abnormal response to the agglutinating agent, ristocetin. Platelet aggregation can be also studied in whole blood using either an impedance aggregometer or a particle counter. Fifteen patients with von Willebrand disease and fifteen normal subjects were studied using both whole blood methods. In the impedance system, normal subjects responded to ristocetin (1 mg/ml) with short lag phases (less than 70 sec) and normal maximum aggregation greater than 5 omega). Only three patients with von Willebrand disease responded with normal maximal aggregation but each of these had a prolonged lag phase, and this may be a useful diagnostic parameter. In the particle counter, discrimination between normals and some von Willebrand disease patients was possible but an overlap between normals and von Willebrand patients is evident. It is concluded that the platelets in patients with von Willebrand disease exhibit the same abnormalities in whole blood as in platelet rich plasma and that the combination of impedance aggregometry and a factor VIII procoagulant assay is a time-efficient and sensitive method to screen for von Willebrand disease.

Humans↗

Platelet function and ABO blood group.

An influence of the ABO blood group on von Willebrand and Factor VIII:C levels is known. Von Willebrand factor interacts with at least two platelet membrane receptors, but the effect of ABO group on platelet function is an unstudied area. The authors examined platelet function in 40 plateletpheresis donors using an impedance lumi-aggregometer. Aggregation responses to collagen, adenosine diphosphate (ADP), and ristocetin were measured and the adenosine triphosphate (ATP) release to thrombin. Twenty donors were Group O and 20 were Group A. Measurements of von Willebrand factor antigen (vWf:Ag), Factor VIII: C, and ristocetin co-factor (RiCoF) in the same group showed reduced levels of vWf:Ag and Factor VIII:C in Group O, as previously reported. The aggregation response to collagen and ADP and the release of ATP did not differ. The aggregation response to ristocetin, however, was better in Group O than in Group A despite the lower vWf:Ag levels. The explanation for this is unclear, but the data suggest an influence of blood group antigens on the interaction between von Willebrand's factor and platelets.

ABO Blood-Group System↗

Whole blood aggregometry. Influence of sample collection and delay in study performance on test results.

The method of sample collection and time interval from venipuncture to test performance is considered to be important in platelet function testing. Platelet function studies can be performed in whole blood with the use of an impedance lumi-aggregometer, and an examination of the influence of these variables on the outcome of such a study is important. Twelve healthy donors had blood drawn with the use of conventional approach for platelet function testing and a Vacutainer method. Platelet function studies were performed at three time points over a three-hour period. No significant differences in results were observed between the methods of collection and the time to test performance. It is concluded that for platelet function screening in whole blood, with the use of an impedance lumi-aggregometer, a Vacutainer sample maintained at room temperature and tested within three hours is satisfactory.

Adenosine Triphosphate↗

Whole blood aggregation using impedance and particle counter methods.

Platelet function in platelet-rich plasma may be evaluated using an optical or electrical impedance method. Platelet function in whole blood may be studied using an impedance or particle counter method. A comparison of these techniques in whole blood has not been performed. Twenty-four healthy subjects were studied using both techniques over a range of concentrations of collagen and adenosine diphosphate (ADP). Although broad similarities exist, discordant patterns occur in individual subjects. The particle counter method is capable of detecting small aggregates and thus is more sensitive. The impedance aggregometer detects only larger aggregate formation. These techniques are complementary rather than competitive and may have considerable potential in profiling platelet function.

Adenosine Diphosphate↗

Intrasplenic lymphoma resembling multiple hematomas in a hemophiliac.

A 42-year-old patient with hemophilia A developed acute left hypochondrial pain 8 days postnephrolithotomy. A colloidal scan indicated multiple hematomas, and conservative management was given. Postoperatively, recurrent discomfort necessitated splenectomy. Multiple space-occupying lesions were found, and the histology was that of a large, noncleaved lymphoma. Contiguous spread outside of the capsule was evident, but abdominal nodes and liver appeared normal. Chemotherapy was administered, with evidence of tumor response, but refractoriness supervened, and the patient died 4 months after the diagnosis. Space-occupying lesions in a hemophiliac are generally ascribed to hematomas. The exposure of this population to the human immunodeficiency virus (HIV) should raise the consideration of a non-Hodgkin lymphoma in any situation where rapid clinical resolution of a hematoma is not occurring.

Adult↗

The effect of the platelet count on the aggregation response and adenosine triphosphate release in an impedance lumi-aggregometer.

Platelet aggregation studies are usually performed in either electrical impedance or optical systems and the release reaction assessed by quantitating adenosine triphosphate (ATP) from luminesence produced by the firefly luciferin-luciferase system. In evaluating the results of such studies, attention is paid to a variety of parameters such as the slope of the aggregation response and the maximum aggregation expressed as percent light transmission in optical and as Ohms in electrical impedance systems. Although threshold platelet counts are frequently cited below which the performance of these studies is technically difficult, the influence of the platelet count within the normal range on the results of such studies has not been prospectively addressed. This study examines the relationship between the aggregation response, ATP release and the platelet count in a lumi-impedance system. It is clear that the platelet count influences the results in this system and requires consideration in the interpretation if an erroneous conclusion is to be avoided.

Adenosine Diphosphate↗

Generation of unidirectionally propagating action potentials using a monopolar electrode cuff.

Unidirectionally propagating action potentials, which can be used to implement transmission failure on peripheral nerve through "collision block," have been generated electrically on cat myelinated peripheral nerve using a monopolar electrode cuff with the conductor positioned closest to the "arrest" end of the cuff. A single cathode located at least 5 mm from the arrest end resulted in unidirectional propagation with minimal current and charge injection. The range of stimulus current values that produced unidirectional propagation increased with increases in longitudinal asymmetry of cathode placement over the range of asymmetries tested (1.7:1 to 7:1). The stimulus current pulse that minimized charge injection was quasitrapezoidal in shape with a plateau pulse width of approximately 350 microseconds and an exponential trailing phase having a fall time (90%-10%) of approximately 600 microseconds These parameters were found to be independent of cuff geometry. Arrest efficiency was not degraded using a cuff of sufficient internal diameter to prevent nerve compression in chronic implantation. The critical current density within the extracellular space of the electrode cuff required to produce conduction failure at the arrest end was estimated to be 0.47 +/- 0.08 mA/mm2.

Action Potentials↗