PubMed Health⌕ Search

Biomedical subjects

S Timmons

Publications and source records attributed to S Timmons.

51 records · Page 3Linked to original sources
PubMed1980

Prostacyclin inhibits mobilisation of fibrinogen-binding sites on human ADP- and thrombin-treated platelets.

Prostacyclin (prostaglandin I2, PGI2), produced by the blood vessel wall is the most potent known inhibitor of platelet aggregation induced by such stimuli as ADP and thrombin. It binds to a specific platelet receptor and activates adenylate cyclase, raising the cyclic AMP level in platelets. This property can be important because platelets participate in several significant interactions. For example, the interaction with fibrinogen or fibrin contributes to the formation of the haemostatic plug. Intact plasma fibrinogen is required for the aggregation of platelets induced by ADP, and endogenous platelet fibrinogen influences thrombin-induced aggregation. We have therefore studied the effect of prostacyclin on the interaction of fibrinogen with human platelets. We now report that prostacyclin inhibits the mobilisation of specific binding sites ('receptors') for fibrinogen on human platelets and that this effect parallels the inhibition of ADP- or thrombin-induced aggregation. The inhibitory effect of prostacyclin may limit the extent of platelet-fibrinogen interaction in vivo and in extracorporeal circulation.

Adenosine Diphosphate↗
PubMed1979

Staphylococci-induced human platelet injury mediated by protein A and immunoglobulin G Fc fragment receptor.

Bloodstream infections with staphylococci are accompanied by thromboembolic complications. We have studied the mechanism of the interaction of staphylococci with human blood platelets. Staphylococci that possess protein A, a bacterial receptor for the Fc fragment of immunoglobulin G (IgG), caused aggregation of human platelets in whole plasma accompanied by release of [(3)H]serotonin. These reactions were time and concentration dependent, requiring two or more staphylococci per platelet to give maximal response within 5 min. The interaction between staphylococci and platelets required the presence of cell wall-bound protein A and of IgG with an intact Fc fragment. It did not require an intact complement system. Cell wall-bound protein A (solid phase) was capable of aggregating human platelets in whole plasma. In contrast, free, solubilized protein A (fluid phase) did not cause measurable aggregation, and release of [(3)H]serotonin was reduced. An excess of free, solubilized protein A blocked aggregation of human platelets induced by staphylococci in whole plasma. The role of the Fc fragment of IgG in the staphylococci-human platelet interaction was demonstrated by an experiment in which free, isolated Fc fragment blocked aggregation of platelets in whole plasma induced by staphylococci. Furthermore, binding of (125)I-protein A to human platelets was demonstrated in the presence of complete IgG with intact Fc fragment but not in the presence of the F(ab)(2) fragment. Binding of the protein A-IgG complex to the human platelet Fc receptor was paralleled by the release of [(3)H]serotonin. These results represent a novel example of the interaction of two phylogenetically different Fc receptors, one on prokaryotic staphylococci and the other on human platelets. Their common ligand, IgG, is amplified by one Fc receptor (protein A) to react with another Fc receptor present on human platelets, which results in membrane-mediated aggregation and release reaction occurring in whole plasma. This mechanism can be of significance in the pathomechanism of thromboembolic complications at the site(s) of intravascular staphylococcal infection.

Binding Sites↗
PubMed1977

Membrane changes in human platelets induced by lipopolysaccharide endotoxin.

The unexplained occurrence of thrombocytopenia in cases of Gramnegative sepsis in man led us, in the light of animal experiments indicating the blood platelet as the target cell for endotoxin, to examine the effect of Salmonella enteritidis lipopolysaccharide B on human platelets. Human platelets were separated from a coat of plasma proteins by Sepharose 2B filtration or by a combined procedure of albumin gradient and Sepharose 2B filtration. The action of endotoxin on human platelets resulted in membrane changes manifested by dose-dependent release of [3H]serotonin and adenine nucleotides. Cytoplasmic marker, lactic dehydrogenase, and lysosomal marker, beta glucuronidase, were retained indicating that the release reaction was selective. Release of [3H]serotonin was specific for endotoxin since other particulates, zymosan and erythrocyte stroma, were without effect. Endotoxin, added to gel-filtered human platelets, induced a significant evolution of platelet factor 3 procoagulant activity. Preincubation of endotoxin with a membrane-rich homogenate of human platelets inhibited its labilizing effect on human platelets thus suggesting an interaction between endotoxin and the platelet membrane itself. Other plausible factors in this interaction [fibrinogen, adenine nucleotides, thrombin, sialic acid residues, and IgG] were eliminated on the basis of a series of control experiments. From the negligible effect of aspirin and indomethacin, we may infer that the interaction of endotoxin with platelets does not depend on the platelet prostaglandin synthesis pathway. The direct interaction of endotoxin with the human platelet membrane comprises a new mechanism which may help to clarify the pathogenesis of vascular and haemostatic disorders accompanying bloodstream infections due to Gram-negative bacteria.

Blood Platelets↗
PubMed1976

Immunoassay of human platelet factor 4(PF4, antiheparin factor) by radial immunodiffusion.

Human platelet factor 4 antigen (PF4 antigen) was measured in platelets and in plasma by means of single radial immunodiffusion. Anti-PF4 antibody obtained in rabbits by injecting highly purified human PF4 was monospecific in double immunodiffusion and in quantitative "rocket" immunoelectrophoresis. A high degree of correlation was observed between the precipitation zones in the radial immunodiffusion method and the amount of purified PF4 (in the range of 0.6 to 50.0 mug per milliliter) or the number of platelets in plasma (in the range of 5 x 10(6) to 1.6 x 10(8) platelets per milliliter applied. The sensitivity of the method was 30 to 125 times higher as compared with clotting assay (antiheparin activity) and the standard error of the method was 2.3 per cent. The method was specific for the antigen present in platelets since human leukocytes and erythrocytes gave negative results. Release of PF4 antigen from washed platelets challenged with thrombin, collagen, ADP, and antigen-antibody complexes was measured by the radial immunodiffusion assay. It usually paralleled the release of 3H-serotonin but PF4 antigen was a more sensitive marker for platelet release reaction. Release of PF4 antigen was usually 2 to 4 times higher than release of the antiheparin activity as measured by clotting assay when both were compared as percentage of total content in platelets. The level of PF4 antigen was determined in platelet-rich plasma (PRP) and platelet-free plasma (PFP) obtained from 12 healthy volunteers. While the mean level of extraplatelet pool of PF4 antigen in PFP was 0.72 +/- 0.92 mug per milliliter, PRP contained 80 +/- 22 mug of PF4 antigen per 10(9) platelets. Addition of thrombin (1 U. per milliliter) liberated all of the PF4 antigen (78 +/- 24 mug) present in PRP but ADP (50 muM) released only 31 +/- 22 mug of PF4 antigen per 10(9) platelets. The presence of heparin did not interfere with the assay of intraplatelet or extraplatelet PF4 by single radial immunodiffusion. The method described represents a simple, sensitive, quantitative, and specific assay for human PF4 antigen possessing antiheparin activity.

Adenosine Diphosphate↗
PubMedDate not supplied

Risk factors for pulmonary embolism in an Irish patient cohort.

INTRODUCTION: The prevention of pulmonary embolism (PE) is an important component of medical care. AIM: To examine the risk factors for venous thromboembolism in an Irish patient cohort with acute PE, and identify cases that may have been preventable. METHODS: Retrospective review of 60 consecutive cases of computed tomography (CT)-confirmed acute PE. RESULTS: The primary thromboembolic risk factors were elective surgery (27%), medical illness (20%), primary immobility (13%) and isolated distal lower limb fracture (7%). A significant proportion (43%) had been hospitalised within the six weeks prior to PE onset. Some patients had undergone 'low risk' procedures, without prophylaxis, but had other significant thromboembolic risk factors that indicated a requirement for prophylaxis. CONCLUSIONS: Hospital- and ward-based thromboprophylaxis guidelines, based on certain categories of patient or procedure, need to be routinely supplemented by an individual risk factor assessment for each patient, to determine those at particularly high risk for venous thromboembolism.

Acute Disease↗
PubMedDate not supplied

Anticonvulsant use in elderly patients in long-term care units.

BACKGROUND: Elderly patients in long-term care units are frailer than their community-dwelling peers and may be more at risk from toxic side-effects of anticonvulsant medication at standard doses. AIM: To examine the prescribing of anticonvulsants to patients in elderly care units. METHODS: Drug prescription sheets and case notes were reviewed. Serum anticonvulsant concentration, renal and liver profiles and albumin level were measured. RESULTS: Anticonvulsants were prescribed to twice as many male as female patients (32 vs 14%; p<0.03) and to 33% of those younger than 80 years of age versus 10% of those aged 80 years or older (p<0.0002). No patient had significant hypoalbuminaemia and routine measurement of serum anticonvulsant concentration did not indicate an alteration of dosage. CONCLUSIONS: Anticonvulsants appear to be well tolerated in these patients. The younger age of those receiving anticonvulsants is inadequately explained by the characteristics of the patient cohort and may reflect a shift towards a younger age in patients requiring anticonvulsants due to increased mortality in this group.

Aged↗
PubMedDate not supplied

The financial implications of falls in older people for an acute hospital.

BACKGROUND: Falls are a common occurrence in older people and frequently lead to hospital admission. There is a current lack of cohesive fall prevention strategies in the Republic of Ireland. AIM: To demonstrate the cost of fall-related admissions to an acute hospital. METHODS: A review of Hospital Inpatient Enquiry (HIPE) data and medical case notes was performed for all fall-related admissions over a one-year period. The cost of fall-related admissions was calculated. In addition a detailed cost analysis was performed to determine the true cost of a hip fracture admission. RESULTS: There were 810 fall-related admissions, resulting in 8,300 acute bed days, and 6,220 rehabilitation bed days, costing euros 10.3 million. Fall-related readmissions resulted in 650 bed-days, bringing the total cost to euros 10.8 million. A typical hip fracture incident admission episode costs euros 14,300. CONCLUSION: Fall-related admissions of olderpeople are a significant financial burden to the health service.

Accidental Falls↗
PubMedDate not supplied

Work force diversity: nursing perspectives.

All too frequently, diversity is viewed negatively or, at best, neutrally. The challenge of diversity is one of embracing it. The extent to which we are successful in meeting this challenge will determine South Carolina's and America's competitiveness and effectiveness in health care and in the global marketplace. Although much of the focus of this article has been work force diversity within nursing, attention to diversity is applicable within all health services markets, where human resources is the primary conduit for progress. Therefore, elements of this report can be generalized to all health care providers, where racial under-representation, in comparison to the populations served, is present.

Cultural Diversity↗