Working as a cardiologist in the USA.
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Cardiology↗
Biomedical subjects
N A Chronos
Publications and source records attributed to N A Chronos.
Aspirin does not affect the flow cytometric detection of fibrinogen binding to, or release of alpha-granules or lysosomes from, human platelets.
1. Aspirin inhibits the conversion of arachidonic acid to thromboxane A2 which reinforces the effects of weak agonists such as ADP in platelets. 2. In this study the effect of aspirin (300 mg/day) on platelet agonist response was measured by whole blood flow cytometry of unfixed blood samples from normal subjects (n = 10), an assay that investigates aggregation-independent changes in the platelet. 3. Fibrinogen binding to unstimulated platelets or to platelets stimulated with ADP or thrombin was unaffected by aspirin. 4. Under the conditions of this assay, platelets undergo a partial degranulation of alpha-granules and lysosomes (evidenced by expression of P-selectin and CD63, respectively) in response to ADP, and full degranulation in response to thrombin. P-selectin expression was paralleled by release of beta-thromboglobulin. None of these events was affected by aspirin. 5. Thromboxane formation was totally prevented by the aspirin treatment, as shown by Born aggregometry in which the platelet aggregatory response to arachidonic acid was abolished and secondary aggregation by ADP was inhibited. 6. The flow cytometric assay can therefore be used to investigate platelets in patients, regardless of aspirin therapy. 7. These findings suggest that platelet fibrinogen binding and the release of platelet alpha-granule and lysosomal contents, in response to stimulation with physiological agonists, can continue in patients despite aspirin therapy. This may help to explain why aspirin is only partially effective in preventing thrombotic events.
Adenosine Diphosphate↗
ADP causes partial degranulation of platelets in the absence of aggregation.
Whole blood flow cytometry has revealed that platelets undergo partial degranulation in response to ADP, in the absence of aggregation, as evidenced by the expression of the P-selectin and CD63 antigens of the alpha-granule and lysosomal membranes respectively. With maximum ADP (10(-5) M) fibrinogen bound to 76.1 +/- 7.2% of platelets but P-selectin and CD63 antigen were expressed on 26.9 +/- 9.8% and 8.6 +/- 3.5% of platelets respectively. Maximum fibrinogen binding, P-selectin and CD63 expression induced by alpha-thrombin were 96.1 +/- 1.4%, 92.8 +/- 2.3% and 77.6 +/- 9.7% respectively. beta-thromboglobulin release from the ADP-stimulated platelets correlated closely with the expression of P-selectin and CD63 (r = 0.98 +/- 0.02 for both antigens). No platelet aggregates were seen by flow cytometry and the absence of aggregation was confirmed by single cell counting. Addition of the GPIIb-IIIa antagonist echistatin, at concentrations that totally blocked fibrinogen binding to ADP-stimulated platelets, had no effect on the expression of the granule membrane antigens. The partial degranulation of normal platelets was independent of thrombin generation since it was not inhibited by hirudin (5 units/ml). In conclusion, ADP is capable of causing partial degranulation of platelets independently of aggregation, fibrinogen binding or thrombin generation. Thus release of potent procoagulant, vasoactive and mitogenic substances from the platelets could continue in the presence of thrombin inhibitors and GPIIb-IIIa antagonists.
Adenosine Diphosphate↗
Self-expanding stents for emergency treatment of acute vessel closure following coronary angioplasty: immediate and long-term results.
Intracoronary stents may be used to treat acute coronary occlusion following balloon angioplasty. We report the immediate and long-term results of emergency implantation of the self-expanding stent (Wallstent) in 39 patients with acute vessel closure. Stents were successfully deployed in 38 patients (97%). Procedural complications occurred in 14 patients (36%); one patient died, two required emergency coronary artery bypass graft surgery, nine sustained myocardial infarcts (one Q wave), and two had acute stent thrombosis successfully treated by intracoronary thrombolysis and repeat angioplasty. Four patients (10%) had femoral artery bleeding, two required surgery. Angiographic follow-up was performed after 6 months in all 34 eligible patients, or earlier for symptoms. Two patients died prior to follow-up angiography. The stented segment was widely patent in 27 of the 34 patients (79%); restenosis within the stent was detected in 4 (12%) and thrombotic stent occlusion occurred in three (9%). Twenty-six of the 39 patients (67%) were free from major cardiac events and symptoms at 1 year. These results suggest that the self-expanding stent provides an attractive alternative to emergency surgery for the treatment of acute coronary occlusion following coronary angioplasty.
Adult↗
Self expanding stents for the management of aorto-ostial stenoses in saphenous vein bypass grafts.
OBJECTIVE: To assess the early and follow up results of implantation of a self expanding stent in aorto-ostial stenoses of vein grafts. DESIGN: Prospective, non-randomised, observational study. SETTING: Tertiary referral centre for cardiac diseases. PATIENTS: Nineteen patients with ostial stenoses of saphenous vein grafts. MAIN OUTCOME MEASURES AND RESULTS: Stents were successfully deployed in all 19 patients with satisfactory angiographic results. In one patient this required two attempts. There were no deaths and no major procedural complications related to ostial stenting. Before discharge two (11%) patients had thrombosis of the ostial stent; one patient had a Q wave myocardial infarction. Femoral artery bleeding occurred in three (16%) patients. Angiographic follow up was performed in 18 patients at a mean of seven months. Restenosis within the ostial stent was detected in three (16%) patients. Twelve (63%) patients had an improved functional status at a mean follow up of nine months. One patient died suddenly at three months. Three (16%) patients required additional revascularisation procedures because of symptoms caused by restenosis within the ostial stent during follow up. CONCLUSIONS: Intracoronary stenting is an attractive treatment for the management of patients with vein graft ostial stenoses.
Catheterization↗
Epinephrine sensitizes human platelets in vivo and in vitro as studied by fibrinogen binding and P-selectin expression.
Epinephrine (Epi) infusion influences platelet activation markers in vivo, but in vitro studies have mainly examined supraphysiological Epi concentrations and have yielded conflicting results. In this study whole-blood flow-cytometric measurements of platelet fibrinogen binding and P-selectin expression were used to compare enhancement of ADP (0.1 to 10 mumol/L)-induced platelet activation by Epi infusion in vivo (0.1 and 0.4 nmol.kg-1.min-1) and by Epi in vitro (10 and 50 nmol/L) in nine healthy volunteers. ADP caused concentration-dependent increases in the percentage of platelets that bound fibrinogen (from 4.4 +/- 0.9% to 69.9 +/- 4.2%) and that expressed P-selectin (from 4.5 +/- 0.5% to 44.2 +/- 3.8%). Fibrinogen and P-selectin binding indices (FgBI and PSBI; calculated from mean fluorescence intensity and percentage of positive cells) also increased from 0.18 +/- 0.03 to 11.70 +/- 1.99 for FgBI and from 0.22 +/- 0.03 to 2.34 +/- 0.29 for PSBI. Epi concentration-dependently enhanced fibrinogen binding and P-selectin expression in vitro (by approximately 30% at the midportion of the ADP curve at 10 nmol/L Epi; P < .001 for both by ANOVAs). High-dose Epi infusion enhanced FgBI similarly and increased maximal P-selectin expression by 38%. Epi (50 nmol/L in vitro) enhanced platelet activation further, whether samples were taken with or without prior Epi infusion. Total expression of glycoprotein IIb/IIIa was unaffected by Epi infusion, but glycoprotein Ib expression per platelet was reduced (P < .05). These in vivo and in vitro effects of Epi on platelet responses to agonist stimulation indicate a prothrombotic potential for sympathoadrenal activation in humans.
Adenosine Diphosphate↗
Profound platelet degranulation is an important side effect of some types of contrast media used in interventional cardiology.
BACKGROUND: Thrombotic complications occurring during coronary angiography and percutaneous transluminal coronary angioplasty (PTCA) are relatively frequent and can be influenced by the type of radiographic contrast media used. Low osmolar contrast media (LOCM), both ionic and nonionic, have been considered to be safer than the older high osmolar contrast media (HOCM), causing less haemodynamic and symptomatic side effects. Recently, however, nonionic LOCM have been associated with an increased incidence of thrombotic events, including coronary occlusion and stroke. METHODS AND RESULTS: The effects of commonly used contrast media on platelets in native blood were investigated using immunolabeling and flow cytometry to detect platelet activation in vitro. A nonionic LOCM (Omnipaque) caused profound platelet degranulation in nearly 80% of platelets compared with 2 to 3% of platelets in the control. Conversely, an ionic HOCM (Urografin) caused only 25% degranulation, whereas an ionic LOCM (Hexabrix) caused no platelet activation and, furthermore, it inhibited the effects of thrombin on platelets. Platelet degranulation, quantified by immunolabeling, was paralleled by release of beta-thromboglobulin and platelet factor 4 from platelet alpha-granules. Blood from patients anticoagulated with heparin and pretreated with standard-dose aspirin in preparation for PTCA showed the same pattern of contrast media-induced platelet activation as normal subjects. CONCLUSIONS: These results suggest that the type of contrast media used during invasive imaging of the vasculature could have a significant effect on platelets. Platelet degranulation within a PTCA-damaged vessel would be increased by a nonionic contrast medium, releasing procoagulant molecules and platelet-derived growth factors into the damaged vessel lumen, which might contribute to acute thrombosis and the initiation of the restenosis process.
Adult↗
New technologies in interventional cardiology.
This review confines itself to the new technologies that are widely used and that are being tested in formal trials. To date there have been few well-performed trials to compare the technologies, a fact that may have opened the way for the inappropriate use of some of these new technologies. This has allowed enthusiasts to perform procedures with as yet unproven tools no better and possibly worse than balloon angioplasty. New technologies can be broadly divided into three categories depending on their intended role: 1) mechanical removal, such as directional atherectomy, extractional atherectomy, and rotational atherectomy, that is designed to debulk lesions and remove atheromatous material, 2) high-energy removal by laser technologies designed to disobliterate lesions without producing the theoretically damaging lateral stretching of normal balloon angioplasty, 3) intraluminal scaffolding through the use of stents designed to give intravascular support, eg, balloon expandable, self-expanding, and temporary removable devices.
Angioplasty, Balloon, Coronary↗
Sonographic diagnosis of portal vein invasion in patients with hepatocellular carcinoma: comparison with arterial portography.
The results of sonographic assessment of the main portal vein were compared with arterial portography in 65 patients with documented hepatocellular carcinoma. When compared with fully-diagnostic angiograms, obtained in 54 patients, sensitivity of ultrasound was 64% with a specificity of 98%. We conclude that ultrasound is a valuable first-line method of detecting portal vein invasion in the preoperative assessment of patients with hepatocellular carcinoma.
Adolescent↗
Enprostil inhibits post-prandial gastrin release: a dose-response study.
In a double-blind placebo-controlled study in nine healthy volunteers, the effects of single doses of oral enprostil (8.75, 17.5, 35 and 70 micrograms), taken before a standard breakfast, were assessed on the post-prandial release of gastrin into the plasma. All doses of enprostil caused a significant dose-related decrease in median post-prandial plasma gastrin concentration (range from -29 to -44%). In the same subjects, two doses of 25 mg indomethacin caused a significant (38%) increase in median post-prandial plasma gastrin concentration.
Adult↗
Twenty four hour intragastric acidity and plasma gastrin concentration in healthy volunteers taking nizatidine 150 mg, nizatidine 300 mg, ranitidine 300 mg, or placebo at 21:00 h.
Nine healthy volunteers were studied on the seventh day of dosing at 21:00 h with nizatidine 150 mg (N 150), nizatidine 300 mg (N 300), ranitidine 300 mg (R 300), or placebo, given in a predetermined random order. The double-blind 24 hour studies, using the Royal Free Hospital standard protocol, simultaneously measured intragastric acidity and plasma gastrin concentration. Compared with placebo, subjects responded to dosing with each H2-antagonist by a significant decrease of 24 hour intragastric acidity (N 150-45%; N 300-49% R 300-56%; p less than 0.01) and a significant rise of plasma gastrin concentration (N 150 + 20%; N 300 + 27%; R 300 + 58%; p less than 0.01). All three drug regimens caused similar significant decreases of nocturnal acidity (N 150-72%; N 300-79%; R 300-85%; p less than 0.01) and increases of nocturnal plasma gastrin concentration (N 150 + 41%; N300 + 52%; R 300 + 80%; p less than 0.01). Dosing with ranitidine 300 mg at 21:00 h also caused a simultaneous significant decrease of morning acidity (-32%; p less than 0.05) with a significant increase of plasma gastrin concentration (+36%; p less than 0.05), but the antisecretory effects of nizatidine 150 or 300 mg at 21:00 h were only observed during the night, with no effect during the morning. No drug regimen had any effect on acidity or plasma gastrin in the afternoon or early evening.
Adult↗
Twenty-four-hour intragastric acidity and plasma gastrin concentration in healthy subjects and patients with duodenal or gastric ulcer, or pernicious anaemia.
Twenty-four-hour intragastric acidity and plasma gastrin concentration were measured in healthy subjects (n = 16), and patients with duodenal (n = 12) or gastric (n = 10) ulceration, or pernicious anaemia (n = 8). Median integrated 24-hour intragastric acidity was highest in duodenal ulcer patients and lowest in pernicious anaemia patients (1148 and 0 mmol.hour litre-1, respectively). Median integrated 24-hour plasma gastrin was highest in pernicious anaemia and lowest in the healthy subjects (9886 and 238 pmol.hour litre-1, respectively). Pernicious anaemia patients have unremitting hypergastrinaemia throughout the 24 hours. The results of this study not only provide a reference range of acidity and plasma gastrin in health and disease, but also will act as a baseline for future studies using antisecretory drugs.
Adult↗
Twenty-four-hour intragastric acidity and plasma gastrin concentration before and during treatment with either ranitidine or omeprazole.
Simultaneous 24-hour intragastric acidity and plasma gastrin concentrations were measured in 12 duodenal ulcer patients before and on the twenty-eighth day of treatment with either ranitidine 150 mg b.d. or omeprazole 20 mg o.m. Median integrated 24-hour intragastric acidity was decreased significantly from 1148 to 490 and 36 mmol.hour litre-1 during treatment with ranitidine and omeprazole, respectively, whilst median intragastric 24-hour plasma gastrin was raised significantly from 328 to 799 and 1519 pmol.hour litre-1 respectively. When the results of all 48 experiments were considered together, there was a significant inverse correlation between the 24-hour integrated values for intragastric acidity and plasma gastrin concentration. Both drugs caused a significant elevation of plasma gastrin throughout the 24 hours, although ranitidine had no effect on intragastric acidity from 1900 to 2200 hours. When compared with similar profiles of acidity and gastrin in pernicious-anaemia patients, the modest elevations of plasma gastrin observed in this study suggest that neither drug will be associated with clinically relevant enterochromaffin-like cell proliferation in duodenal ulcer patients.
Adult↗