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2.
Trop Biomed ; 39(1): 126-134, 2022 Mar 01.
Article in English | MEDLINE | ID: mdl-35507935

ABSTRACT

Coronavirus Disease 2019 (COVID-19) has been spreading like a wildfire everywhere in the globe. It has been challenging the global health care system ever since the end of 2019, with its virulence and pathogenicity. Recent studies have shown the association between ABO blood group, Rhesus blood type and susceptibility to COVID-19 infection. Various studies and few meta-analyses have been done and some might be inconsistent; therefore, this meta-analysis was done to assess the relationship between different ABO and Rhesus blood types on the susceptibility to COVID-19 infections. This meta-analysis assessed the odds ratio of COVID-19 infection of different ABO and Rhesus blood types. Subgroup analyses according to (1) age and gender matched; (2) different blood group antigens; (3) Rhesus positive and negative of each blood group were carried out. Publication bias and Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) were also done to assess the risk of bias in these publications. It was found that blood group A showed significant difference in odds ratio of COVID-19 infection (OR, 1.16; 95% CI, 1.08-1.24). Blood group AB showed significant difference in odds ratio when studies with lower QUADAS-2 score were removed. This means that populations with blood group A and AB are more likely to be infected with COVID-19. As there is a higher tendency that blood group A and AB to be infected with COVID- 19, precautious care should be taken by these populations.


Subject(s)
COVID-19 , ABO Blood-Group System , Humans , SARS-CoV-2
3.
Tropical Biomedicine ; : 126-134, 2022.
Article in English | WPRIM (Western Pacific) | ID: wpr-936419

ABSTRACT

@#Coronavirus Disease 2019 (COVID-19) has been spreading like a wildfire everywhere in the globe. It has been challenging the global health care system ever since the end of 2019, with its virulence and pathogenicity. Recent studies have shown the association between ABO blood group, Rhesus blood type and susceptibility to COVID-19 infection. Various studies and few meta-analyses have been done and some might be inconsistent; therefore, this meta-analysis was done to assess the relationship between different ABO and Rhesus blood types on the susceptibility to COVID-19 infections. This meta-analysis assessed the odds ratio of COVID-19 infection of different ABO and Rhesus blood types. Subgroup analyses according to (1) age and gender matched; (2) different blood group antigens; (3) Rhesus positive and negative of each blood group were carried out. Publication bias and Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) were also done to assess the risk of bias in these publications. It was found that blood group A showed significant difference in odds ratio of COVID-19 infection (OR, 1.16; 95% CI, 1.08-1.24). Blood group AB showed significant difference in odds ratio when studies with lower QUADAS-2 score were removed. This means that populations with blood group A and AB are more likely to be infected with COVID-19. As there is a higher tendency that blood group A and AB to be infected with COVID19, precautious care should be taken by these populations.

4.
Int J Tuberc Lung Dis ; 14(5): 642-9, 2010 May.
Article in English | MEDLINE | ID: mdl-20392360

ABSTRACT

BACKGROUND: Patients with chronic obstructive pulmonary disease (COPD) who survive an episode of acute hypercapnic respiratory failure (AHRF) after treatment with non-invasive ventilation (NIV) have a high risk of recurrent AHRF. We hypothesised that continuation of NIV at home in these patients would reduce the likelihood of recurrent AHRF. METHODS: A pilot prospective randomised controlled study was designed to compare continuation of active home NIV and continuous positive airway pressure (CPAP) 5 cm H(2)O (controls) in COPD patients who had survived an episode of AHRF treated with acute NIV. Patients with significant obstructive sleep apnoea, non-COPD causes of AHRF, adverse psychosocial circumstances and serious comorbidities were excluded. The primary end-point was recurrent AHRF requiring acute NIV, intubation or resulting in death in the first year. RESULTS: Twenty-three patients were randomised to receive home NIV and 24 received CPAP. There was no significant difference in the baseline characteristics between the two study groups. The proportion of patients developing recurrent AHRF in the NIV and the CPAP groups was 38.5% vs. 60.2% at 1 year (P = 0.039). Four and eight patients, respectively, were withdrawn from the CPAP and NIV groups before the end of the pre-defined study duration. CONCLUSIONS: In selected COPD patients with AHRF treated with acute NIV, continuation with home NIV is associated with a lower risk of recurrent severe COPD exacerbation with AHRF when compared with CPAP.


Subject(s)
Acidosis, Respiratory/therapy , Continuous Positive Airway Pressure/methods , Pulmonary Disease, Chronic Obstructive/complications , Respiration, Artificial/methods , Acidosis, Respiratory/etiology , Aged , Female , Home Care Services, Hospital-Based , Humans , Hypercapnia/etiology , Hypercapnia/therapy , Male , Middle Aged , Pilot Projects , Prospective Studies , Pulmonary Disease, Chronic Obstructive/therapy , Recurrence , Severity of Illness Index
5.
Int J Tuberc Lung Dis ; 13(9): 1167-73, 2009 Sep.
Article in English | MEDLINE | ID: mdl-19723409

ABSTRACT

SETTING: Tertiary referral centres. OBJECTIVE: To provide comprehensive updates on the aetiologies, angiographic findings and outcomes of bronchial artery embolisation (BAE) for life-threatening haemoptysis in Hong Kong. DESIGN: Retrospective review of clinical records of consecutive patients presenting with life-threatening haemoptysis from 2000 to 2006. RESULTS: There were 3006 admissions due to haemoptysis involving 2260 patients during the study period; of these, 251 patients had life-threatening haemoptysis. Pulmonary tuberculosis (PTB) (active or inactive) and bronchiectasis were the main underlying causes. BAE was attempted in 167 patients. There was a high prevalence of bilateral bronchial arterial abnormalities (31.7%), presence of abnormal non-bronchial arteries (41.3%) and presence of broncho-pulmonary shunt (38.9%). BAE had a high immediate success rate of 95.7%, with a 5-year recurrence rate of 45.0%. Recurrent life-threatening haemoptysis was independently associated with past history of haemoptysis (P = 0.024), presence of broncho-pulmonary shunt (P = 0.013), and incomplete embolisation (P = 0.002). Complications were uncommon (<5%) and self-limiting. CONCLUSIONS: In Hong Kong, about one tenth of admissions due to haemoptysis were life-threatening. PTB and bronchiectasis were the major causes. Complications due to BAE were uncommon and self-limiting, with super-selective catheters.


Subject(s)
Bronchial Arteries/abnormalities , Bronchiectasis/complications , Embolization, Therapeutic , Hemoptysis , Hemostatic Techniques , Tuberculosis, Pulmonary/complications , Aged , Aged, 80 and over , Asian People , Bronchial Arteries/diagnostic imaging , Bronchiectasis/diagnostic imaging , Bronchiectasis/ethnology , Embolization, Therapeutic/adverse effects , Female , Hemoptysis/diagnostic imaging , Hemoptysis/ethnology , Hemoptysis/etiology , Hemoptysis/mortality , Hemoptysis/therapy , Hemostatic Techniques/adverse effects , Hong Kong/epidemiology , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Proportional Hazards Models , Radiography , Recurrence , Retrospective Studies , Risk Assessment , Risk Factors , Time Factors , Treatment Outcome , Tuberculosis, Pulmonary/diagnostic imaging , Tuberculosis, Pulmonary/ethnology
6.
Mar Pollut Bull ; 57(6-12): 744-57, 2008.
Article in English | MEDLINE | ID: mdl-18358499

ABSTRACT

A long-term programme for monitoring toxic substances in the marine environment was established in Hong Kong in 2004, focusing on chemicals of potential ecological and health concern. The programme ran on 3-year cycles, with the first two years monitoring marine water, sediment, biota, and the third year monitoring pollution sources. Twenty-four priority chemicals were measured, including dioxins/furans, dioxin-like PCBs, total PCBs, PAHs, DDTs, HCHs, TBTs, phenol, nonylphenol (NP), NP ethoxylates, PBDEs and metals. Results from the first three years of monitoring indicate that toxic substances in the Hong Kong marine environment were within the range reported for the coastal waters in China and other regions, but generally lower than in the Pearl River Estuary. The levels met the standards for protecting aquatic life and human consumption. Sewage effluent, stormwater and river water were possible sources of phenolic compounds; whereas air deposition or regional pollution, rather than local discharges, may contribute to the dioxins/furans, PAHs and PCBs found in the marine environment.


Subject(s)
Environmental Monitoring , Hazardous Substances/analysis , Water Pollutants, Chemical/analysis , Animals , Fishes/physiology , Geologic Sediments/chemistry , Hong Kong , Invertebrates/chemistry , Marine Biology , Pacific Ocean , Seawater/chemistry
7.
Eur Respir J ; 25(1): 12-4, 2005 Jan.
Article in English | MEDLINE | ID: mdl-15640317

ABSTRACT

Severe acute respiratory syndrome (SARS) is a highly infectious respiratory infection with a high mortality. The duration of infectivity is unknown. The RT-PCR positivity for SARS-associated coronavirus (SARS-CoV) was followed in 45 virologically confirmed SARS patients. Serial RT-PCRs for SARS-CoV were performed in the nasopharyngeal aspirate, stool and urine of 45 SARS patients who survived until discharge. All patients had at least one site that was positive for SARS-CoV on presentation. Time to RT-PCR conversion was studied in all patients. There were 15 males (33.3%) and 30 females (66.7%), with a mean+/- SD age of 40.7+/-14.7 yrs. The median (range) time of RT-PCR conversion was 30 days (2-81). On discharge from the hospital, 18 (40%) remained RT-PCR positive in at least one site. For patients with positive RT-PCR on discharge, the median (range) time to RT-PCR conversion after discharge was 13 days (2-60). A significant proportion of severe acute respiratory syndrome patients remained RT-PCR positive for severe acute respiratory syndrome-associated coronavirus for a substantial duration after discharge. The clinical significance is unknown and this finding merits further study. It is prudent to advise patients to adhere to strict personal hygiene on discharge until RT-PCR becomes negative.


Subject(s)
DNA, Viral/analysis , Reverse Transcriptase Polymerase Chain Reaction , Severe Acute Respiratory Syndrome/diagnosis , Severe acute respiratory syndrome-related coronavirus/isolation & purification , Adolescent , Adult , Cohort Studies , Confidence Intervals , Female , Humans , Male , Middle Aged , Probability , Prognosis , Retrospective Studies , Risk Assessment , Sensitivity and Specificity , Severe Acute Respiratory Syndrome/virology , Severity of Illness Index , Time Factors , Viral Load
8.
Genomics ; 74(2): 142-54, 2001 Jun 01.
Article in English | MEDLINE | ID: mdl-11386750

ABSTRACT

We have developed a high-information-content fingerprinting (HICF) system for bacterial artificial chromosome (BAC) clones using a Type IIS restriction endonuclease, HgaI, paired with a Type II restriction endonuclease, RsaI. In the method described, unknown five-base overhangs generated with HgaI are partially or fully sequenced by modified fluorescent dideoxy terminators. Using an in-lane size standard labeled with a fifth dye, fragments are characterized by both the size and the sequence of its terminal one to five bases. The enhanced information content associated with this approach significantly increases the accuracy and efficiency of detecting shared fragments among BAC clones. We have compared data obtained from this method to predicted HICF patterns of 10 fully sequenced BACs. We have further applied HICF to 555 BAC clones to assemble contigs spanning 16p11.2 to 16p13.1 of human chromosome 16.


Subject(s)
Chromosomes, Artificial, Bacterial , DNA Restriction Enzymes/metabolism , Sequence Analysis, DNA/methods , Chromosomes, Human, Pair 16 , Contig Mapping , Humans , Models, Genetic
9.
Am J Cardiol ; 87(1): 82-5, 2001 Jan 01.
Article in English | MEDLINE | ID: mdl-11137839

ABSTRACT

Alcohol intake, especially in the form of red wine, has been shown to inhibit platelet function. However, whether alcohol in spirits may inhibit platelet-dependent thrombosis in humans up to 6 hours after ingestion is unknown and was assessed in this study. Platelet thrombus that is formed on exposure of an aortic media (simulating deep arterial injury or plaque rupture) to flowing blood was assessed in an ex vivo Badimon's superfusion chamber at shear rates of 754 or 2,546 seconds(-1) (simulating flow in normal or stenosed arteries). Twelve healthy subjects were studied before and at 20 minutes and 6 hours after consumption of 2 ounces of 40% alcohol. Blood alcohol level was 1.1+/-0. 1, 8.2+/-0.7, and 1.3+/-0.2 mmol/L at baseline, 20 minutes and 6 hours, respectively, after alcohol consumption (analysis of variance [ANOVA] p = 0.0001). Compared with baseline, platelet thrombus formation at the low shear rate flow was significantly decreased by 57% and 61% at 20 minutes and 6 hours, respectively, after alcohol intake (ANOVA p = 0.0001). Platelet thrombus deposition at the high shear rate was similarly inhibited to 68% and 64% of baseline values at 20 minutes and 6 hours, respectively (ANOVA p = 0.003). Men and women showed equal benefit. Thus, moderate alcohol intake in humans significantly inhibited platelet thrombus deposition under low and high shear rates of arterial flow conditions. This antithrombotic effect of a single alcohol drink, persisting for 6 hours and even after blood alcohol level has returned to baseline, may be clinically relevant to the cardioprotective effects of alcohol in men and women.


Subject(s)
Alcohol Drinking , Ethanol/pharmacology , Platelet Aggregation/drug effects , Thrombosis/prevention & control , Adult , Analysis of Variance , Arm/blood supply , Ethanol/blood , Female , Humans , Male , Regional Blood Flow , Single-Blind Method , Time Factors , Veins/physiology
10.
J Am Coll Cardiol ; 36(7): 2311-6, 2000 Dec.
Article in English | MEDLINE | ID: mdl-11127478

ABSTRACT

OBJECTIVES: The purpose of this study was to determine whether acute withdrawal of nitroglycerin (NTG) during hemodynamic tolerance is associated with platelet hypersensitivity. BACKGROUND: Nitroglycerin is an effective antianginal medication but its use is limited by the development of tolerance and rebound. We have previously demonstrated a sustained inhibition of platelet function during continued use of NTG, but whether cessation of NTG is associated with an increase in platelet function that may contribute to rebound is unknown. METHODS: Normal porcine aortic media were exposed to flowing arterial blood from pigs (n = 8) treated continuously with NTG patches (Nitrodur 0.8 mg/h) for 48 h. Platelet function, blood pressure and the responses to angiotensin II infusion were evaluated before, during and after NTG treatment. RESULTS: Mean arterial pressure fell by 15% after 3 h of treatment compared with control, returned to baseline by 48 h and increased significantly 2 h after drug removal. Autologous 51Cr-labelled platelet deposition on the aortic media was reduced by 30% after 48 h of continuous NTG administration compared with baseline (p = 0.02) and remained decreased 2 h after cessation of NTG therapy. Platelet aggregation to thrombin decreased in parallel to the decrease in platelet deposition. Blood pressure increase after intravenous injection of 10 microg of angiotensin II was blunted during treatment with NTG but increased significantly 2 h after cessation of nitrate therapy when compared with baseline. CONCLUSIONS: Supersensitivity of the vessel wall to vasoconstrictors such as angiotensin 11, but not platelet hyperactivity, may contribute to the rebound phenomenon after acute nitrate withdrawal.


Subject(s)
Blood Platelets/drug effects , Blood Pressure/drug effects , Nitroglycerin/pharmacology , Vasodilator Agents/pharmacology , Angiotensin II/pharmacology , Animals , Blood Platelets/physiology , Blood Pressure/physiology , Drug Tolerance , Nitroglycerin/therapeutic use , Platelet Aggregation/drug effects , Swine , Vasodilator Agents/therapeutic use
11.
Bioorg Med Chem ; 7(12): 2937-44, 1999 Dec.
Article in English | MEDLINE | ID: mdl-10658599

ABSTRACT

Endothal (1diacid) and [3H]cantharidic acid ([3H]CA) bind with high affinity to the catalytic subunit of protein phosphatase 2A (PP2A). PP2A in liver cytosol was greatly stabilized with 30% glycerol as a preliminary step in the potential use of endothal-type derivatives for affinity chromatography. We report here the first introduction of a functionalizable group into endothal which allows retention of binding site affinity (assayed as [3H]CA binding in mouse liver cytosol). 2-Carboxymethylendothal anhydride (7) was prepared in two steps and 97% overall yield from cis-aconitic anhydride and furan. The potency of 7 was retained on conversion to two 2-carboxymethyl esters but not to two 2-(n-alkylcarboxamidomethyl) analogues.


Subject(s)
Affinity Labels/chemistry , Dicarboxylic Acids/chemistry , Phosphoprotein Phosphatases/metabolism , Affinity Labels/chemical synthesis , Affinity Labels/metabolism , Animals , Catalytic Domain , Dicarboxylic Acids/chemical synthesis , Dicarboxylic Acids/metabolism , Enzyme Inhibitors/chemical synthesis , Enzyme Inhibitors/chemistry , Enzyme Inhibitors/metabolism , Enzyme Stability , Hydrogen-Ion Concentration , In Vitro Techniques , Liver/enzymology , Magnetic Resonance Spectroscopy , Mice , Phosphoprotein Phosphatases/antagonists & inhibitors , Phosphoprotein Phosphatases/chemistry , Protein Phosphatase 2 , Structure-Activity Relationship , Temperature
12.
Circulation ; 95(5): 1308-13, 1997 Mar 04.
Article in English | MEDLINE | ID: mdl-9054864

ABSTRACT

BACKGROUND: Nitroglycerin has been shown to possess antiplatelet properties in both animals and humans. Tolerance to the hemodynamic effects of nitroglycerin develops with continuous therapy, but it is unclear whether there is tolerance to its antiplatelet effect. METHODS AND RESULTS: Tolerance to nitroglycerin was studied by exposing porcine aortic media to flowing arterial blood from control pigs (n = 9) or pigs treated with continuous nitroglycerin patches (Nitro-dur, 0.8 mg/h; n = 11) at a shear rate of 3397 s-1 for 3 minutes. Relative to baseline, mean arterial pressure fell by approximately 10% at 3 and 24 hours (P < .05) but returned to baseline at 48 hours of continuous nitroglycerin treatment, whereas no significant changes were observed in control animals. Autologous 51Cr-labeled platelet deposition (x 10(6)/cm2) on the aortic media at baseline and 3, 24, and 48 hours remained stable in control animals, with mean values of 94.8 +/- 5.9, 89.4 +/- 8.3, 89.3 +/- 8.8, and 84.3 +/- 5.7, respectively. However, in pigs treated continuously with nitroglycerin for 48 hours, platelet deposition was reduced significantly at 3 (65.9 +/- 4.8), 24 (63.8 +/- 6.4), and 48 hours (56.5 +/- 7.3) of nitroglycerin treatment compared with baseline (93.1 +/- 3.6). Platelet aggregation induced by thrombin also decreased at 3 (12.4 +/- 1.3), 24 (12.6 +/- 1.7), and 48 hours (10.8 +/- 1.6) of nitroglycerin treatment compared with baseline (16.3 +/- 1.4) but remained unchanged in the control group. Also, nitroglycerin treatment increased intraplatelet cGMP at 3, 24, and 48 hours compared with baseline. CONCLUSIONS: This study demonstrates the persistent inhibition of platelet function and platelet deposition on an injured arterial wall by continuous nitroglycerin therapy despite hemodynamic tolerance.


Subject(s)
Blood Platelets/physiology , Hemodynamics/drug effects , Nitroglycerin/pharmacology , Platelet Aggregation Inhibitors , Platelet Aggregation/drug effects , Tunica Media/physiology , Vasodilator Agents/pharmacology , Administration, Cutaneous , Analysis of Variance , Animals , Aorta/drug effects , Aorta/physiology , Blood Platelets/drug effects , Blood Pressure/drug effects , Cyclic GMP/blood , Drug Tolerance , Nitroglycerin/administration & dosage , Swine , Time Factors , Tunica Media/drug effects , Vasodilator Agents/administration & dosage
13.
Circulation ; 92(11): 3172-7, 1995 Dec 01.
Article in English | MEDLINE | ID: mdl-7586300

ABSTRACT

BACKGROUND: Hypercholesterolemia is a risk factor for coronary disease, and platelet reactivity is increased with hypercholesterolemia, suggesting a prethrombotic risk. The aim of this study was to measure mural platelet thrombus formation on an injured arterial wall in a model simulating vessel stenosis and plaque rupture in hypercholesterolemic coronary disease patients before and after cholesterol reduction. METHODS AND RESULTS: Thirty-two patients with stable coronary disease were studied. Platelet thrombus formation and serum lipids were measured in 16 hypercholesterolemic patients (cholesterol > 5.2 mmol/L) before and after a mean of 2.5 months of pravastatin therapy (40 mg/d) and in 16 normocholesterolemic control patients. Thrombus formation was assessed by exposing porcine aortic media to the patient's flowing venous blood for 3 minutes at a shear rate of 754 or 2546 s-1 at 37 degrees C in an ex vivo superfusion chamber. Quantitative morphometric platelet thrombus formation at baseline was higher in the hypercholesterolemic patients at both the high and low shear rates: 4.8 +/- 1.0 and 3.3 +/- 0.7 micron 2/mm, respectively, compared with normocholesterolemic patients: 2.1 +/- 0.5 and 1.6 +/- 0.4 micron 2/mm (both P < .05). In the hypercholesterolemic patients, pravastatin decreased total cholesterol from 6.5 +/- 0.2 to 4.5 +/- 0.2 mmol/L and LDL cholesterol from 4.5 +/- 0.2 to 2.8 +/- 0.1 mmol/L (both P < .05). Platelet thrombus formation at high and low shear rates decreased to 2.0 +/- 0.3 and 1.3 +/- 0.3 micron 2/mm, respectively (both P < .05). CONCLUSIONS: Thus, hypercholesterolemia is associated with an enhanced platelet thrombus formation on an injured artery, increasing the propensity for acute thrombosis. Platelet thrombus formation at both high and low shear rates decreased as total and LDL cholesterol levels were reduced with pravastatin. Cholesterol lowering may therefore reduce the risk of acute coronary events in part by reducing the thrombogenic risk.


Subject(s)
Anticholesteremic Agents/therapeutic use , Blood Platelets/drug effects , Coronary Disease/epidemiology , Hypercholesterolemia/drug therapy , Pravastatin/therapeutic use , Thrombosis/prevention & control , Animals , Aorta/pathology , Case-Control Studies , Cholesterol/blood , Cholesterol, LDL/blood , Coronary Disease/blood , Coronary Disease/prevention & control , Female , Humans , Hypercholesterolemia/blood , Hypercholesterolemia/epidemiology , Male , Middle Aged , Models, Cardiovascular , Risk Factors , Swine , Thrombosis/blood , Time Factors , Tunica Media/pathology
14.
Circulation ; 92(9): 2432-6, 1995 Nov 01.
Article in English | MEDLINE | ID: mdl-7586342

ABSTRACT

BACKGROUND: Smoking is associated with an increased risk of myocardial infarction and sudden death. Platelet activation and thrombosis at sites of vessel stenosis and injury or plaque disruption play a crucial role in these acute coronary events. Thus, the aim of this study was to determine whether cigarette smoking acutely increases platelet thrombus formation on an injured arterial surface at local shear rates typical of a stenotic artery. METHODS AND RESULTS: Twelve habitual smokers with stable coronary disease, on aspirin 325 mg/d, were studied immediately before and 5 minutes after smoking two cigarettes each. Ex vivo platelet thrombus formation on porcine arterial media (simulating deep arterial injury) was measured after exposure to the patient's circulating venous blood for 3 minutes in cylindrical flow chambers at 37 degrees C. The flow chambers were designed to produce shear rates of 754 or 2546 s-1, the latter being typical of the high shear rates produced by vessel stenosis. Plasma catecholamine, thromboxane B2, and 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha) levels and whole blood platelet aggregation responses to thrombin were also measured before and after smoking. Compared with before smoking, morphometrically measured platelet thrombus formation on arterial media at shear rates of 754 and 2546 s-1 increased by an average of 48% (P = .19) and 64% (P = .014), respectively, after smoking. Plasma epinephrine increased by more than twofold after smoking (P = .026). Plasma thromboxane B2 and 6-keto-PGF1 alpha levels did not change. Smoking also increased whole blood platelet aggregation to thrombin (P < or = .05). CONCLUSIONS: These results suggest that smoking-enhanced platelet thrombosis may be an important contributory mechanism for acute coronary events in smokers that is not prevented by aspirin treatment. Catecholamine release and heightened platelet aggregation response to in vivo agonists may contribute to the prothrombotic effects of smoking.


Subject(s)
Aspirin/therapeutic use , Coronary Disease/complications , Coronary Disease/drug therapy , Coronary Thrombosis/etiology , Platelet Aggregation , Smoking/adverse effects , Adult , Aged , Animals , Aorta/physiopathology , Coronary Thrombosis/drug therapy , Coronary Thrombosis/physiopathology , Female , Humans , Male , Middle Aged , Risk Factors , Swine , Tunica Media/physiopathology
15.
Circulation ; 92(8): 2299-305, 1995 Oct 15.
Article in English | MEDLINE | ID: mdl-7554215

ABSTRACT

BACKGROUND: The infusion sleeve is a novel drug-delivery catheter system designed to deliver an agent under controlled conditions into the arterial wall at the site of angioplasty. The purpose of the present study was to characterize the delivery agent via the infusion sleeve in ex vivo and in vivo models. METHODS AND RESULTS: The delivery of horseradish peroxidase via the infusion sleeve was studied in a porcine explanted heart model. Under physiological conditions, arteries underwent balloon injury (approximately 10% overstretch), after which horseradish peroxidase (2.5 mL) was delivered at specific pressures. Cross-sectional analysis demonstrated greater staining when the agent was delivered at increasing pressures. The infusion sleeve was evaluated in an in vivo canine coronary model. With an infusion sleeve loaded over a standard dilatation catheter through a 9F guide, overstretch balloon injury was performed, after which fluoresceinated heparin was delivered. Animals were killed 2 hours after delivery. Fluoresceinated heparin-treated segments demonstrated high fluorescence signals, localizing with smooth muscle cell nuclei with less activity in the interstitium. The functional significance of intramural heparin delivery was studied in a porcine carotid model. In the presence of 111In-labeled platelets, arteries underwent overstretch injury followed by delivery of heparin (50 or 100 units/kg) or vehicle. Platelet deposition was reduced at 30 minutes (57%, P < .01) and 12 hours (39%, P = .06) compared with saline controls. CONCLUSIONS: Agent delivery via the infusion sleeve is pressure dependent; transmural delivery is possible with minimal disruption of arterial wall architecture; the infusion sleeve is compatible with standard angioplasty equipment; and heparin delivery at the site of balloon injury significantly reduces platelet deposition in a porcine model for a minimum of 12 hours.


Subject(s)
Angioplasty, Balloon, Coronary , Anticoagulants/administration & dosage , Coronary Disease/therapy , Drug Delivery Systems/instrumentation , Heparin/administration & dosage , Angioplasty, Balloon , Angioplasty, Balloon, Coronary/instrumentation , Animals , Carotid Stenosis/etiology , Carotid Stenosis/prevention & control , Coronary Disease/prevention & control , Dogs , Equipment Design , Horseradish Peroxidase/administration & dosage , Infusion Pumps , Recurrence
16.
Am Heart J ; 129(3): 445-51, 1995 Mar.
Article in English | MEDLINE | ID: mdl-7872169

ABSTRACT

Physiopathologic events after arterial injury are largely influenced by blood element reactions with the injured surface. To determine acute arterial reactivity to injury, simultaneous chromium 51-labeled platelet deposition and indium 111-labeled neutrophil adhesion were quantified at the site of different degrees of carotid arterial injury by balloon dilatation in 21 normal pigs. The degree of vasoconstriction distally to the dilated areas was also quantified angiographically. Arteries were classified histologically as (1) uninjured with intact endothelium; (2) mildly injured with endothelial desquamation; or (3) deeply injured with lesions extending beyond internal elastic lamina, exposing the media. We found that, compared to mild injury, deep injury was associated with greater platelet deposition (38.2 +/- 5.7 x 10(6)/cm2 vs 7.8 +/- 0.9 x 10(6)/cm2; p < 0.05), neutrophil adhesion (30.6 +/- 4.1 x 10(4)/cm2 vs 10.2 +/- 2.9 x 10(4)/cm2; p < 0.05), and vasoconstrictive response (45.5% +/- 3.2% vs 26.7% +/- 2.8%; p < 0.05). Although distally to both types of injuries, noninjured arterial segments with intact endothelium were thromboresistant to platelet deposition, neutrophil adhesion to intact endothelium was much higher after deep injury (2.2 +/- 0.4 x 10(4)/cm2) compared to mild injury (0.36 +/- 0.1 x 10(4)/cm2; p < 0.05). Like platelet deposition, neutrophil adhesion is influenced by the severity of arterial injury; both may therefore be implicated in thrombogenesis and vascular responsiveness after arterial injury in vivo.


Subject(s)
Carotid Arteries/physiopathology , Carotid Arteries/ultrastructure , Endothelium, Vascular/physiopathology , Endothelium, Vascular/ultrastructure , Neutrophils/physiology , Platelet Aggregation , Vasoconstriction , Angioplasty, Balloon/adverse effects , Animals , Carotid Artery Injuries , Cell Adhesion , Swine
17.
Circulation ; 90(2): 997-1002, 1994 Aug.
Article in English | MEDLINE | ID: mdl-8044973

ABSTRACT

BACKGROUND: Experimental studies in vitro suggest that neutrophils can modulate platelet function and vasomotor responses. In the present study, the interactions among neutrophils, platelets, and arterial responses to injury in vivo were assessed. METHODS AND RESULTS: The acute thrombotic and vasomotor responses of porcine carotid arteries to balloon injury in vivo were evaluated in three groups of animals: neutropenic pigs treated (n = 11) or not treated (n = 12) with aspirin and healthy untreated control pigs (n = 15). Neutropenia was achieved by treatment with cyclophosphamide (50 mg/kg, 4 days before the experiment), which decreased circulating leukocyte count by 92% and almost abolished neutrophil aggregation to N-formyl-methionyl-leucyl-phenylalanine without affecting blood platelet count, hematocrit, hemoglobin concentration, or whole blood platelet aggregation to ADP. 51Cr platelet deposition on deeply injured and uninjured arterial segments was not statistically influenced by neutrophil depletion, whereas the angiographic vasoconstrictive response at the site of endothelial injury distally was significantly reduced by 41% from 46.3 +/- 2.9% in the control group to 27.2 +/- 4.1% in the neutropenic group (P < .05). Aspirin treatment in combination with neutropenia produced a 50% reduction in whole blood platelet aggregation, resulted in a significant inhibition of platelet deposition to deeply injured arteries, and decreased vasoconstriction by 66% to 15.6 +/- 3.0% (P < .05 versus control and neutropenic). CONCLUSIONS: Neutrophils can influence the vasoconstrictive response at the site of endothelial injury in vivo. In addition to platelets, neutrophil interaction with the injured vessel wall may be implicated in the pathophysiological response to arterial injury in vivo.


Subject(s)
Angioplasty, Balloon/adverse effects , Carotid Artery Injuries , Neutrophils/physiology , Platelet Adhesiveness/physiology , Vasoconstriction/physiology , Animals , Aspirin/therapeutic use , Carotid Arteries/pathology , Carotid Arteries/physiopathology , Neutropenia/physiopathology , Platelet Aggregation/physiology , Swine , Tunica Intima/pathology
18.
Am J Cardiol ; 73(15): 1058-62, 1994 Jun 01.
Article in English | MEDLINE | ID: mdl-8198030

ABSTRACT

Nitroglycerin provides an external source of nitric oxide which stimulates guanylate cyclase and produces vasodilatation and inhibition of platelet function. The antithrombotic effects of intravenous nitroglycerin were recently documented in various experimental models and in patients with unstable angina. This protocol was designed to evaluate whether these effects could also be detected with transdermal nitroglycerin in patients with stable angina. In a randomized, double-blind, controlled parallel trial, 22 patients received transdermal nitroglycerin, 0.6 mg/hour (11 patients), or placebo (11 patients). Platelet aggregation to adenosine diphosphate (ADP) and to thrombin was measured in whole blood. Thrombus formation was assessed on porcine aortic media exposed to the patient's venous blood for 3 minutes at shear rates of 2,546 and 754 s-1. Platelet aggregation to ADP decreased from 7.7 +/- 0.8 to 5.3 +/- 0.8 ohms (p < 0.05) with nitroglycerin, and to thrombin from 15.6 +/- 1.2 to 12 +/- 1.2 ohms (p < 0.05). Thrombus size at the high-shear rate decreased from 2.8 +/- 0.7 to 1.0 +/- 0.3 microns 2 (p < 0.05), and at the low-shear rate from 2.5 +/- 0.5 to 1.0 +/- 0.2 microns 2 (p < 0.05). Placebo had no significant effect on platelet aggregation and platelet thrombus deposition. These parameters were all reduced by > or = 20% in 8 patients taking nitroglycerin but only in 3 patients taking placebo (p < 0.05). Transdermal nitroglycerin significantly inhibits platelet aggregation and mural thrombus formation in patients with angina pectoris.


Subject(s)
Angina Pectoris/drug therapy , Fibrinolytic Agents/pharmacology , Nitroglycerin/pharmacology , Administration, Cutaneous , Adult , Aged , Angina Pectoris/blood , Angina Pectoris/physiopathology , Double-Blind Method , Female , Fibrinolytic Agents/administration & dosage , Hemodynamics/drug effects , Humans , Male , Middle Aged , Nitroglycerin/administration & dosage , Platelet Aggregation Inhibitors/pharmacology , Risk Factors
19.
Arterioscler Thromb ; 14(3): 331-5, 1994 Mar.
Article in English | MEDLINE | ID: mdl-8123636

ABSTRACT

Nitric oxide (NO) synthesized from cultured endothelial cells inhibits platelet aggregation and adhesion to subendothelial extracellular matrix and may contribute to the thromboresistance of the endothelium. NO has also been shown to inhibit neutrophil aggregation and adherence to postcapillary venules. Whether NO derived from the intact endothelium of an arterial wall can influence platelet and neutrophil adhesion under whole-blood arterial flow conditions was evaluated in this study. Porcine aortic segments with intact endothelium were exposed to flowing porcine arterial blood for 5 minutes at a shear rate of 424 sec-1. Pretreatment of the endothelium with the physiological precursor of NO, L-arginine (2 mmol/L), reduced 111In-labeled neutrophil adhesion by 32% from 10.2 +/- 1.6 to 6.9 +/- 1.3 x 10(3)/cm2 (P < .05), relative to control. This effect was reversed by the inhibitor of NO synthesis, N omega-nitro-L-arginine methyl ester (L-NAME, 5 mmol/L) (8.2 +/- 3.0 versus 8.6 +/- 3.2 x 10(3)/cm2 for control; P = NS). Pretreatment of the endothelium with D-arginine (2 mmol/L) did not influence neutrophil adhesion (8.7 +/- 2.0 versus 8.6 +/- 2.0 x 10(3)/cm2 for control; P = NS). The intact endothelium, which is normally thromboresistant, shows a low basal level of 51Cr activity, corresponding to a platelet adhesion less than 0.5 x 10(6)/cm2, and this thromboresistance was not significantly influenced by L-arginine. These results indicate that NO derived from an intact arterial endothelium under whole-blood arterial flow conditions may be an important modulator of neutrophil interaction with the intact endothelium.


Subject(s)
Endothelium, Vascular/physiology , Neutrophils/physiology , Nitric Oxide/physiology , Animals , Arginine/analogs & derivatives , Arginine/pharmacology , Cell Adhesion , Female , Male , NG-Nitroarginine Methyl Ester , Swine
20.
Am J Cardiol ; 73(5): 333-8, 1994 Feb 15.
Article in English | MEDLINE | ID: mdl-8109546

ABSTRACT

The platelet-aggregatory response, platelet-release factors and markers of thrombin generation in vivo were studied prospectively in 53 patients participating in a randomized clinical trial evaluating the influence of nicardipine on the progression of coronary atherosclerosis. Coronary lesions were measured quantitatively and progression was defined as a decrease in minimum diameter by > or = 0.4 mm. At repeat angiography 24 months after study entry, 20 of the 53 patients had progression of 28 coronary narrowings. Only thrombin-induced enhanced platelet aggregation differentiated patients with from those without coronary disease progression, with an estimated odds ratio of 2.49 (95% confidence interval 1.10 to 5.66). The aggregatory response to adenosine diphosphate, collagen, epinephrine and platelet-activating factor were not different in the 2 groups of patients, nor were measurements of platelet factor 4, beta-thromboglobulin, thromboxane B2, 6-keto-prostaglandin F1 alpha and fibrinopeptide A. During 46.8 months of follow-up after repeat angiography, coronary events occurred in 11 of the 20 with and 6 of the 33 without progression (difference 37%, p = 0.013, confidence interval 11 to 63%). Those with coronary disease progression and an enhanced thrombin-induced platelet aggregation had a worse prognosis than those with no disease progression and a low thrombin-induced platelet aggregation. Thus, patients with coronary disease progression and future coronary events have an enhanced thrombin-induced platelet aggregation. This platelet abnormality may be a marker of increased risk and may play a causative role in the development of coronary events.


Subject(s)
Coronary Disease/blood , Coronary Disease/physiopathology , Platelet Aggregation/physiology , 6-Ketoprostaglandin F1 alpha/blood , Coronary Angiography , Coronary Disease/prevention & control , Double-Blind Method , Female , Fibrinopeptide A/analysis , Follow-Up Studies , Humans , Male , Middle Aged , Nicardipine/therapeutic use , Placebos , Platelet Aggregation/drug effects , Platelet Factor 4/analysis , Prospective Studies , Survival Rate , Thrombin/pharmacology , Thromboxane B2/blood , beta-Thromboglobulin/analysis
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