Genotoxicity of hydrazino-phtalazine antihypertensive drugs assessed by an in vitro micronucleus assay

Oral anticoagulant therapy is effective antithrombotic treatment for several indications. The results of prothrombin time monitoring should be reported as the International Normalized Ratio (INR). An INR of 2 to 3 is the recommended therapeutic range for all indications except for the prevention of systemic embolism in patients with mechanical heart valves and for the long-term treatment of patients with myocardial infarction, for whom an INR range of 2.5 to 3.5 is recommended. Oral anticoagulant therapy with warfarin sodium is the preferred approach for preventing stroke in most patients with atrial fibrillation. The available data suggest that warfarin is more effective than aspirin. Aspirin, 325 mg/d, is indicated for patients in whom warfarin is contraindicated or in patients less than 75 years of age who are at low risk for stroke because risk factors are absent. In patients 75 years of age or more, close monitoring of warfarin treatment is prudent to avoid major bleeding due to poor anticoagulant control. In selected patients, patient-self-monitoring and adjustment of warfarin treatment using a portable prothrombin time monitor may be effective and safe.     

Combined warfarin and antiplatelet therapy after St. Jude Medical valve replacement for mitral valve disease

OBJECTIVES: The clinical effect of combined warfarin and antiplatelet therapy on the incidence of stroke and postoperative complications after mitral (plus aortic) valve replacement was studied and compared with that observed with warfarin therapy alone. BACKGROUND: It has been reported that combined warfarin and antiplatelet therapy may be effective but may be associated with an increased hemorrhagic risk. Therefore, definite benefits of the treatment in patients with an implanted prosthetic valve have not been clearly documented. METHODS: Between January 1980 and December 1992, 195 patients with a St. Jude Medical valve at the mitral (plus aortic) position were assigned to receive treatment with either warfarin alone (125 patients) or warfarin plus antiplatelet agents (70 patients), such as dipyridamole (150 or 300 mg daily, 14 patients) or ticlopidine (200 or 400 mg daily, 56 patients). A minimal dose of aspirin (10 to 40 mg) was added (29 patients) if the maximal platelet aggregation rate by collagen was not reduced. The target thrombotest level was 10% to 20%. RESULTS: The two treatment groups were similar with regard to gender and age distribution. The number of patients with atrial fibrillation, left atrial thrombus, history of previous stroke, simultaneous aortic valve operation and previously performed valve procedures were comparable in the two groups. Actuarial survival rate at 10 years was 98.3 +/- 1.7% (mean +/- SD) in the warfarin plus antiplatelet group and 90.3 +/- 3.2% in the warfarin group (p < 0.05 at 1 and 9 to 12 years). The actuarial stroke-free rate at 10 years was 95.3 +/- 3.4% and 84.3 +/- 3.8%, respectively (p < 0.05 by the generalized Wilcoxon test). The actuarial complication-free rate at 10 years was 89.4 +/- 4.3% and 67.9 +/- 4.8%, respectively (p < 0.05 by the generalized Wilcoxon test). No hemorrhagic complications were seen in the warfarin plus antiplatelet group. CONCLUSIONS: The results strongly indicate the effectiveness and safety of combined warfarin plus antiplatelet treatment after St. Jude Medical valve replacement for mitral (plus aortic) valve disease.     

Patient outcomes after reoperation on the lumbar spine

A prospective, randomized trial was conducted to compare the effectiveness and safety of warfarin given in two regimens in prevention of venous thrombosis after total knee replacement. Adult patients scheduled for primary or revision total knee replacement were randomly assigned to receive either a "two-step" warfarin regimen beginning 10-14 days pre-operatively or, alternatively, to begin warfarin the night before surgery. Post-operatively, the dose was adjusted in both groups to achieve a target International Normalized Ratio (INR) of 2.2 and prophylaxis was continued until venography on post-operative days five through nine. Bleeding was assessed by surgical blood loss, transfusion requirements, changes in hematocrit, and clinically identified bleeding complications. The occurrence of deep vein thrombosis was nearly the same in the two treatment groups, 39% in patients randomized to the two-step regimen as compared to 38% in those beginning the night before surgery. The occurrence of proximal vein thrombosis was also similar, 5% versus 7% (p = NS). Patients in the two-step group received 1.33 +/- 1.26 transfusions compared to 0.95 +/- 1.22 in the night before group (p < 0.05) and also had a lower nadir post-operative hematocrit of 26.7 +/- 3.1 as compared to 28.5 +/- 3.2 (p < 0.0001). Major bleeding complications were associated with excessively prolonged INRs and occurred in five patients in the two-step group and two in the night before group. Patients in both groups who developed thrombosis had a significantly lower INR on post-operative days two and three compared to those without thrombosis. We conclude that a prophylactic warfarin regimen for prevention of deep vein thrombosis after total knee replacement beginning the night before surgery is more convenient and may be associated with less bleeding than a regimen beginning warfarin 10-14 days pre-operatively. Careful control of anticoagulant intensity is needed to achieve maximum effectiveness and avoidance of bleeding complications.     

Antithrombotic therapy prescribed for patients with non-rheumatic atrial fibrillation

Patients with non-rheumatic atrial fibrillation have a fivefold increased risk of stroke. Warfarin reduces this risk by approximately two thirds, but evidence for benefit from aspirin is less compelling. We assessed whether our current practice reflects the message of the trials. In a retrospective case record study we reviewed notes of 131 patients with atrial fibrillation (AF), mean age 79 (range 53-95) years, admitted to a medical unit (72) or geriatric assessment unit (59). Thirty-two patients had paroxysmal AF. Of 115 patients with nonrheumatic AF, 36 (31%) had one or more recorded contraindication to anti-coagulation. Although 79 patients (69%) had no recorded contraindication to warfarin, only 2 took warfarin and 15 aspirin prior to admission. Ten patients commenced warfarin and 8 aspirin before discharge. Thirty-nine patients (53%) without contraindication, were discharged without antithrombotic therapy. Despite evidence to support anticoagulating patients with non-rheumatic AF, this rarely occurs.     

Oral anticoagulant prophylaxis and epidural catheter removal

BACKGROUND AND OBJECTIVES: The use of regional anesthesia in patients receiving anticoagulants is controversial. The purpose of this review is to document the incidence of neurologic complications with insertion and removal of an epidural catheter in patients receiving oral anticoagulants and antiplatelet medication. METHODS: A retrospective review was made of the charts of 459 patients who underwent hip pinning or hip or knee replacement under regional anesthesia and received postoperative epidural analgesia and warfarin thromboembolism prophylaxis. The number of patients receiving preoperative antiplatelet therapy and warfarin, as well as baseline coagulation parameters, was documented. For patients who had postoperative epidural analgesia, the prothrombin time on the day of epidural catheter removal was obtained. Neurologic complications during the hospital stay were noted. RESULTS: Spinal anesthesia was administered to 47 patients and epidural anesthesia and postoperative analgesia to 412. Before surgery, antiplatelet therapy was given to 270 and warfarin to 180 patients, with some patients receiving both. The mean +/- SD preoperative prothrombin and partial thromboplastin times were 10.8 +/- 1.2 seconds (normal, 9.6-11.1 seconds) and 27.5 +/- 3.5 seconds (normal, 24.6-33.2 seconds), respectively. Blood on needle or catheter insertion was noted in 21 patients, all of whom were taking antiplatelet medication and/or warfarin. Epidural catheters remained postoperatively for a mean of 43.6 +/- 12.5 hours (range 5-118 hours). The mean prothrombin time on the day of epidural catheter removal was 14.1 +/- 3.2 seconds. Four postoperative peripheral neuropathies were detected. There was no clinical evidence of spinal hematoma in any patient. CONCLUSIONS: Epidural catheter placement and removal in patients taking oral anticoagulants appears to be safe. Careful monitoring of the patient for evidence of spinal hematoma after epidural catheter removal is recommended.     

Changes in plasma warfarin levels and variations in steady-state prothrombin times

OBJECTIVE: To determine the relative contribution of changes in the plasma warfarin level to variation in the serial steady-state prothrombin times. METHODS: This was a prospective observational cohort study performed at two outpatient anticoagulation clinics. Serial prothrombin times and paired plasma total warfarin levels were determined in a convenience sample of otherwise healthy patients who required long-term oral anticoagulation therapy with warfarin. RESULTS: Serial measurements were obtained from 129 patients, 60 of whom provided three or more serial samples. Analysis of covariance showed a highly significant (p = 0.0001) relationship between the anticoagulant effect and the logarithm of the warfarin concentration (R2 = 0.75), with 15.3% of the total variance attributable to the effect of warfarin and 31.1% attributable to individual variation in sensitivity to warfarin. In an analysis of the subjects who had three or more serial measurements, the mean weighted correlation coefficient for the relationship between the logarithm of the warfarin concentration and the anticoagulant response varied widely, from strongly negative to strongly positive, and as the range of observed prothrombin times increased, stronger positive correlation was observed. CONCLUSIONS: In this cohort, the plasma warfarin level was a strong predictor of observed changes in serial prothrombin time measurements. However, the correlation between clotting times and warfarin levels varied widely among subjects, particularly when the range of observed prothrombin times was moderate. This suggests that in these subjects, other factors, such as measurement error or pharmacodynamic changes, played a major role.     

Incidence and characteristics of fall-related emergency department visits

BACKGROUND: Patients with acute ischemic syndromes (AIS) suffer high rates of recurrent ischemic events despite aspirin treatment. Long-term therapy with oral anticoagulants in addition to aspirin may reduce this risk. We studied the effects of long-term warfarin at 2 intensities in patients with AIS without ST elevation in 2 consecutive randomized controlled studies. METHODS AND RESULTS: In phase 1, after the cessation of 3 days of intravenous antithrombotic therapy, 309 patients were randomized to receive fixed low-dose (3 mg/d) warfarin for 6 months that produced a mean international normalized ratio (INR) of 1.5+/-0.6 or to standard therapy. Eighty-seven percent of patients received aspirin in both groups. The rates of cardiovascular (CV) death, new myocardial infarction (MI), and refractory angina at 6 months were 6.5% in the warfarin group and 3.9% in the standard therapy group (relative risk [RR], 1. 66; 95% CI, 0.62 to 4.44; P=0.31). The rates of death, new MI, and stroke were 6.5% in the warfarin group and 2.6% in the standard therapy group (RR, 2.48; 95% CI, 0.80 to 7.75; P=0.10). The overall rate of rehospitalization for unstable angina was 21% and did not differ significantly between the groups. Four patients in the warfarin group (2.6%) and none in the control group experienced a major bleed (RR, 2.48; 95% CI, 0.80 to 7.75), and there was a significant excess of minor bleeds in the warfarin group (14.2% versus 2.6%; RR, 5.46; 95% CI, 1.93 to 15.5; P=0.001). In phase 2, the protocol was modified, and 197 patients were randomized <48 hours from the onset of symptoms to receive warfarin at an adjusted dose that produced a mean INR of 2.3+/-0.6 or standard therapy for 3 months. Eighty-five percent received aspirin in both groups. The rates of CV death, new MI, and refractory angina at 3 months were 5. 1% in the warfarin group and 12.1% in the standard group (RR, 0.42; 95% CI, 0.15 to 1.15; P=0.08). The rates of all death, new MI, and stroke were 5.1% in the warfarin group and 13.1% in the standard therapy group (RR, 0.39; 95% CI, 0.14 to 1.05; P=0.05). Significantly fewer patients were rehospitalized for unstable angina in the warfarin group than in the control group (7.1% and 17.2%, respectively; RR, 0.42; 95% CI, 0.18 to 0.96; P=0.03). Two patients in the warfarin group and 1 in the control group experienced a major bleed, and there was a significant excess of minor bleeds in the warfarin group (28.6% versus 12.1%; RR, 2.36; 95% CI, 1.37 to 4.36; P=0.004). CONCLUSIONS: Long-term treatment with moderate-intensity warfarin (INR, 2.0 to 2.5) plus aspirin but not low-intensity warfarin (INR, 1.5) plus aspirin appears to reduce the rate of recurrent ischemic events in patients with AIS without ST elevation.     

Variations in prothrombin time and international normalized ratio over 24 hours in warfarin-treated patients

STUDY OBJECTIVE: To determine the variation of prothrombin times and international normalized ratio (INR) over 24 hours in humans. DESIGN: Prospective, parallel study. SETTING: University-affiliated general clinical research center. PATIENTS: Six patients receiving long-term warfarin therapy and six sex-matched controls. INTERVENTIONS: Warfarin was administered to the patients at 6:00 P.M. MEASUREMENTS AND MAIN RESULTS: Prothrombin times and INR were determined every 2 hours over 24 hours. Time of study entry, meals, and sleep cycles were controlled. A significant cosinor rhythm for prothrombin times and INR (p < or = 0.03) occurred in warfarin-treated patients, suggesting that diurnal variation occurs. The mean difference between the peak and trough prothrombin times was 1.8 +/- 0.9 seconds (range 0.8-3 sec) with a mean change of 9.3% +/- 3.7%. The peak prothrombin time and INR values occurred between 4:00 A.M. and 8:00 A.M. in five patients, and trough values between 6:00 P.M. and midnight in five. No significant cosinor rhythm was noted for controls (p > 0.5). CONCLUSION: Significant variations in prothrombin time and INR occurred in patients receiving warfarin therapy, with the highest values occurring in the morning and the lowest in the evening. These results may have clinical implications for patients receiving either high- or low-intensity warfarin therapy.     

Antithrombotic therapy after coronary stent placement

Subacute stent thrombosis and hemorrhagic complications due to intensive anticoagulant therapy limit the clinical benefit of coronary stenting. Antithrombotic therapy after coronary stent placement has not been standardized yet. From January 1994 to December 1995 a total of 338 Palmaz-Schatz stents were implanted in 285 patients. Procedural success rate was 98.8%. In the initial period, after stent placement, patients were treated with acetylsalicylic acid (ASA) and warfarin (135 patients, Group A), while subsequently, according to the results of other studies, patients were treated with ASA plus ticlopidine (146 patients, Group B). Two hours after sheath removal, Group A patients were treated with intravenous heparin until therapeutic INR (2.5-3.5) was reached; warfarin was stopped 3 months later. In Group B patients 2 hours after sheath removal a treatment with subcutaneous heparin 25,000 IU/die plus ticlopidine 500 mg/die was started. Subcutaneous heparin was maintained until hospital discharge, ticlopidine was stopped after 1 month and ASA was maintained indefinitely. There were no significant differences in baseline characteristics between the two groups. Most patients had unstable angina and in the majority of cases the stent was implanted due to intimal dissection after balloon dilation. Eleven patients had subacute thrombosis of the stent (3.9%): 9 patients were in Group A (6%) and 2 patients were in Group B (1.3%; p = 0.04). Seven patients (6 in Group A, 1 in Group B) were treated with emergency coronary angioplasty and 3 (2 in Group A, 1 in Group B) with coronary bypass; nevertheless 7 patients (6 in Group A, 1 in Group B) had an acute myocardial infarction. Eight patients (6 in Group A, 2 in Group B) had major bleeding due to a large groin hematoma requiring blood transfusion or vascular surgery. In conclusion, after coronary stenting antithrombotic therapy with ASA plus ticlopidine, as compared with anticoagulant therapy, reduces the incidence of both cardiac events and hemorrhagic complications.     

13C-Octanoic acid breath test for gastric emptying rate of solids

We performed a retrospective chart review of 60 patients after mechanical heart valve replacement to assess warfarin sensitivity. The overall international normalized ratio (INR) on day 3 of therapy was 4.1+/-3.9 (range 1.1-17.1). In a control group of 100 patients who received anticoagulation for atrial fibrillation, pulmonary embolism, and deep vein thrombosis, the overall mean INR at day 3 was 1.9+/-0.7 (range 1.0-4.9). The difference between groups was statistically significant (p<0.05). We conclude that patients receiving warfarin after mechanical heart valve replacement are more sensitive to the drug than those receiving it for other indications, and reduced dosages may be necessary during the first 3 days after valve replacement.     

Oral delivery of anticoagulant doses of heparin. A randomized, double-blind, controlled study in humans

BACKGROUND: Parenteral heparin is the anticoagulant of choice in hospitalized patients. Continued anticoagulation is achieved by subcutaneous administration of low-molecular-weight heparin or with an orally active anticoagulant such as warfarin. An oral heparin formulation would avoid the inconvenience of subcutaneous injection and the unfavorable drug interactions and adverse events associated with warfarin. A candidate delivery agent, sodium N-[8(-2-hydroxybenzoyl)amino]caprylate (SNAC), was evaluated with escalating oral heparin doses in a randomized, double-blind, controlled clinical study for safety, tolerability, and effects on indexes of anticoagulation. METHODS AND RESULTS: Increases in activated partial thromboplastin time (aPTT), anti-factors IIa and Xa, and tissue factor pathway inhibitor (TFPI) concentrations were detected when normal volunteers were dosed with 10.5 g SNAC/20000 IU heparin by gavage in some subjects. For the entire group, 30000 IU SNAC and heparin elevated TFPI from 74.9+/-7.6 to 254.2+/-12.3 mg/mL (P<0.001) 1 hour after dosing (P<0.001). Similar changes occurred in anti-factor IIa and anti-factor Xa. aPTT rose from 28+/-0.5 to 42.2+/-6.3 seconds 2 hours after dosing (P<0.01). No significant changes in vital signs, physical examination, ECGs, or clinical laboratory values were observed. Neither 30000 IU heparin alone nor 10.5 g SNAC alone altered the hemostatic parameters. Emesis was associated with 10.5 g SNAC. A taste-masked preparation of SNAC 2.25 g was administered orally with heparin 30000 to 150000 IU. Both aPTT and anti-factor Xa increased with escalating doses of heparin. This preparation was well tolerated. Conclusions-Heparin, administered orally in combination with the delivery agent SNAC, produces significant elevations in 4 indexes of anticoagulant effect in healthy human volunteers. These results establish the feasibility of oral delivery of anticoagulant doses of heparin in humans and may have broader implications for the absorption of macromolecules.     

Comparison of anticoagulant control among patients attending general practice and a hospital anticoagulant clinic

Management of patients receiving oral anticoagulant therapy was assessed in general practice and a dedicated hospital anticoagulant clinic. The demographic characteristics of patients in both groups were similar, as were the indications for anticoagulation therapy and the duration of treatment. General practice patients were reviewed significantly more frequently, with a median interval of 16 days compared with 42 days for hospital patients (P < 0.001). Twenty four per cent of general practice visits and 26% of hospital attendances resulted in an alteration to the warfarin dosage. Overall, 52% of general practice thrombotest results lay within the ranges recommended by the British Society for Haematology, compared with 45% of hospital results (P < 0.001). There was no difference in the rate of complications in general practice and the hospital clinic. In this study, the anticoagulant control achieved in a general practice setting was superior to that in a dedicated hospital outpatient clinic, although control was far from ideal in either setting.     

Augmentation of the neuromuscular blocking effects of cisatracurium during desflurane, sevoflurane, isoflurane or total i.v. anaesthesia

We recently performed a laparoscopic cholecystectomy on three patients receiving preoperative oral anticoagulant therapy. The patients requiring anticoagulants for pre-existing cardiac conditions have the following risks at surgery: thromboembolism, hemorrhage, endocarditis, and cardiopulmonary dysfunction. In patients receiving anticoagulant therapy, one must thus maintain a balanced international normalized ratio of the prothrombin time to prevent thromboembolism or hemorrhage. Warfarin sodium was discontinued preoperatively in all patients. Heparin sodium was individualized according to each patient's risk of thromboembolism. As a result, these patients all underwent a laparoscopic cholecystectomy without complications. Attention was paid to achieve hemostasis in the operative field and the trocar inserted sites during the procedure. The administration of warfarin sodium was resumed on the first postoperative day in all patients. Restarting warfarin sodium early also helps to simplify postoperative management. A broad spectrum of antibiotic therapy was also used to reduce the risk of endocarditis. Each patient's cardiopulmonary function was carefully monitored. The minimal invasion experienced during a laparoscopic cholecystectomy may thus facilitate the management of gallstones in patients receiving systemic anticoagulation treatment based on the findings of this limited series.     

Retrospective and prospective analyses of the treatment of overanticoagulated patients

STUDY OBJECTIVE: To compare withholding warfarin therapy with low-dose (2.5 mg) oral vitamin K therapy in excessively anticoagulated patients without bleeding complications. DESIGN: Prospective and retrospective studies. SETTING: Anticoagulation clinic at a Veterans Affairs institution. PATIENTS: Twenty-eight men were matched according to initial international normalized ratio (INR) and INR goal ranges. INTERVENTIONS: The retrospective arm of the study consisted of chart reviews of overanticoagulated patients whose warfarin doses were held until therapeutic INR values were reached. The prospective arm included overanticoagulated patients who were administered a single 2.5-mg dose of oral vitamin K. MEASUREMENTS AND MAIN RESULTS: Mean days to therapeutic INR values were 2.3+/-0.6 and 1.4+/-0.6 (p=0.001), and mean reduction in INR 1 day after treatment intervention was 1.32+/-0.79 and 3.46+/-1.31 (p<001) U for the withholding and vitamin K groups, respectively. CONCLUSION: Compared with withholding the warfarin dose, administration of 2.5 mg of oral vitamin K to excessively anticoagulated patients receiving warfarin significantly reduced the time required to reach a therapeutic INR as well as final INR.     

Effectiveness of intravenous administration of Fe-gluconate-Na complex to maintain adequate body iron stores in hemodialysis patients

The evolution of body iron stores was prospectively analyzed during a stable erythropoiesis period in 27 subjects (14 males and 13 females) on hemodialysis for more than 2 years in order to clarify the iron requirements of these patients and the effectiveness and safety of the administration of sodium ferric gluconate as a method to maintain adequate body iron stores. All patients had a stable hemoglobin level (variation < 1 g/dl). Sixteen subjects were on maintenance recombinant human erythropoietin therapy at regular doses. All patients received intravenous sodium ferric gluconate for 6 months (62.5 mg/month). The iron requirements were estimated as the difference between the amount of iron administered and the variation of body iron stores (calculated by the empirical formula of Cook and coworkers). The hemoglobin remained stable (basal 10.7 +/- 1.1, at 6th month 10.6 +/- 1 g/dl). Considering all cases, there were no significant variations in body iron stores (basal 457 +/- 273, at 6th month 451 +/- 316 mg). The patients were classified into three groups according to whether their body iron stores decreased (group A, n = 8), remained stable (group B, n = 11), or increased (group C, n = 8). There were no differences among groups concerning sex, age, time on hemodialysis, or erythropoietin therapy. However, there were statistically significant differences concerning their basal body iron stores (group A 457 +/- 228 mg. group B 563 +/- 146, and group C 230 +/- 297 mg; p < 0.05, analysis of variance). The iron needs, considering the total group, were 2.12 +/- 2 mg/day. There were no differences in iron requirements according to sex, but menstruating women had higher iron needs than the nonmenstruating ones (4.29 +/- 2 vs. 2.08 +/- 1.45 mg/day; p < 0.01). The iron requirements in patients on erythropoietin therapy were higher than in those without (2.63 +/- 1.59 vs. 1.88 +/- 1.68 mg/day; p < 0.05). However, excluding the menstruating women, the iron need in patients on erythropoietin were similar to those in subjects without this treatment (2.16 +/- 1.13 vs. 1.88 +/- 1.68 mg/day). All patients showed good compliance with an excellent tolerance. We have observed that in subjects on maintenance erythropoietin therapy, the iron requirements are stable. The administration of sodium ferric gluconate is safe and efficient in maintaining adequate body iron stores.     

Physicians and surgeons during the French intervention and the Second Empire

Little is known about the frequency of adverse events in the year following stent placement in patients treated with aspirin and ticlopidine, without warfarin. We analyzed the first such 234 consecutive patients treated at our hospital between October 1994 and December 1995. Their mean age was 62+/-12 years; 40% had had a prior myocardial infarction, 22% had undergone coronary artery bypass surgery, and 65% had multivessel disease. The indication for stent placement was dissection or abrupt closure in 24% of patients and suboptimal balloon angioplasty results in 14%; placement was elective in 62% of patients. Three hundred forty-five coronary segments were treated in the 234 patients; 305 stents (1.3 stents/patient) were placed. Palmaz-Schatz coronary stents (75%), Gianturco-Roubin stents (21%), and Johnson & Johnson biliary stents (4%) were used. Mean nominal stent size was 3.4+/-0.4 mm. High-pressure inflations (> or = 14 atm, mean 17+/-2) were performed in all patients. The mean residual stenosis was 3+/-5% by visual estimate. Intravascular ultrasound was utilized to facilitate stent placement in 53% of patients. Mean follow-up was 1.6+/-0.5 years. There were no deaths, Q-wave myocardial infarctions, coronary artery bypass operations, or repeat angioplasty procedures required during the remainder of the hospitalization or in 30 days after stent placement; stent thrombosis did not occur. Kaplan-Meier analysis of adverse events in the 6 months following the procedure revealed a mortality rate of 0.9%; the rate of myocardial infarction (Q-wave or non-Q-wave) was 1.3%. Bypass surgery was performed in 0.9% and angioplasty for in-stent restenosis was performed in 9.5% of patients. Any 1 of these events occurred in 11.7% of patients in the 6 months after the procedure. The corresponding event rates at 1 year were 1.3%, 2.2%, 3.5%, and 12.2%, respectively; any 1 of these events occurred in 16.5% of patients. In patients receiving intracoronary stents of varying designs followed by high-pressure postdeployment inflations in whom an excellent visual angiographic result is achieved, antithrombotic therapy with aspirin and ticlopidine is associated with a very low frequency of adverse cardiovascular events in the 12 months following the procedure regardless of the indication for stent placement.     

Primary antiphospholipid syndrome with recurrent transient ischemic attacks: report of a case and its successful treatment

A 35-year-old woman was admitted to our hospital with complaints of a two-year history of recurrent, daily episodes of transient ischemic attacks; the symptoms consisted of scotoma of her left eye, vertical diplopia, and paresthesia of her right arm. The presence of lupus anticoagulants and anticardiolipin antibodies led to the diagnosis of antiphospholipid syndrome (APS). After thrombotest values had decreased to 30% (international normalized ratio: 1.5) with warfarin, her symptoms did not recur. This suggests that anticoagulant therapy is effective for the prevention of recurrence of ischemic events complicated by primary APS, even when they occur repeatedly.     

Influence of metoclopramide on the pharmacokinetics of 8-methoxypsoralen

VISX 20/20 excimer laser was used to correct myopia from 1.00 to 16.00 diopters on 529 myopia eyes in 306 patients. All the patients were followed up for 3 to 12 months (8.1 +/- 3.1 months). At the 12th postoperative month, 0.5-3 grade corneal haze occurred in 62.1% of eyes in high myopia eyes, and only 8.8% in low and moderate myopia eyes (P < 0.01). The factors of formation of the corneal haze were the central corneal thickness, methods of removing epithelium and the number of laser pulses. The results suggest that the photorefractive keratectomy is regarded safe in correction of low and moderate myopia, but not in high myopia.     

A simplified high-performance liquid chromatographic method for direct determination of warfarin enantiomers and their protein binding in stroke patients

A simplified method for direct determination of warfarin enantiomers by high-pressure liquid chromatography with fluorescence detection has been developed. This method involves solid phase extraction of warfarin in plasma, precolumn derivatization to form diastereoisomeric esters, and post-column reaction to discriminate each enantiomer separately. Ultrafiltration was employed in the separation of unbound warfarin enantiomers. Twelve plasma samples from six stroke patients taking warfarin regularly were analyzed. The average concentration of total warfarin was 0.47 +/- 0.17 mg/L for the S-isomer and 0.69 +/- 0.18 mg/L for the R-isomer. The average protein binding was 99.67 +/- 0.33% for S-warfarin and 99.44 +/- 0.33% for R-warfarin. This methodology provides a quick and reliable technique for determining enantiomeric protein binding of warfarin in clinical settings.