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PubMed1995

Randomized double-blind comparison of two doses of Hirulog with heparin as adjunctive therapy to streptokinase to promote early patency of the infarct-related artery in acute myocardial infarction.

BACKGROUND: An improved survival rate is a consequence of successful reperfusion of the infarct-related artery. This double-blind, randomized trial investigated the potential of Hirulog, a direct thrombin inhibitor, to improve the early patency rates obtained with streptokinase and aspirin. METHODS AND RESULTS: Angiographic patency of the culprit coronary artery lesion was assessed 90 and 120 minutes after the initiation of streptokinase and aspirin and again after 4 +/- 2 days in 68 patients with acute myocardial infarction. Patients were randomized to Hirulog 0.5 mg/kg per hour for 12 hours followed by 0.1 mg/kg per hour (low dose), Hirulog 1.0 mg/kg per hour for 12 hours followed by placebo (high dose), or to heparin 5000 U bolus followed by 1000 U/h titrated to an activated partial thromboplastin time (aPTT) 2 to 2.5 times control after 12 hours. At 90 minutes, TIMI flow grade 2 or 3 was observed in 96% of patients treated with the low dose of Hirulog, in 79% with the high dose, and in 46% with heparin (P = .006) and TIMI flow grade 3 was observed in 85%, 61%, and 31% of patients, respectively (P = .008). At 120 minutes, these figures were 100%, 82%, and 62% for TIMI flow grades 2 and 3 (P = .046) and 92%, 68%, and 46% for TIMI flow grade 3 (P = .014). At 90 minutes, the relative risk for restoring TIMI flow grade 3 was 2.77 with Hirulog 0.5 mg/kg per hour compared with heparin (95% confidence limits, 1.21 to 6.35; P < .001) and 1.4 compared with Hirulog 1.0 mg/kg per minute (95% confidence limits, 1.00 to 1.51; P = .04). Patients who received a placebo infusion after 12 hours experienced more clinical events and reocclusion during the following 4 days than patients in the other two groups. CONCLUSION: Hirulog yields higher early patency rates in the culprit coronary artery than heparin when used as adjunctive therapy to streptokinase and aspirin in the early phase of acute myocardial infarction. High doses are not required and may be less effective than lower doses, which suggests that too much thrombin inhibition may be harmful.

Aspirin↗

PubMed2005

Plasma lipoproteins and apolipoproteins as predictors of cardiovascular risk and treatment benefit in the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER).

BACKGROUND: Statins are important in vascular disease prevention in the elderly. However, the best method of selecting older patients for treatment is uncertain. We assessed the role of plasma lipoproteins as predictors of risk and of treatment benefit in the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER). METHOD AND RESULTS: The association of LDLc and HDLc with risk was examined in the 5804 70- to 82-year-old subjects of PROSPER. Baseline LDLc showed no relation to risk of the primary end point in the placebo group (P=0.27), nor did on-treatment LDLc in the pravastatin group (P=0.12). HDLc was inversely associated with risk in subjects on placebo (P=0.0019) but not in those on pravastatin (P=0.24). Risk reduction on pravastatin treatment was unrelated to baseline LDLc (P=0.38) but exhibited a significant interaction with HDLc (P=0.012). Subjects in the lowest 2 quintiles of HDLc (<1.15 mmol/L) had a risk reduction of 33% (hazard ratio, 0.67; 95% confidence limits, 0.55, 0.81; P<0.0001), whereas those with higher HDLc showed no benefit (RR, 1.06; 95% confidence limits, 0.88, 1.27; P=0.53). During follow-up, there was no relation between achieved level of LDLc or HDLc and risk. However, the change in the LDLc/HDLc ratio on statin treatment appeared to account for the effects of therapy. CONCLUSIONS: In people >70 years old, HDLc appears to be a key predictor of risk and of treatment benefit. Findings in PROSPER suggest that statin therapy could usefully be targeted to those with HDLc <1.15 mmol/L or an LDLc/HDLc ratio >3.3.

Aged↗

PubMed1992

Trap-vaccinate-release and oral vaccination for rabies control in urban skunks, raccoons and foxes.

Two rabies control tactics, trap-vaccinate-release (T-V-R) and oral vaccination were used for the control of rabies in skunks (Mephitis mephitis), raccoons (Procyon lotor), and foxes (Vulpes vulpes) in metropolitan Toronto, Canada. Using T-V-R, a mean of 45% to 72% (95% confidence limits of 40% to 81%) of the skunks and a mean of 17% to 68% (95% confidence limits of 14% to 76%) of the raccoons in a 60 km2 area of Toronto were vaccinated against rabies between 1987 and 1991. The area has been free of skunk rabies from May 1989 to April 1992. Forty-five rabies cases were diagnosed during 1980 to 1986. In contrast, only three skunk cases have been reported since the vaccination program began in July 1987. The T-V-R area also remained rabies free during an epizootic of skunk rabies in metropolitan Toronto during 1991. Following distribution of rabies vaccine-baits throughout the ravines of metropolitan Toronto, June 1989 to December 1991, 46% to 80% of the Toronto fox population was immunized during 1989, 1990 and 1991. Only one case of fox rabies was reported in metropolitan Toronto since vaccination began, compared to 80 cases reported between 1982 and 1988. The area has been free of reported fox rabies from October 1990 to April 1992.

Administration, Oral↗

PubMed1990

[Antibiotic prophylaxis in cesarean sections without high risk of infection. Therapeutic trial of cefotetan versus placebo].

Caesarean sections are performed with an ever increasing frequency, and their morbidity rate due to infection varies between 35 and 40 per cent. The effectiveness of antibiotic prophylaxis has been demonstrated in caesarean sections with a high risk of infection, but few studies have been devoted to caesarean sections without this high risk. The purpose of our study was to evaluate the effectiveness of antibiotic therapy in this second type of caesarean section since its postoperative infection rate is not negligible (about 25 per cent). We therefore set up a two-centre randomized trial comparing two groups of 133 women without any particular risk of infection. At the moment of umbilical cord clamping, one group received cefotetan 1 g intravenously, while the other group received an intravenous injection of a placebo solution. The postoperative infection rate was 12.5 per cent in the treatment group and 26.9 per cent in the control group (P less than 0.05). The relative risk in the placebo-treated women was 2.15 (95 per cent confidence limits, 1.41 to 3.28). Antibiotic prophylaxis prevented 53.5 per cent of postoperative infections (95 per cent confidence limits, 29 to 69.5 per cent). Moreover, in the treatment group infections were less severe, resulting in a significant decrease in hospital stay and a lower overall cost. We conclude that antibiotic prophylaxis with cefotetan is effective in caesarean sections without a high risk of infection, as it significantly reduces the postoperative morbidity due to infection.

Abscess↗

PubMed1986

A case-control study of hepatocellular carcinoma and the hepatitis B virus, cigarette smoking, and alcohol consumption.

A case-control study was undertaken to evaluate the roles of the hepatitis B virus (HBV), cigarette smoking, and alcohol use in the etiology of hepatocellular carcinoma (HCC). A major purpose of the study was to evaluate the effect of cigarette smoking on HCC among hepatitis B surface antigen (HBsAg)-negative persons, since it had been suggested that the relative effect of cigarette smoking on HCC was higher among HBsAg-negative persons than among HBsAg-positive persons. Eighty-six cases and 161 hospital controls were included in the study. This study confirmed the strong relationship between the HBV and HCC. Twelve of 67 cases and none of 63 controls were chronically infected with HBV as evidenced by serum HBsAg. The study also found a moderately strong relationship between alcohol use and HCC. The results of the present study do not support the hypothesis that cigarette smoking is a risk factor for HCC. Among all subjects, the relative rate of HCC for cigarette smokers compared with nonsmokers after adjustment for alcohol consumption was 1.0 with 95% confidence limits, 0.5 to 1.8. Among HBsAg-negative subjects, the relative rate was 1.1 with 95% confidence limits, 0.5 to 2.4. There was also no consistent dose-response relationship between quantity smoked and HCC in this study.

Adult↗

PubMed1986

A rapid method of theophylline assay in the physician's office.

A competitive fluorescent enzyme immunoassay for theophylline is described which employs a theophylline monoclonal antibody. Fifty-two samples were assayed by this method and by high pressure liquid chromatography. The coefficient of correlation contrasting the methods equaled 0.979. The coefficient of determination was 0.959. The standard error of the correlation coefficient was 1.392. The bias of the immunoassay method versus high pressure liquid chromatography was 0.8 with 95% confidence limits of 0.4 to 1.2. In the same 52 patients, the precision of 1.6 with 95% confidence limits of 1.3 to 1.9 was obtained. There are numerous advantages of this new method compared with high pressure liquid chromatography. For the practicing physician, the rapid immunoassay for theophylline described here is proper for office application.

Asthma↗

PubMed1984

Soft tissue sarcoma and exposure to phenoxyherbicides and chlorophenols in New Zealand.

Phenoxyherbicides, including (2,4,5-trichlorophenoxy)acetic acid (CAS: 93-76-5), have been widely used in New Zealand for over 30 years. In the light of Swedish studies reporting an association between exposure to phenoxyherbicides or chlorophenols and soft tissue sarcoma, a case-control study was undertaken that involved interviewing 82 subjects (cases) with soft tissue sarcoma and 92 controls with other types of cancer. For those potentially exposed to phenoxyherbicides for more than 1 day not in the 5 years before cancer registration, the estimate of relative risk was 1.3, with 90% confidence limits of 0.6-2.5. The comparable relative risk estimate for chlorophenol exposure was 1.5, with 90% confidence limits of 0.5-4.5. The discovery of cases in trichlorophenol manufacturing plants in the United States lended support to the Swedish findings, but further studies are needed to conclude whether human exposure to these chemicals truly increases the risk of soft tissue sarcoma.

2,4,5-Trichlorophenoxyacetic Acid↗

PubMed1995

Serum hyaluronan is increased in malignant lymphoma.

The serum concentration of hyaluronan (HYA) was measured in 41 patients with malignant lymphoma, including 21 patients with non-Hodgkin's malignant lymphoma and 20 patients with Hodgkin's disease. Thirty-four patients were studied at diagnosis. The remaining 7 patients had relapsing or resistant disease. The patients were categorized into four stages according to conventional staging procedures. The median serum HYA concentration in patients with malignant lymphoma was significantly higher (median 40.7 ng/ml; 95% confidence limits 26.1-57.6 ng/ml) than in an age-matched healthy reference group (median 14.5 ng/ml, 95% confidence limits 11-19.4 ng/ml) (P = 0.00032). The highest serum HYA levels were found in patients with relapsing/resistant disease, all being in stages III and IV (median 181.5; range 11.9-500 ng/ml), as compared to previously untreated patients (median 29.8; range 9.1-108) (P = 0.0002) and controls (median 14.2; range 6.7-51.2). Decreased uptake and degradation of HYA owing to malignant transformation of lymphatic tissue is the most plausible explanation to these findings.

Adolescent↗

PubMed1989

Constructing a cut-off point for a quantitative diagnostic test.

This paper is concerned with the problem of constructing a suitable cut-off point for a quantitative diagnostic test from a sample of diseased and non-diseased individuals, when the specificity and/or sensitivity required for the resulting diagnostic classification rule are specified. Statistical procedures are discussed which yield an explicit cut-off point, together with the necessary confidence limits on the true specificity and sensitivity of the test operating at this point (by contrast to confidence limits referring to an unknown optimal choice of the cut-off point). Sample size formulae are derived, showing a relative efficiency of up to 1.5 for a new procedure introduced in this paper over the usual procedure based on tolerance limits.

Biopsy↗

PubMed1986

Duration of warfarin anticoagulant therapy and the probabilities of recurrent thromboembolism and hemorrhage.

To determine the association of duration of warfarin anticoagulant therapy after hospitalization for venous thromboembolism with the probability of recurrent thromboembolism and with the risks of hemorrhage, medical records of 2,422 patients hospitalized in 1970 through 1980 with pulmonary embolism, thrombophlebitis, or both were reviewed. Multivariate life-table analyses were performed for 370 patients who had positive results of venography or pulmonary angiography, or who had lung scanning evidence of a "high probability" of pulmonary embolism and no history of the disease. For these patients, warfarin therapy for more than six weeks was not associated with a lower risk of recurrent thromboembolism when compared with warfarin therapy for one through six weeks (risk of recurrence for seven to 26 weeks of treatment 0.8; 95 percent confidence limits 0.3 and 2.5; risk of recurrence for more than 26 weeks of treatment 1.1; 95 percent confidence limits 0.4 and 3.1). The longer the warfarin therapy, the higher the risk of medically important complications from therapy. From one week through five years, the probability of major hemorrhage increased almost linearly: 10 percent for 12 weeks, 18 percent at one year, 26 percent at two years, and 41 percent at five years. This study suggests that intensive, long-term warfarin anticoagulation, in patients with a first episode of venous thromboembolism and no predisposing condition, is associated with more toxicity than efficacy and should be abandoned.

Actuarial Analysis↗

PubMed1985

The clinical value of rapid C-reactive protein measurement in cerebro-spinal fluid.

C-Reactive protein (CRP) has been measured in 90 consecutive CSF specimens using both latex agglutination and an immunoradiometric assay (IRMA). In the 60 CSF specimens otherwise normal by standard biochemical and microbiological criteria, the median CRP level was 32 micrograms/l (95% confidence limits, 0-108 micrograms/l) and in the remaining abnormal specimens the median level was 176 micrograms/l (95% confidence limits, 110-325 micrograms/l, p = 0.001). C-Reactive protein was detected by a commercial latex agglutination kit at a level of approximately 120 micrograms/l and all significant CNS bacterial infections were positive (7 bacterial meningitis, 2 infected shunts). In addition, viral encephalitis, extensive intracranial malignancy and subarachnoid haemorrhage gave positive agglutinations, but not in every case. A further nine specimens with a minor elevation of CRP level were detected by IRMA (median 76 micrograms/l), but this was of little practical significance. We have shown that normal CSF C-reactive protein levels are very low and we conclude that latex agglutination set at a sensitivity of 120 micrograms/l, although only semi-quantitative, is a rapid and useful method to assess CSF C-reactive protein in routine clinical practice and, when positive, is strong supporting evidence for bacterial infection.

C-Reactive Protein↗

PubMed2006

Simultaneous adsorption at the liquid/solid and liquid/gas interfaces.

Physical adsorption from binary or higher-order liquid mixtures on solids is often accompanied by adsorption phenomena at the liquid/gas interface. As long as the adsorption effects are comparable, both interfaces have to be included in the respective thermodynamic equations. A purely phenomenological thermodynamic description in terms of excess quantities is given of the simultaneous adsorption from multicomponent liquid mixtures at the liquid/solid and liquid/gas interfaces. In order to illustrate the thermodynamic procedure, the individual and simultaneous adsorption excess isotherms of three binary liquid mixtures at the liquid/Teflon and liquid/vapor interfaces are calculated from experimental surface-tension and contact-angle data taken from the literature. Special attention is focused on the estimation of error in calculated adsorption isotherms. A line of approach is given to find the confidence limits of adsorption isotherms that cover the entire mole fraction scale. The isotherms as well as their confidence limits are presented and discussed.

Journal Article↗

PubMed2006

Freedom from atrial arrhythmias after classic maze III surgery: a 10-year experience.

OBJECTIVES: We studied the persistence of favorable outcome, the occurrence of new atrial arrhythmias, and sinus node dysfunction in patients who underwent the maze III procedure. METHODS: Preoperative, in-hospital, and follow-up data of 203 patients who underwent the maze III procedure between June 1993 and June 2003 were collected. A total of 139 patients underwent the maze procedure for lone atrial fibrillation, and 64 patients underwent the maze procedure and concomitant cardiac surgery. RESULTS: There was no 30-day postoperative mortality. During a mean follow-up of 4.0 +/- 2.6 years, 12 patients (6%) died (2 cardiac related). At the end of follow-up, freedom from supraventricular arrhythmias was 80% for the lone atrial fibrillation group and 64% for the concomitant atrial fibrillation group. Freedom from stroke during follow-up was 100% in the lone atrial fibrillation group and 97% in the concomitant group. Multivariate analysis revealed that rhythm at 1-year follow-up (P < .001; odds ratio 9.56, 95% confidence limits 3.92-23.31) and preoperative left atrium dimension (P = .028; odds ratio 1.06 for every millimeter, 95% confidence limits 1.01-1.12) were predictors of success at the end of follow-up. CONCLUSIONS: This study shows that the favorable results of the maze III procedure in terms of freedom from supraventricular arrhythmias persist in most patients for at least 4 years.

Arrhythmias, Cardiac↗

PubMed1998

Influence of myocardial infarction, coronary artery bypass surgery, and stroke on cognitive impairment in late life.

Relations between cognitive test scores in later life and prior myocardial infarction (MI), coronary artery bypass graft surgery (CABG), and stroke were examined for this study. Subjects were 3,734 Japanese-American men (80% of surviving Honolulu Heart Program cohort) aged 71 to 93 years at the time of cognitive testing. Impairment was defined as scoring below the 16th percentile on a validated cognitive assessment scale. Prior MI, stroke, and CABG were established using hospital surveillance, history, and record review. After adjustment for age, years of education, and years of childhood spent in Japan, men with prior stroke were significantly more likely than others to have poor cognitive performance (odds ratio 4.4, 95% confidence limits 3.0 to 6.7). History of > 1 stroke was associated with an odds ratio of 50 (95% confidence limits 10.5 to 238.3). There was no significant association between cognitive performance and > or = 1 prior MI or history of CABG. Time between events and cognitive function testing did not affect results. Analyses support a significant association between clinical stroke and persistent cognitive impairment, but fail to implicate CABG or MI.

Aged↗

PubMed1997

Timing of first recurrence of syncope predicts syncopal frequency after a positive tilt table test result.

OBJECTIVES: This study sought to determine whether the time to first recurrence of syncope after a positive isoproteremol-tilt table test result accurately predicts the eventual frequency of syncope. BACKGROUND: Both patient care and future clinical trials involving patients with neuromediated syncope will require a simple measure that reflects the frequency of syncope. The time from tilt table testing to the first recurrence of syncope might be such a measure. METHODS: A cohort of 46 patients with syncope, in a university outpatient clinic, who had at least one syncopal spell after a positive isoproterenol-tilt table test result were followed up for up to 6.5 years (mean [+/-SD] 48 +/- 14 months). The time from tilt table testing to the first recurrence of syncope was correlated. RESULTS: A total of 40 of 46 patients had more than one recurrent spell, with a median of eight recurrent spells. The time to the first syncopal spell predicted the frequency of spells with r = -0.79 (p < 0.001), whereas the time to the second spell predicted the frequency with r = -0.92 (p < 0.001). Patients who fainted within 1 month of tilt testing had a geometric mean frequency of 1.35 spells/month (95% confidence limits 0.49, 3.74) compared with patients who fainted 1 to 24 months after testing (0.12 spells/months; 95% confidence limits 0.07 to 0.18, p < 0.001). Finally, the frequency of syncopal spells bore no relation to the duration of follow-up. CONCLUSIONS: The time to the first recurrent spell predicts the frequency of syncopal spells after a positive tilt table test result, and the instantaneous risk of syncope is constant.

Adult↗

PubMed1998

Age and sex distribution of suspected adverse drug reactions to newly marketed drugs in general practice in England: analysis of 48 cohort studies.

AIMS: Little is known about the frequency with which suspected adverse drug reactions are seen by general practitioners after the prescription of newly marketed drugs. We investigated age and sex specific incidence rates of suspected adverse drug reactions recorded by general practitioners in England after the prescription of selected newly marketed drugs. METHODS: Information was collected from 48 national cohort studies of newly marketed drugs studied by prescription-event monitoring. Questionnaires were sent to prescribers asking for details of events and suspected adverse drug reactions recorded in the patients' notes occurring after the drugs were prescribed. RESULTS: During the 48 cohort studies, a total of 513608 patients were investigated, of which 221781 (43.2%) were males and 285862 (55.7%) were females. The overall incidence of suspected adverse drug reactions in males was 12.9 per 10000 patient-months of exposure (95% confidence limits 12.3 to 13.5), and in females was 20.6 per 10000 patient-months of exposure (95% confidence limits 19.9 to 21.3). The overall age-standardised relative risk of an adverse drug reaction in females compared with males was 1.6 (1.5-1.7). This sex difference was significant in all age groups above 19 years of age, and was relatively consistent across all age groups (chi2 test for heterogeneity = 9.2, P=0.3). The highest rate of recording in males was in the 50-59 year age group, and in females was in the 30-39 year age group. CONCLUSIONS: In general practice in England, suspected adverse drug reactions to newly marketed drugs are recorded more often in adults aged between 30 and 59 years of age and are 60% more common in women than in men. The sex difference occurs in all age groups over 19 years of age.

Adult↗

PubMed2004

Deep hypothermic circulatory arrest and the femoral-to-radial arterial pressure gradient.

OBJECTIVES: To determine the femoral-to-radial arterial pressure gradient, as well as the factors associated with them, in patients receiving cardiopulmonary bypass (CPB) with profound hypothermia and circulatory arrest. DESIGN: Retrospective automated hemodynamic record review. SETTING: University hospital. PARTICIPANTS: Patients undergoing pulmonary thromboendarterectomy with deep hypothermic circulatory arrest. MEASUREMENTS AND MAIN RESULTS: The automated hemodynamic records of 54 consecutive patients undergoing pulmonary thromboendarterectomy with deep hypothermic circulatory arrest were reviewed, comparing the femoral and radial arterial pressures throughout the intraoperative period. In 20 of the patients, the hemodynamic data from the first 16 postoperative hours were also studied. Forty-one of 54 (76%) of the patients exhibited a mean arterial gradient of at least 10 mmHg either during or after CPB, femoral being higher. Clinically significant gradients were noted throughout the CPB period and the post-CPB period in these patients. In the 54 patients studied, the systolic blood pressure (SBP) gradient was 32 +/- 19 mmHg after CPB (95% confidence limits 28.2 mmHg, 39.0 mmHg), and the mean arterial pressure (MAP) gradient was 6.3 +/- 4.9 mmHg (95% confidence limits 5.5 mmHg, 8.6 mmHg). The duration of clinically significant SBP (>10 mmHg) and MAP (>5 mmHg) gradients in the postoperative period were 5.2 +/- 5.7 hours and 5.8 +/- 7.2 hours, respectively. Advanced age correlated with high post-CPB pressure gradients in this population and was associated with prolonged postoperative resolution of the gradients. CONCLUSIONS: The femoral-to-radial arterial pressure gradients, particularly systolic, after CPB, were greater and of longer duration in these patients undergoing deep hypothermic circulatory arrest than gradients previously reported for routine CPB. Central arterial pressure monitoring is recommended for patients undergoing deep hypothermic circulatory arrest, being valuable both for intraoperative and postoperative care.

Age Factors↗

PubMed1985

A prospective study of postmenopausal estrogen therapy and coronary heart disease.

To clarify the possible role of postmenopausal estrogen use in coronary heart disease, we surveyed 121,964 female nurses, aged 30 to 55 years, with mailed questionnaires, beginning in 1976. Information on hormone use and other potential risk factors was updated and the incidence of coronary heart disease was ascertained through additional questionnaires in 1978 and 1980, with a 92.7 per cent follow-up. End points were documented by medical records. During 105,786 person-years of observation among 32,317 postmenopausal women who were initially free of coronary disease, 90 women had either nonfatal myocardial infarctions (65 cases) or fatal coronary heart disease (25 cases). As compared with the risk in women who had never used postmenopausal hormones, the age-adjusted relative risk of coronary disease in those who had ever used them was 0.5 (95 per cent confidence limits, 0.3 and 0.8; P = 0.007), and the risk in current users was 0.3 (95 per cent confidence limits, 0.2 and 0.6; P = 0.001). The relative risks were similar for fatal and nonfatal disease and were unaltered after adjustment for cigarette smoking, hypertension, diabetes, high cholesterol levels, a parental history of myocardial infarction, past use of oral contraceptives, and obesity. These data support the hypothesis that the postmenopausal use of estrogen reduces the risk of severe coronary heart disease.

Adult↗