Anticoagulant properties, clinical efficacy and safety of efegatran, a direct thrombin inhibitor, in patients with unstable angina.
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AIMS: Thrombin plays a key role in the clinical syndrome of unstable angina. We investigated the safety and efficacy of five dose levels of efegatran sulphate, a direct thrombin inhibitor, compared to heparin in patients with unstable angina. METHODS: Four hundred and thirty-two patients with unstable angina were enrolled. Five dose levels of efegatran were studied sequentially, ranging from 0.105 mg. kg(-1). h(-1)to 1.2 mg. kg(-1). h(-1)over 48 h. Safety was assessed clinically, with reference to bleeding and by measuring clinical laboratory parameters. Efficacy was assessed by the number of patients experiencing any episode of recurrent ischaemia as measured by computer-assisted continuous ECG ischaemia monitoring. Clinical end-points were: episodes of recurrent angina, myocardial infarction, coronary intervention (PTCA or CABG), and death. RESULTS: Efegatran demonstrated dose dependent ex-vivo anticoagulant activity with the highest dose level of 1.2 mg. kg(-1). h(-1)resulting in steady state mean activated partial thromboplastin time values of approximately three times baseline. Thrombin time was also increased. Neither of the efegatran doses studied were able to suppress myocardial ischaemia during continuous ECG ischaemia monitoring to a greater extent than that seen with heparin. There were no statistically significant differences in clinical outcome or major bleeding between the efegatran and heparin groups. Minor bleeding and thrombophlebitis occurred more frequently in the efegatran treated patients. CONCLUSION: Administration of efegatran sulphate at levels of at least 0.63 mg. kg(-1). h(-1)provided an anti-thrombotic effect which is at least comparable to an activated partial thromboplastin time adjusted heparin infusion. There was no excess of major bleeding. The level of thrombin inhibition by efegatran, as measured by activated partial thromboplastin time, appeared to be more stable than with heparin. Thus, like other thrombin inhibitors, efegatran sulphate is easier to administer than heparin. However, no clinical benefits of efegatran over heparin were apparent. (+info)
Effect of high versus low ambient humidity on the severity of obstructive sleep apnoea.
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BACKGROUND: Surface tension forces appear to make a significant contribution to upper airway closure in patients with obstructive sleep apnoea (OSA). It is possible that drying of the upper airway mucosa at night might contribute to these surface tension forces and the severity of OSA might therefore change with alteration of the ambient humidity. METHODS: A randomised single blind crossover study of high ambient relative humidity (HRH) versus low ambient relative humidity (LRH) was performed in 12 men of mean (SD) age 49 (9) years with mild OSA (apnoea/hypopnoea index (AHI) 14 (5.2)). On one night patients slept in continuous HRH (85 (4)%, range 80-93%) and on the other in LRH (16 (4)%, range 11-22%). RESULTS: The AHI was similar on the HRH and LRH nights (mean difference 3; 95% CI -2 to 9, p = 0.20 and no statistically significant differences in AHI were observed on the two nights after standardising for body position and sleep stage. Sleep stage distribution and the proportion of time spent in the supine position were similar on the HRH and LRH nights. The number of non-respiratory arousals was also similar on the two nights. CONCLUSION: Altering ambient humidity alone has no significant impact on the severity of OSA. (+info)
Pulmonary effects of short-term exposure to low levels of toluene diisocyanate in asymptomatic subjects.
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Isocyanates may be involved in the development of chronic obstructive airway disease among exposed workers. A short-term exposure to toluene diisocyanate (TDI) at concentrations near the permissible levels was investigated to examine whether there was an association with changes in pulmonary function tests and in potential markers of airway injury and inflammation in bronchial lavage (BL) and bronchoalveolar lavage (BAL). Seventeen subjects without respiratory symptoms (eight smokers and nine nonsmokers) were exposed once to ambient air and once to TDI (5 parts per billion (ppb) for 6 h followed by 20 ppb for 20 min) in a randomized, single-blind sequence. Pulmonary function tests were repeatedly assessed during exposure and BAL was performed 1 h after each exposure. Biochemical studies on lavage fluids included albumin, immunoglobulins, antiproteases (alpha2-macroglobulin and alpha1-proteinase inhibitor), potential indicators of epithelial cell function (secretory component and Clara cell protein), and cytokines (tumour necrosis factor-alpha, interleukin (IL)-4, IL-5, IL-6, and IL-8). Exposure to TDI caused a modest decrease in specific airway conductance (sGaw) (p=0.053) and in maximal expiratory flow at 25% of forced vital capacity (MEF25%) (p=0.015) when compared with ambient air. Exposure to TDI resulted in a slight increase in BAL albumin level (TDI: 26.4+/-12.5 versus air: 21.8+/-8.6 microg x mL(-1), p=0.044) and in BL alpha2-macroglobulin concentration (TDI: 0.07+/-0.061 versus air: 0.05+/-0.04 microg x mL(-1), p=0.021). This study suggests that exposure to low toluene disocyanate concentrations is associated with minimal but detectable changes in airway calibre and in epithelial barrier permeability. The pulmonary effects of long-term exposure to low levels of isocyanates require further investigation. (+info)
Recovery profile, costs, and patient satisfaction with propofol and sevoflurane for fast-track office-based anesthesia.
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BACKGROUND: Office-based surgery is becoming increasingly popular because of its cost-saving potential Both propofol and sevoflurane are commonly used in the ambulatory setting because of their favorable recovery profiles. This clinical investigation was designed to compare the clinical effects, recovery characteristics, and cost-effectiveness of propofol and sevoflurane when used alone or in combination for office-based anesthesia. METHODS: One hundred four outpatients undergoing superficial surgical procedures at an office-based surgical center were randomly assigned to one of three general anesthetic groups. In groups I and II, propofol 2 mg/kg was administered for induction followed by propofol 75-150 microg x kg(-1) x min(-1) (group I) or sevoflurane 1-2% (group II) with N2O 67% in oxygen for maintenance of anesthesia In group m, anesthesia was induced and maintained with sevoflurane in combination with N2O 67% in oxygen. Local anesthetics were injected at the incision site before skin incision and during the surgical procedure. The recovery profiles, costs of drugs, and resources used, as well as patient satisfaction, were compared among the three treatment groups. RESULTS: Although early recovery variables (e.g., eye opening, response to commands, and sitting up) were similar in all three groups, the times to standing up and to be "home ready" were significantly prolonged when sevoflurane-N2O was used for both induction and maintenance of anesthesia. The time to tolerating fluids, recovery room stay, and discharge times were significantly decreased when propofol was used for both induction and maintenance of anesthesia. Similarly, the incidence of postoperative nausea and vomiting and the need for rescue antiemetics were also significantly reduced after propofol anesthesia. Finally, the total costs and patient satisfaction were more favorable when propofol was used for induction and maintenance of office-based anesthesia CONCLUSION: Compared with sevoflurane-N2O, use of propofol-N2O for office-based anesthesia was associated with an improved recovery profile, greater patient satisfaction, and lower costs. There were significantly more patients who were dissatisfied with the sevoflurane anesthetic technique. (+info)
Complementary clinical benefits of coronary-artery stenting and blockade of platelet glycoprotein IIb/IIIa receptors. Evaluation of Platelet IIb/IIIa Inhibition in Stenting Investigators.
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BACKGROUND: Inhibition of the platelet glycoprotein IIb/IIIa receptor with the monoclonal-antibody fragment abciximab reduces the acute ischemic complications associated with percutaneous coronary revascularization, whereas coronary-stent implantation reduces restenosis. We conducted a trial to determine the efficacy of abciximab and stent implantation in improving long-term outcome. METHODS: A total of 2399 patients were randomly assigned to stent implantation and placebo, stent implantation and abciximab, or balloon angioplasty and abciximab. The patients were followed for six months. RESULTS: At six months, the incidence of the composite end point of death or myocardial infarction was 11.4 percent in the group that received a stent and placebo, as compared with 5.6 percent in the group that received a stent and abciximab (hazard ratio, 0.47; 95 percent confidence interval, 0.33 to 0.68; P<0.001) and 7.8 percent in the group assigned to balloon angioplasty and abciximab (hazard ratio, 0.67; 95 percent confidence interval, 0.49 to 0.92; P=0.01). The hazard ratio for stenting plus abciximab as compared with angioplasty plus abciximab was 0.70 (95 percent confidence interval, 0.48 to 1.04; P=0.07). The rate of repeated revascularization of the target vessel was 10.6 percent in the stent-plus-placebo group, as compared with 8.7 percent in the stent-plus-abciximab group (hazard ratio, 0.82; 95 percent confidence interval, 0.59 to 1.13; P=0.22) and 15.4 percent in the angioplasty-plus-abciximab group (hazard ratio, 1.49; 95 percent confidence interval, 1.13 to 1.97; P=0.005). The hazard ratio for stenting plus abciximab as compared with angioplasty plus abciximab was 0.55 (95 percent confidence interval, 0.41 to 0.74; P<0.001). Among patients with diabetes, the combination of abciximab and stenting was associated with a lower rate of repeated target-vessel revascularization (8.1 percent) than was stenting and placebo (16.6 percent, P=0.02) or angioplasty and abciximab (18.4 percent, P=0.008). CONCLUSIONS: For coronary revascularization, abciximab and stent implantation confer complementary long-term clinical benefits. (+info)
The role of syringe filters in harm reduction among injection drug users.
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OBJECTIVES: Three filters were tested for in situ efficacy in reducing bacterial contamination associated with injection drug use. METHODS: In a self-matched control design with blinded laboratory testing, injection drug users were asked to use 3 filters in random succession when loading their syringes with drug solute. RESULTS: The 0.22-micron filter proved significantly better than both the cigarette filter (relative risk [RR] = 18.0) and the 20-micron filter (RR = 4.5) in rendering syringes bacteria-free. CONCLUSIONS: The 15- to 20-micron syringe filter currently provided injection drug users in Switzerland does not significantly reduce contamination associated with common bacterial infections among users. Filters with pore width 1/100th as large are recommended. (+info)
Immune response to pneumococcal conjugate and polysaccharide vaccines in otitis-prone and otitis-free children.
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We compared responses to pneumococcal conjugate and polysaccharide vaccines in 48 otitis-free and 64 otitis-prone children. Pre- and postimmunization concentrations of antibodies to pneumococcal serotypes 6B, 14, 19F, and 23F were measured by enzyme-linked immunosorbent assay. Postimmunization mean concentrations of antibodies to all four serotypes were significantly higher for children receiving conjugate vaccine than for those receiving polysaccharide vaccine; the difference in responses was primarily due to a better response to conjugate vaccine in the otitis-prone group. Significantly higher postimmunization concentrations of antibodies to all four serotypes and to one of the four serotypes were found in otitis-prone children and otitis-free children who received conjugate vaccine, respectively. Pneumococcal conjugate vaccine has the potential to reduce the incidence of disease due to vaccine serotypes, even among children with recurrent otitis media. (+info)
Phenobarbital compared with phenytoin for the treatment of neonatal seizures.
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BACKGROUND: Seizures occur in 1 to 2 percent of neonates admitted to an intensive care unit. The treatment is usually with either phenobarbital or phenytoin, but the efficacy of the two drugs has not been compared directly. METHODS: From 1990 to 1995, we studied 59 neonates with seizures that were confirmed by electroencephalography. The neonates were randomly assigned to receive either phenobarbital or phenytoin intravenously, at doses sufficient to achieve free plasma concentrations of 25 microg per milliliter for phenobarbital and 3 microg per milliliter for phenytoin. Neonates whose seizures were not controlled by the assigned drug were then treated with both drugs. Seizure control was assessed by electroencephalographic criteria. RESULTS: Seizures were controlled in 13 of the 30 neonates assigned to receive phenobarbital (43 percent) and 13 of the 29 neonates assigned to receive phenytoin (45 percent; P=1.00). When combined treatment is considered, seizure control was achieved in 17 (57 percent) of the neonates assigned to receive phenobarbital first and 18 (62 percent) of those assigned to receive phenytoin first (P=0.67). The severity of the seizures was a stronger predictor of the success of treatment than was the assigned agent. Neonates with mild seizures or with seizures that were decreasing in severity before treatment were more likely to have their seizures end, regardless of the treatment assignment. CONCLUSIONS: Phenobarbital and phenytoin are equally but incompletely effective as anticonvulsants in neonates. With either drug given alone, the seizures were controlled in fewer than half of the neonates. (+info)