Prospective, randomized trial of prolonged intracoronary urokinase infusion for chronic total occlusions in native coronary arteries

OBJECTIVES: The purpose of this study was to determine the safety and efficacy of three dosing regimens of intracoronary urokinase for facilitated angioplasty of chronic total native coronary artery occlusions. BACKGROUND: Percutaneous transluminal coronary angioplasty of chronically occluded (>3 months) native coronary arteries is associated with low initial success secondary to an inability to pass the guide wire beyond the occlusion. METHODS: Patients were enrolled if a chronic total occlusion >3 months old could not be crossed with standard angioplasty equipment. Of the 101 patients enrolled, 41 had successful guide wire passage and were excluded from urokinase treatment. The remaining 60 patients were randomized to receive one of three intracoronary dosing regimens of urokinase over 8 h (group A = 0.8 million U; group B = 1.6 million U; group C = 3.2 million U), and angioplasty was again attempted after completion of the urokinase infusion in 58 patients. RESULTS: Coronary angioplasty was successful in 32 patients (53%) (group A 52%, group B 50%, group C 59%, p = 0.86). This study had a 90% power to detect at least a 50% difference between dosing groups at alpha 0.05. Bleeding complications requiring blood transfusion did not differ significantly among the dosing groups (A 0%, B 15%, C 6%, p = 0.14), although major bleeding episodes were less common in group A (p < 0.05). There were no major procedural or in-hospital complications. Angiographic follow-up in 69% of the patients with successful angioplasty revealed target vessel patency in 91% but an angiographic restenosis rate of 59%. CONCLUSIONS: A prolonged supraselective intracoronary infusion of urokinase can be safely administered and may facilitate angioplasty of chronic total occlusions. Lower doses of urokinase are equally effective and result in fewer bleeding complications than do higher dosage regimens. Vessel patency is frequently maintained, but restenosis remains a problem.     

Attachment relationships in infant twins: the effect of co-twin presence during separation from mother

In this study the roles of the mother and the co-twin in inhibiting emotional arousal and reducing manifest distress of a twin who had been isolated in a modified strange situation were compared. The subjects were 15 children, each a member of a twin pair. The subjects were placed in a playroom under three conditions in the following order: (a) mother and twins present; (b) twins together, mother absent; (c) subject isolated from both co-twin and mother. The episodes in which all partners were together were alternated with brief separations. The subjects' distress was minimal when they were separated from the mother with the co-twin present. Upon reunion, stable social behavior was quickly restored. However, separation from the mother and co-twin produced a high level of distress for the subjects. When reunited, the isolated twin initiated physical contact with the mother, soliciting and receiving comfort from her. Furthermore, the distress of the isolated twin was transmitted to the co-twin who had remained with the mother during the isolation period. The nonisolated twin also solicited comfort from the mother. The presence of the co-twin during the reunion following isolation had little effect in reducing the subject twin's distress.     

Mechanical stresses on cargo during ground operations in air transport

Mechanical stresses from the shocks and vibrations to which air cargo is exposed during transport and handling at airports have been investigated. Field trials were carried out at Arlanda Airport, Stockholm, and John F. Kennedy Airport, New York. It was found that when products are transported in the airport area, they are exposed to much higher stresses than during actual flight. Especially severe conditions were registered during transport at John F. Kennedy Airport. Measured stresses are related to the ground and mode of driving within the airport area, as well as to location on the pallet wagon. Guidelines as regards design of realistic, simulating test programs for product and package design are reported. Future development possibilities and suggestions for further research within the area are discussed.     

Predicting Accuracy of Early Cost Estimates Based on Estimate Quality

The accuracy of an estimate is measured by how well the estimated cost compares to the actual total installed cost. The accuracy of an early estimate depends on four determinants: (1) who was involved in preparing the estimate; (2) how the estimate was prepared; (3) what was known about the project; and (4) other factors considered while preparing the estimate. This paper presents results of a research effort that developed an estimate scoring system to measure the impact of these four determinants on estimate accuracy. The estimate scoring system consists of 45 elements and is organized into 4 divisions. Data were collected from 67 projects, representing $5.6 billion in total installed costs, and used to correlate the estimate scores with estimated versus actual costs. Statistical analyses determined the relative influence of the 45 elements, based on collected project data. The results showed a significant correlation between the estimate score and the accuracy of the estimate. Computer software, the Estimate Score Program (ESP), was developed to automate the scoring procedure, assess estimate accuracy, and predict contingency, based on historical cost data. The estimator can enter the base estimate into ESP and then rate the estimate, relative to each of the 45 elements. ESP automatically calculates the estimate score, as the user rates each element. The user can query the ESP historical database to view the estimate scores and estimate accuracy of similar projects. A cumulative probability S-curve, generated by ESP, is based on projects selected in the query and the estimate score of interest. The user can also predict the cost range—upper and lower limits—of a desired confidence level. ESP can be used to “check” the amount of contingency determined by other methods, as well as a method of predicting its own contingency.     

GII public policy issues

National information infrastructure (NII) public policy issues apply to the development of the global information infrastructure (GII) as well. Individual privacy rights; prevention of malicious behavior by irresponsible individuals; protecting the interests of computer system owners, operators, users, and the general public from computer crime; excluding unauthorized access; and preventing destruction of national computer systems (e.g.. interbank transaction systems) are issues that can be endemic to GII operations. More recent issues, such as the need for high-definition television standards, expand the global challenges. Hence, the body of work performed by the Committee on Communications and Information Policy (CCIP) for the IEEE-USA. Which focused on public policy issues of the NII, can serve as a set of lessons learned that should be considered by the GII community. The article identifies the NII issues and concerns to the CCIP, outlines the recommendations already made, and indicates how they relate to the GII     

Mosquito-Plasmodium interactions in response to immune activation of the vector

A molecular model was built for human lecithin:cholesterol acyltransferase (LCAT) based upon the structural homology between this enzyme and lipases (Peelman et al. 1998. Prot. Sci. 7: 585-597). We proposed that LCAT belongs to the alpha/beta hydrolase fold family, and that the central domain of LCAT consists of a mixed seven-stranded beta-pleated sheet with four alpha-helices and loops linking the beta-strands. The catalytic triad of LCAT was identified as Asp345 and His377, as well as Ser181. This model is used here for the interpretation of the structural defects linked to the point mutations identified in LCAT, which cause either familial LCAT deficiency (FLD) or fish-eye disease (FED). We show that these mutations occur in separate domains of the 3D structure of the enzyme. Most mutations causing familial LCAT deficiency are either clustered in the vicinity of the catalytic triad or affect conserved structural elements in LCAT. Most mutations causing fish-eye disease are localized on the outer hydrophilic surface of the amphipathic helical segments. These mutations affect only minimally the overall structure of the enzyme, but are likely to impair the interaction of the enzyme with its co-factor and/or substrate.     

Regulation of K+ channel mRNA expression by stimulation of adenosine A2a-receptors in cultured rat microglia

Previous investigations suggest that the expression of K+ channels in cultured rat microglia is related to the activation status of these cells. Both, lipopolysaccharide (LPS) and agents that raise intracellular cyclic AMP have been shown to inhibit microglial proliferation. LPS also regulates the mRNA expression levels of K+ channels in cultured microglia, which led us to investigate possible regulatory interactions between K+ channels and adenosine A2a-receptors, which are coupled to the cAMP-signal transduction pathway. The selective adenosine A2a-receptor agonist CGS 21680 induced enhanced mRNA expression of both Kv1.3 and ROMK1, as well as an elevation of Kv1.3 protein. The selective adenosine A2a-receptor antagonist aminophenol (ZM 241385) and the nonselective antagonist 8-phenyltheophylline (8-PT) inhibited these effects. Elevations of cyclic AMP by use of dibutyryl cyclic AMP (dbcAMP), phosphodiesterase-inhibitor (RO 20-1724), forskolin, or cholera toxin (CTX), strongly enhanced Kv1.3-mRNA expression, but decreased ROMK1-mRNA levels. Results from experiments with actinomycin D suggest that K+ channel mRNA levels in cultured microglia were regulated by altered mRNA synthesis. Evidently, the CGS 21680-induced effects upon Kv1.3 were mediated via an increase in intracellular cyclic AMP, whereas ROMK1-mRNA expression appeared to be regulated by coupling of adenosine A2a-receptors to an alternative pathway, which involves activation of protein kinase C (PKC). It is concluded that the cyclic AMP second messenger system in microglia is not only involved in regulation of K+ channel activity, but also in regulation of de novo K+ channel synthesis.