Pharmacokinetics of ciprofloxacin in ICU patients on continuous veno-venous haemodiafiltration

Objectives: To investigate the pharmacokinetics of intravenous ciprofloxacin 200 mg every 8 h in critically ill patients on continuous veno-venous haemodiafiltration (CVVHDF), one form of continuous renal replacement therapy (CRRT). Design and setting: Open, prospective clinical study in a multidisciplinary, intensive care unit in a university-affiliated tertiary referral hospital. Patients: Sis critically ill patients with acute renal failure on CVVHDF. Interventions: Timed blood and ultrafiltrate samples were collected to allow pharmacokinetics and clearances to be calculated of initial and subsequent doses of 200 mg intravenous ciprofloxacin. CVVHD was performed with 1 l/h of dialysate and 2 l/h of predilution filtration solution, producing 3 lih of dialysis effluent. The blood was pumped at 200 ml/min using a Gambro BMM-10 blood pump through a Hospal AN69HF haemofilter,. Measurements and results: Ten pharmacokinetic profiles were measured. The CVVHDF displayed a urea clearance of 42 +/- 3 ml/min, and removed ciprofloxacin with a clearance of 37 +/- 7 ml/min. This rate was 2-2.5 greater than previously published for ciprofloxacin in other forms of CRRT. On average the CVVHDF was responsible for clearing a fifth of all ciprofloxacin eliminated (21 +/- 10%). The total body clearance of ciprofloxacin was 12.2 +/- 4.3 l/h. The trough concentration following the initial dose was 0.7 +/- 0.3 mg/l. The area under the plasma concentration time curves over a 24-h period ranged from 21 to 55 mg .h l(-1). Conclusions: Intravenous ciprofloxacin 600 mg/day in critically ill patients using this form of CRRT produced adequate plasma levels for many resistant microbes found in intensive care units.

Analysis of the study design and manuscript deficiencies in research articles submitted to Emergency Medicine

Objective: To describe and analyse the study design and manuscript deficiencies in original research articles submitted to Emergency Medicine. Methods: This was a retrospective, analytical study. Articles were enrolled if the reports of the Section Editor and two reviewers were available. Data were extracted from these reports only. Outcome measures were the mean number and nature of the deficiencies and the mean reviewers’ assessment score. Results: Fifty-seven articles were evaluated (28 accepted for publication, 19 rejected, 10 pending revision). The mean (± SD) number of deficiencies was 18.1 ± 6.9, 16.4 ± 6.5 and 18.4 ± 6.7 for all articles, articles accepted for publication and articles rejected, respectively (P = 0.31 between accepted and rejected articles). The mean assessment scores (0–10) were 5.5 ± 1.5, 5.9 ± 1.5 and 4.7 ± 1.4 for all articles, articles accepted for publication and articles rejected, respectively. Accepted articles had a significantly higher assessment score than rejected articles (P = 0.006). For each group, there was a negative correlation between the number of deficiencies and the mean assessment score (P > 0.05). Significantly more rejected articles ‘… did not further our knowledge’ (P = 0.0014) and ‘… did not describe background information adequately’ (P = 0.049). Many rejected articles had ‘… findings that were not clinically or socially significant’ (P = 0.07). Common deficiencies among all articles included ambiguity of the methods (77%) and results (68%), conclusions not warranted by the data (72%), poor referencing (56%), inadequate study design description (51%), unclear tables (49%), an overly long discussion (49%), limitations of the study not described (51%), inadequate definition of terms (49%) and subject selection bias (40%). Conclusions: Researchers should undertake studies that are likely to further our knowledge and be clinically or socially significant. Deficiencies in manuscript preparation are more frequent than mistakes in study design and execution. Specific training or assistance in manuscript preparation is indicated.

Design of a polyepitope construct for the induction of HLA-A0201-restricted HIV 1-specific CTL responses using HLA-A*0201 transgenic, H-2 class IKO mice

HLA-A*0201 transgenic, H-2D(b)/mouse beta2-microglobulin double-knockout mice were used to compare and optimize the immunogenic potential of 17HIV 1-derived, HLA-A0201-restricted epitopic peptides. A tyrosine substitution in position 1 of the epitopic peptides, which increases both their affinity for and their HLA-A0201 molecule stabilizing capacity, was introduced in a significant proportion, having verified that such modifications enhance their immunogenicity in respect of their natural antigenicity. Based on these results, a 13-polyepitope construct was inserted in the pre-S2 segment of the hepatitis B middle glycoprotein and used for DNA immunization. Long-lasting CTL responses against most of the inserted epitopes could be elicited simultaneously in a single animal with cross-recognition in several cases of their most common natural variants.

An inverse design method for elliptical MRI magnets

An inverse, current density mapping (CDM) method has been developed for the design of elliptical cross-section MRI magnets. The method provides a rapid prototyping system for unusual magnet designs, as it generates a 3D current density in response to a set of target field and geometric constraints. The emphasis of this work is on the investigation of new elliptical coil structures for clinical MRI magnets. The effect of the elliptical aspect ratio on magnet performance is investigated. Viable designs are generated for symmetric, asymmetric and open architecture elliptical magnets using the new method. Clinically relevant attributes such as reduced stray field and large homogeneous regions relative to total magnet length are included in the design process and investigated in detail. The preliminary magnet designs have several novel features.

Compact clinical MRI magnet design using a multilayer current density approach

In this work, a new method of optimization is successfully applied to the theoretical design of compact, actively shielded, clinical MRI magnets. The problem is formulated as a two-step process in which the desired current densities on multiple, cc-axial surface layers are first calculated by solving Fredholm equations of the first kind. Non-linear optimization methods with inequality constraints are then invoked to fit practical magnet coils to the desired current densities. The current density approach allows rapid prototyping of unusual magnet designs. The emphasis of this work is on the optimal design of short, actively-shielded MRI magnets for whole-body imaging. Details of the hybrid numerical model are presented, and the model is used to investigate compact, symmetric, and asymmetric MRI magnets. Magnet designs are presented for actively-shielded, symmetric magnets of coil length 1.0 m, which is considerably shorter than currently available designs of comparable dsv size. Novel, actively-shielded, asymmetric magnet designs are also presented in which the beginning of a 50-cm dsv is positioned just 11 cm from the end of the coil structure, allowing much improved access to the patient and reduced patient claustrophobia. Magn Reson Med 45:331540, 2001. (C) 2001 Wiley-Liss, Inc.

The stochastic design of force-minimized compact magnets for high-field magnetic resonance imaging applications

New designs for force-minimized compact high-field clinical MRI magnets are described. The design method is a modified simulated annealing (SA) procedure which includes Maxwell forces in the error function to be minimized. This permits an automated force reduction in the magnet designs while controlling the overall dimensions of the system. As SA optimization requires many iterations to achieve a final design, it is important that each iteration in the procedure is rapid. We have therefore developed a rapid force calculation algorithm. Novel designs for short 3- and 4-T clinical MRI systems are presented in which force reduction has been invoked. The final designs provide large homogeneous regions and reduced stray fields in remarkable short magnets. A shielded 4-T design that is approximately 30% shorter than current designs is presented. This novel magnet generates a full 50-cm diameter homogeneous region.

Transient mesenteric ischaemic episodes tracked by continuous jejunal PCO2 monitoring during liquid feeding

Objective: To test the effect of liquid feeds on the responses to splanchnic ischaemia of a continuous rapid response PCO2 sensor inserted in the jejunum. Design: Prospective experimental animal study in a university research laboratory. Subjects: Adult male Wistar rats. Interventions: Adult male Wistar rats (285-425 g) were anaethetised with sodium pentobarbitone 60 mg/ kg i.p. and ventilated with 100 % oxygen and isoflurane via tracheostomy to a PaCO2 of 30-40 mmHg. A sensor was inserted into the mid-jejunum to record PCO2 every second. Distal aortic pressure was transduced. Four control rats received no feeds whilst in another four rats liquid feed was infused into the proximal jejunum at 3 ml/h. In each rat five episodes of splanchnic ischaemia were induced by 2-min elevations of an aortic sling to a mean distal aortic pressure of 30 mmHg. Measurements and main results: PCO2 elevations were always detectable, usually less than a minute from the onset of splanchnic ischaemia in both fed and unfed rats, with no difference in mean times to detectable response. In the fed rats there was a small but significant increase in the time to peak sensor response (196 +/- 16 vs. 180 +/- 12 s) and a trend towards an elevated mean baseline luminal PCO2 (67 +/- 9 vs. 55 +/- 4 mmHg). Conclusions: Brief episodes of splanchnic ischaemia were tracked successfully by a rapid response jejunal continuous PCO2 sensor during the infusion of a proprietary liquid feed preparation despite minor changes in PCO2 response characteristics and a possible elevation in baseline luminal PCO2.

The design of hazard risk assessment matrices for ranking occupational health risks and their application in mining and minerals processing

Two hazard risk assessment matrices for the ranking of occupational health risks are described. The qualitative matrix uses qualitative measures of probability and consequence to determine risk assessment codes for hazard-disease combinations. A walk-through survey of an underground metalliferous mine and concentrator is used to demonstrate how the qualitative matrix can be applied to determine priorities for the control of occupational health hazards. The semi-quantitative matrix uses attributable risk as a quantitative measure of probability and uses qualitative measures of consequence. A practical application of this matrix is the determination of occupational health priorities using existing epidemiological studies. Calculated attributable risks from epidemiological studies of hazard-disease combinations in mining and minerals processing are used as examples. These historic response data do not reflect the risks associated with current exposures. A method using current exposure data, known exposure-response relationships and the semi-quantitative matrix is proposed for more accurate and current risk rankings.

Mathematical methods for spatially cohesive reserve design

The problem of designing spatially cohesive nature reserve systems that meet biodiversity objectives is formulated as a nonlinear integer programming problem. The multiobjective function minimises a combination of boundary length, area and failed representation of the biological attributes we are trying to conserve. The task is to reserve a subset of sites that best meet this objective. We use data on the distribution of habitats in the Northern Territory, Australia, to show how simulated annealing and a greedy heuristic algorithm can be used to generate good solutions to such large reserve design problems, and to compare the effectiveness of these methods.

A zero-augmented gamma mixed model for longitudinal data with many zeros

In many occupational safety interventions, the objective is to reduce the injury incidence as well as the mean claims cost once injury has occurred. The claims cost data within a period typically contain a large proportion of zero observations (no claim). The distribution thus comprises a point mass at 0 mixed with a non-degenerate parametric component. Essentially, the likelihood function can be factorized into two orthogonal components. These two components relate respectively to the effect of covariates on the incidence of claims and the magnitude of claims, given that claims are made. Furthermore, the longitudinal nature of the intervention inherently imposes some correlation among the observations. This paper introduces a zero-augmented gamma random effects model for analysing longitudinal data with many zeros. Adopting the generalized linear mixed model (GLMM) approach reduces the original problem to the fitting of two independent GLMMs. The method is applied to evaluate the effectiveness of a workplace risk assessment teams program, trialled within the cleaning services of a Western Australian public hospital.

Developmental genetics of red cell indices during puberty: A longitudinal twin study

Red cell number and size increase during puberty, particularly in males. The aim of the present study was to determine whether expression of genes affecting red cell indices varied with age and sex. Haemoglobin, red cell count, and mean cellular volume were measured longitudinally on 578 pairs of twins at twelve, fourteen and sixteen years of age. Data were analysed using a structural equation modeling approach, in which a variety of univariate and longitudinal simplex models were fitted to the data. Significant heritability was demonstrated for all variables across all ages. The genes involved did not differ between the sexes, although there was evidence for sex limitation in the case of haemoglobin at age twelve. Longitudinal analyses indicated that new genes affecting red cell indices were expressed at different stages of puberty. Some of these genes affected the different red cell indices pleiotropically, while others had effects specific to one variable only.

Current density mapping approach for design of clinical magnetic resonance imaging magnets

Novel current density mapping (CDM) schemes are developed for the design of new actively shielded, clinical magnetic resonance imaging (MRI) magnets. This is an extended inverse method in which the entire potential solution space for the superconductors has been considered, rather than single current density layers. The solution provides an insight into the required superconducting coil pattern for a desired magnet configuration. This information is then used as an initial set of parameters for the magnet structure, and a previously developed hybrid numerical optimization technique is used to obtain the final geometry of the magnet. The CDM scheme is applied to the design of compact symmetric, asymmetric, and open architecture 1.0-1.5 T MRI magnet systems of novel geometry and utility. A new symmetric 1.0-T system that is just I m in length with a full 50-cm diameter of the active, or sensitive, volume (DSV) is detailed, as well as an asymmetric system in which a 50-cm DSV begins just 14 cm from the end of the coil structure. Finally a 1.0-T open magnet system with a full 50-cm DSV is presented. These new designs provide clinically useful homogeneous regions and have appropriately restricted stray fields but, in some of the designs, the DSV is much closer to the end of the magnet system than in conventional designs. These new designs have the potential to reduce patient claustrophobia and improve physician access to patients undergoing scans. (C) 2002 Wiley Periodicals, Inc.

An inverse design of an open, head/neck RF coil for MRI

Radio-frequency (RF) coils are a necessary component of magnetic resonance imaging (MRI) systems. When used in transmit operation, they act to generate a homogeneous RF magnetic field within a volume of interest and when in receive operation, they act to receive the nuclear magnetic resonance signal from the RF-excited specimen. This paper outlines a procedure for the design of open RF coils using the time-harmonic inverse method. This method entails the calculation of an ideal current density on a multipaned planar surface that would generate a specified magnetic field within the volume of interest. Because of the averaging effect of the regularization technique in the matrix solution, the specified magnetic field is shaped within an iterative procedure until the generated magnetic field matches the desired magnetic field. The stream-function technique is used to ascertain conductor positions and a method of moments package is then used to finalize the design. An open head/neck coil was designed to operate in a clinical 2T MRI system and the presented results prove the efficacy of this design methodology.