Antibiotic pharmacodynamics in surgical prophylaxis: an association between intraoperative antibiotic concentrations and efficacy

The objective of this study was to characterize the relationship between gentamicin concentrations during surgery and the development of wound infection following colorectal operations. Despite decades of research in surgical prophylaxis, the relationship between intraoperative antibiotic concentrations and postoperative infection and the concentrations required for effective prophylaxis have not been established. A pharmacodynamic analysis was conducted using data from a previous prospective, randomized, double-blind clinical study which compared two dosage regimens of gentamicin plus metronidazole for prophylaxis in connection with elective colorectal surgery. Univariate and multivariate analyses of risk factors for postoperative wound infection were conducted, and the relationship between intraoperative gentamicin concentrations and surgical outcome was characterized. The gentamicin concentration at the time of surgical closure was one of the strongest independent risk factors for infection (P = 0.02), along with the presence of diabetes mellitus (P = 0.02), stoma (P = 0.04), and advanced age (P = 0.05). Gentamicin concentrations at closure of less than 0.5 mg/liter were associated with an infection rate of 80% (representing 8 of 10 patients with concentrations below that level) (P = 0.003). Receiver operating characteristic curve analysis identified a critical closure concentration of 1.6 mg/liter for effective surgical prophylaxis (P = 0.002; sensitivity, 70.8%; specificity, 65.9%). This study provides new and important information on antibiotic pharmacodynamics in surgical prophylaxis. It demonstrates the critical effect of the antibiotic concentration at closure on wound infection and suggests a significant association between the concentration and other well-established risk factors, like the timing of preoperative antibiotic administration and surgery duration.     

α/β–T Cell Receptor (TCR)+CD4−CD8− (NKT) Thymocytes Prevent Insulin-dependent Diabetes Mellitus in Nonobese Diabetic (NOD)/Lt Mice by the Influence of Interleukin (IL)-4 and/or IL-10

We have previously shown that nonobese diabetic (NOD) mice are selectively deficient in α/β-T cell receptor (TCR)⁺CD4⁻CD8⁻ NKT cells, a defect that may contribute to their susceptibility to the spontaneous development of insulin-dependent diabetes mellitus (IDDM). The role of NKT cells in protection from IDDM in NOD mice was studied by the infusion of thymocyte subsets into young female NOD mice. A single intravenous injection of 10⁶ CD4^−/lowCD8⁻ or CD4⁻CD8⁻ thymocytes from female (BALB/c × NOD)F1 donors protected intact NOD mice from the spontaneous onset of clinical IDDM. Insulitis was still present in some recipient mice, although the cell infiltrates were principally periductal and periislet, rather than the intraislet pattern characteristic of insulitis in unmanipulated NOD mice. Protection was not associated with the induction of “allogenic tolerance” or systemic autoimmunity. Accelerated IDDM occurs after injection of splenocytes from NOD donors into irradiated adult NOD recipients. When α/β-TCR⁺ and α/β-TCR⁻ subsets of CD4⁻CD8⁻ thymocytes were transferred with diabetogenic splenocytes and compared for their ability to prevent the development of IDDM in irradiated adult recipients, only the α/β-TCR⁺ population was protective, confirming that NKT cells were responsible for this activity. The protective effect in the induced model of IDDM was neutralized by anti–IL-4 and anti–IL-10 monoclonal antibodies in vivo, indicating a role for at least one of these cytokines in NKT cell-mediated protection. These results have significant implications for the pathogenesis and potential prevention of IDDM in humans.     

Characterization of the natural killer T-cell response in an adoptive transfer model of atherosclerosis

Natural killer T (NKT) cells have recently been implicated in atherogenesis, primarily for their ability to recognize and respond to lipid antigens. Because the atherosclerotic lesion is characterized by the retention and modification of lipids in the vascular wall, NKT cells may be involved in promoting the local vascular inflammatory response. Here, we investigate the proatherogenic role of NKT cells in an adoptive transfer model of atherosclerosis, using as recipients immune-deficient, atherosclerosis-susceptible RAG1(-/-)LDLR(-/-) mice. The adoptive transfer of an NKT cell-enriched splenocyte population from Valpha14Jalpha18 T-cell receptor transgenic mice resulted in a 73% increase in aortic root lesion area compared with recipients of NKT cell-deficient splenocytes derived from CD1d(-/-) mice after 12 weeks of Western-type diet feeding. The total serum from hypercholesterolemic mice leads to a small but significant activation of Valpha14Jalpha18 T-cell receptor-expressing hybridoma line by dendritic cells that is CD1d-dependent. Therefore, these studies demonstrate that NKT cells are proatherogenic in the absence of exogenous stimulation, and this activity is likely associated with endogenous lipid antigens carried by lipoproteins in the circulation and perhaps also in the atherosclerotic plaque.     

Accelerating reconstruction of reference digital tomosynthesis using graphics hardware

The successful implementation of digital tomosynthesis (DTS) for on-board image guided radiation therapy (IGRT) requires fast DTS image reconstruction. Both target and reference DTS image sets are required to support an image registration application for IGRT. Target images are usually DTS image sets reconstructed from on-board projections, which can be accomplished quickly using the conventional filtered backprojection algorithm. Reference images are DTS image sets reconstructed from digitally reconstructed radiographs (DRRs) previously generated from conventional planning CT data. Generating a set of DRRs from planning CT is relatively slow using the conventional ray-casting algorithm. In order to facilitate DTS reconstruction within a clinically acceptable period of time, we implemented a high performance DRR reconstruction algorithm on a graphics processing unit of commercial PC graphics hardware. The performance of this new algorithm was evaluated and compared with that which is achieved using the conventional software-based ray-casting algorithm. DTS images were reconstructed from DRRs previously generated by both hardware and software algorithms. On average, the DRR reconstruction efficiency using the hardware method is improved by a factor of 67 over the software method. The image quality of the DRRs was comparable to those generated using the software-based ray-casting algorithm. Accelerated DRR reconstruction significantly reduces the overall time required to produce a set of reference DTS images from planning CT and makes this technique clinically practical for target localization for radiation therapy.     

Evaluation of three types of reference image data for external beam radiotherapy target localization using digital tomosynthesis (DTS)

Digital tomosynthesis (DTS) is a fast, low-dose three-dimensional (3D) imaging approach which yields slice images with excellent in-plane resolution, though low plane-to-plane resolution. A stack of DTS slices can be reconstructed from a single limited-angle scan, with typical scan angles ranging from 10 degrees to 40 degrees and acquisition times of less than 10 s. The resulting DTS slices show soft tissue contrast approaching that of full cone-beam CT. External beam radiotherapy target localization using DTS requires the registration of on-board DTS images with corresponding reference image data. This study evaluates three types of reference volume: original reference CT, exact reference DTS (RDTS), and a more computationally efficient approximate reference DTS (RDTSapprox), as well as three different DTS scan angles (22 degrees, 44 degrees, and 65 degrees) for the DTS target localization task. Three-dimensional mutual information (MI) shared between reference and onboard DTS volumes was computed in a region surrounding the spine of a chest phantom, as translations spanning +/-5 mm and rotations spanning +/-5 degrees were simulated along each dimension in the reference volumes. The locations of the MI maxima were used as surrogates for registration accuracy, and the width of the MI peaks were used to characterize the registration robustness. The results show that conventional treatment planning CT volumes are inadequate reference volumes for direct registration with on-board DTS data. The efficient RDTSapprox method also appears insufficient for MI-based registration without further refinement of the technique, though it may be suitable for manual registration performed by a human observer. The exact RDTS volumes, on the other hand, delivered a 3D DTS localization accuracy of 0.5 mm and 0.50 along each axis, using only a single 44 degrees coronal on-board DTS scan of the chest phantom.     

Disciplinary power and the process of training informal carers on stroke units

This article examines the process of training informal carers on stroke units using the lens of power. Care is usually assumed as a kinship obligation but the state has long had an interest in framing the carer and caring work. Training carers in healthcare settings raises questions about the power of the state and healthcare professionals as its agents to shape expectations and practices related to the caring role. Drawing on Foucault's notion of disciplinary power, we show how disciplinary forms of power exercised in interactions between healthcare professionals and carers shape the engagement and resistance of carers in the process of training. Interview and observational field note extracts are drawn from a multi‐sited study of a training programme on stroke units targeting family carers of people with stroke to consider the consequences of subjecting caring to this intervention. We found that the process of training informal carers on stroke units was not simply a matter of transferring skills from professional to lay person, but entailed disciplinary forms of power intended to shape the conduct of the carer. We interrogate the extent to which a specific kind of carer is produced through such an approach, and the wider implications for the participation of carers in training in healthcare settings and the empowerment of carers.     

The impact of aid on health outcomes in Uganda

The health sector has attracted significant foreign aid; however, evidence on the effectiveness of this support is mixed. This paper combines household panel data with geographically referenced subnational foreign aid data to investigate the contribution of health aid to health outcomes in Uganda. Using a difference‐in‐differences approach, we find that aid had a strong effect on reducing the productivity burden of disease indicated by days of productivity lost due to illness but was less effective in reducing disease prevalence. Consequently, health aid appeared to primarily quicken recovery times rather than prevent disease. In addition, we find that health aid was most beneficial to individuals who lived closest to aid projects. Apart from the impact of aid, we find that aid tended to not be targeted to localities with the worse socioeconomic conditions. Overall, the results highlight the importance of allocating aid close to subnational areas with greater need to enhance aid effectiveness.     

Commercial filming of prehospital patient care

Commercial filming of patients in the hospital and now the prehospital environment is becoming increasingly common. Television programmes that focus on medical emergencies with real footage of events remain highly successful and can make compelling viewing for both medical professionals and the general public alike. Recently several commentators have questioned the ethical aspects of filming in hospital emergency departments, and noted the lack of available evidence. This article reviews commercial filming and its impact in the prehospital environment and examines the ethical implications and current guidance in this unique setting.     

Airway surface liquid recovered by lavage with perfluorocarbon liquid in cats

BACKGROUND: Airway surface liquid (ASL) is difficult to sample. Lavage with an immiscible perfluorocarbon (PFC) liquid to recover ASL was evaluated in cats. MATERIALS AND METHODS: Six wild-type cats underwent bronchoscopic lavage with a PFC (perfluorohexane), with the bronchoscope wedged in the feline equivalent of the right lower lobe. Two cats (control animals) were lavaged with a saline vehicle only. Four procedures were performed on each animal at 2-3-week intervals. Ionic composition of ASL was determined by flame photometry. RESULTS: Cats lavaged with PFC showed significantly more acute respiratory distress than those lavaged with saline (respiratory rate following procedure: PFC, 47 +/- 5 min-1 vs. saline, 27 +/- 2 min-1, P < 0.05; O2 saturation: PFC 80 +/- 1% vs. saline, 91 +/- 1%, P < 0.01). The PFC group also had clinical evidence of chronic respiratory compromise (mean respiratory rate before next anaesthetic; PFC, 37 +/- 2 min-1 vs. saline, 20 +/- 3 min-1, P < 0.01). The PFC-lavaged lungs demonstrated persistent radiographic changes and histological evidence of small airways obstruction with distal alveolar damage. Six PFC lavages yielded ASL samples (> 100 microL) which were sufficient for analysis. Mean (+/- SEM) ionic concentrations in these samples were Na+ 157.4 +/- 14.5 mmol L-1, Cl- 150.5 +/- 16.8 mmol L-1 and K+ 10.1 +/- 1.7 mmol L-1. CONCLUSIONS: Perfluorocarbon lavage can be used to collect unmodified ASL from the distal lung. However, repeated lavage with perfluorohexane was associated with significant pathological changes in this study.