Measurement of extravascular lung water to diagnose severe reperfusion lung injury following pulmonary endarterectomy: a prospective cohort clinical validation study.

The measurement of extravascular lung water is a relatively new technology which has not yet been well validated as a clinically useful tool. We studied its utility in patients undergoing pulmonary endarterectomy as they frequently suffer reperfusion lung injury and associated oedematous lungs. Such patients are therefore ideal for evaluating this new monitor. We performed a prospective observational cohort study during which extravascular lung water index measurements were taken before and immediately after surgery and postoperatively in intensive care. Data were analysed for 57 patients; 21 patients (37%) experienced severe reperfusion lung injury. The first extravascular lung water index measurement after cardiopulmonary bypass failed to predict severe reperfusion lung injury, area under the receiver operating characteristic curve 0.59 (95%CI 0.44-0.74). On intensive care, extravascular lung water index correlated most strongly at 36 h, area under the receiver operating characteristic curve 0.90 (95%CI 0.80-1.00). Peri-operative extravascular lung water index is not a useful measure to predict severe reperfusion lung injury after pulmonary endarterectomy, however, it does allow monitoring and measurement during the postoperative period. This study implies that extravascular lung water index can be used to directly assess pulmonary fluid overload and that monitoring patients by measuring extravascular lung water index during their intensive care stay is useful and correlates with their clinical course. This may allow directed, pre-empted therapy to attenuate the effects and improve patient outcomes and should prompt further studies.

Evaluation of a novel in-line point-of-care blood gas analyser.

Point-of-care testing is becoming increasingly relevant to the practice of anaesthesia and critical care medicine, especially in terms of minimisation of sample volumes and decreased time to decision making. We performed a prospective observational study to evaluate a novel, in-line blood gas analysis device against a conventional benchtop model, and assessed it while placing the enrolled patients under extreme physiological conditions, specifically deep hypothermic circulatory arrest. Eight patients were studied, and had between seven and 11 samples analysed for seven variables (pH, pCO2 , pO2 , HCO3 (-) , base excess [BE], K(+) and haematocrit [Hct]), using the device during the process of cooling to 20 °C on cardiopulmonary bypass, and subsequent rewarming to normothermia. After Passing-Bablok analysis, the variables were evaluated for bias, limits of agreement and percentage error at above and below 30 °C. Of the measured variables, only pH (percentage error 2.4%) and potassium (19.8%) demonstrated acceptable (< 30%) percentage error over the full range of temperatures measured. Carbon dioxide, when stratified by temperature, was acceptable (< 30 °C percentage error 24.6%, > 30 °C percentage error 9.9%), but the overall percentage error of the dataset (45.8%) was excessively high. Bicarbonate and haematocrit both had an acceptable percentage error above 30 °C (25.2% and 18.5%, respectively), but similar to carbon dioxide, percentage error for the full range of temperatures exceeded 30%. These data differ from previous work examining this device, and highlights the difference between derived measures using different apparatuses when exposed to extreme physiological conditions.

NS6180, a new K(Ca) 3.1 channel inhibitor prevents T-cell activation and inflammation in a rat model of inflammatory bowel disease.

BACKGROUND AND PURPOSE: The K(Ca) 3.1 channel is a potential target for therapy of immune disease. We identified a compound from a new chemical class of K(Ca) 3.1 inhibitors and assessed in vitro and in vivo inhibition of immune responses. EXPERIMENTAL APPROACH: We characterized the benzothiazinone NS6180 (4-[[3-(trifluoromethyl)phenyl]methyl]-2H-1,4-benzothiazin-3(4H)-one) with respect to potency and molecular site of action on K(Ca) 3.1 channels, selectivity towards other targets, effects on T-cell activation as well as pharmacokinetics and inflammation control in colitis induced by 2,4-dinitrobenzene sulfonic acid, a rat model of inflammatory bowel disease (IBD). KEY RESULTS: NS6180 inhibited cloned human K(Ca) 3.1 channels (IC(50) = 9 nM) via T250 and V275, the same amino acid residues conferring sensitivity to triarylmethanes such as like TRAM-34. NS6180 inhibited endogenously expressed K(Ca) 3.1 channels in human, mouse and rat erythrocytes, with similar potencies (15-20 nM). NS6180 suppressed rat and mouse splenocyte proliferation at submicrolar concentrations and potently inhibited IL-2 and IFN-γ production, while exerting smaller effects on IL-4 and TNF-α and no effect on IL-17 production. Antibody staining showed K(Ca) 3.1 channels in healthy colon and strong up-regulation in association with infiltrating immune cells after induction of colitis. Despite poor plasma exposure, NS6180 (3 and 10 mg·kg(-1) b.i.d.) dampened colon inflammation and improved body weight gain as effectively as the standard IBD drug sulfasalazine (300 mg·kg(-1) q.d.). CONCLUSIONS AND IMPLICATIONS: NS6180 represents a novel class of K(Ca) 3.1 channel inhibitors which inhibited experimental colitis, suggesting K(Ca) 3.1 channels as targets for pharmacological control of intestinal inflammation.

Prognostic and aetiological factors in chronic thromboembolic pulmonary hypertension.

Several prognostic variables have previously been identified in patients with chronic thromboembolic pulmonary hypertension (CTEPH). Specific medical conditions have also been associated with the development and prognosis of CTEPH. Using a national registry, the current authors have assessed the prognostic value of a larger number of variables and have also attempted to validate the clinical importance of previously identified aetiological factors. Baseline information for all 469 CTEPH patients diagnosed in the UK pulmonary hypertension service between January 2001 and June 2006 was collected from hospital records. Although univariate analysis confirmed the prognostic importance of pulmonary resistance, in multivariate analysis gas transfer and exercise capacity predicted pulmonary endarterectomy perioperative mortality. Cardiac index and exercise capacity independently predicted outcome in patients with nonoperable disease. Previous splenectomy was noted in 6.7% of patients, being significantly more common in patients with nonoperable than operable disease (13.7 versus 3.6%). Medical risk factors were not found to predict mortality. In a large national cohort, predictors of outcome in patients with both operable and nonoperable chronic thromboembolic pulmonary hypertension have been identified. These may be useful in planning treatment. The aetiological importance of previously identified medical risk factors has been confirmed, although the current authors were unable to validate their prognostic strength.

Using cognitive work analysis to explore activity allocation within military domains.

Cognitive work analysis (CWA) is frequently advocated as an approach for the analysis of complex socio-technical systems. Much of the current CWA literature within the military domain pays particular attention to its initial phases; work domain analysis and contextual task analysis. Comparably, the analysis of the social and organisational constraints receives much less attention. Through the study of a helicopter mission planning system software tool, this paper describes an approach for investigating the constraints affecting the distribution of work. The paper uses this model to evaluate the potential benefits of the social and organisational analysis phase within a military context. The analysis shows that, through its focus on constraints, the approach provides a unique description of the factors influencing the social organisation within a complex domain. This approach appears to be compatible with existing approaches and serves as a validation of more established social analysis techniques. As part of the ergonomic design of mission planning systems, the social organisation and cooperation analysis phase of CWA provides a constraint-based description informing allocation of function between key actor groups. This approach is useful because it poses questions related to the transfer of information and optimum working practices.

Post-160-km race illness rates and decreases in granulocyte respiratory burst and salivary IgA output are not countered by quercetin ingestion.

This study measured the influence of the flavonoid quercetin on immune changes and incidence rates of upper respiratory tract infections in ultramarathoners competing in the 160-km Western States Endurance Run. Sixty-three runners were randomized to quercetin and placebo groups, and under double-blinded methods ingested 1000 mg/day quercetin for 3 wks before, during, and 2 wks after the race. Thirty-nine of the 63 subjects (n = 18 for quercetin, n = 21 for placebo) finished the race and provided blood and saliva samples the morning before the race and 15 - 30 min postrace. Upper respiratory tract infections were assessed during the week before and the 2-wk period after the race using an illness symptom checklist. Race times did not differ significantly between quercetin and placebo groups. Significant pre- to postrace decreases were measured for natural killer cells (43 %), granulocyte respiratory burst activity (55 %), and salivary IgA output (48 %), and increases for neutrophil (288 %) and monocyte (211 %) cell counts, with no significant group differences. Postrace illness rates did not differ between groups. In conclusion, quercetin supplementation for 3 wks before and 2 wks after the Western States Endurance Run had no effect on illness rates, perturbations in leukocyte subset counts, or decreases in granulocyte respiratory burst activity and salivary IgA.

Delayed presentation of right ventricular bullet embolus.

Venous bullet embolism to the heart is a rare complication of penetrating gunshot trauma. There are little data regarding long-term follow-up of missiles retained in the right ventricle. We report a rare case of right ventricular bullet embolus following a left-sided thoracic gunshot wound. The patient presented with delayed onset of cardiac irritability symptoms 4 years after injury.

Risk stratification for training in cardiac surgery.

BACKGROUND: There is a potential conflict of interest in providing the best possible outcome for patients undergoing cardiac surgery and good training for junior cardiac surgeons. METHODS: We analysed training with reference to volume of work, risk stratification and outcome for consultant and trainee procedures. The Parsonnet system was used for risk stratification. A retrospective audit was performed for a 6-year period. RESULTS: During the study period, 6037 operations were performed, of which 2166 were carried out by trainees. Direct consultant assistance in a trainee operation varied between 17% and 51% and increased towards the end of the study period. Of the operations performed by trainees, 88% were CABG. The median Parsonnet score for consultant operations was 9 compared with 4 for trainees. Actual mortality was below predicted for all surgeons. Morbidity was also lowest for trainees (10%). CONCLUSIONS: With appropriate case selection, trainees in cardiac surgery can achieve good results. As training changes in the UK, trainees should receive increased supervised exposure to a wider range of procedure to compensate for a lower volume of workload.

Recurrent arterial embolization from a metastatic germ cell tumor invading the left atrium.

Arterial embolization of a malignant tumor is extremely rare. We report an unusual case of a young adult man who presented with acute lower limb ischemia and a mass in the right lung and left atrium. These clinical manifestations were the result of metastases and embolization from a germ cell tumor and were the first indication of malignancy in this patient. The importance of appropriate investigations in the subsequent treatment is stressed.

Ischaemic preconditioning reduces troponin T release in patients undergoing coronary artery bypass surgery.

OBJECTIVE: To investigate whether ischaemic preconditioning could reduce myocardial injury, as manifest by troponin T release, in patients undergoing elective coronary artery bypass surgery. DESIGN: Randomised controlled trial. SETTING: Cardiothoracic unit of a tertiary care centre. PATIENTS: Patients with three vessel coronary artery disease and stable angina admitted for first time elective coronary artery bypass surgery were invited to take part in the study; 33 patients were randomised into control or preconditioning groups. INTERVENTION: Patients in the preconditioning group were exposed to two additional three minute periods of myocardial ischaemia at the beginning of the revascularisation operation, before the ischaemic period used for the first coronary artery bypass graft distal anastomosis. MAIN OUTCOME MEASURE: Serum troponin T concentration at 72 hours after cardiopulmonary bypass. RESULTS: The troponin T assays were performed by blinded observers at a different hospital. All patients had undetectable serum troponin T (< 0.1 microgram/l) before cardiopulmonary bypass, and troponin T was raised postoperatively in all patients. At 72 hours, serum troponin T was lower (P = 0.05) in the preconditioned group (median 0.3 microgram/l) than in the control group (median 1.4 micrograms/l). CONCLUSIONS: The direct application of a preconditioning stimulus in clinical practice has been shown, for the first time, to protect patients against irreversible myocyte injury.

Telemedicine: caring for patients across boundaries.

Telemedicine combines computer, video and telecommunications to provide healthcare to patients at distant sites. With the improved camera and transmission technologies of the 1990s, telemedicine can be used in a variety of situations. There are two basic technological systems: live interactive video and still image ("store and forward"). Potential users include patients who live in rural or difficult to reach geographic areas, who are confined (i.e. prison inmates), Telemedicine can allow ambulatory patients to continue living at home rather than moving into costly nursing facilities. Home telemedicine also allows greater responsiveness and higher frequency of visits by home care nurses, potentially reducing future hospital visits and costs. Two home telemedicine models are the personal telemedicine unit and the enhanced personal telemedicine module with pc-based video. Telemedicine technologies developed by the military for use on the battlefield that could be adapted for civilian use include medical simulations, individual monitoring devices and biosensors, portable retinal display monitors, life support for trauma/transport, and diagnostic ultrasound imagery. Ultimately, the benefits of telemedicine will be consistency of care, easy access to specialized consultants, higher responsiveness to patient needs, and lower overall healthcare costs.

Ischaemic preconditioning and cardiac surgery.

OBJECTIVE: This review discusses the phenomenon of ischaemic preconditioning and its potential application to cardiac surgery. The biology of ischaemic preconditioning is explained and the more limited evidence suggesting that the human heart can be preconditioned is discussed. METHODS AND RESULTS: It is now accepted that the heart is capable of short-term rapid adaptation in response to brief ischaemia so that during a subsequent, more severe ischaemic insult myocardial necrosis is delayed-ischaemic preconditioning. The infarct-delaying properties of ischaemic preconditioning have been observed in all species studied. Five minutes of ischaemia is enough to initiate preconditioning and the protective period lasts for 1-2 h. Laboratory experiments have demonstrated that the stimulation of adenosine receptors initiates preconditioning and the intracellular signal transduction mechanisms involve protein kinase C and ATP-dependent potassium channels, although there may be some differences between species. An analysis of studies on myocardial infarction in humans has revealed that some patients reporting angina in the days before infarction have a better outcome and this may be due to the ischaemia causing preconditioning. More direct evidence has come from an investigation of patients undergoing percutaneous transluminal angioplasty in whom the ST-segment changes induced by balloon inflation were more marked during the first inflation than the second. In patients undergoing coronary artery bypass grafting the decline in ATP content during the first 10 min of ischaemia was reduced in patients subjected to a brief preconditioning protocol. CONCLUSIONS: Preconditioning is a powerful and reproducible method of protecting the myocardium from irreversible ischaemic injury. There is now evidence indicating that the human heart can be preconditioned. However, more trials are necessary in patients undergoing cardiac surgery before the role of preconditioning as a means of myocardial protection can be assessed.

Preconditioning the human myocardium: recent advances and aspirations for the development of a new means of cardioprotection in clinical practice.

Ischemic preconditioning has been shown to be one of the most powerful means of protecting the myocardium from ischemic injury in experimental animal models, although the mechanism is incompletely understood. In this review we discuss the evidence for preconditioning occurring in ischemic syndromes in humans, whether the human myocardium can be preconditioned, and whether preconditioning would have a place as a therapeutic tool in clinical practice. Some studies evaluating patients after acute myocardial infarction have shown a better outcome in patients reporting angina before the onset of the infarction, but this is not a universal finding, and it is difficult to exclude other confounding factors, such as collateral flow, from influencing the results. More controlled prospective studies have evaluated patients undergoing percutaneous transluminal coronary angioplasty and have found less ST-segment change and less reported angina during the second balloon inflation when compared with the first. Again, it is impossible to completely exclude other causes for this effect, but the dependence on mechanisms that are known to be important for preconditioning in animal models does suggest the phenomena are the same. Further experiments using isolated human atrial muscle have shown that human myocardium can be preconditioned and that the mechanisms involved are similar to those elucidated in animal models (adenosine, protein kinase C, and ATP-dependent potassium channels). In clinical medicine preconditioning is most likely to benefit patients when it is used to protect against the ischemia induced by cardiac surgery. In this respect, a study has shown that in patients undergoing coronary artery bypass grafts, the reduction in ATP occurring during the first ischemic period is attenuated in those given an ischemic preconditioning protocol beforehand. Despite these advances, it is likely that the full potential of preconditioning in clinical practice will not be realized until the whole mechanism of protection is understood and a safe pharmacological "preconditioning" agent becomes available.

Ischaemic preconditioning in a model of global ischaemia: infarct size limitation, but no reduction of stunning.

It is well known that ischaemic preconditioning delays infarct size during regional ischaemic insults. However, the extent of this protective effect against different ischaemia periods has not been established, and any reduction in stunning has been difficult to demonstrate with regional models. In this study we have investigated ischaemic preconditioning in a buffer-perfused isolated rabbit heart model with a global ischaemic insult, and measured both infarct volume and functional recovery. Experiments were performed with three ischaemia time periods of 15, 20 and 30 min at 37 degrees C. Infarct volume (expressed as a percentage of left ventricular volume) was measured by tetrazolium staining after 2 hours reperfusion, and left ventricular developed pressure with an intraventricular balloon. Hearts preconditioned with 5 min ischaemia and 10 min reperfusion were compared with a control group. In this model, preconditioning resulted in a 57% reduction in infarct volume compared with control hearts (P = 0.02) subjected to 20 min of global ischaemia, but the degree of this infarct delaying effect was dependent on the ischaemia time and was only 37% (P = 0.02) and 11% (N.S.) with a 30 min and 15 min ischaemic challenge respectively. Recovery of post-ischaemic left ventricular developed pressure as a percentage of the pre-ischaemic value correlated very well with infarct volume in control r = -0.82 (P < 0.001) and preconditioned r = -0.78 (P < 0.001) groups, and the slope of the regression lines was similar for both groups. These results demonstrate that the degree of protection produced by preconditioning is not uniform but varies with the length of the ishaemic insult. By measuring both infarct volume and functional recovery we have been able to confirm that any post-ischaemic improvement in global left ventricular function produced by preconditioning is secondary to reduced infarction, and hence that preconditioning does not attenuate stunning.