Continuous Normothermic Ex Vivo Kidney Perfusion Is Superior to Brief Normothermic Perfusion Following Static Cold Storage in Donation After Circulatory Death Pig Kidney Transplantation.

Hypothermic preservation is known to cause renal graft injury, especially in donation after circulatory death (DCD) kidney transplantation. We investigated the impact of cold storage (SCS) versus short periods of normothermic ex vivo kidney perfusion (NEVKP) after SCS versus prolonged, continuous NEVKP with near avoidance of SCS on kidney function after transplantation. Following 30 min of warm ischemia, kidneys were removed from 30-kg Yorkshire pigs and preserved for 16 h with (A) 16 h SCS, (B) 15 h SCS + 1 h NEVKP, (C) 8 h SCS + 8 h NEVKP, and (D) 16 h NEVKP. After contralateral kidney resection, grafts were autotransplanted and pigs followed up for 8 days. Perfusate injury markers such as aspartate aminotransferase and lactate dehydrogenase remained low; lactate decreased significantly until end of perfusion in groups C and D (p < 0.001 and p = 0.002). Grafts in group D demonstrated significantly lower serum creatinine peak when compared to all other groups (p < 0.001) and 24-h creatinine clearance at day 3 after surgery was significantly higher (63.4 ± 19.0 mL/min) versus all other groups (p < 0.001). Histological assessment on day 8 demonstrated fewer apoptotic cells in group D (p = 0.008). In conclusion, prolonged, continuous NEVKP provides superior short-term outcomes following DCD kidney transplantation versus SCS or short additional NEVKP following SCS.

Normothermic Ex Vivo Kidney Perfusion Following Static Cold Storage-Brief, Intermediate, or Prolonged Perfusion for Optimal Renal Graft Reconditioning?

Normothermic ex vivo kidney perfusion (NEVKP) demonstrated superior results compared to hypothermic storage in donation after circulatory death (DCD) kidney transplantation. It is unknown whether an optimal perfusion time exists following hypothermic storage to allow for the recovery of renal grafts from cold ischemic injury. In a porcine model of DCD kidney autotransplantation, the impact of initial static cold storage (SCS) (8 h) followed by various periods of NEVKP recovery was investigated: group A, 8 hSCS only (control); group B, 8 hSCS + 1 hNEVKP (brief NEVKP); group C, 8 hSCS + 8 hNEVKP (intermediate NEVKP); and group D, 8 hSCS + 16 hNEVKP (prolonged NEVKP). All grafts were preserved and transplanted successfully. One animal in group D was sacrificed and excluded by postoperative day 3 due to hind limb paralysis, but demonstrated good renal function. Postoperative graft assessment during 8 days' follow-up demonstrated lowest levels of peak serum creatinine for intermediate (C) and prolonged (D) NEVKP (p = 0.027). Histological assessment on day 8 demonstrated a significant difference in tubular injury (p = 0.001), with highest values for group B. These results suggest that longer periods of NEVKP following SCS are feasible and safe for postponing surgical transplant procedure and superior to brief NEVKP, reducing the damage caused during cold ischemic storage of renal grafts.

Prognostic factors for survival after complete resections of synchronous lung cancers in multiple lobes: pooled analysis based on individual patient data.

BACKGROUND: Some reports suggest that patients with synchronous multiple foci of nonsmall-cell lung cancers (NSCLC) distributed in multiple lobes have a poor prognosis, even when there is no extrathoracic metastasis. The vast majority of such patients do not receive surgical treatment. For those who undergo surgery, prognostic factors are unclear. PATIENTS AND METHODS: We systematically reviewed the literature on surgery for synchronous NSCLC in multiple lobes published between 1990 and 2011. Individual patient data were used to obtain adjusted hazard ratios (HRs) in each dataset and pooled analyses were carried out. RESULTS: Six studies contributed 467 eligible patients for analysis. The median overall survival was 52.0 months [95% confidence interval 45.6-63.7]. Male gender and advanced age were associated with a decreased survival: HRs 1.64 (1.22, 2.22) and 1.40 (1.20, 1.80) per 20-year increment, respectively. Patients with cancers distributed in one lung had a higher mortality risk than those with bilateral disease: HRs 1.45 (1.06, 2.00). N1 or N2 had a decreased survival compared with N0: HRs 1.68 (1.12, 2.51) and 1.94 (1.33, 2.82), respectively. There was a trend toward increased mortality among patients with different histology: HRs 1.29 (0.96, 1.75). CONCLUSION: Advanced age, male gender, nodal involvement, and unilateral tumor location were poor prognostic factors.

Assessing the sensitivity of habitats to fishing: from seabed maps to sensitivity maps.

In the Welsh part of the Irish Sea, a method was developed for assessing the sensitivity of different seabed habitats to existing fishing activities, across a range of potential fishing intensities. The resistance of 31 habitats and their associated biological assemblage to damage by 14 categories of fishing activity were assessed along with the rate at which each habitat would recover following impact (resilience). Sensitivity was scored based on a combination of the resistance of a habitat to damage and its subsequent rate of recovery. The assessments were based, wherever possible, on scientific literature, with expert judgement used to extrapolate results to habitat and gear combinations not directly examined in the published literature. The resulting sensitivity matrices were then subject to further peer review at a series of workshops. Following consensus on the habitat sensitivity, these data were combined with the most resolved sea-floor habitat maps. These habitat sensitivity maps can help inform the development of site-specific management plans, as well as having a place in spatial planning and aiding managers in developing dialogue with other stakeholders. A case study of their application is provided.

Fractalkine and CX3CR1 mediate a novel mechanism of leukocyte capture, firm adhesion, and activation under physiologic flow.

Leukocyte migration into sites of inflammation involves multiple molecular interactions between leukocytes and vascular endothelial cells, mediating sequential leukocyte capture, rolling, and firm adhesion. In this study, we tested the role of molecular interactions between fractalkine (FKN), a transmembrane mucin-chemokine hybrid molecule expressed on activated endothelium, and its receptor (CX3CR1) in leukocyte capture, firm adhesion, and activation under physiologic flow conditions. Immobilized FKN fusion proteins captured resting peripheral blood mononuclear cells at physiologic wall shear stresses and induced firm adhesion of resting monocytes, resting and interleukin (IL)-2-activated CD8(+) T lymphocytes and IL-2-activated NK cells. FKN also induced cell shape change in firmly adherent monocytes and IL-2-activated lymphocytes. CX3CR1-transfected K562 cells, but not control K562 cells, firmly adhered to FKN-expressing ECV-304 cells (ECV-FKN) and tumor necrosis factor alpha-activated human umbilical vein endothelial cells. This firm adhesion was not inhibited by pertussis toxin, EDTA/EGTA, or antiintegrin antibodies, indicating that the firm adhesion was integrin independent. In summary, FKN mediated the rapid capture, integrin-independent firm adhesion, and activation of circulating leukocytes under flow. Thus, FKN and CX3CR1 mediate a novel pathway for leukocyte trafficking.

Identifying barriers, conflict and opportunity in managing aquatic ecosystems.

Inland aquatic ecosystems play an important part in the delivery and support of ecosystem services. However, these ecosystems are subject to stressors associated with human activities such as invasive species introduction and landscape alteration. There is a delicate balance between maintaining good status of the ecosystem whilst meeting the needs of those stakeholders dependent on the ecosystem services it supplies, and where there are many different stakeholders, each with different aspirations and dependencies on the ecosystem, it can be difficult to strike a balance on suitable management measures to put in place. A better understanding of the interactions between the human and ecological functions of the ecosystem (a socio-ecological systems (SES) approach) can enable an effective dialogue to be opened to secure management solutions of best fit. In this study we took a SES approach to explore the dependencies and interactions in the Lough Erne catchment with a range of stakeholders representing the use of the Lough. In particular, we explored how individual stakeholder goals were perceived to be affected by both the biodiversity and activities found in the catchment. Results suggest there are distinct components deemed integral to the success of stakeholder goals in this system, including 'key habitat components' and 'policy relevant species', as well as activities associated with 'conservation and recreation' and 'scientific research'. Those components which were seen to limit the potential achievement of most goals included invasive species, and in particular, more recently introduced invasives, as well as extractive industries. Consideration of the similarity in goals based on their perceived interactions with the activities and biodiversity of the system indicated that there were shared dependencies between some stakeholders, but also differences that highlight the potential for conflict. Future management scenarios should take consideration of the key limiting and enabling factors identified here.

Introducing the H2020 AQUACROSS project: Knowledge, Assessment, and Management for AQUAtic Biodiversity and Ecosystem Services aCROSS EU policies.

The AQUACROSS project was an unprecedented effort to unify policy concepts, knowledge, and management of freshwater, coastal, and marine ecosystems to support the cost-effective achievement of the targets set by the EU Biodiversity Strategy to 2020. AQUACROSS aimed to support EU efforts to enhance the resilience and stop the loss of biodiversity of aquatic ecosystems as well as to ensure the ongoing and future provision of aquatic ecosystem services. The project focused on advancing the knowledge base and application of Ecosystem-Based Management. Through elaboration of eight diverse case studies in freshwater and marine and estuarine aquatic ecosystem across Europe covering a range of environmental management problems including, eutrophication, sustainable fisheries as well as invasive alien species AQUACROSS demonstrated the application of a common framework to establish cost-effective measures and integrated Ecosystem-Based Management practices. AQUACROSS analysed the EU policy framework (i.e. goals, concepts, time frames) for aquatic ecosystems and built on knowledge stemming from different sources (i.e. WISE, BISE, Member State reporting within different policy processes, modelling) to develop innovative management tools, concepts, and business models (i.e. indicators, maps, ecosystem assessments, participatory approaches, mechanisms for promoting the delivery of ecosystem services) for aquatic ecosystems at various scales of space and time and relevant to different ecosystem types.

The use of gamification in the teaching of disease epidemics and pandemics.

With the launch of the teaching excellence framework, teaching in higher education (HE) is under greater scrutiny than ever before. Didactic lecture delivery is still a core element of many HE programmes but there is now a greater expectation for academics to incorporate alternative approaches into their practice to increase student engagement. These approaches may include a large array of techniques from group activities, problem-based learning, practical experience and mock scenarios to newly emerging approaches such as flipped learning practices and the use of gamification. These participatory forms of learning encourage students to become more absorbed within a topic that may otherwise be seen as rather 'dry' and reduce students engagement with, and therefore retention of, material. Here we use participatory-based teaching approaches in microbiology as an example to illustrate to University undergraduate students the potentially devastating effects that a disease can have on a population. The 'threat' that diseases may pose and the manner in which they may spread and/or evolve can be challenging to communicate, especially in relation to the timescales associated with these factors in the case of an epidemic or pandemic.

Post-feeding activity of Lucilia sericata (Diptera: Calliphoridae) on common domestic indoor surfaces and its effect on development.

Developmental data of forensically important blowflies used by entomologists to estimate minimum post mortem interval (mPMI) are established under controlled laboratory conditions for various temperature ranges throughout the stages of egg, 1st-3rd instar, puparia, and adult fly emergence. However, environmental conditions may influence the patterns of development and behaviour of blowflies, potentially impacting on these established development rates. Previous studies investigating indoor colonisation have focused on the delay to oviposition, with behaviour during the post-feeding phase in this setting often overlooked. The environment in which third instar larvae disperse when searching for a pupariation site may vary drastically at both outdoor and indoor scenarios, influencing the activity and distance travelled during this phase and possibly affecting developmental rates. This study investigated the effect of eight common domestic indoor surfaces on dispersal time, distance travelled, and behaviour of post-feeding Lucilia sericata as well as any resulting variation in development. It was found that pupariation and puparia length within a pupariation medium of sawdust (often used in laboratory settings) produced comparable results with that of carpeted environments (those deemed to be 'enclosed'). Non-carpeted environments (those which were 'exposed') produced a delay to pupariation likely due to increased activity and energy expenditure in searching for pupariation sites which enabled burial. In addition, the observed speed of travel during dispersal was seen via time lapse photography to be greater within 'exposed' conditions. Larvae which dispersed upon burnt laminate flooring were observed to travel faster than in all other conditions and showed the only significant variation (P=0.04) in the day of emergence in comparison to the control condition of sawdust. This study has demonstrated that wandering phase activity is affected by the environmental surface which has potential implications for estimating both the distance travelled by dispersing larvae in indoor conditions and with further research, may be a consideration in mPMI calculations.

Changes in behaviour drive inter-annual variability in the at-sea distribution of northern gannets.

The at-sea distribution of seabirds primarily depends on the distance from their breeding colony, and the abundance, distribution and predictability of their prey, which are subject to strong spatial and temporal variation. Many seabirds have developed flexible foraging strategies to deal with this variation, such as increasing their foraging effort or switching to more predictable, less energy dense, prey, in poor conditions. These responses may vary both within and between individuals, and understanding this variability is vital to predict the population-level impacts of spatially explicit environmental disturbances, such as offshore windfarms. We conducted a multi-year tracking study in order to investigate the inter-annual variation in the foraging behaviour and location of a population of northern gannets breeding on Alderney in the English Channel. To do so, we investigated the link between individual-level behaviour and population-level behaviour. We found that a sample of gannets tracked in 2015 had longer trip durations, travelled further from the colony and had larger core foraging areas and home range areas than gannets tracked in previous years. This inter-annual variation may be associated with oceanographic conditions indexed by the North Atlantic Oscillation (NAO). Our findings suggest that this inter-annual variation was driven by individuals visiting larger areas in all of their trips rather than individuals diversifying to visit more, distinct areas. These findings suggest that, for gannets at least, if prey becomes less abundant or more widely distributed, more individuals may be required to forage further from the colony, thus increasing their likelihood of encountering pressures from spatially explicit anthropogenic disturbances.

Community variability and ecological functioning: 40 years of change in the North Sea benthos.

Using established associations between species traits (life history, morphological and behavioural characteristics) and key ecological functions, we applied biological traits analysis (BTA) to investigate the consequences of 40 years of change in two North Sea benthic communities. Ecological functioning (trait composition) was found to be statistically indistinguishable across periods that differed significantly in taxonomic composition. A temporary alteration to functioning was, however, inferred at both sampling stations; coinciding with the North Sea regime shift of the 1980s. Trait composition recovered after 1 year at the station located inside the grounds of a trawl fishery, whereas the station located outside the main area of fishing activity underwent a six-year period of significantly altered, and temporally unstable, trait composition. A further alteration to functioning was inferred at the fished station, when the population of a newly established species rapidly increased in numbers. The results suggest that density compensation by characteristically similar (redundant) taxa acts to buffer changes to ecological functioning over time, but that functional stability is subject to aperiodic disruption due to substitutions of dissimilar taxa or uncompensated population fluctuations. The rate at which ecological functioning stabilises and recovers appears to be dependent on environmental context; e.g. disturbance regime.

Psychotherapy for the treatment of depression: a comprehensive review of controlled outcome research.

Previous quantitative reviews of research on the efficacy of psychotherapy for depression have included only a subset of the available research or limited their focus to a single outcome measure. The present review offers a more comprehensive quantitative integration of this literature. Using studies that compared psychotherapy with either no treatment or another form of treatment, this article assesses (a) the overall effectiveness of psychotherapy for depressed clients, (b) its effectiveness relative to pharmacotherapy, and (c) the clinical significance of treatment outcomes. Findings from the review confirm that depressed clients benefit substantially from psychotherapy, and these gains appear comparable to those observed with pharmacotherapy. Initial analysis suggested some differences in the efficacy of various types of treatment; however, once the influence of investigator allegiance was removed, there remained no evidence for the relative superiority of any 1 approach. In view of these results, the focus of future research should be less on differentiating among psychotherapies for depression than on identifying the factors responsible for improvement.

Lowering the calcium concentration in St. Thomas' Hospital cardioplegic solution improves protection during hypothermic ischemia.

The concentration of calcium (1.2 mmol/L) in clinical St. Thomas' Hospital cardioplegic solution was chosen several years ago after dose-response studies in the normothermic isolated heart. However, recent studies with creatine phosphate in St. Thomas' Hospital solution demonstrated that additional myocardial protection during hypothermia resulted principally from its calcium-lowering effect in the solution. The isolated working rat heart model was therefore used to establish the optimal calcium concentration in St. Thomas' Hospital solution during lengthy hypothermic ischemia (20 degrees C, 300 minutes). The calcium content of standard St. Thomas' Hospital solution was varied from 0.0 to 1.5 mmol/L in eight treatment groups (n = 6 for each group). During ischemia, hearts were exposed to multidose cardioplegia (3 minutes every 30 minutes). Postischemic recovery of function was expressed as a percentage of preischemic control values. Release of creatine kinase and the time to return of sinus rhythm during the reperfusion period were also measured. These dose-response studies during hypothermic ischemia revealed a broad range of acceptable calcium concentrations (0.3 to 0.9 mmol/L), which appear optimal in St. Thomas' Hospital solution at 0.6 mmol/L. This concentration improved the postischemic recovery of aortic flow from 22.0% +/- 5.9% with control St. Thomas' Hospital solution (calcium concentration 1.2 mmol/L) to 86.0% +/- 4.0% (p less than 0.001). Other indices of functional recovery showed similar dramatic results. Creatine kinase release was reduced 84% (p less than 0.01) in the optimal calcium group. Postischemic reperfusion arrhythmias were diminished with the loser calcium concentration, with a significant decrease in the time between initial reperfusion until the return of sinus rhythm. In contrast, acalcemic St. Thomas' Hospital solution precipitated the calcium paradox with massive enzyme release and no functional recovery. Unlike prior published calcium dose-response studies at normothermia, these results demonstrate that the optimal calcium concentration during clinically relevant hypothermic ischemia is considerably lower than that of normal serum ionized calcium (1.2 mmol/L) and appears ideal at 0.6 mmol/L to realize even greater cardioprotective and antiarrhythmic effects with St. Thomas' Hospital solution.

Pleural tenting during upper lobectomy decreases chest tube time and total hospitalization days.

OBJECTIVE: A prolonged air leak after an upper lobectomy is a major determinant of morbidity and hospital stay. Creation of a pleural tent after upper lobectomy was used to investigate whether obliterating the usual postoperative intrapleural apical space with the parietal pleura would help shorten chest tube time. METHODS: From August, 1994, through January, 1997, 48 consecutive patients undergoing an isolated upper lobectomy for a neoplasm were reviewed. Twenty-eight patients had creation of a pleural tent and 20 patients did not. Demographic and clinical profiles of both groups were not significantly different. Chest tubes were removed when there was no air leak for 48 hours and chest tube drainage was less than 75 ml per 8 hours. RESULTS: The tented patients had significantly shorter mean air leak (tented 1.6 +/- 0.3 days vs nontented 3.9 +/- 1.2 days, p = 0.04), mean chest tube total drainage (tented 1619.5 +/- 95.5 ml vs nontented 2476.3 +/- 346.4 ml, p = 0.009), mean chest tube duration (tented 4.0 +/- 0.2 days vs nontented 6.6 +/- 1.0 days, p = 0.004), mean total hospitalization time (tented 6.4 +/- 0.4 days vs nontented 8.6 +/- 1.0 days, p = 0.02). No operative deaths occurred. Morbidity was not significantly different between groups. CONCLUSIONS: (1) Creation of a pleural tent at the time of upper lobectomy appears to significantly reduce chest tube time and shorten hospitalization. (2) No morbidity or mortality was associated with this simple, quick procedure. (3) Surgeons should consider creation of a pleural tent at the time of upper lobectomy.

Localized pleural mesothelioma. The clinical spectrum.

Localized pleural mesotheliomas are rare tumors that have a variety of clinical presentations, from an asymptomatic solitary nodule to a massive, highly symptomatic neoplasm filling most of the pleural cavity. Two cases are reported which show the clinical spectrum of the more common benign variant. The clinical differentiation between the benign tumor as well as the less frequent malignant neoplasms of localized mesotheliomas has been disappointing. Complete surgical resection is the preferred treatment for both types and is usually curative with the benign mesothelioma.

The potential hazard of particulate contamination of cardioplegic solutions.

The potential hazard of particulate debris in unfiltered cardioplegic solutions was assessed using the isolated rat heart preparation. Five intravenous solutions were evaluated: These were manufactured by three pharmaceutical firms (two United States and one British) and are commonly used as bases for preparing clinical cardioplegic solutions. Particles were counted in each solution, and each fell well within the limits for particle contamination defined by both the United States and the British Pharmacopoeias. Intracoronary continuous infusion of each solution over 20 minutes at constant temperature and pressure (20 degrees C, 60 cm H2O) resulted in a progressive reduction in coronary flow (mean reduction 55.7% +/- 6.6%) due to a rise in coronary vascular resistance; filtration of these same solutions through a 0.8 micron filter just prior to their entry into the heart largely prevented these coronary vascular changes. The filter was examined by scanning electron microscopy and showed amorphous and crystalline debris. Nifedipine (0.1 mumol/L) added to the cardioplegic solution reduced by almost 50% the impairment in coronary flow seen in the unfiltered group. In more clinically relevant studies of 180 minutes of hypothermic (20 degrees C) ischemia using multidose cardioplegia (3 minutes every 30 minutes), hearts infused with filtered solution recovered almost 90% of their preischemic functional capacity. Hearts receiving identical but unfiltered solution, however, essentially failed to recover (p less than 0.001) and had significantly higher levels of creatine kinase leakage. These results suggest that commercially produced solutions conforming to limits of particulate contamination acceptable for intravenous administration may prove harmful if given unfiltered directly into coronary arteries, with the likely mechanism of action being particle-induced coronary vasoconstriction.

Creatine phosphate: an additive myocardial protective and antiarrhythmic agent in cardioplegia.

The potential for enhancing myocardial protection by adding high-energy phosphates to cardioplegic solutions was investigated in a rat heart model of cardiopulmonary bypass and ischemic arrest. Creatine phosphate (CP) was evaluated as an additive to the St. Thomas' Hospital cardioplegic solution. Dose-response studies (CP 0 to 50 mmol/L) revealed 10.0 mmol/L as the optimal concentration which improved recovery of aortic flow and cardiac output after a 40 minute period of normothermic (37 degrees C) ischemic arrest from 21.2% +/- 5.4% and 32.8% +/- 4.6% in the CP-free control group to 82.5% +/- 3.7% and 82.6% +/- 4.2% (p less than 0.001), respectively. Creatine kinase (CK) leakage was reduced by 68.7% (p less than 0.001) in the CP group. With hypothermic (20 degrees C) ischemia (240 minutes) and multidose (every 30 minutes) cardioplegia, recoveries of aortic flow and cardiac output were improved from 33.1% +/- 8.4% and 42.2% +/- 7.7% in the CP-free control group to 77.9% +/- 4.2% and 79.6% +/- 4.3% (p less than 0.001), respectively, in the drug group. In addition to improving function and decreasing CK release, CP reduced reperfusion arrhythmias, significantly decreasing the time between cross-clamp removal and return of regular rhythm and also completely obviating the need for electrical defibrillation. 51Chromium-ethylenediaminetetraacetic acid (51Cr-EDTA), an extracellular space marker, was used to study the disappearance of CP from the cardioplegic solution during its stasis in the heart. Upon reperfusion, two thirds of the infused dose appeared unchanged in the coronary effluent; the remainder was either degraded or accumulated by the myocardium. Despite its alleged inability to enter the myocardial cell, exogenous CP exerts potent protective and antiarrhythmic effects when added to the St. Thomas' Hospital cardioplegic solution. Although the mechanism of action remains to be elucidated, it may involve binding or uptake of the drug.

Enhanced myocardial protection with high-energy phosphates in St. Thomas' Hospital cardioplegic solution. Synergism of adenosine triphosphate and creatine phosphate.

The potential for improving myocardial protection with the high-energy phosphates adenosine triphosphate and creatine phosphate was evaluated by adding them to the St. Thomas' Hospital cardioplegic solution in the isolated, working rat heart model of cardiopulmonary bypass and ischemic arrest. Dose-response studies with an adenosine triphosphate range of 0.05 to 10.0 mmol/L showed 0.1 mmol/L to be the optimal concentration for recovery of aortic flow and cardiac output after 40 minutes of normothermic (37 degrees C) ischemic arrest (from 24.1% +/- 4.4% and 35.9% +/- 4.1% in the unmodified cardioplegia group to 62.6% +/- 4.7% and 71.0% +/- 3.0%, respectively, p less than 0.001). Adenosine triphosphate at its optimal concentration (0.1 mmol/L) also reduced creatine kinase leakage by 39% (p less than 0.001). Postischemic arrhythmias were also significantly reduced, which obviated the need for electrical defibrillation and reduced the time to return of regular rhythm from 7.9 +/- 2.0 minutes in the control group to 3.5 +/- 0.4 minutes in the adenosine triphosphate group. Under more clinically relevant conditions of hypothermic ischemia (20 degrees C, 270 minutes) with multidose (every 30 minutes) cardioplegia, adenosine triphosphate addition improved postischemic recovery of aortic flow and cardiac output from control values of 26.8% +/- 8.4% and 35.4% +/- 6.3% to 58.0% +/- 4.7% and 64.4% +/- 3.7% (p less than 0.01), respectively, and creatine kinase leakage was significantly reduced. Parallel hypothermic ischemia studies (270 minutes, 20 degrees C) using the previously demonstrated optimal creatinine phosphate concentration (10.0 mmol/L) gave nearly identical improvements in recovery and enzyme leakage. The combination of the optimal concentrations of adenosine triphosphate and creatine phosphate resulted in even greater myocardial protection; aortic flow and cardiac output improved from their control values of 26.8% +/- 8.4% and 35.4% +/- 6.3% to 79.7% +/- 1.1 and 80.7% +/- 1.0% (p less than 0.001), respectively. In conclusion, both extracellular adenosine triphosphate and creatine phosphate alone markedly improve the cardioprotective properties of the St. Thomas' Hospital cardioplegic solution during prolonged hypothermic ischemic arrest, but together they act additively to provide even greater protection.

Particle-induced coronary vasoconstriction during cardioplegic infusion. Characterization and possible mechanisms.

We have characterized an isolated rat heart preparation in which particles induce transient coronary vasoconstriction. Exploiting the fact that all commercially available intravenous solutions contain permissible levels of contaminant particles (usually 2 to 20 micron in diameter), we investigated whether these particles have any adverse effect upon coronary flow. A commercially available intravenous solution was modified to produce the St. Thomas' Hospital cardioplegic solution. Constant-pressure infusion of this solution over a 20 minute period caused a 46.2% +/- 5.1% reduction in coronary flow. This flow impairment could be limited to 13.3% +/- 3.5% by the incorporation of a 0.8 micron in-line filter. In hearts perfused with particle-containing solution followed by ultrafiltered solutions, the impairment of coronary flow was reversed within 1 minute. This quick reversal indicates that the particles were impairing flow not by physical occlusion of vessels but by triggering some form of transient vasoconstriction. In studies with filters of varying porosity (between 0.8 and 15.0 micron), the phenomenon was shown to be attributable to relatively small numbers of particles greater than 10.0 micron in diameter. In studies of myocardial protection, it was shown that the impairment of solution delivery and distribution caused by particles could severely reduce the protective properties of a chemical cardioplegic solution; hearts subjected to 180 minutes of hypothermic (20 degrees C) ischemic arrest with multidose (3 minutes every 30 minutes) cardioplegia recovered almost completely upon reperfusion if a filtered (0.8 micron) solution was used, but failed to recover when unfiltered, commercially prepared solutions were used. In an attempt to define the mechanisms underlying the particle-induced vasoconstriction, we conducted dose-response studies in which various vasoactive agents were used in an attempt to combat the effects of the particles. At their optimal concentrations, procaine (10.0 mmol/L), nifedipine (0.1 mumol/L), and adenosine triphosphate (1.0 mmol/L) completely prevented the problem; lidocaine and dipyridamole partially alleviated the effect; verapamil and isosorbide dinitrate were ineffective. These results indicate that several mechanisms acting at a small vessel level might contribute to the particle-induced vasoconstriction.

Pulmonary resection for invasive Aspergillus infections in immunocompromised patients.

Standard antifungal medical therapy of invasive pulmonary aspergillosis that occurs in immunocompromised patients with hematologic diseases with neutropenia or in liver transplant recipients results in less than a 5% survival. In view of these dismal mortality rates, we adopted an aggressive approach with resection of the involved area of lung along with systemic antifungal therapy when localized invasive pulmonary aspergillosis developed in these patients. Between January 1987 and December 1993, 14 patients with hematologic diseases and 2 liver transplant recipients underwent resection of acute localized pulmonary masses suggestive of invasive pulmonary aspergillosis a median of 7.5 days (range 1 to 45 days) after the diagnosis was clinically suggested and confirmed by chest computed tomographic scans. Operative procedures done included two pneumonectomies, one bilobectomy with limited thoracoplasty, nine lobectomies, and five wedge resections (one patient with hematologic disease had two procedures). All patients were treated before and after the operation with antifungal agents. Nine (64%) of 14 patients with hematologic disease and 2 (100%) of 2 liver transplant recipients survived the hospitalization with no evidence of recurrent Aspergillus infection after a median 8 months of follow-up (range 3 to 82 months). The five hospital deaths (all patients with hematologic diseases) occurred a median of 20 days after operation from diffuse alveolar hemorrhage in three, graft-versus-host disease in one, and multiple organ system failure with presumed disseminated Aspergillus infection in one. Four of the five deaths were in patients with allogeneic bone marrow transplants. Two of the three patients requiring resection of multiple foci of infection died, as did the only patient who was preoperatively ventilator dependent. In immunocompromised patients with hematologic diseases or liver transplantation with invasive pulmonary aspergillosis, early pulmonary resection should be strongly considered when the characteristic clinical and radiographic pictures appear.