Study of B-cell subpopulations in lung transplant recipients with posttransplant infection.

BACKGROUND: Posttransplant infection after lung transplantation is a common feature due to the immunodeficiency induced by the immunosuppressive load. AIM: To assess B-cell subsets in lung transplant recipients suffering at least one episode of infection within the first year posttransplantation. METHODS: Twenty-eight lung transplant recipients were enrolled in the study. Their overall mean age was 56.6 ± 10.7 years and 10 were women (35.7%). All recipients were treated with steroids, tacrolimus, and mycophenolate mofetil. B-cell subset levels were measured in peripheral blood before as well as 7, 14, 30, 60, 90, and 180 days posttransplantation. RESULTS: No difference in the absolute number of B-cell subsets was observed within the first year of follow-up. However, pre-germinal center-activated naïve B cells (Bm2'), defined as IgD(+)CD38(++), were increased among patients displaying infections within the first year. The increased Bm2' subset was accompanied by a decrease in the double negative (CD27(-)IgD(-)) B-cell population. CONCLUSION: Infections in lung transplant recipients were associated with an increase in the Bm2' subset even before transplantation. It is possible that Bm2' cells have a role in response to infection in lung transplantation.

[Lung transplantation using donors 55 years and older]. / Trasplante pulmonar con donantes de edad marginal (≥ 55 años).

OBJECTIVE: We analyzed short, medium and long-term mortality in transplant recipients who received lungs from donors aged 55 years or more. PATIENTS AND METHODS: All patients who underwent lung transplantation from donors aged 55 years or more were included. The association between the different study variables and early death and death at 1 year and 5 years was studied. A logistic regression model was used to study the association between early death and variables with a trend towards significance (P<.2) in the bivariate analysis. The risk factors for mortality at 1 year and 5 years were analyzed with a Cox regression model. The Kaplan-Meier method was used to analyze survival. RESULTS: A total of 33 patients were included. The probability of survival was 90.9%, 78.5% and 44.8% at 1 month, 1 year, and 5 years after lung transplantation, respectively. The elevated age of the recipient (P=.16) and single-lung transplantation (P=.09) were the variables associated to or with a trend towards significant associations with mortality. CONCLUSIONS: The final decision to accept a lung graft should be based on individual evaluation of each donor and recipient. However, given the lack of lung donors, donors aged 55 years or more should be considered for lung transplantation.

Is exposure temperature a confounding factor for the assessment of reproductive parameters of New Zealand mudsnails Potamopyrgus antipodarum (Gray)?

Potamopyrgus antipodarum is a promising test organism often used in ecotoxicology testing, both in laboratory and in field exposure experiments. It has been recommended for use in the development of an OECD reproduction test. However, exposure temperature is important to take into account when assessing reproduction and related biomarkers, because it can act as a confounding factor inducing variability in physiological values. The effect of three environmentally realistic exposure temperatures (8, 16 and 24°C) was examined with respect to the number of neonates born, the number of embryos in the brood pouch and the duration of embryonic development. We also measured additional markers likely to be related to the modulation of reproductive performance, such as vertebrate-like sex steroid, energy status and vitellin-like proteins. Exposure temperature had a significant effect on reproduction in P. antipodarum, on both the duration of embryonic development and the quantity of embryos and neonates. The consequences of these observations must not be neglected when using this species in laboratory and field experiments. This study determined suitable temperatures for field experiments and a mean duration for embryonic development independent of temperature. In addition to steroid levels, energy status and Vn-like protein levels were only slightly modified by exposure temperature between 8 and 24°C. Thus, they can be easily implemented and their variations related to anthropogenic factors during field exposure of mudsnails.

Comprehensive biological effects of a complex field poly-metallic pollution gradient on the New Zealand mudsnail Potamopyrgus antipodarum (Gray).

The Lot River is known to be contaminated by metals, mainly cadmium and zinc, due to a former Zn ore treatment plant in the watershed of the Riou-Mort, a tributary of the Lot River. Many studies have been performed to characterize contamination, but few have assessed its consequences on the biological responses of organisms along the gradient. We exposed adult and juvenile New Zealand freshwater mudsnails Potamopyrgus antipodarum at several sites along the gradient of metal contamination for 28 days. Biological responses were monitored at different levels: individual (survival, growth and fecundity), tissue and biochemical (energy status and vertebrate-like sex steroid levels) to better understand the toxicity mechanisms involved. Accumulation of Cd and Zn was high during exposure. Most of the biological effects observed could be linked to this contamination and were concentration-dependent. Histological lesions of the digestive gland were observed, with hypertrophy of calcium cells and vacuolization of digestive cells. Such effects are likely to explain the decrease of energy status (triglycerides and proteins), juvenile growth and adult fecundity observed at the most polluted site. However the magnitude of the fall in fecundity cannot be attributed only to these tissular effects, indicating another mode of action of Cd or possible confounding factors. Steroid accumulation in snails indicated only organic pollution. Histopathological effects proved the most sensitive endpoint to metal (Cd and Zn) contamination.

Sensitivity of New Zealand mudsnail Potamopyrgus antipodarum (Gray) to a specific aromatase inhibitor.

The freshwater prosobranch Potamopyrgus antipodarum (Molluska, Hydrobiidea, Smith 1889) has been proposed as a suitable species to assess the impact of endocrine disrupting compounds (EDC) in aquatic ecosystems. Steroid hormone biosynthesis pathway is potentially an important target for EDC, and vertebrate-like sex steroids seem to play a functional role in the control of mollusk reproduction. To assess the response and the sensitivity of P. antipodarum to disrupters of the steroid hormone biosynthesis pathway, we have experienced the action of a specific vertebrate aromatase inhibitor, fadrozole, acting on 17beta-estradiol synthesis in two separate 28 and 42d exposures. Fadrozole had effects consistent with the expected mechanism of action. A decrease of the reproduction parameters (such as on the number of neonates and number of embryos in the brood pouch) in a dose-dependant manner was observed. The steroids levels were also impaired with the ratio 17beta-estradiol/testosterone decreased by half in exposed snails. This shift of the steroids balance was accompanied by some alteration in the gonads histology and immunohistochemistry in fadrozole-exposed snails. This study highlights the value role of P. antipodarum as a test species for assessing EDC effects in aquatic wildlife.

Effects of fluoxetine on the reproduction of two prosobranch mollusks: Potamopyrgus antipodarum and Valvata piscinalis.

Fluoxetine is a widely used antidepressant, frequently found in aquatic ecosystems. We investigated its effects on two freshwater prosobranch gastropods: Valvata piscinalis (European valve snail) and Potamopyrgus antipodarum (New Zealand mudsnail), which have different reproductive modes. The fecundity of V. piscinalis (cumulate number of eggs at day 42) was not affected with an NOEC of 100 mvg/L nominal concentration (69 microg/L measured concentration). The mudsnail P. antipodarum responded in a biphasic dose-effect curve at low concentrations. The cumulate number of neonates at day 42 had an LOEC of 100 microg/L (69 microg/L) and an NOEC of 33.3 microg/L (13 microg/L), whereas the embryos in the brood pouch at day 42 only showed an LOEC of 3.7 microg/L (1 microg/L). We also observed histological effects in P. antipodarum (gonadal thickness). Among the sexual steroids we measured only testosterone which varied, independent of reproduction. Moreover the use of two closely related species highlights the interspecific variability.

Fluoxetine effects assessment on the life cycle of aquatic invertebrates.

Fluoxetine is a serotonin re-uptake inhibitor, generally used as an antidepressant. It is suspected to provoke substantial effects in the aquatic environment. This study reports the effects of fluoxetine on the life cycle of four invertebrate species, Daphnia magna, Hyalella azteca and the snail Potamopyrgus antipodarum exposed to fluoxetine spiked-water and the midge Chironomus riparius exposed to fluoxetine-spiked sediments. For D. magna, a multi-generational study was performed with exposition of newborns from exposed organisms. Effects of fluoxetine could be found at low measured concentrations (around 10microgl(-1)), especially for parthenogenetic reproduction of D. magna and P. antipodarum. For daphnids, newborns length was impacted by fluoxetine and the second generation of exposed individuals showed much more pronounced effects than the first one, with a NOEC of 8.9microgl(-1). For P. antipodarum, significant decrease of reproduction was found for concentrations around 10microgl(-1). In contrast, we found no effect on the reproduction of H. azteca but a significant effect on growth, which resulted in a NOEC of 33microgl(-1), expressed in nominal concentration. No effect on C. riparius could be found for measured concentrations up to 59.5mgkg(-1). General mechanistic energy-based models showed poor relevance for data analysis, which suggests that fluoxetine targets specific mechanisms of reproduction.

Physiological and behavioural responses of Gammarus pulex (Crustacea: Amphipoda) exposed to cadmium.

The aim of this study was to investigate the effects of cadmium on physiological and behavioural responses in Gammarus pulex. In a first experiment, cadmium LC50s for different times were evaluated in 264 h experiment under continuous mode of exposure (LC50(96 h)=82.1 microgL(-1), LC50(120 h)=37.1 microgL(-1), LC50(168 h)=21.6 microgL(-1), LC50(264 h)=10.5 microgL(-1)). In a second experiment, the physiological and behavioural responses of the amphipod exposed to cadmium (0, 7.5 and 15 microgL(-1)) were investigated under laboratory conditions. The mortality and the whole body cadmium concentration of organisms exposed to cadmium were significantly higher than in controls. Concerning physiological responses, cadmium exposure exerted a significant decrease on osmolality and haemolymph Ca(2+) concentration, but not on haemolymph Na(+) and Cl(-) concentrations, whereas the Na(+)/K(+)-ATPase activity was significantly increased. Behavioural responses, such as feeding rate, locomotor and ventilatory activities, were significantly reduced in Cd exposed organisms. Mechanism of cadmium action and consequent energetic reallocation in favour of maintenance functions (i.e., osmoregulation) are discussed. The results of this study indicate that osmolality and locomotor activity in G. pulex could be effective ecophysiological/behavioural markers to monitor freshwater ecosystem and to assess the health of organisms.

Energy-based modeling to study population growth rate and production for the midge Chironomus riparius in ecotoxicological risk assessment.

Effects of toxicants are commonly assessed at individual level, whereas the aim of ecotoxicology is to protect ecosystems. We recently built energy-based models to describe and predict growth, emergence and reproduction of the midge Chironomus riparius [Péry (2002) Environ. Toxicol. Chem. 21, 2507-13]. Here we use these models to derive effects at the population level from effects at individual levels. The first endpoint we consider is population growth rate, which is a commonly studied endpoint at the population level. This parameter is informative relative to the risk of disappearance of the population. We also examined the production of organisms per generation or per time unity at population equilibrium, the study of which is allowed by our models and accounts for energy transfers. Such a study is crucial to predict effects on ecosystems, for species of the Chironomidae are keystone species, being the main food source of many other species, including birds and fish. We show in our study that the disappearance of the population can only occur in cases of very severe toxicity (99% decrease of reproduction, more than 97% mortality during a 10 days survival test or a difference of mean emergence times between males and females of more than 10 days). Concerning production of organisms, we show that reproduction decrease has little effect on it, that mortality of young larvae has an impact that cannot be neglected and that mortality of old larvae and delay of emergence has a strong effect. Our study suggests that bioassays should focus on an EC50 for reproduction, a LC30 for young instars, and a No Effect Concentration for old instars (growth and mortality) to prevent effects at the population level.

Influence of preservation solution on early lung function (Euro-Collins vs Perfadex).

BACKGROUND: This clinical study was performed to evaluate the efficiency of 2 different preservation solutions (Euro-Collins [EC] vs Perfadex [P]) on organ function in human lung transplantation. METHODS: The donor lungs for 46 patients were flushed either with EC solution (25 cases, EC group) or Perfadex (21 cases, P group). Transplant function was assayed using PaO2/FiO2 ratio after transplantation upon intensive care unit (ICU) arrival and at 12 and 24 hours later (T1, T2, and T3, respectively). We also compared the duration of mechanical ventilatory support and ICU stay. RESULTS: The PO2/FiO2 ratio was significantly better in the P than EC group at T1, T2, and T3. The duration of mechanical ventilatory support and ICU stay were lower also in P group, whereas age, sex, aetiology of lung disease, donor, PaO2/FiO2 ratio, and ischemia time did not show differences between the 2 groups. CONCLUSIONS: Our data on graft function tend to confirm better graft preservation using the P preservation solution.

Survival tests with Chironomus riparius exposed to spiked sediments can profit from DEBtox model.

DEBtox model is a biologically based model used to analyse aquatic toxicity data (The analysis of aquatic toxicity data, VU University Press, Amsterdam, The Netherlands, 1996, 149pp.). To date, it has not been used to analyse sediment survival tests, mainly because this would require daily counting of survivors, which is difficult for benthic organisms. In the present study, we adapted survival toxicity tests with the midge Chironomus riparius to permit survival data analysis with DEBtox. To validate the adaptation proposed, we exposed organisms to two chemicals, copper and methiocarb. We exposed larvae of second, third and fourth instar to different concentrations of the tested compounds and two different diets to assess the influence of diet and instar on DEBtox parameter estimates. Daily counting of organisms did not affect survival and did not lead to much more effort when compared to usual tests. Moreover, the analysis profited much from use of the DEBtox model. It was possible, with only survival data to estimate and validate the kinetics of the compounds, to predict survival during the recovery of exposed organisms and to assess the influence of food availability on toxicity. Food availability did not influence methiocarb toxicity, but copper was more toxic to food-limited organisms when a threshold concentration was exceeded. Comparison of parameters estimate also helped in understanding the differences in toxicity responses between instars. For the two compounds we studied, the difference was entirely explained by differences in threshold values.

[Reimplantation edema in the transplanted lung. Reperfusion-ischemia or hydrostatic edema?]. / Edema de reimplantación en el trasplante pulmonar. ¿Isquemia-reperfusión o edema hidrostático?

The development of non cardiogenic pulmonary edema or pulmonary reimplantation response after lung transplantation has been well described. The cause is ischemic vascular injury of the allograft, results in increased permeability of the lung after reperfusion, in turn leading to interstitial and alveolar edema. We report two cases of pulmonary reimplantation response after bilateral sequential lung transplantation. Massive pink frothy fluid was noted in the orifice of the double-lumen endobronchial tube. Blood and endobronchial fluid samples were collected for protein electrophoresis. We conclude that, in spite of the severity of reimplantation response, this complication can be resolved early when the cause is mainly hydrostatic.

[Changes in PCO2 and pH gradients in a canine model of experimental acute hemorrhage]. / Modificaciones de las diferencias arteriovenosas de PCO2 (Da-vPCO2) y pH (Da-vpH) en un modelo experimental canino de hemorragia aguda.

OBJECTIVE: To study changes in arterial-venous PCO2 pressures (Da-vPCO2) and in pH (Da-vpH) in an experimental dog model of acute bleeding. To emphasize the utility of monitoring these variables in situations of acute bleeding. ANIMALS AND METHOD: Eighteen dogs were anesthesized and monitored while being subjected to gradual bleeding. Gasometric and hemodynamic variables were recorded at the following moments: baseline, stage I (15% of volemic loss), stage Ib (20%), stage II (25%), stage IIb (30%) and stage III (35%). RESULTS: No significant differences in pH or PCO2 in either arterial or mixed venous blood were found. Bleeding induced a constant and progressive increase in Da-vPCO2 that correlated with changes in volume (r = -0.56, p < 0.001), SvO2 (r = 0.71; p < 0.001), Da-vO2 gradient (r = 0.62; p < 0.001) and cardiac output (r = 0.63; p < 0.001). CONCLUSIONS: Gradual bleeding caused a constant and significant increase of Da-vPCO2. Monitoring such changes in states of circulatory insufficiency may be useful for evaluating tissue ischemia.

[Heart rupture following thoracic blunt trauma]. / Rotura cardíaca tras traumatismo torácico cerrado.

We describe a 39-year-old woman who suffered rupture of the left auricula as a result of a non-penetrating chest wound received in a traffic accident. Rupture of the heart chambers after trauma is not infrequent, but survival is extremely rare. The patient was released from care and has suffered no subsequent complications.

Managing the termination of a hospital system from your provider network: a case study.

In 1992, a decision was reached by Medica Choice, a large open-access HMO with over 350,000 members, to terminate their contact with a large five-hospital system. In this article, the authors discuss the details of this termination, identify the organizational strategies for successfully managing the contract termination of a major hospital system from a health plan's provider network, attempt to identify the possible pitfalls in managing such a transition, and offer suggested guidelines for tactical planning for similar situations.