Opportunities and limits of commercial farm data to study the genetic determinism of feed efficiency throughout lactation in dairy sheep.

The collective economic and environmental interest of the whole dairy sheep sector is to reduce feed costs and the negative impact of milk production on the environment. Thus, this study focused on the characterisation and genetic selection potential of feed efficiency in the Lacaune breed. Estimates for feed efficiency in dairy ewes are limited, mainly due to a lack of individual feed intake measurements in the sheepfold or in the pasture. We estimated the genetic parameters for two approximated (not entirely based on individual data) feed efficiency traits (lactation feed conversion ratio (LFCR) and residual energy intake (REI)) and daily milk yield (DMY) at different stages of lactation and throughout lactation. The accuracy of the efficiency traits was first evaluated on samples from Lacaune dairy ewes that were monitored individually, especially for their feed intake. Then, feed efficiency estimation methods were applied on eight commercial farms corresponding to 4 680 Lacaune dairy ewes over two milk lactations (30 854 records). Animals were collectively (for a large part of feed intake) or individually (for milk performance and dynamics of body fat reserves) monitored at different lactation stages. The heritabilities of LFCR and REI were estimated over lactations at 0.10 ± 0.01 and 0.11 ± 0.01, respectively. High genetic correlations were observed between the two efficiency traits and milk production traits, with a genetic correlation between LFCR and DMY of 0.74 ± 0.04 and between REI and DMY of -0.79 ± 0.04. A strong influence of environmental factors such as farm, year of milk production and lactation stage affected the genetic link between REI and milk production traits. Efficiency values observed in early lactation when animals were bred in the sheepfold were less genetically correlated with values obtained later in lactation when animals were grass-fed. However, individual characterisation of feed efficiency remains difficult due to the collective feeding context in dairy ewe farms.

Alternative hormone-free reproduction management of a dairy sheep flock disrupts the farm's annual feeding system calendar and its associated strategies.

Hormone-free (HF) reproduction in dairy sheep is a way to meet current societal demands, but it requires being prepared for collateral impacts on related system components. The efficiency of HF practices (e.g., using the male effect for estrus induction and synchronization) is uncertain compared with hormonal treatment (HT). For example, these practices can lead to higher variability in the flock physiological stage patterns throughout the year, which has direct consequences for feeding regimens. The objective of this work was to simulate the impacts of HF reproduction management, including artificial insemination (AI), on the temporal distribution of productive performance and nutritional requirements of a conventional dairy sheep flock. Using the REPROsheep2.0 model, 6 scenarios were compared over one typical production season for the same flock (n = 597 Lacaune ewes) intensively reared in the Roquefort region of France. These scenarios depicted reproduction with HT and AI in mid-May (Early); HT and AI in July (Summer Late); HT and AI in November (Autumn Late); and their HF versions (HF-Early; HF-Summer Late, and HF-Autumn Late, respectively). In all HF scenarios, a reduction in the number of ewes lambing and consequently in the annual milk production of the farm was observed (-1 to -7%). This affected annual performance with a subsequent decrease of total annual nutritional requirements (-2 to -6%). The HF scenarios resulted in a staggering of lambing events with a 7- to 14-d shift in the appearance of milk production peaks and related nutritional requirements compared with the HT scenarios. Transitioning from conventional to HF reproduction management, while preserving AI, would increase farm workload, lengthen milking period operations, and necessitate a readjustment of feeding management strategies with regard to available feed resources. Depending on the production season, the observed delay in the distribution of nutritional requirements could be either an attractive or an unfavorable outcome for farmers. The delay may be concordant, for example, with the recently observed impacts of climate change on seasonal forage availability in Mediterranean regions (less spring herbage production and warmer temperatures) that are affecting farmers' decision-making about the most efficient use of forage and feed resources.

Measuring liveweight changes in lactating dairy ewes with an automated walk-over-weighing system.

Monitoring liveweight (LW) is an important part of sound management practices at the individual and flock level (e.g., controlling for nutritional status based on body condition, reproduction, and health-related issues), but it is time consuming and stressful. To our knowledge, no literature has reported on the evaluation of automated weighing systems in dairy sheep as an alternative to conventional static scales. The objective of this research was to evaluate the practical feasibility of using an automated walk-over-weighing (WoW) prototype to measure daily LW changes in dairy ewes without human intervention. We used adult Lacaune dairy ewes in 2 complementary trials conducted indoors. Trial 1 aimed at evaluating the repeatability, precision, and accuracy of LW measures recorded using WoW scales compared with a static scale (the gold standard). Forty-two adult ewes (LW ± standard deviation = 71.3 ± 10.4 kg) were randomly drafted from the main flock and used in a 1-day session. The trial included 3 passages. In each passage, ewes were weighed first on a static scale; once a static position was achieved and LW recorded, they continued the circuit and immediately traversed the WoW scale for an automated LW record. Trial 2 aimed to demonstrate the feasibility of using the WoW device under real-world conditions in a dairy sheep-farming system. The WoW scale was installed in the exit race of the milking parlor and evaluated over 7 wk with adult ewes in mid lactation (n = 93; LW 78.5 ± 8.1 kg). Once the ewes were acclimated to the WoW system, 1 group of ewes (n = 48) continued to receive the same feeding regimen (controls), and the other group (n = 45) underwent a nutritional challenge [challenged; 2 wk of undernutrition and then back to control regimen (refeeding) for 1 wk]. We evaluated the ability of the WoW to detect small changes in LW. We collected LW data (2 weighings per ewe per day) from the WoW after each of the 2 milking sessions (morning and evening). We also obtained LW values by weighing the ewes using a static scale once a week. The automated WoW system showed substantial agreement with the gold standard when assessed using Lin's concordance correlation coefficient and Bland and Altman's method, largely due to high repeatability. The WoW system was adequate for detecting small daily variations in LW during undernutrition and refeeding periods. Misbehaviors resulted in spurious WoW values in trial 2, requiring us to use filtration methods to exclude outlier weights and allow meaningful assessment of small LW changes. The WoW system evaluated here is an alternative to the static scales conventionally used on dairy sheep farms. If sound filtration of raw data is applied, WoW could contribute to the close (daily) monitoring of individual LW without operator intervention (i.e., voluntary weighing) and taking animal welfare into account (i.e., no stress related to the weighing session on static scales).

An assessment of Walk-over-Weighing to estimate short-term individual forage intake in sheep.

The main limitation for determining feed efficiency of freely grazing ruminants is measurement of daily individual feed intake. This paper describes an investigation that assessed a method for estimating intake of forage based on changes in BW of ewes. A total of 24 dry and non-pregnant Romane ewes (12 hoggets, HOG; mean±SD 51.8±2.8 kg BW; body condition score (BCS) 2.6±0.2; and 12 adults, ADU; 60.4±8.5 kg BW; BCS 2.7±0.8) were selected for the study and moved from their rangeland system to a confined pen with controlled conditions and equipped with individual automatic feeders. The experiment lasted for 28 days (21 days adaptation and 7 days feed intake measurement). Ewes were fed hay and trained to use the electronic feeders (one feeding station per ewe) in which actual daily intake (H intake24) was measured. The pens were designed to maximize movement of trained ewes through an automated Walk-over-Weighing device, by using water and mineral salts as attractants. Total individual intake of hay measured in the automatic feeder at each meal (H intake) was compared with indirect estimates of feed intake determined using differences in the BW of the ewes (∆BW) before and 1 h following morning and afternoon feeding at fixed times. The BW, BCS, H intake, H intake24, as well as plasma non-esterified fatty acids (NEFA), glucose and insulin profiles were determined. The BW was higher in ADU v. HOG but BCS was not affected by parity. The H intake24 was affected by day of experiment as a consequence of reduced availability and intake of water on one day. Plasma glucose, NEFA and insulin were not affected by parity or day of experiment. The H Intake was and ∆BW tended to be higher in the morning in HOG, whereas H intake was and ∆BW tended to be higher in ADU at the afternoon meal. Irrespective of parity or feeding time, there was very strong correlation (r 2=0.93) between H intake and ∆BW. This relationship confirms that our indirect method of estimating individual forage intake was reliable within the strictly controlled conditions of the present experiment. The method appears suitable for use in short-term intensive group feeding situations, and has potential to be further developed for longer-term forage intake studies, with a view to developing a method for freely grazing ruminants.

Polyethylene glycol marker measured with NIRS gives a reliable estimate of the rangeland intake of grazing sheep.

Polyethylene glycol (PEG) measured with NIRS is known to be a valuable faecal marker when used in indoor experiments. In order to verify whether it can be used at pasture, an experiment was conducted with two trials. In trial 1, six Romane breed adult dry ewes placed in metabolism cages were fed daily with natural, freshly cut rangeland from a fertilised or unfertilised paddock for 6 weeks. Three ewes did not receive PEG and the three others were dosed with 10 g of PEG in solution form once daily until the end of the experiment to measure in vivo dry matter digestibility and PEG recovery rate for each forage quality. At the same time (trial 2), 15 ewe lambs and 14 lactating adult ewes suckling one or two lambs were allowed to graze together on the same herbage as that cut for indoor ewes. All animals were initially equipped with faecal bags emptied twice daily for collecting total faeces, and eight ewe lambs and seven adults were dosed once daily with 10 g of PEG. Faecal grab samples were collected for 4 to 5 days for each forage quality grazed. Indoor trial 1 showed that PEG had no effect on dry matter intake (DMI) or on digestibility. PEG recovery rates measured on fertilised (77.7%) and unfertilised (82.1%) forage were not different (P>0.05). PEG recovery rates measured at pasture did not differ (P>0.05) between pasture quality and animal type with an average value of 68.9%. Faecal output measured with bags or estimated with PEG and calculated DMI were not different (P>0.05) when PEG recovery rate measured at pasture was used. Conversely, using indoor PEG recovery values, significantly (P<0.05) or tended to overestimate faecal output. In conclusion, PEG could be used as a faecal marker administered at a minimal dose of 1% of DMI with a recovery rate measured under pasture conditions for pasture intake measurements on a group of animals at the same physiological stage but not for individual measurements.

The effects of parity, litter size, physiological state, and milking frequency on the metabolic profile of Lacaune dairy ewes.

Effects of parity (primiparous, PRIM vs multiparous, MULT) and litter size (singletons, SING vs twins, TWIN) on metabolic profiles from 1 wk before lambing to the end of lactation were studied in 48 Lacaune dairy ewes reared in confinement during most of the year and grazed on improved pastures at the end of lactation (summer). Another group of 48 ewes was incorporated during the milking period (ie, from 1 wk after weaning), to measure the effects of milking frequency (1 vs 2 milkings per day) on intake, milk production and composition, and body energy usage. Thus, in a 2 × 2 × 2 factorial design, ewes (n = 96) were allocated to homogeneous groups according to body weight (BW) and body condition score (BCS) and were monitored from late pregnancy to late lactation as a function of parity (PRIM, n = 48; MULT, n = 48), litter size (LSi) (SING, n = 40; TWIN, n = 56) and daily milking frequency (FREQ; milked once, ONE; n = 48; or twice, TWO; n = 48). Individual BW, BCS, plasma metabolites, and metabolic hormones were measured regularly (ie, 9 consecutive sampling dates). The BW was higher in MULT but no differences because of LSi or FREQ were detected at the intra-parity group level. The BCS was higher in MULT and in ewes with SING throughout the experiment. The latter was related to the demands for body reserves mobilization, as expressed by higher nonesterified fatty acids and ß-hydroxybutyrate concentrations in ewes with TWIN from late pregnancy to weaning (35 d postpartum) in both PRIM and MULT ewes. This was consistent with higher insulin in MULT and higher triiodothyronine, leptin and insulin-like growth factor 1 in ewes with SING during this period. Differences in energy balance because of FREQ were evident after interpretation of plasma nonesterified fatty acids, glucose, insulin, and leptin concentration during the milking period. At similar feed intakes, ewes in ONE were in positive balance with regard to TWO. Overall, clear effects of parity, LSi, physiological states, and FREQ on metabolic profiles were found because of differences in nutrient partitioning when combining these experimental factors. Without considering FREQ, changes in metabolic measures in milking period were marginal compared with the periparturient adjustments performed until weaning to compensate energy deficiencies.

Polyethylene glycol compared with ytterbium oxide as a total faecal output marker to predict organic matter intake of dairy ewes fed indoors or at pasture.

Several external markers can be used for estimating total faecal output in view of assessing ruminant intake at pasture. Among them, ytterbium (Yb) has been used for many years in various conditions. Polyethylene glycol (PEG) is a promising external marker because it can be rapidly determined using near-infrared spectroscopy (NIRS). The study consisted of 24 adult lactating dairy ewes over three periods (P1, P2 and P3), fed with three different diets: P1, total mixed ration (TMR); P2, Italian ryegrass (IRG); and P3, pasture. After an adaptation period, the ewes were administered a daily dose of ytterbium oxide (0.35 g/day) and PEG (20 g/day) for 2 weeks. During the last week, the daily organic matter intake (OMIOBS) was measured. Faecal samples were collected at milking time (0800 and 1600 h) to determine marker content, using only samples collected in the morning (PEGm) or by averaging samples (Yb, PEGma). Faecal marker content made it possible to assess total faecal output, either using the two recovery rates for PEG (0.98 or 0.87) or not. The OMIOBS was assessed on the basis of total faeces estimated with Yb (OMIYb) or PEG (OMIPEG), and the digestibility was calculated on the basis of feed analysis. With total TMR (P1), the OMIPEG, corrected with recovery rate (OMIPEGm98) or not corrected (OMIPEGm) was 2.40 kg/day and 2.50 kg/day, respectively, and was not different (P>0.05) from OMIOBS (2.51 kg/day), whereas OMIYb was lower (2.14 kg/day) (P<0.001). With IRG (P2), OMIPEGm98 (1.67 kg/day), OMIPEGm87 (1.51 kg/day) and OMIYb (1.59 kg/day) were not different (P>0.05) from OMIOBS (1.57 kg/day). With pasture (P3), the OMIPEGm (1.54 kg/day) and OMIPEGm98 (1.48 kg/day) were not different (P>0.05) from the OMI assessed from the biomass measurement (1.52 kg/day). The OMIYb (1.36 kg/day) was lower (P<0.05) but not different from OMIPEGm98 and OMIPEGm87. Spearman's rank correlation between OMIOBS and other OMIs (predicted with Yb or PEG P1 and P2) showed that it is possible to rank animals using PEG when there is a sufficiently wide range of OMIOBS (1.65 to 2.8 kg/day in P1) but not within a narrower range (1.47 to 1.72 kg/day in P2). In conclusion, the present study confirms that PEG is a valuable external faecal marker, easy to prepare (solution), administer and determine (NIRS). It can be used to assess intake with numerous animals at pasture, but only for groups, and not to quantitatively estimate individual OMI.

A method for estimating dry forage intake by sheep using polyethylene glycol as a faecal marker measured with NIRS.

In experiments based on ruminants' individual dry matter intake (DMI) assessment, several external markers can be used to estimate faecal output when total faeces collection is not possible. However, preparation of the markers to be administered and analytical procedures used for marker content determination are time-consuming thus strongly limiting the number of animals involved in the experiments. In this paper, polyethylene glycol (PEG, molecular weight 6000 da) was tested as a faecal marker. Four trials were conducted on dry, non-lactating ewes kept in digestibility crates that allowed individual measurements. The overall experiment was designed to assess the major factors that could lessen the effectiveness of this method, assuming that the use of grab samples of faeces is sufficient. Trial 1 was designed to test two levels of PEG (20 and 40 g/day) administered in two equal amounts. Trial 2 was designed to test the effect of either a single morning (0800 h) dose (20 g/day) or a twice daily administration (0800 and 1600 h) of the same fractionated dose. Trial 3 was designed to test a 20 g/day dose of PEG administered once daily to ewes fed with hays of different qualities: medium (MH) and low (LH). In trial 4, a lower dose of PEG (10 g/day) was administered once a day to ewes fed with fresh oat-vetch forage. It was demonstrated that PEG could be precisely estimated (average prediction error = 3.47 g/kg) with near-infrared reflectance spectroscopy (NIRS). On the basis of the four trials, it has been proved that PEG administration (20 and 40 g/day) did not significantly affect the DMI of ewes fed dry diets (trials 1, 2 and 3), whereas there was an unexpected increase of DMI for ewes fed exclusively with green feed (trial 4) without DM digestibility modification. Providing PEG as a single dose (0800 h) or split into two equal parts (0800 and 1600 h) did not alter the estimated DMI. Considering the interest of grab sampling, there were clear variations of PEG in faeces with higher concentrations observed at 0800 and 1600 h and lower concentrations at 1400 h. Consequently, with PEG (measured with NIRS) administered once and using the grab sampling procedure (morning collection), it is possible to estimate the DMI of dry feeds with good accuracy. For green feeds, more research is needed as the estimated results are still highly variable.

Maternal periconceptional undernutrition in Merinos d'Arles sheep: 1. Effects on pregnancy and reproduction results of dams and offspring growth performances.

Maternal undernutrition during gestation can condition offspring adult health, with the periconceptional period pointed out as a key period. The aim of this study was to evaluate the effects of maternal periconceptional undernutrition on pregnancy and offspring growth performance in sheep. 52 Merinos d'Arles ewes were fed to requirements (control group, C), whereas 64 ewes received 50% of their dietary needs from -15 to +30 days post-conception (restricted group, R). Thereafter, both groups were fed according to needs. Maternal body weight (BW), body condition score (BCS) and Non Esterified Fatty Acids (NEFA), progesterone, leptin and cortisol plasma concentrations were monitored weekly during the restriction period and the following month, then monthly until weaning. Lambs were weighed weekly until weaning at 22 kg BW, then monthly. Plasma leptin was monitored monthly in lambs. The BW, BCS, and leptin concentrations were significantly decreased, whereas NEFA and cortisol concentrations were increased in R dams. Maximum progesterone concentration was higher in R ewes that had a high (10-25%) vs. low (0-10%) BW loss during restriction (27.9 ± 2.59 vs. 20.8 ± 2.00 ng/mL, P < 0.05). Overall, gestation was significantly longer in the R group (151.0 ± 0.3 vs. 149.4 ± 0.4 days, P < 0.001). There was no difference between groups for pregnancy rates, prolificacy, birth weight and lamb mortality, but the proportion of male lambs was significantly higher in the R group, only for singletons (16/26 vs. 9/26, P < 0.05). Lamb growth was not significantly modified by treatment. Leptin concentrations at birth were significantly lower in R vs. C males (6.15 ± 0.13 ng/mL vs. 7.42 ± 0.36 ng/mL, P < 0.05), whereas in females, leptin concentrations were significantly higher in R vs. C lambs at 4 mo of age (7.31 ± 0.27 ng/mL vs. 6.41 ± 0.29 ng/mL, P < 0.05). These results indicate that maternal periconceptional undernutrition in a hardy breed does not significantly affect lamb birth weight and growth rates, in contrast to previous reports in other breeds, suggesting that caution must be taken when extrapolating programming data between breeds and breeding conditions.

Outcomes of hospitalisation for right heart failure in pulmonary arterial hypertension.

The aim of this study was to examine the causes and outcomes of hospitalisation in patients with pulmonary arterial hypertension (PAH). 205 consecutive hospitalisations occurring between 2000 and 2009 in 90 PAH patients were studied. The leading causes for hospitalisation were right heart failure (RHF; 56%), infection (16%) and bleeding disorders (8%). For patients with RHF, in-hospital mortality was 14% overall, 46% for patients receiving inotropes and 48% for those admitted to the intensive care unit. The predictors for in-hospital mortality were the presence of connective tissue disease (CTD) (OR 4.92), systolic blood pressure <100 mmHg (OR 4.32) and Na ≤ 136 mEq · L(-1) (OR 4.29). Mortality after discharge was 13, 26 and 35% at 3, 6 and 12 months, respectively. World Health Organization functional class prior to admission, renal dysfunction, Charlson comorbidity index, and the presence of CTD were all predictors of mortality after discharge. Hyponatraemia and low systolic blood pressure upon admission and underlying CTD are the main prognostic factors for in-hospital mortality in patients with PAH admitted for RHF. The short-term outcomes after discharge are poor and remarkably worse in patients with underlying CTD or renal impairment. Early recognition of these factors may guide decisions regarding more aggressive therapy, including consideration for lung transplantation.

Disproportionate elevation of N-terminal pro-brain natriuretic peptide in scleroderma-related pulmonary hypertension.

N-terminal pro-brain natriuretic peptide (NT-proBNP) is a marker of neurohormonal activation that is useful in the diagnosis and prognosis of various forms of pulmonary arterial hypertension (PAH). We sought to characterise and compare NT-proBNP in a cohort of PAH related to systemic sclerosis (PAH-SSc) and idiopathic PAH (IPAH) patients. NT-proBNP levels, collected from PAH-SSc and IPAH patients followed prospectively, were compared and correlated with haemodynamic variables. Cox proportional hazard models were created to assess the predictive value of NT-proBNP. 98 patients (55 PAH-SSc, 43 IPAH) were included. Haemodynamics were similar, except for lower mean pulmonary arterial pressure in PAH-SSc. NT-proBNP levels were significantly higher in PAH-SSc (3,419+/-3,784 versus 1,393+/-1,633 pg x mL(-1); p<0.01) and were more closely related to haemodynamics in PAH-SSc than IPAH. 28 patients died. NT-proBNP predicted survival (hazard ratio (HR) 3.18; p<0.01) in the overall cohort; however, when stratified by group, predicted survival only in PAH-SSc (HR 3.07, p<0.01 versus 2.02, p = 0.29 in IPAH). This is the first description showing NT-proBNP levels are 1) significantly higher in PAH-SSc than IPAH despite less severe haemodynamic perturbations, and 2) stronger predictors of survival in PAH-SSc, suggesting that neurohormonal regulation may differ between PAH-SSc and IPAH. Future studies to define pertinent mechanisms are warranted.

Estimating pulmonary artery pressures by echocardiography in patients with emphysema.

In patients with emphysema being evaluated for lung volume reduction surgery, Doppler echocardiography has been used to screen for pulmonary hypertension as an indicator of increased peri-operative risk. To determine the accuracy of this test, the present authors compared the results of right heart catheterisations and Doppler echocardiograms in 163 patients participating in the cardiovascular substudy of the National Emphysema Treatment Trial. Substudy patients had both catheterisation and Doppler echocardiography performed before and after randomisation. In 74 paired catheterisations and echocardiograms carried out on 63 patients, the mean values of invasively measured pulmonary artery systolic pressures and the estimated right ventricular systolic pressures were similar. However, using the World Health Organization's definitions of pulmonary hypertension, echocardiography had a sensitivity of 60%, specificity of 74%, positive predictive value of 68% and a negative predictive value of 67% compared with the invasive measurement. Bland-Altman analysis revealed a bias of 0.37 kPa with 95% limits of agreement from -2.5-3.2 kPa. In patients with severe emphysema, echocardiographic estimates of pulmonary artery pressures correlate very weakly with right heart catheterisations, and the test characteristics (e.g. sensitivity, specificity, etc.) of echocardiographic assessments are poor.

Addition of sildenafil to bosentan monotherapy in pulmonary arterial hypertension.

Combination therapy has been recommended for the treatment of pulmonary arterial hypertension (PAH). However, there is scant information on combination therapy after failure of monotherapy, particularly in patients with scleroderma-associated PAH (PAH-SSD). From a group of 82 consecutive patients with PAH who received initial bosentan monotherapy, a total of 13 idiopathic PAH (IPAH) and 12 PAH-SSD patients requiring additional therapy with sildenafil were studied. Sildenafil was added for clinical deterioration based upon symptoms, New York Heart Association (NYHA) classification or 6-min walk distance (6MWD). Clinical data and haemodynamics were collected at baseline. Assessments were made at 1-3-month intervals. At baseline, there were no differences in demographics, NYHA classification, haemodynamics or 6MWD between the two groups. After initiation of bosentan, both groups experienced clinical improvement but ultimately deteriorated (median time to monotherapy failure 792 versus 458 days for IPAH and PAH-SSD patients, respectively). After addition of sildenafil, more IPAH patients tended to improve in NYHA class (five out of 13 versus two out of 12) and walked further (mean difference in 6MWD 47+/-77 m versus -7+/-40 m) compared with PAH-SSD patients. In conclusion, addition of sildenafil after bosentan monotherapy failure improved New York Heart Association class and 6-min walk distance in idiopathic pulmonary arterial hypertension patients but failed to improve either parameter in scleroderma-associated pulmonary arterial hypertension patients. Additional studies are needed to assess the tolerability and efficacy of this combination in patients with scleroderma-associated pulmonary arterial hypertension.

Acute respiratory distress syndrome complicating Plasmodium vivax malaria.

Malaria is one of the most common infectious diseases in the world, and severe respiratory complications have been described mainly in association with Plasmodium falciparum. We describe a case of acute respiratory distress syndrome complicating infection with P. vivax in the setting of relatively low parasitemia in a 47-yr-old woman after a brief trip to Papua New Guinea. A review of the literature shows that pulmonary complications of P. vivax are rare but occur more frequently than generally acknowledged. Pathogenic mechanisms of these complications are discussed.

Management of venous thromboembolic disease in the chronically critically ill patient.

Although PE is the most common preventable cause of death among U.S. hospital patients, proper treatment of thromboembolism and adequate prophylaxis in high-risk patients have been shown to be effective in saving lives. Because clinical symptoms and signs of thromboembolic disease are often nonspecific, early diagnosis and treatment rely on the capacity of physicians to adequately identify a patient at risk, choose the appropriate diagnostic modalities in a cost-effective fashion, and promptly initiate treatment. The diagnosis of VTE is particularly challenging in patients who are in the post acute period of a complex medical or surgical illness. Avenues that need to be further explored include various diagnostic tests such as spiral CT, MR imaging, and transesophageal echocardiography, which are less invasive than the present gold standard of pulmonary angiography. Also needed are better clinical data regarding the optimal choice of preventive therapy (e.g., unfragmented heparin or LMWH or mechanical devices) and clinical outcome of such therapy in patients with prolonged illness.

Phosphorylation of xanthine dehydrogenase/oxidase in hypoxia.

The enzyme xanthine oxidase (XO) has been implicated in the pathogenesis of several disease processes, such as ischemia-reperfusion injury, because of its ability to generate reactive oxygen species. The expression of XO and its precursor xanthine dehydrogenase (XDH) is regulated at pre- and posttranslational levels by agents such as lipopolysaccharide and hypoxia. Posttranslational modification of the protein, for example through thiol oxidation or proteolysis, has been shown to be important in converting XDH to XO. The possibility of posttranslational modification of XDH/XO through phosphorylation has not been adequately investigated in mammalian cells, and studies have reported conflicting results. The present report demonstrates that XDH/XO is phosphorylated in rat pulmonary microvascular endothelial cells (RPMEC) and that phosphorylation is greatly increased ( approximately 50-fold) in response to acute hypoxia (4 h). XDH/XO phosphorylation appears to be mediated, at least in part, by casein kinase II and p38 kinase as inhibitors of these kinases partially prevent XDH/XO phosphorylation. In addition, the results indicate that p38 kinase, a stress-activated kinase, becomes activated in response to hypoxia (an approximately 4-fold increase after 1 h of exposure of RPMEC to hypoxia) further supporting a role for this kinase in hypoxia-stimulated XDH/XO phosphorylation. Finally, hypoxia-induced XDH/XO phosphorylation is accompanied by a 2-fold increase in XDH/XO activity, which is prevented by inhibitors of phosphorylation. In summary, this study shows that XDH/XO is phosphorylated in hypoxic RPMEC through a mechanism involving p38 kinase and casein kinase II and that phosphorylation is necessary for hypoxia-induced enzymatic activation.

Lung redox homeostasis: emerging concepts.

This symposium was organized to present some aspects of current research pertaining to lung redox function. Focuses of the symposium were on roles of pulmonary endothelial NADPH oxidase, xanthine oxidase (XO)/xanthine dehydrogenase (XDH), heme oxygenase (HO), transplasma membrane electron transport (TPMET), and the zinc binding protein metallothionein (MT) in the propagation and/or protection of the lung or other organs from oxidative injury. The presentations were chosen to reflect the roles of both intracellular (metallothionein, XO/XDH, and HO) and plasma membrane (NADPH oxidase, XO/XDH, and unidentified TPMET) redox proteins in these processes. Although the lung endothelium was the predominant cell type under consideration, at least some of the proposed mechanisms operate in or affect other cell types and organs as well.

Bilateral diaphragm paralysis secondary to central von Recklinghausen's disease.

Bilateral paralysis of the diaphragm is either idiopathic or associated with several medical conditions, including trauma or thoracic surgery, viral infections, and neurologic congenital or degenerative disorders. We describe the case of a 36-year-old man with a history of neurofibromatosis who developed severe bilateral diaphragmatic paralysis from involvement of the phrenic nerve roots with neurofibromas. The patient manifested progressive exertional dyspnea and debilitating orthopnea requiring the use of noninvasive mechanical ventilation at night. A review of the literature reveals that neurofibromatosis is an unrecognized cause of diaphragmatic paralysis.