Comparison of ultrasound-guided transmuscular quadratus lumborum block catheter technique with surgical pre-peritoneal catheter for postoperative analgesia in abdominal surgery: a randomised controlled trial.

Following abdominal surgery, the provision of postoperative analgesia with local anaesthetic infusion through both transmuscular quadratus lumborum block and pre-peritoneal catheter have been described. This study compared these two methods of postoperative analgesia following laparotomy. Eighty-two patients 18-85 years of age scheduled to undergo elective surgery were randomly allocated to receive either transmuscular quadratus lumborum block or pre-peritoneal catheter block. In the transmuscular quadratus lumborum group, an 18-gauge Tuohy needle was passed through the quadratus lumborum muscle under ultrasound guidance to reach its anterior aspect. A 20-ml bolus of ropivacaine 0.375% was administered and catheters placed bilaterally. In the pre-peritoneal catheter group, 20 ml of ropivacaine 0.375% was infiltrated at each of three subcutaneous sub-fascial levels, and pre-peritoneal plane catheters were placed bilaterally. Both groups received an infusion of ropivacaine 0.2% at 5 ml.h-1 , continued up to 48 h along with a multimodal analgesic regime that included regular paracetamol and patient-controlled analgesia with fentanyl. The primary end-point was postoperative pain score on coughing, assessed using a numerical rating score (0-10). Secondary outcomes were pain score at rest, fentanyl usage until 48 h post-operation, satisfaction scores and costs. There was no treatment difference between the two groups for pain score on coughing (p = 0.24). In the transmuscular quadratus lumborum group, there was a reduction in numerical rating score at rest (p = 0.036) and satisfaction scores on days 1 and 30 (p = 0.004, p = 0.006, respectively), but fentanyl usage was similar. In the transmuscular quadratus lumborum group, the highest and lowest blocks observed in the recovery area were T4 and L1, respectively. The transmuscular quadratus lumborum technique cost 574.64 Australian dollars more per patient than the pre-peritoneal catheter technique.

Haemodynamic effects of parenteral vs. enteral paracetamol in critically ill patients: a randomised controlled trial.

Paracetamol is a commonly used drug in the intensive care unit. There have been reports in the literature of an association with significant hypotension, a potentially important interaction for labile critically ill patients. Route of administration may influence the incidence of hypotension. This single-centre, prospective, open-label, randomised, parallel-arm, active-control trial was designed to determine the incidence of hypotension following the administration of paracetamol to critically ill patients. Fifty adult patients receiving paracetamol for analgesia or pyrexia were randomly assigned to receive either the parenteral or enteral formulation of the drug. Paracetamol concentrations were measured at baseline and at multiple time points over 24 h. The maximal plasma paracetamol concentration was significantly different between routes; 156 vs. 73 micromol.l(-1) [p = 0.0005] following the first dose of parenteral or enteral paracetamol, respectively. Sixteen hypotensive events occurred in 12 patients: parenteral n = 12; enteral n = 4. The incident rate ratio for parenteral vs. enteral paracetamol was 2.94 (95% CI 0.97-8.92; p = 0.06). The incidence of hypotension associated with paracetamol administration is higher than previously reported and tends to be more frequent with parenteral paracetamol.

Hydrochemical profiles in urban groundwater systems: New insights into contaminant sources and pathways in the subsurface from legacy and emerging contaminants.

It has long been known that groundwaters beneath urban areas carry a fingerprint from urban activities but finding a consistent tracer for anthropogenic influence has proved elusive. The varied sources of urban contaminants means that a single consistent and inexpensive means of tracing the fate of urban contaminants is not generally possible and multiple tracers are often required to understand the contaminant sources and pathways in these complex systems. This study has utilized a combination of micro-organic (MO) contaminants and inorganic hydrochemistry to trace recharge pathways and quantify the variability of groundwater quality in multi-level piezometers in the city of Doncaster, UK. A total of 23 MOs were detected during this study, with more compounds consistently detected during higher groundwater table conditions highlighting the importance of sampling under different hydrological conditions. Four of the compounds detected are EU Water Framework Directive priority substances: atrazine, simazine, naphthalene and DEHP, with a maximum concentration of 0.18, 0.03, 0.2, 16µg/l respectively. Our study shows that the burden of the banned pesticide atrazine persists in the Sherwood Sandstone and is detected at two of the three study sites. Emerging contaminants are seen throughout the borehole profiles and provide insights into transient pathways for contaminant migration in the sub-surface. Long term changes in inorganic hydrochemistry show possible changes in contaminant input or the dissolution of minerals. Nitrate was detected above 50mg/l but on the whole nitrate concentrations have declined in the intervening years either due to a reduction of nitrate application at the surface or a migration of peak nitrate concentrations laterally or to greater depth. This study shows that multiple tracers together with multi-level piezometers can give a better resolution of contaminant pathways and variable flow regimes within the relatively uncomplicated aquifer of the Sherwood Sandstone compared with single long screened wells.

Temperature effects on hatching and viability of Juvenile Gill Lice, Salmincola californiensis.

Salmonids of the genus Oncorhynchus, distributed throughout the Pacific Rim, can be infected by the gill lice species Salmincola californiensis (Dana, 1852), which makes them one of the most broadly distributed gill lice species. Despite their broad distribution and valuable obligate salmonid hosts, relatively little is known about S. californiensis. We evaluated effects of temperature on timing of S. californiensis hatching and survival of copepodids, and provide information on brood size and variability. Our results suggest that temperature was a primary driver of timing of S. californiensis hatching and post-hatching survival. Prior to this study, the free-swimming stage of S. californiensis was reported to survive approximately 2 days without a suitable host. We observed active copepodids 13 days after hatch with some individuals from most (>90%) viable egg sacs at all temperature treatments surviving ≥5 days. Our findings indicate that warmer temperatures could increase development rates of gill lice at certain life stages, potentially increasing fecundity. This information coupled with predictions that warmer water temperatures could intensify crowding of coldwater fishes, stress, and parasite transmission suggests that climate change could exacerbate negative effects of S. californiensis on ecologically and economically important salmonids.

Placental expression of adenosine A(2A) receptor and hypoxia inducible factor-1 alpha in early pregnancy, term and pre-eclamptic pregnancies: interactions with placental renin-angiotensin system.

Hypoxia-inducible factors (HIFs), adenosine and tissue renin-angiotensin-system (RAS) promote angiogenesis and vascularisation. We investigated the temporal expression placental adenosine A2AR receptor and HIF-1α in early pregnancy and at delivery in normotensive (NT) and pre-eclamptic (PE) women. Results were compared to our previously reported angiotensin receptor data. Expression of A2AR and HIF-1α was highest at ≤10 weeks, positively correlated through pregnancy and was higher in PE than NT at delivery. The A2AR associated with the AT4R only in early pregnancy. We suggest adenosine and RAS may interact to promote placentation with a potential adaptation to poor placental perfusion in PE.

Using UHF proximity loggers to quantify male-female interactions: a scoping study of estrous activity in cattle.

Reproductive efficiency is an important determinant of profitable cattle breeding systems and the success of assisted reproductive techniques (ART) in wildlife conservation programs. Methods of estrous detection used in intensive beef and dairy cattle systems lack accuracy and remain the single biggest issue for improvement of reproductive rates and such methods are not practical for either large-scale extensive beef cattle enterprises or free-living mammalian species. Recent developments in UHF (ultra high frequency) proximity logger telemetry devices have been used to provide a continuous pair-wise measure of associations between individual animals for both livestock and wildlife. The objective of this study was to explore the potential of using UHF telemetry to identify the reproductive cycle phenotype in terms of intensity and duration of estrus. The study was conducted using Belmont Red (interbred Africander Brahman Hereford-Shorthorn) cattle grazing irrigated pasture on Belmont Research Station, northeastern Australia. The cow-bull associations from three groups of cows each with one bull were recorded over a 7-week breeding season and the stage of estrus was identified using ultrasonography. Telemetry data from bull and cows, collected over 4 8-day logger deployments, were log transformed and analyzed by ANOVA. Both the number and duration of bull-cow affiliations were significantly (P<0.001) greater in estrous cows compared to anestrus cows. These results support the development of the UHF technology as a hands-off and noninvasive means of gathering socio-sexual information on both wildlife and livestock for reproductive management.

Genome-wide association studies of female reproduction in tropically adapted beef cattle.

The genetics of reproduction is poorly understood because the heritabilities of traits currently recorded are low. To elucidate the genetics underlying reproduction in beef cattle, we performed a genome-wide association study using the bovine SNP50 chip in 2 tropically adapted beef cattle breeds, Brahman and Tropical Composite. Here we present the results for 3 female reproduction traits: 1) age at puberty, defined as age in days at first observed corpus luteum (CL) after frequent ovarian ultrasound scans (AGECL); 2) the postpartum anestrous interval, measured as the number of days from calving to first ovulation postpartum (first rebreeding interval, PPAI); and 3) the occurrence of the first postpartum ovulation before weaning in the first rebreeding period (PW), defined from PPAI. In addition, correlated traits such as BW, height, serum IGF1 concentration, condition score, and fatness were also examined. In the Brahman and Tropical Composite cattle, 169 [false positive rate (FPR) = 0.262] and 84 (FPR = 0.581) SNP, respectively, were significant (P < 0.001) for AGECL. In Brahman, 41% of these significant markers mapped to a single chromosomal region on BTA14. In Tropical Composites, 16% of these significant markers were located on BTA5. For PPAI, 66 (FPR = 0.67) and 113 (FPR = 0.432) SNP were significant (P < 0.001) in Brahman and Tropical Composite, respectively, whereas for PW, 68 (FPR = 0.64) and 113 (FPR = 0.432) SNP were significant (P < 0.01). In Tropical Composites, the largest concentration of PPAI markers were located on BTA5 [19% (PPAI) and 23% (PW)], and BTA16 [17% (PPAI) and 18% (PW)]. In Brahman cattle, the largest concentration of markers for postpartum anestrus was located on BTA3 (14% for PPAI and PW) and BTA14 (17% PPAI). Very few of the significant markers for female reproduction traits for the Brahman and Tropical Composite breeds were located in the same chromosomal regions. However, fatness and BW traits as well as serum IGF1 concentration were found to be associated with similar genome regions within and between breeds. Clusters of SNP associated with multiple traits were located on BTA14 in Brahman and BTA5 in Tropical Composites.

Expression of AT1R, AT2R and AT4R and their roles in extravillous trophoblast invasion in the human.

The placental renin-angiotensin system (RAS) is active from early pregnancy and may have a role in placentation. Angiotensin II (AngII) acts via binding to receptor types AT1R and AT2R. Recently smaller peptide members of the angiotensin family have been recognised as having biological relevance. Angiotensin (3-8) (AngIV) has a specific receptor (AT4R) and evokes hypertrophy, vasodilatation and vascular inflammatory response. The aim of this study was to characterise placental expression of AT1R, AT2R and AT4R, and to determine whether AngII and AngIV regulate extravillous trophoblast (EVT) invasion, apoptosis and proliferation. Placental samples were obtained from women undergoing elective surgical termination of pregnancy (TOP) at 8-10 weeks gestation (early TOP), 12-14 weeks gestation (mid TOP) or at delivery following normal pregnancy or with pre-eclampsia (PE). Immunohistochemistry and qRT-PCR were performed to determine placental mRNA and protein expression of AT1R, AT2R and AT4R at all gestational ages. EVT invasion following culture with AngII or AngIV was assessed in early placental tissue using Matrigel invasion assays. Invasion was assessed on day 6 of culture and placental explants were harvested for immunohistochemical analysis of apoptosis and proliferation. The results from qRT-PCR and immunohistochemistry showed placental AT1R expression which did not vary with gestation. The highest levels of expression of AT2R were found in early and mid TOP placentae compared to term pregnancy. Expression of AT4R was increased in term placentae, with a significant reduction in PE placentae. Moreover, culture with AngIV or AngII increased EVT invasion from placental explants, which showed increased trophoblast proliferation and reduced apoptosis. This study has characterised expression of AT4R and AT1R and AT2R in human placenta throughout normal pregnancy and in PE. Both AngIV and AngII may play an important role in normal pregnancy.

Differential expression and distribution of placental glutathione peroxidases 1, 3 and 4 in normal and preeclamptic pregnancy.

Preeclampsia is a pregnancy-specific condition affecting 2-7% of women and a leading cause of perinatal and maternal morbidity and mortality; it may also predispose the mother and fetus to increased risks of adult cardiovascular disease. The selenoprotein glutathione peroxidases (GPxs) have critical roles in regulating antioxidant status. OBJECTIVES, STUDY DESIGN AND MAIN OUTCOME MEASURES: Immunohistochemical measurements of GPx1, GPx3 and GPx4 protein expression were performed on samples taken from three standardised sampling sites between the cord insertion and the periphery of the placenta from 12 normotensive, and 12 preeclamptic women to establish if their expression differed between sampling sites. Total GPx activities were also examined from the three sampling sites of these placentae. RESULTS: There were highly significant reductions in overall immunohistochemical staining of all 3 GPxs in the preeclampsia compared to normotensive placentae (GPx1: P=0.016; GPx3: P=0.003; GPx4: P<0.001). Furthermore, graded differences in expression between the standardised placental sampling sites were also found for GPx3 (higher in the inner region, P=0.05) and GPx4 (higher in the periphery, P=0.02) but not GPx1. Placental GPx enzyme activity was also significantly reduced in tissue from preeclamptic women as compared to normotensive women (P=0.007; the difference was more pronounced nearest the cord insertion). CONCLUSIONS: We have shown highly significant reductions in expression of all three major classes of GPx in placentae from women with preeclampsia, and distribution gradients in activity, which may relate to the differential oxygenation of regions of the placenta.

Cantilever-based sensing: the origin of surface stress and optimization strategies.

Many interactions drive the adsorption of molecules on surfaces, all of which can result in a measurable change in surface stress. This article compares the contributions of various possible interactions to the overall induced surface stress for cantilever-based sensing applications. The surface stress resulting from adsorption-induced changes in the electronic density of the underlying surface is up to 2-4 orders of magnitude larger than that resulting from intermolecular electrostatic or Lennard-Jones interactions. We reveal that the surface stress associated with the formation of high quality alkanethiol self-assembled monolayers on gold surfaces is independent of the molecular chain length, supporting our theoretical findings. This provides a foundation for the development of new strategies for increasing the sensitivity of cantilever-based sensors for various applications.

Decidual leucocyte populations in early to late gestation normal human pregnancy.

Most research on human decidual leucocytes to date has focused on the predominant CD56+ uterine natural killer (uNK) cell population in early pregnancy. Few reports have documented decidual leucocyte populations after 13 weeks gestation and in late pregnancy. Placental bed (decidua basalis) and non-placental bed (decidua parietalis) biopsies from normal pregnancies were taken from women undergoing termination of pregnancy in the 1st and 2nd trimesters and following Caesarean section in the 3rd trimester. Immunohistochemistry was used to quantify the numbers of decidual cells expressing CD56, CD3, CD8, CD94, NKG2A and CD14 and double labelled CD161+CD3+ NKT-like cells. Although a significant reduction in CD56+ uNK cells was found in 3rd trimester samples compared with 1st and 2nd trimester decidua, a substantial residual CD56+ leucocyte population was identified in 3rd trimester decidua. Expression of the KIR CD94/NKG2A mirrored that of CD56 at all gestational ages, providing an explanation for the absence of cytotoxic responses at the fetal-maternal interface. There was no difference in leucocyte populations between decidua basalis and decidua parietalis. Double immunohistochemical labelling revealed small numbers of decidual CD3+CD56+ and CD8+CD56+ cells, which decreased in number at term, and CD161+CD3+ cells, which increased in number at term. No differences in leucocyte populations were detected between decidua parietalis and decidua basalis. In contrast to previous reports, a substantial residual CD56+ cell population was demonstrated in 3rd trimester decidua. Decidual cytotoxic T-lymphocytes did not alter in number during gestation, while in contrast CD14+ macrophages decreased at term, representing the smallest decidual population assessed.

Influence of birth weight on gene regulators of lipid metabolism and utilization in subcutaneous adipose tissue and skeletal muscle of neonatal pigs.

Epidemiological studies suggest that low-birth weight infants show poor neonatal growth and increased susceptibility to metabolic syndrome, in particular, obesity and diabetes. Adipose tissue development is regulated by many genes, including members of the peroxisome proliferator-activated receptor (PPAR) and the fatty acid-binding protein (FABP) families. The aim of this study was to determine the influence of birth weight on key adipose and skeletal muscle tissue regulating genes. Piglets from 11 litters were ranked according to birth weight and 3 from each litter assigned to small, normal, or large-birth weight groups. Tissue samples were collected on day 7 or 14. Plasma metabolite concentrations and the expression of PPARG2, PPARA, FABP3, and FABP4 genes were determined in subcutaneous adipose tissue and skeletal muscle. Adipocyte number and area were determined histologically. Expression of FABP3 and 4 was significantly reduced in small and large, compared with normal, piglets in adipose tissue on day 7 and in skeletal muscle on day 14. On day 7, PPARA and PPARG2 were significantly reduced in adipose tissue from small and large piglets. Adipose tissue from small piglets contained more adipocytes than normal or large piglets. Birth weight had no effect on adipose tissue and skeletal muscle lipid content. Low-birth weight is associated with tissue-specific and time-dependent effects on lipid-regulating genes as well as morphological changes in adipose tissue. It remains to be seen whether these developmental changes alter an individual's susceptibility to metabolic syndrome.

Bacterial delivery of a novel cytolysin to hypoxic areas of solid tumors.

The efficacy of current anti-cancer gene therapies is limited by the inability of gene vectors to penetrate the poorly vascularized, hypoxic regions of tumors, leaving these sites untreated. We describe a new approach for targeting gene therapy to these sites, which employs an attenuated strain of the non-pathogenic bacterium, Salmonella typhimurium, carrying an exogenous (that is, reporter or therapeutic) gene under the regulation of a new, highly hypoxia-inducible promoter (FF+20(*)). This bacterial vector was seen to rapidly migrate into, and thrive in, hypoxic areas of both mammary tumor spheroids grown in vitro and orthotopic mammary tumors after systemic injection. Using the reporter gene construct, FF+20(*)-lacZ, we show that bacterial expression of high levels of beta-galactosidase occurred only in hypoxic/necrotic sites of spheroids and tumors. We then replaced the reporter gene with one encoding a novel cytotoxic protein (HlyE) and showed that this was also expressed by bacteria only in hypoxic regions of murine mammary tumors. This resulted in a marked increase in tumor necrosis and reduced tumor growth. Our system represents a promising new strategy for delivering gene therapy to poorly vascularized regions of tumors and shows, for the first time, the efficacy of HlyE as an anti-tumor agent.

Hypertension and impaired renal function accompany juvenile obesity: the effect of prenatal diet.

Obesity has been suggested to have a detrimental impact on kidney structure and function, leading to focal glomerulosclerosis and hypertension. It is also associated with hyperleptinemia and elevated renal sympathetic nerve activity. Prenatal undernutrition promotes postnatal obesity, hypertension, and an altered renal structure and function. In this study, we examined the effects of prenatal nutrient restriction and juvenile obesity in sheep. We found that juvenile obesity led to chronic hyperleptinemia and reduced renal function as assessed by nuclear scintigraphy. Additional factors include hypertension, glomerulosclerosis, and increased kidney apoptosis. Prenatal undernutrition, synchronous with early kidney development, coupled postnatally with juvenile obesity had no effect on systemic pathophysiological sequalae associated with obesity per se. Hypertension, hyperleptinemia, and poor renal function were all observed in this group. All indices of renal pathology such as increased expression of proinflammatory cytokines, angiotensin II, glucocorticoid receptors, and increased apoptosis and glomerulosclerosis were entirely absent in obese prenatally undernourished offspring. Our data indicate that juvenile obesity per se leads to systemic hypertension and renal structural and functional pathology. Prenatal undernutrition effectively abolishes any renal histopathology associated with juvenile obesity.

Assessment of outcome over a 10-year period of patients admitted to a multidisciplinary adult intensive care unit with haematological and solid tumours.

The risk factors for time to mortality, censored at 30 days, of patients admitted to an adult teaching hospital ICU with haematological and solid malignancies were assessed in a retrospective cohort study. Patients, demographics and daily ICU patient data, from admission to day 8, were identified from a prospective computerized database and casenote review in consecutive admissions to ICU with haematological and solid tumours over a 10-year period (1989-99). The cohort, 108 ICU admissions in 89 patients was of mean age (+/-SD) 55+/-14 years; 43% were female. Patient diagnoses were leukaemia (35%), lymphoma (38%) and solid tumours (27%). Median time from hospital to ICU admission was five days (range 0-67). On ICU admission, 50% had septic shock and first day APACHE II score was 28+/-9. Forty-six per cent of patients were ventilated. ICU and 30-day mortality were 39% and 54% respectively. Multivariate Cox model predictors (P<0.05), using only ICU admission day data were: Charlson comorbidity index (CCI), time to ICU admission (days) and mechanical ventilation. For daily data (admission through day 8), predictors were: cohort effect (2nd vs 1st five-year period); CCI; time to ICU admission (days); APACHE II score and mechanical ventilation. Outcomes were considered appropriate for severity of illness and demonstrated improvement over time. Ventilation was an independent outcome determinant. Controlling for other factors, mortality has improved over time (1st vs 2nd five year period). Analysis restricted to admission data alone may be insensitive to particular covariate effects.

Surface stress, kinetics, and structure of alkanethiol self-assembled monolayers.

The surface stress induced during the formation of alkanethiol self-assembled monolayers (SAMs) on gold from the vapor phase was measured using a micromechanical cantilever-based chemical sensor. Simultaneous in situ thickness measurements were carried out using ellipsometry. Ex situ scanning tunneling microscopy was performed in air to ascertain the final monolayer structure. The evolution of the surface stress induced during coverage-dependent structural phase transitions reveals features not apparent in average ellipsometric thickness measurements. These results show that both the kinetics of SAM formation and the resulting SAM structure are strongly influenced both by the surface structure of the underlying gold substrate and by the impingement rate of the alkanethiol onto the gold surface. In particular, the adsorption onto gold surfaces having large, flat grains produces high-quality self-assembled monolayers. An induced compressive surface stress of 15.9 +/- 0.6 N/m results when a c(4x2) dodecanethiol SAM forms on gold. However, the SAMs formed on small-grained gold are incomplete and an induced surface stress of only 0.51 +/- 0.02 N/m results. The progression to a fully formed SAM whose alkyl chains adopt a vertical (standing-up) orientation is clearly inhibited in the case of a small-grained gold substrate and is promoted in the case of a large-grained gold substrate.

Application of a molecular method for the detection of group A rotaviruses in raw and treated water.

Group A human rotaviruses (HRVs) are the most important aetiological agents of acute viral gastroenteritis in infants and young children in both developing and industrialised countries. Rotaviruses are resistant to many chemical disinfectants and reportedly survive well in treated tapwater and sewage. In this study a group A specific reverse transcriptase-polymerase chain reaction (RT-PCR) followed by a nested-PCR was applied for the detection of HRVs in raw and treated drinking-water samples drawn at a water reclamation plant. For a period of two years (July 2000 to June 2002), borehole, raw and treated drinking-water samples were collected weekly. Viruses were recovered from the water samples using a glass wool adsorption-elution technique followed by secondary concentration using precipitation with polyethylene glycol. In the first year of the study group A HRVs were detected in 11% sewage samples, 8% partially treated waters and 5% final treated drinking waters. The results of the second year of the study showed the presence of group A HRVs in 11% sewage and untreated surface water samples, 15% partially treated water and 6.5% final treated drinking waters. No HRVs were detected in the water samples from the boreholes. The presence of group A HRVs in treated drinking-water samples suggested that this water could be a potential source of infection to consumers. The data also implied that either the water treatment did not remove HRVs or the treated water was contaminated post-treatment.

Modelling thirty-day mortality in the Acute Respiratory Distress Syndrome (ARDS) in an adult ICU.

Variables predicting thirty-day outcome from Acute Respiratory Distress Syndrome (ARDS) were analysed using Cox regression structured for time-varying covariates. Over a three-year period, 1996-1998, consecutive patients with ARDS (bilateral chest X-ray opacities, PaO2/FiO2 ratio of <200 and an acute precipitating event) were identified using a prospective computerized data base in a university teaching hospital ICU. The cohort, 106 mechanically ventilated patients, was of mean (SD) age 63.5 (15.5) years and 37% were female. Primary lung injury occurred in 45% and 24% were postoperative. ICU-admission day APACHE II score was 25 (8); ARDS onset time from ICU admission was 1 day (median: range 0-16) and 30 day mortality was 41% (95% CI: 33%-51%). At ARDS onset, PaO2/FiO2 ratio was 92 (31), 81% had four-quadrant chest X-ray opacification and lung injury score was 2.75 (0.45). Average mechanical ventilator tidal volume was 10.3 ml/predicted kg weight. Cox model mortality predictors (hazard ratio, 95% CI) were: APACHE II score, 1.15 (1.09-1.21); ARDS lag time (days), 0.72 (0.58-0.89); direct versus indirect injury, 2.89 (1.45-5.76); PaO2/FiO2 ratio, 0.98 (0.97-0.99); operative versus non-operative category, 0.24 (0.09-0.63). Time-varying effects were evident for PaO2/FiO2 ratio, operative versus non-operative category and ventilator tidal volume assessed as a categorical predictor with a cut-point of 8 ml/kg predicted weight (mean tidal volumes, 7.1 (1.9) vs 10.7 (1.6) ml/kg predicted weight). Thirty-day survival was improved for patients ventilated with lower tidal volumes. Survival predictors in ARDS were multifactorial and related to patient-injury-time interaction and level of mechanical ventilator tidal volume.

Possible involvement of inositol phosphoglycan-P in human parturition.

Preterm labour is a major cause of neonatal morbidity and mortality but the pathophysiology that underlies preterm labour is unknown. Inositolphosphoglycans (IPGs) comprise a ubiquitous family of putative carbohydrate second messengers and they have been linked to the pathogenesis of various conditions, including diabetes and pre-eclampsia. Studying IPG-P levels in normal and pre-eclamptic pregnancies, we noticed a constant rise of urinary IPG-P levels in all women at the time of delivery. A prospective pilot study of urinary IPG-P levels in 23 non-labouring and labouring women with uncomplicated pregnancies has, therefore, been performed. Levels of urinary IPG-P were significantly higher in labour than in the non-labouring group (P<0.0001). These higher levels have been found in both spontaneous and induced labour. The clinical significance of this observation with particular reference to the onset of labour itself is discussed.